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1. Patient-reported outcomes for measuring sleep disturbance in pediatric atopic dermatitis: Cross-sectional study of the Patient Reported Outcomes Measurement Information System pediatric sleep measures and actigraphy

Author

James W. Griffith, Anna B. Fishbein, Amy S. Paller, Christopher B. Forrest, Frank J. Penedo, and Jennifer Lor

Subjects
Sleep disorder, Patient-Reported Outcomes Measurement Information System, medicine.medical_specialty, Cross-sectional study, business.industry, Actigraphy, Dermatology, Atopic dermatitis, medicine.disease, Sleep in non-human animals, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Cronbach's alpha, Quality of life, 030220 oncology & carcinogenesis, medicine, Physical therapy, business
Abstract

Background Most children with atopic dermatitis(AD) suffer from sleep disturbance, but reliable and valid assessment tools are lacking. Objectives To test PROMIS (Patient Reported Outcomes Measurement Information System) sleep measures in pediatric AD and to develop an algorithm to screen, assess and intervene to reduce sleep disturbance. Methods A cross-sectional study was conducted with AD children ages 5-17 years and one parent(n=61), who completed sleep, itch, and AD-specific questionnaires; clinicians assessed disease severity. All children wore actigraphy watches for 1-week-objective sleep assessment. Results PROMIS sleep disturbance parent-proxy-reliability was high (Cronbach's α=0.90) and differentiated among Patient Oriented Eczema Measure (POEM)-determined disease severity groups (mean±SD in mild vs. moderate vs. severe was 55.7±7.5 vs. 59.8±10.8 vs. 67.1±9.5, p Limitations This was a local sample. Conclusions Sleep disturbance in pediatric AD should be screened using the POEM sleep question, with further assessment using the PROMIS sleep disturbance measure or objective sleep monitoring if needed.

Published
2023

2. Brain atrophy and endovascular treatment effect in acute ischemic stroke

Author

Daniel Bos, Aad van der Lugt, Charles B. L. M. Majoie, Sven Pr Luijten, Adriaan C.G.M. van Es, Diederik W.J. Dippel, Wim H. van Zwam, Yvo B.W.E.M. Roos, Frank J. Wolters, Robert J. van Oostenbrugge, Kars C.J. Compagne, Klinische Neurowetenschappen, MUMC+: MA Neurologie (3), RS: Carim - B05 Cerebral small vessel disease, MUMC+: Hersen en Zenuw Centrum (3), Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: Carim - B06 Imaging, Neurology, ACS - Atherosclerosis & ischemic syndromes, Amsterdam Neuroscience - Neurovascular Disorders, Radiology and Nuclear Medicine, ACS - Microcirculation, Radiology & Nuclear Medicine, and Epidemiology

Subjects
CT scan, medicine.medical_specialty, Ischemic stroke, medicine.diagnostic_test, business.industry, Computed tomography, Functional recovery, medicine.disease, Atrophy, Neurology, Internal medicine, Secondary analysis, VOLUME, SCORE, medicine, Cardiology, Endovascular treatment, acute stroke therapy, business, Acute ischemic stroke, POPULATION
Abstract

Background Brain atrophy is suggested to impair the potential for functional recovery after acute ischemic stroke. We assessed whether the effect of endovascular treatment is modified by brain atrophy in patients with acute ischemic stroke due to large vessel occlusion. Methods We used data from MR CLEAN, a multicenter trial including patients with acute ischemic stroke due to anterior circulation large vessel occlusion randomized to endovascular treatment plus medical care (intervention) versus medical care alone (control). We segmented total brain volume (TBV) and intracranial volume (ICV) on baseline non-contrast computed tomography (n = 410). Next, we determined the degree of atrophy as the proportion of brain volume in relation to head size (1 − TBV/ICV) × 100%, analyzed as continuous variable and in tertiles. The primary outcome was a shift towards better functional outcome on the modified Rankin Scale expressed as adjusted common odds ratio. Treatment effect modification was tested using an interaction term between brain atrophy (as continuous variable) and treatment allocation. Results We found that brain atrophy significantly modified the effect of endovascular treatment on functional outcome (P for interaction = 0.04). Endovascular treatment led to larger shifts towards better functional outcome in the higher compared to the lower range of atrophy (adjusted common odds ratio, 1.86 [95% CI: 0.97–3.56] in the lowest tertile vs. 1.97 [95% CI: 1.03–3.74] in the middle tertile vs. 3.15 [95% CI: 1.59–6.24] in the highest tertile). Conclusion Benefit of endovascular treatment is larger in the higher compared to the lower range of atrophy, demonstrating that advanced atrophy should not be used as an argument to withhold endovascular treatment.

Published
2022

4. Examining replicability in addictions research: How to assess and ways forward

Author

Frank J. Schwebel, Matthew R. Pearson, Katie Witkiewitz, and Dylan K. Richards

Subjects
Male, Replication crisis, Matching (statistics), Data collection, Alcohol Drinking, Data Collection, Medicine (miscellaneous), Replicate, Alcohol use disorder, medicine.disease, Article, Confidence interval, Behavior, Addictive, Alcoholism, Psychiatry and Mental health, Clinical Psychology, Research Design, Replication (statistics), medicine, Humans, Female, Psychology, Project MATCH, Randomized Controlled Trials as Topic, Clinical psychology
Abstract

Objective The high rate of statistically significant findings in the sciences that do not replicate in a new sample has been described as a "replication crisis." Few replication attempts have been conducted in studies of alcohol use disorder (AUD), and the best method for determining whether a finding replicates has not been explored. The goal of the current study was to conduct direct replications within a multisite AUD-randomized controlled trial and to test a range of replication metrics. Method We used data from a large AUD clinical trial (Project Matching Alcoholism Treatments and Client Heterogeneity [Project MATCH], n = 1,726) to simulate direct replication attempts. We examined associations between drinking intensity and negative alcohol-related consequences (Model 1), sex differences in drinking intensity (Model 2), and reductions in drinking following treatment (Model 3). We treated each of the 11 data collection sites as unique studies such that each subsample was treated as an "original" study, and the remaining 10 subsamples were viewed as "replication" studies. Replicability metrics included the consistency of statistical significance, overlapping confidence intervals, and consistency of the direction of the effect. We also tested effect replication and heterogeneity using meta-analysis. Results We observed between 0% and 100% replicability across the replicability metrics depending on which subsample was treated as the "original" study. Meta-analyses indicated results were more similar across subsamples with no significant heterogeneity for Models 1 and 2. Conclusions We recommend researchers focus on effect sizes and use meta-analysis to evaluate the level of replicability. We also encourage direct replication attempts and sharing of data and code to facilitate direct replication. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Published
2022

5. Mediators of lifestyle intervention effects on neonatal adiposity

Author

Lima, Rodrigo Antunes, Desoye, Gernot, Simmons, David, van Poppel, Mireille Nicoline Maria, Devlieger, Roland, Galjaard, Sander, Corcoy, Rosa, Adelantado, Juan M., Dunne, Fidelma, Harreiter, Jürgen, Kautzky-Willer, Alexandra, Damm, Peter, Mathiesen, Elisabeth R., Jensen, Dorte M., Andersen, Lise Lotte, Tanvig, Mette, Lapolla, Annunziata, Dalfra, Maria Grazia, Bertolotto, Alessandra, Wender-Ozegowska, Ewa, Zawiejska, Agnieszka, Hill, David J., Snoek, Frank J., Jelsma, Judith G.M., Obstetrics & Gynecology, Medical psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Amsterdam Reproduction & Development (AR&D), Public and occupational health, and Medical Psychology

Subjects
Leptin, Physiology, Fatty Acids, Nonesterified, law.invention, 03 medical and health sciences, 0302 clinical medicine, NEFA, Randomized controlled trial, SDG 3 - Good Health and Well-being, law, Pregnancy, 030225 pediatrics, Lifestyle intervention, Medicine, Humans, Obesity, Life Style, Adiposity, business.industry, Infant, Newborn, medicine.disease, Cord blood, Pediatrics, Perinatology and Child Health, Gestation, Female, business, Body mass index, 030217 neurology & neurosurgery
Abstract

We evaluated possible mediators underlying lifestyle intervention effects on neonatal adiposity, assessed with sum of skinfolds and cord blood leptin. This is a secondary analysis of the DALI study, a randomised controlled trial in nine European countries. Pregnant women with a pre-pregnancy body mass index of ≥29 kg/m2 were randomly assigned to counselling for healthy eating (HE), physical activity (PA), HE&PA combined, or to usual care. We considered five maternal metabolic factors at 24–28 and 35–37 weeks of gestation, and four cord blood factors as possible mediators of the effect of combined HE&PA counselling on neonatal adiposity. From all potential mediators, the intervention only affected cord blood non-esterified fatty acids (NEFA), which was higher in the HE&PA group compared to UC (0.068 (mmol/L), 95% CI: 0.004 to 0.133). Cord blood NEFA did not mediate the HE&PA intervention effects on neonatal sum of skinfolds or cord blood leptin, based on an indirect effect on skinfolds of 0.018 (mm), 95% CI: −0.217 to 0.253 and an indirect effect on leptin of −0.143 (μg/l), 95% CI: −0.560 to 0.273. The Dali study observed reductions in neonatal adiposity in pregnant women with obesity, but we were not able to identify the underlying metabolic pathway.

Published
2022

6. Ketamine therapy for chronic pain in The Netherlands: a nationwide survey

Author

Thomas J P Mangnus, Maaike Dirckx, Krishna D Bharwani, Dirk L. Stronks, Frank J P M Huygen, and Anesthesiology

Subjects
Analgesics, medicine.medical_specialty, business.industry, Dosing regimen, Chronic pain, Treatment Setting, Inpatient setting, Nationwide survey, medicine.disease, Anesthesiology and Pain Medicine, Complex regional pain syndrome, Pain Clinics, Emergency medicine, medicine, Humans, Ketamine, Neurology (clinical), Chronic Pain, business, Complex Regional Pain Syndromes, Netherlands, medicine.drug
Abstract

Objectives Ketamine is used to treat chronic refractory pain. However, there are no scientific guidelines for ketamine use in the Netherlands. The aim of this survey was to provide an overview of the use of ketamine for chronic pain in the Netherlands. Methods All pain clinics in the Netherlands were contacted. A digital survey, available from June 2019 to January 2020, was sent to 68 pain clinics. The survey was completed by one pain physician as a representative of the entire pain department. The survey included questions about ketamine treatment indications, administration, dose, duration, treatment repetition and the inpatient or outpatient setting. Results The survey was completed by 51 pain clinics (75.0%). Thirty-one clinics used ketamine for chronic pain treatment. The most common indication was Complex Regional Pain Syndrome (83.9%). Pain clinics administered ketamine via intravenous infusions (96.8%), iontophoresis (61.3%), subcutaneous (3.2%) or oral administration (3.2%). Intravenous ketamine treatment was offered in an inpatient setting in 14 pain clinics, in both an inpatient and outpatient setting in 11 pain clinics and in six pain clinics in an outpatient setting. In the outpatient setting, the median starting dose was 5 mg/h (IQR=17.5–5). The median maximum dose was 27.5 mg/h (IQR=100–11.9). The median infusion duration was 6 h (IQR=8–4). In the inpatient setting, the median starting dose was 5 mg/h (IQR=5–1.5) and the median maximum dose was 25 mg/h (IQR=25–14). Patients were admitted to hospital for a median of 4 days (IQR=5–1). Conclusions The results of this Dutch nationwide survey study show that there are heterogeneous treatment protocols with different indications, treatment setting and dosing regimen for the treatment of chronic pain with ketamine. This study encourages the formulation of a broader consensus and the development of evidence based guidelines for ketamine treatment.

Published
2022

7. Development and external validation of a prediction model for tube feeding dependency for at least four weeks during chemoradiotherapy for head and neck cancer

Author

Annemie M. W. J. Schols, Lot A. Devriese, Rebecca T. Karsten, Chris H.J. Terhaard, Frank J. P. Hoebers, Roy I. Lalisang, Sander M. J. van Kuijk, Ann Hoeben, Jan de Boer, Laura W. J. Baijens, Anna C.H. Willemsen, Annemieke Kok, Johannes H.A.M. Kaanders, Susanne R. Pereboom, Arash Navran, Remco de Bree, Chantal M. L. Driessen, Carla M.L. van Herpen, RS: NUTRIM - R3 - Respiratory & Age-related Health, Pulmonologie, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, KNO, RS: GROW - R2 - Basic and Translational Cancer Biology, MUMC+: MA Keel Neus Oorheelkunde (9), Radiotherapie, RS: CAPHRI - R2 - Creating Value-Based Health Care, MUMC+: KIO Kemta (9), Interne Geneeskunde, and MUMC+: MA Medische Oncologie (9)

Subjects
OROPHARYNGEAL CANCER, Male, medicine.medical_specialty, medicine.medical_treatment, GUIDELINES, Radiation Dosage, Critical Care and Intensive Care Medicine, Feeding and Eating Disorders, All institutes and research themes of the Radboud University Medical Center, Enteral Nutrition, Prediction model, Predictive Value of Tests, PERCUTANEOUS ENDOSCOPIC GASTROSTOMY, Clinical Decision Rules, medicine, Clinical endpoint, Humans, TERM SWALLOW FUNCTION, Netherlands, Retrospective Studies, RISK, Gastrostomy, Nutrition and Dietetics, PROPHYLACTIC GASTROSTOMY, Predictors, Head neck cancer, Squamous Cell Carcinoma of Head and Neck, business.industry, Head and neck cancer, Weight change, Tube feeding, Chemoradiotherapy, CHEMOTHERAPY, Middle Aged, medicine.disease, Head and neck squamous-cell carcinoma, Radiation therapy, Head and Neck Neoplasms, PLACEMENT, Female, Radiology, business, Biomarkers, RADIOTHERAPY, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Cohort study
Abstract

Background & aims: Patients who receive chemoradiotherapy or bioradiotherapy (CRT/BRT) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) often experience high toxicity rates interfering with oral intake, causing tube feeding (TF) dependency. International guidelines recommend gastrostomy insertion when the expected use of TF exceeds 4 weeks. We aimed to develop and externally validate a prediction model to identify patients who need TF > 4 weeks and would benefit from prophylactic gastrostomy insertion. Methods: A retrospective multicenter cohort study was performed in four tertiary head and neck cancer centers in the Netherlands. The prediction model was developed using data from University Medical Center Utrecht and the Netherlands Cancer Institute and externally validated using data from Maastricht University Medical Center and Radboud University Medical Center. The primary endpoint was TF dependency >4 weeks initiated during CRT/BRT or within 30 days after CRT/BRT completion. Potential predictors were extracted from electronic health records and radiotherapy dose-volume parameters were calculated. Results: The developmental and validation cohort included 409 and 334 patients respectively. Multi variable analysis showed predictive value for pretreatment weight change, texture modified diet at baseline, ECOG performance status, tumor site, N classification, mean radiation dose to the contralateral parotid gland and oral cavity. The area under the receiver operating characteristics curve for this model was 0.73 and after external validation 0.62. Positive and negative predictive value for a risk of 90% or higher for TF dependency >4 weeks were 81.8% and 42.3% respectively. Conclusions: We developed and externally validated a prediction model to estimate TF-dependency >4 weeks in LAHNSCC patients treated with CRT/BRT. This model can be used to guide personalized decision-making on prophylactic gastrostomy insertion in clinical practice. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Published
2022

8. Multicenter assessment of outcomes and complications associated with transforaminal versus anterior lumbar interbody fusion for fractional curve correction

Author

Thomas J. Buell, Christopher I. Shaffrey, Shay Bess, Han Jo Kim, Eric O. Klineberg, Virginie Lafage, Renaud Lafage, Themistocles S. Protopsaltis, Peter G. Passias, Gregory M. Mundis, Robert K. Eastlack, Vedat Deviren, Michael P. Kelly, Alan H. Daniels, Jeffrey L. Gum, Alex Soroceanu, D. Kojo Hamilton, Munish C. Gupta, Douglas C. Burton, Richard A. Hostin, Khaled M. Kebaish, Robert A. Hart, Frank J. Schwab, Christopher P. Ames, and Justin S. Smith

Subjects
Adult, Male, Pelvic tilt, medicine.medical_specialty, Lordosis, Scoliosis, medicine, Humans, Prospective Studies, Aged, Retrospective Studies, Fixation (histology), Lumbar Vertebrae, Cobb angle, business.industry, General Medicine, Middle Aged, Lumbar Curve, medicine.disease, Surgery, Oswestry Disability Index, Spinal Fusion, Treatment Outcome, Quality of Life, Female, business, Lumbosacral joint
Abstract

OBJECTIVE Few studies have compared fractional curve correction after long fusion between transforaminal lumbar interbody fusion (TLIF) and anterior lumbar interbody fusion (ALIF) for adult symptomatic thoracolumbar/lumbar scoliosis (ASLS). The objective of this study was to compare fractional correction, health-related quality of life (HRQL), and complications associated with L4–S1 TLIF versus those of ALIF as an operative treatment of ASLS. METHODS The authors retrospectively analyzed a prospective multicenter adult spinal deformity database. Inclusion required a fractional curve ≥ 10°, a thoracolumbar/lumbar curve ≥ 30°, index TLIF or ALIF performed at L4–5 and/or L5–S1, and a minimum 2-year follow-up. TLIF and ALIF patients were propensity matched according to the number and type of interbody fusion at L4–S1. RESULTS Of 135 potentially eligible consecutive patients, 106 (78.5%) achieved the minimum 2-year follow-up (mean ± SD age 60.6 ± 9.3 years, 85% women, 44.3% underwent TLIF, and 55.7% underwent ALIF). Index operations had mean ± SD 12.2 ± 3.6 posterior levels, 86.6% of patients underwent iliac fixation, 67.0% underwent TLIF/ALIF at L4–5, and 84.0% underwent TLIF/ALIF at L5–S1. Compared with TLIF patients, ALIF patients had greater cage height (10.9 ± 2.1 mm for TLIF patients vs 14.5 ± 3.0 mm for ALIF patients, p = 0.001) and lordosis (6.3° ± 1.6° for TLIF patients vs 17.0° ± 9.9° for ALIF patients, p = 0.001) and longer operative duration (6.7 ± 1.5 hours for TLIF patients vs 8.9 ± 2.5 hours for ALIF patients, p < 0.001). In all patients, final alignment improved significantly in terms of the fractional curve (20.2° ± 7.0° to 6.9° ± 5.2°), maximum coronal Cobb angle (55.0° ± 14.8° to 23.9° ± 14.3°), C7 sagittal vertical axis (5.1 ± 6.2 cm to 2.3 ± 5.4 cm), pelvic tilt (24.6° ± 8.1° to 22.7° ± 9.5°), and lumbar lordosis (32.3° ± 18.8° to 51.4° ± 14.1°) (all p < 0.05). Matched analysis demonstrated comparable fractional correction (−13.6° ± 6.7° for TLIF patients vs −13.6° ± 8.1° for ALIF patients, p = 0.982). In all patients, final HRQL improved significantly in terms of Oswestry Disability Index (ODI) score (42.4 ± 16.3 to 24.2 ± 19.9), physical component summary (PCS) score of the 36-item Short-Form Health Survey (32.6 ± 9.3 to 41.3 ± 11.7), and Scoliosis Research Society–22r score (2.9 ± 0.6 to 3.7 ± 0.7) (all p < 0.05). Matched analysis demonstrated worse ODI (30.9 ± 21.1 for TLIF patients vs 17.9 ± 17.1 for ALIF patients, p = 0.017) and PCS (38.3 ± 12.0 for TLIF patients vs 45.3 ± 10.1 for ALIF patients, p = 0.020) scores for TLIF patients at the last follow-up (despite no differences in these parameters at baseline). The rates of total complications were similar (76.6% for TLIF patients vs 71.2% for ALIF patients, p = 0.530), but significantly more TLIF patients had rod fracture (28.6% of TLIF patients vs 7.1% of ALIF patients, p = 0.036). Multiple regression analysis demonstrated that a 1-mm increase in L4–5 TLIF cage height led to a 2.2° reduction in L4 coronal tilt (p = 0.011), and a 1° increase in L5–S1 ALIF cage lordosis led to a 0.4° increase in L5–S1 segmental lordosis (p = 0.045). CONCLUSIONS Operative treatment of ASLS with L4–S1 TLIF versus ALIF demonstrated comparable mean fractional curve correction (66.7% vs 64.8%), despite use of significantly larger, more lordotic ALIF cages. TLIF cage height had a significant impact on leveling L4 coronal tilt, whereas ALIF cage lordosis had a significant impact on restoration of lumbosacral lordosis. The advantages of TLIF may include reduced operative duration and hospitalization; however, associated HRQL was inferior and more rod fractures were detected in the TLIF patients included in this study.

Published
2021

9. Outcomes of translumbar embolization of type II endoleaks following endovascular abdominal aortic aneurysm repair

Author

John F. Charitable, Thomas S. Maldonado, Frank J. Veith, Neal S. Cayne, Caron B. Rockman, Glenn R. Jacobowitz, Karan Garg, and Peter Patalano

Subjects
Male, medicine.medical_specialty, Time Factors, Endoleak, medicine.medical_treatment, Embolization procedure, Risk Assessment, Coronary artery disease, Blood Vessel Prosthesis Implantation, Lumbar, Aneurysm, Risk Factors, medicine, Humans, Cyanoacrylates, Embolization, Aged, Retrospective Studies, business.industry, Endovascular Procedures, medicine.disease, Embolization, Therapeutic, Confidence interval, Abdominal aortic aneurysm, Surgery, Treatment Outcome, Retreatment, Female, Cardiology and Cardiovascular Medicine, Ligation, business, Platelet Aggregation Inhibitors, Aortic Aneurysm, Abdominal
Abstract

Presence of an endoleak can compromise aneurysm exclusion after endovascular abdominal aortic aneurysm repair (EVAR). Type II endoleaks (T2Es) are most common and may cause sac expansion. We report outcomes of translumbar embolization (TLE) of T2Es following EVAR.We conducted a retrospective chart review of patients with T2E after EVAR treated with TLE from 2011 to 2018 at a single academic institution. Treatment indications were the presence of persistent T2E and aneurysm growth ≥5 mm. Sac stabilization was defined as growth ≤5 mm throughout the follow-up period.Thirty consecutive patients were identified. The majority were men (n = 24), with a mean age of 74.3 years (95% confidence interval [CI], 70.9-77.6 years). The most common comorbidities were hypertension (83.3%) and coronary artery disease (54.0%). The mean maximal sac diameter at T2E discovery was 5.8 cm (95% CI, 5.4-6.2 cm). The mean time to intervention from endoleak discovery was 33.7 ± 28 months with a mean growth of 0.84 cm (95% CI, 0.48-1.2 cm) during that time period. The mean follow-up time after TLE was 19.1 months (95% CI, 11.1-27.2 months). Twenty-eight patients were treated with cyanoacrylate glue (CyG) alone, and two were treated with CyG plus coil embolization (CE). There was immediate complete endoleak resolution as assessed intraoperatively, and sac stabilization in 15 cases (50.0%). Eleven patients (36.7%) had evidence of persistent T2E on initial imaging after the embolization procedure; additional follow-up revealed eventual sac stabilization at a mean of 21.3 ± 7.2 months, and therefore, these patients did not require further intervention. In the remaining four cases (13.3%), there was persistent T2E after the initial TLE, requiring a second intervention. Repeat TLE stabilized growth in three of these four patients after a mean of 17.6 ± 12.9 months. One patient required open sacotomy and ligation of lumbar vessels due to continued persistence of the T2E and continued aneurysm growth. There were no ischemic complications related to the embolization procedures. Factors associated with persistent endoleak after initial embolization were larger aneurysm diameter at the time of initial endoleak identification (P .001) and the use of antiplatelet agents (P .02). The use of anticoagulation was not a significant risk factor for endoleak recurrence or aneurysm growth after TLE.TLE of T2E is a safe and effective treatment option for T2E with aneurysm growth following EVAR. Patients taking antiplatelet medication and those with larger aneurysms at the time of endoleak identification appear to be at increased risk for persistent endoleak and need for subsequent procedures following initial TLE. These patients may require more intensive monitoring and follow-up.

Published
2021

10. Orthopedic disease burden in adult patients with symptomatic lumbar scoliosis: results from a prospective multicenter study

Author

Keith H. Bridwell, Christopher I. Shaffrey, Christine R. Baldus, Michael P. Kelly, Frank J. Schwab, Shay Bess, Christopher P. Ames, Jon D. Lurie, Elizabeth L. Yanik, and Justin S. Smith

Subjects
Male, Aging, medicine.medical_treatment, Cost of Illness, 80 and over, Prospective Studies, Aged, 80 and over, education.field_of_study, Clinical Article, Lumbar Vertebrae, Cobb angle, Pain Research, Rehabilitation, General Medicine, Middle Aged, Oswestry Disability Index, Treatment Outcome, Scoliosis, Cohort, Female, Chronic Pain, Adult, medicine.medical_specialty, Clinical Sciences, Joint ligament, Population, Pain, Clinical Research, spine deformity, medicine, Humans, education, lumbar, Aged, Retrospective Studies, scoliosis, business.industry, Arthritis, Neurosciences, medicine.disease, Arthroplasty, Surgery, Good Health and Well Being, Orthopedics, fracture, Musculoskeletal, Orthopedic surgery, Quality of Life, arthroplasty, orthopedic disease burden, business, Follow-Up Studies
Abstract

OBJECTIVE Although the health impact of adult symptomatic lumbar scoliosis (ASLS) is substantial, these patients often have other orthopedic problems that have not been previously quantified. The objective of this study was to assess disease burden of other orthopedic conditions in patients with ASLS based on a retrospective review of a prospective multicenter cohort. METHODS The ASLS-1 study is an NIH-sponsored prospective multicenter study designed to assess operative versus nonoperative treatment for ASLS. Patients were 40–80 years old with ASLS, defined as a lumbar coronal Cobb angle ≥ 30° and Oswestry Disability Index ≥ 20, or Scoliosis Research Society-22 questionnaire score ≤ 4.0 in pain, function, and/or self-image domains. Nonthoracolumbar orthopedic events, defined as fractures and other orthopedic conditions receiving surgical treatment, were assessed from enrollment to the 4-year follow-up. RESULTS Two hundred eighty-six patients (mean age 60.3 years, 90% women) were enrolled, with 173 operative and 113 nonoperative patients, and 81% with 4-year follow-up data. At a mean (± SD) follow-up of 3.8 ± 0.9 years, 104 nonthoracolumbar orthopedic events were reported, affecting 69 patients (24.1%). The most common events were arthroplasty (n = 38), fracture (n = 25), joint ligament/cartilage repair (n = 13), and cervical decompression/fusion (n = 7). Based on the final adjusted model, patients with a nonthoracolumbar orthopedic event were older (HR 1.44 per decade, 95% CI 1.07–1.94), more likely to have a history of tobacco use (HR 1.63, 95% CI 1.00–2.66), and had worse baseline leg pain scores (HR 1.10, 95% CI 1.01–1.19). CONCLUSIONS Patients with ASLS have high orthopedic disease burden, with almost 25% having a fracture or nonthoracolumbar orthopedic condition requiring surgical treatment during the mean 3.8 years following enrollment. Comparisons with previous studies suggest that the rate of total knee arthroplasty was considerably greater and the rates of total hip arthroplasty were at least as high in the ASLS-1 cohort compared with the similarly aged general US population. These conditions may further impact health-related quality of life and outcomes assessments of both nonoperative and operative treatment approaches in patients with ASLS.

Published
2021

11. Socioeconomic inequalities in the food environment and body composition among school-aged children

Author

Frank J. van Lenthe, Famke J.M. Mölenberg, Alex Burdorf, Maartje P. Poelman, Joreintje D. Mackenbach, Susana Santos, Epidemiology and Data Science, APH - Health Behaviors & Chronic Diseases, Public Health, Erasmus MC other, and Pediatrics

Subjects
Male, Index (economics), Inequality, Adolescent, Epidemiology, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, Medicine (miscellaneous), Childhood obesity, Article, Body Mass Index, Cohort Studies, SDG 3 - Good Health and Well-being, Environmental health, Food Quality, Medicine, Humans, Life Science, Mass index, Child, Consumption and Healthy Lifestyles, Socioeconomic inequalities, media_common, Nutrition, Netherlands, Preventive medicine, Nutrition and Dietetics, business.industry, digestive, oral, and skin physiology, medicine.disease, Cross-Sectional Studies, Risk factors, Socioeconomic Factors, Body Composition, Consumptie en Gezonde Leefstijl, Generation R, Female, business, Body mass index, Food environment
Abstract

Background There is limited evidence regarding socioeconomic inequalities of exposure to the food environment and its contribution to childhood obesity. Methods We used data from 4235 children from the Generation R Study, a large birth-cohort conducted in the city of Rotterdam, The Netherlands. We included 11,277 person-observations of body mass index (BMI) and 6240 person-observations of DXA-derived fat mass index (FMI) and fat-free mass index (FFMI) when children were between 4 and 14 years. We applied linear regression models to evaluate changes in the relative and absolute exposure of fast-food outlets, and the healthiness of the food environment within 400 m from home by maternal education. Furthermore, we used individual-level fixed-effects models to study changes in the food environment to changes in BMI, FMI and FFMI. Results Children from lower educated mothers were exposed to more fast-food outlets at any time-point between the age of 4 and 14 years. Over a median period of 7.1 years, the absolute (0.6 fast-food outlet (95% CI: 0.4–0.8)) and relative (2.0%-point (95% CI: 0.7–3.4)) amount of fast-food outlets increased more for children from lower as compared to higher educated mothers. The food environment became more unhealthy over time, but no differences in trends were seen by maternal education level. Changes in the food environment were not associated with subsequent changes in BMI, FMI and FFMI. For children from lower educated mothers not exposed to fast-food at first, we found some evidence that the introduction of fast-food was associated with small increases in BMI. Conclusions Our findings provide evidence of widening inequalities in exposure to fast-food in an already poor food environment. Access to more fast-food outlets does not seem to have an additional impact on BMI in contemporary contexts with ubiquitous fast-food outlets.

Published
2021

12. Global coronal decompensation and adult spinal deformity surgery: comparison of upper-thoracic versus lower-thoracic proximal fixation for long fusions

Author

Thomas J. Buell, Christopher I. Shaffrey, Han Jo Kim, Eric O. Klineberg, Virginie Lafage, Renaud Lafage, Themistocles S. Protopsaltis, Peter G. Passias, Gregory M. Mundis, Robert K. Eastlack, Vedat Deviren, Michael P. Kelly, Alan H. Daniels, Jeffrey L. Gum, Alex Soroceanu, D. Kojo Hamilton, Munish C. Gupta, Douglas C. Burton, Richard A. Hostin, Khaled M. Kebaish, Robert A. Hart, Frank J. Schwab, Shay Bess, Christopher P. Ames, and Justin S. Smith

Subjects
Adult, medicine.medical_specialty, Kyphosis, Scoliosis, Thoracic Vertebrae, Humans, Medicine, Decompensation, Prospective Studies, Retrospective Studies, Fixation (histology), Lumbar Vertebrae, business.industry, Minimal clinically important difference, General Medicine, medicine.disease, Surgery, Pseudarthrosis, Spinal Fusion, Coronal plane, Quality of Life, business, Complication, Follow-Up Studies
Abstract

OBJECTIVE Deterioration of global coronal alignment (GCA) may be associated with worse outcomes after adult spinal deformity (ASD) surgery. The impact of fusion length and upper instrumented vertebra (UIV) selection on patients with this complication is unclear. The authors’ objective was to compare outcomes between long sacropelvic fusion with upper-thoracic (UT) UIV and those with lower-thoracic (LT) UIV in patients with worsening GCA ≥ 1 cm. METHODS This was a retrospective analysis of a prospective multicenter database of consecutive ASD patients. Index operations involved instrumented fusion from sacropelvis to thoracic spine. Global coronal deterioration was defined as worsening GCA ≥ 1 cm from preoperation to 2-year follow-up. RESULTS Of 875 potentially eligible patients, 560 (64%) had complete 2-year follow-up data, of which 144 (25.7%) demonstrated worse GCA at 2-year postoperative follow-up (35.4% of UT patients vs 64.6% of LT patients). At baseline, UT patients were younger (61.6 ± 9.9 vs 64.5 ± 8.6 years, p = 0.008), a greater percentage of UT patients had osteoporosis (35.3% vs 16.1%, p = 0.009), and UT patients had worse scoliosis (51.9° ± 22.5° vs 32.5° ± 16.3°, p < 0.001). Index operations were comparable, except UT patients had longer fusions (16.4 ± 0.9 vs 9.7 ± 1.2 levels, p < 0.001) and operative duration (8.6 ± 3.2 vs 7.6 ± 3.0 hours, p = 0.023). At 2-year follow-up, global coronal deterioration averaged 2.7 ± 1.4 cm (1.9 to 4.6 cm, p < 0.001), scoliosis improved (39.3° ± 20.8° to 18.0° ± 14.8°, p < 0.001), and sagittal spinopelvic alignment improved significantly in all patients. UT patients maintained smaller positive C7 sagittal vertical axis (2.7 ± 5.7 vs 4.7 ± 5.7 cm, p = 0.014). Postoperative 2-year health-related quality of life (HRQL) significantly improved from baseline for all patients. HRQL comparisons demonstrated that UT patients had worse Scoliosis Research Society–22r (SRS-22r) Activity (3.2 ± 1.0 vs 3.6 ± 0.8, p = 0.040) and SRS-22r Satisfaction (3.9 ± 1.1 vs 4.3 ± 0.8, p = 0.021) scores. Also, fewer UT patients improved by ≥ 1 minimal clinically important difference in numerical rating scale scores for leg pain (41.3% vs 62.7%, p = 0.020). Comparable percentages of UT and LT patients had complications (208 total, including 53 reoperations, 77 major complications, and 78 minor complications), but the percentage of reoperated patients was higher among UT patients (35.3% vs 18.3%, p = 0.023). UT patients had higher reoperation rates of rod fracture (13.7% vs 2.2%, p = 0.006) and pseudarthrosis (7.8% vs 1.1%, p = 0.006) but not proximal junctional kyphosis (9.8% vs 8.6%, p = 0.810). CONCLUSIONS In ASD patients with worse 2-year GCA after long sacropelvic fusion, UT UIV was associated with worse 2-year HRQL compared with LT UIV. This may suggest that residual global coronal malalignment is clinically less tolerated in ASD patients with longer fusion to the proximal thoracic spine. These results may inform operative planning and improve patient counseling.

Published
2021

13. Optimization of a technology‐supported physical activity promotion intervention for breast cancer survivors: Results from Fit2Thrive

Author

Linda M. Collins, Ronald T. Ackermann, Bonnie Spring, David Cella, Whitney A. Welch, Siobhan M. Phillips, Lisa Auster-Gussman, Erin Cullather, Emily Izenman, Jing Song, Payton Solk, Madelyn Whitaker, Kerry S. Courneya, Juned Siddique, and Frank J. Penedo

Subjects
Adult, Technology, Cancer Research, medicine.medical_specialty, Population, Physical activity, Monitoring, Ambulatory, Breast Neoplasms, Article, law.invention, Breast cancer, Cancer Survivors, Randomized controlled trial, law, Intervention (counseling), Accelerometry, Humans, Medicine, Accelerometer data, education, Exercise, education.field_of_study, business.industry, Behavior change, Mean age, Middle Aged, medicine.disease, Mobile Applications, Self Care, Oncology, Physical therapy, Female, business, human activities
Abstract

BACKGROUND The benefits of moderate to vigorous physical activity (MVPA) for breast cancer survivors are well established. However, most are insufficiently active. Fit2Thrive used the Multiphase Optimization Strategy methodology to determine the effect of 5 intervention components on MVPA in this population. METHODS Two hundred sixty-nine participants (mean age, 52.5 years; SD, 9.9 years) received a core intervention (the Fit2Thrive self-monitoring app and Fitbit) and were randomly assigned to 5 intervention components set to on/off in a full factorial experiment: support calls, deluxe app, buddy, online gym, and text messages. The intervention was delivered over 12 weeks with a 12-week follow-up. MVPA was measured via accelerometry at the baseline (T1), at 12 weeks (T2), and at 24 weeks (T3). The main effects and interaction effects at each time point were examined for all components. RESULTS Trial retention was high: 91.8% had valid accelerometer data at T2 or T3. Across all conditions, there were significant increases in MVPA (+53.6 min/wk; P < .001) and in the proportion of survivors meeting MVPA guidelines (+22.3%; P < .001) at T2 that were maintained but attenuated at T3 (MVPA, +24.6 min/wk; P < .001; meeting guidelines, +12.6%; P < .001). No individual components significantly improved MVPA, although increases were greater for the on level versus the off level for support calls, buddy, and text messages at T2 and T3. CONCLUSIONS The Fit2Thrive core intervention (the self-monitoring app and Fitbit) is promising for increasing MVPA in breast cancer survivors, but the components provided no additional increases in MVPA. Future research should evaluate the core intervention in a randomized trial and determine what components optimize MVPA behaviors in breast cancer survivors.

Published
2021

14. Physical Activity in Women With Hypothyroidism on Thyroid Hormone Therapy: Associated Factors and Perceived Barriers and Benefits

Author

Janine H. Stubbe, Jeannette A. C. Lankhaar, Ellen Kemler, and Frank J G Backx

Subjects
Gerontology, Thyroid Hormones, Multivariate analysis, medicine.medical_treatment, Physical fitness, Population, Levothyroxine, Hypothyroidism, Surveys and Questionnaires, Humans, Medicine, Orthopedics and Sports Medicine, Liothyronine, education, Exercise, Univariate analysis, education.field_of_study, business.industry, Middle Aged, medicine.disease, Comorbidity, Cross-Sectional Studies, Female, Hormone therapy, business, medicine.drug
Abstract

Background: The purpose of this study was to analyze factors associated with physical activity (PA) and to identify perceived barriers and benefits of PA among patients with hypothyroidism on thyroid hormone therapy. Methods: This survey-based cross-sectional study was conducted among members of the Dutch thyroid patient organization. Self-reported data on respondents’ PA levels and demographic, clinical, and physical health variables were collected. Moreover, perceived barriers and benefits to PA were identified. Respondents were categorized as physically active when meeting the recommended Dutch PA guidelines and physically inactive otherwise. To compare physically active and inactive respondents, potential confounders were entered into univariate analyses. Factors showing significant correlations (P Results: About 1724 female respondents (mean age 53.0 [11.6] y) were included; 16.1% reported meeting the PA recommendations. Multivariate analysis showed that factors associated with PA included levothyroxine/liothyronine therapy, comorbidities, self-perceived physical fitness, and diminished physical endurance. Overall, physically related barriers to PA were rated highest. Conclusions: The vast majority of treated hypothyroid respondents are physically inactive and experience long-term exercise intolerance. Considering the health implications of physical inactivity, promotion of regular PA is of key importance in this population.

Published
2021

15. Saturated fat ingestion stimulates proatherogenic inflammation in polycystic ovary syndrome

Author

Jiaping Xue, Robert V. Considine, Anthony J. Acton, Frank J. Gonzalez, and Ola A Abdelhadi

Subjects
Adult, medicine.medical_specialty, Adolescent, Physiology, Endocrinology, Diabetes and Metabolism, Saturated fat, Inflammation, Young Adult, Physiology (medical), Internal medicine, medicine, Humans, Ingestion, business.industry, Fatty Acids, Hyperandrogenism, nutritional and metabolic diseases, Atherosclerosis, Lipid Metabolism, medicine.disease, Dietary Fats, Obesity, Polycystic ovary, Androgen secretion, Endocrinology, Heart Disease Risk Factors, Body Composition, Disease Progression, Diet, Atherogenic, Female, medicine.symptom, business, Dyslipidemia, Polycystic Ovary Syndrome, Research Article
Abstract

Inflammation and dyslipidemia are often present in polycystic ovary syndrome (PCOS). We determined the effect of saturated fat ingestion on circulating heat shock protein-70 (HSP-70) and mononuclear cell (MNC) toll-like receptor-2 (TLR2) gene expression, activator protein-1 (AP-1) activation, and matrix matalloproteinase-2 (MMP-2) protein in women with PCOS. Twenty reproductive-age women with PCOS (10 lean, 10 with obesity) and 20 ovulatory controls (10 lean, 10 with obesity) participated in the study. HSP-70 was measured in serum and TLR2 mRNA and protein, AP-1 activation, and MMP-2 protein were quantified in MNC from blood drawn while fasting and 2, 3, and 5 h after saturated fat ingestion. Insulin sensitivity was derived from an oral glucose tolerance test (IS(OGTT)). Androgen secretion was assessed from blood drawn while fasting and 24, 48, and 72 h after human chorionic gonadotropin (HCG) administration. In response to saturated fat ingestion, serum HSP-70, TLR2 gene expression, activated AP-1, and MMP-2 protein were greater in lean women with PCOS compared with lean controls and in women with PCOS and obesity compared with controls with obesity. Both PCOS groups exhibited lower IS(OGTT) and greater HCG-stimulated androgen secretion compared with control subjects of their respective weight classes. Lipid-stimulated proatherogenic inflammation marker responses were negatively correlated with IS(OGTT) and positively correlated with abdominal adiposity and HCG-stimulated androgen secretion. In PCOS, saturated fat ingestion stimulates proatherogenic inflammation independent of obesity. This effect is greater when PCOS is combined with obesity compared with obesity alone. Abdominal adiposity and hyperandrogenism may perpetuate proatherogenic inflammation. NEW & NOTEWORTHY This paper demonstrates that in polycystic ovary syndrome (PCOS), ingestion of saturated fat triggers a molecular pathway of inflammation known to drive atherogenesis. This effect is independent of obesity as it occurs in lean women with PCOS and not in lean ovulatory control subjects. Furthermore, the combined effects of PCOS and obesity are greater compared with obesity alone.

Published
2021

16. The Management of Type 1 Diabetes in Adults. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

Author

Amy Hess-Fischl, M. Sue Kirkman, Irl B. Hirsch, Barbara Ludwig, Anne L. Peters, Eric Renard, Richard I. G. Holt, Tomasz Klupa, Ruth S. Weinstock, Jeremy Pettus, J. Hans DeVries, Jay S. Skyler, Frank J. Snoek, Kirsten Nørgaard, University of Southampton, University Hospital Southampton NHS Foundation Trust, University of Amsterdam [Amsterdam] (UvA), Amsterdam UMC, Profil Institute for Metabolic Research GmbH, University of Chicago, Seattle University [Seattle], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), IT University of Copenhagen, Steno Diabetes Center of Copenhagen, University of California [San Diego] (UC San Diego), University of California, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), University of Miami Leonard M. Miller School of Medicine (UMMSM), Vrije Universiteit Amsterdam [Amsterdam] (VU), SUNY Upstate Medical University, State University of New York (SUNY), Keck School of Medicine [Los Angeles], University of Southern California (USC), Amsterdam UMC - Amsterdam University Medical Center, IT University of Copenhagen (ITU), University of California (UC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Guerineau, Nathalie C., Medical psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Amsterdam Reproduction & Development (AR&D), General Internal Medicine, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Endocrinology, Medical Psychology, University of Zurich, and Holt, Richard I G

Subjects
Blood Glucose, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 10265 Clinic for Endocrinology and Diabetology, 0302 clinical medicine, Diabetic ketoacidosis, Glucose monitoring, Diagnosis, Health care, Insulin, Medicine, Adjunctive therapy, 030212 general & internal medicine, Psychosocial care, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, 3. Good health, [SDV] Life Sciences [q-bio], 2712 Endocrinology, Diabetes and Metabolism, Type 1 diabetes, Psychosocial, Schedule of care, Adult, medicine.medical_specialty, Consensus, Consensus Report, 610 Medicine & health, 030209 endocrinology & metabolism, Hypoglycemia, 03 medical and health sciences, Diabetes mellitus, Internal Medicine, Hypoglycemic Agents, Humans, Association (psychology), Exercise, Nutrition, American diabetes association, Advanced and Specialized Nursing, Transplantation, business.industry, Blood Glucose Self-Monitoring, medicine.disease, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, 2724 Internal Medicine, Family medicine, Hypoglycaemia, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) convened a writing group to develop a consensus statement on the management of type 1 diabetes in adults. The writing group has considered the rapid development of new treatments and technologies and addressed the following topics: diagnosis, aims of management, schedule of care, diabetes self-management education and support, glucose monitoring, insulin therapy, hypoglycaemia, behavioural considerations, psychosocial care, diabetic ketoacidosis, pancreas and islet transplantation, adjunctive therapies, special populations, inpatient management and future perspectives. Although we discuss the schedule for follow-up examinations and testing, we have not included the evaluation and treatment of the chronic microvascular and macrovascular complications of diabetes as these are well-reviewed and discussed elsewhere. The writing group was aware of both national and international guidance on type 1 diabetes and did not seek to replicate this but rather aimed to highlight the major areas that healthcare professionals should consider when managing adults with type 1 diabetes. Though evidence-based where possible, the recommendations in the report represent the consensus opinion of the authors. [Figure not available: see fulltext.]

Published
2021

17. Quality metrics in adult spinal deformity surgery over the last decade: a combined analysis of the largest prospective multicenter data sets

Author

Ferran Pellisé, Miquel Serra-Burriel, Alba Vila-Casademunt, Jeffrey L. Gum, Ibrahim Obeid, Justin S. Smith, Frank S. Kleinstück, Shay Bess, Javier Pizones, Virginie Lafage, Francisco Javier S. Pérez-Grueso, Frank J. Schwab, Douglas C. Burton, Eric O. Klineberg, Christopher I. Shaffrey, Ahmet Alanay, and Christopher P. Ames

Subjects
medicine.medical_specialty, business.industry, General Medicine, Scoliosis, Odds ratio, medicine.disease, Oswestry Disability Index, Surgery, Patient recruitment, Quality of life, Radiological weapon, Health care, Medicine, Observational study, business
Abstract

OBJECTIVE The reported rate of complications and cost of adult spinal deformity (ASD) surgery, associated with an exponential increase in the number of surgeries, cause alarm among healthcare payers and providers worldwide. The authors conjointly analyzed the largest prospective available ASD data sets to define trends in quality-of-care indicators (complications, reinterventions, and health-related quality of life [HRQOL] outcomes) since 2010. METHODS This is an observational prospective longitudinal cohort study. Patients underwent surgery between January 2010 and December 2016, with > 2 years of follow-up data. Demographic, surgical, radiological, and HRQOL (i.e., Oswestry Disability Index, SF-36, Scoliosis Research Society-22r) data obtained preoperatively and at 3, 6, 12, and 24 months after surgery were evaluated. Trends and changes in indicators were analyzed using local regression (i.e., locally estimated scatterplot smoothing [LOESS]) and adjusted odds ratio (OR). RESULTS Of the 2286 patients included in the 2 registries, 1520 underwent surgery between 2010 and 2016. A total of 1151 (75.7%) patients who were treated surgically at 23 centers in 5 countries met inclusion criteria. Patient recruitment increased progressively (2010–2011 vs 2015–2016: OR 1.64, p < 0.01), whereas baseline clinical characteristics (age, American Society of Anesthesiologists class, HRQOL scores, sagittal deformity) did not change. Since 2010 there has been a sustained reduction in major and minor postoperative complications observed at 90 days (major: OR 0.59; minor: OR 0.65; p < 0.01); at 1 year (major: OR 0.52; minor: 0.75; p < 0.01); and at 2 years of follow-up (major: OR 0.4; minor: 0.80; p < 0.01) as well as in the 2-year reintervention rate (OR 0.41, p < 0.01). Simultaneously, there has been a slight improvement in the correction of sagittal deformity (i.e., pelvic incidence–lumbar lordosis mismatch: OR 1.11, p = 0.19) and a greater gain in quality of life (i.e., Oswestry Disability Index 26% vs 40%, p = 0.02; Scoliosis Research Society-22r, self-image domain OR 1.16, p = 0.13), and these are associated with a progressive reduction of surgical aggressiveness (number of fused segments: OR 0.81, p < 0.01; percent pelvic fixation: OR 0.66, p < 0.01; percent 3-column osteotomies: OR 0.63, p < 0.01). CONCLUSIONS The best available data show a robust global improvement in quality metrics in ASD surgery over the last decade. Surgical complications and reoperations have been reduced by half, while improvement in disability increased and correction rates were maintained, in patients with similar baseline characteristics.

Published
2021

18. Characteristics and outcomes of over 300,000 patients with COVID-19 and history of cancer in the United States and Spain

Author

Lana Yin Hui Lai, Daniel R. Morales, Talita Duarte-Salles, Thomas Falconer, Carlos Areia, Jitendra Jonnagaddala, Kristin Kostka, Christian G. Reich, Daniel Prieto-Alhambra, Lisa M. Schilling, Dalia Dawoud, Clair Blacketer, Marc A. Suchard, Isabelle Soerjomataram, Frank J. DeFalco, George Hripcsak, Osaid Alser, Jose D. Posada, Fredrik Nyberg, Laura Hester, William Carter, Lin Zhang, Michael E. Matheny, Sergio Fernandez-Bertolin, Ying Zhang, Waheed Ul Rahman Ahmed, María Aragón, Heba Alghoul, Karthik Natarajan, Asieh Golozar, Mengchun Gong, Martina Recalde, Patrick B. Ryan, Aedín C. Culhane, Andrea Pistillo, Vignesh Subbian, Kristine E. Lynch, Thamir M. Alshammari, Albert Prats-Uribe, Yang Shen, Donna R. Rivera, Diana Puente, Anthony G. Sena, Hokyun Jeon, Karishma Shah, Elena Roel, Nigam H. Shah, Eng Hooi Tan, Paula Casajust, Scott L. DuVall, Matthew Spotniz, Anna Ostropolets, Annalisa Trama, and Medical Informatics

Subjects
Male, Databases, Factual, Outcome Assessment, Epidemiology, Comorbidity, outcomes, Medical and Health Sciences, Cohort Studies, Risk Factors, Neoplasms, Outcome Assessment, Health Care, Prevalence, 80 and over, Medicine, Young adult, Aetiology, Child, Cancer, Aged, 80 and over, cohort, Hematology, Middle Aged, Hospitalization, Infectious Diseases, Cohort, oncology, Female, Patient Safety, Cohort study, Human, Adult, Urologic Diseases, medicine.medical_specialty, Adolescent, Databases, Young Adult, Rare Diseases, SDG 3 - Good Health and Well-being, Clinical Research, Internal medicine, Influenza, Human, Breast Cancer, Humans, Adverse effect, Pandemics, Factual, Aged, Immunosuppression Therapy, business.industry, SARS-CoV-2, Prevention, COVID-19, medicine.disease, United States, Influenza, Health Care, Good Health and Well Being, El Niño, Spain, Observational study, business, 2.4 Surveillance and distribution
Abstract

Background: We described the demographics, cancer subtypes, comorbidities, and outcomes of patients with a history of cancer and coronavirus disease 2019 (COVID-19). Second, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza. Methods: We conducted a cohort study using eight routinely collected health care databases from Spain and the United States, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: (i) diagnosed with COVID-19, (ii) hospitalized with COVID-19, and (iii) hospitalized with influenza in 2017 to 2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes. Results: We included 366,050 and 119,597 patients diagnosed and hospitalized with COVID-19, respectively. Prostate and breast cancers were the most frequent cancers (range: 5%–18% and 1%–14% in the diagnosed cohort, respectively). Hematologic malignancies were also frequent, with non-Hodgkin's lymphoma being among the five most common cancer subtypes in the diagnosed cohort. Overall, patients were aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 2% to 14% and from 6% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n = 67,743) had a similar distribution of cancer subtypes, sex, age, and comorbidities but lower occurrence of adverse events. Conclusions: Patients with a history of cancer and COVID-19 had multiple comorbidities and a high occurrence of COVID-19-related events. Hematologic malignancies were frequent. Impact: This study provides epidemiologic characteristics that can inform clinical care and etiologic studies.

Published
2021

19. Disparities in Treatment with Direct-Acting Hepatitis C Virus Antivirals Persist Among Adults Coinfected with HIV and Hepatitis C Virus in US Clinics, 2010–2018

Author

Qingjiang Hou, Kimberly Carlson, Frank J. Palella, Jun Li, Ellen Tedaldi, Marcus D. Durham, Gina M. Simoncini, and Kate Buchacz

Subjects
Adult, viruses, Hepatitis C virus, Human immunodeficiency virus (HIV), HIV Infections, Hepacivirus, medicine.disease_cause, Antiviral Agents, medicine, Humans, Longitudinal Studies, Aged, Coinfection, business.industry, Public Health, Environmental and Occupational Health, virus diseases, Hepatitis C, Chronic, medicine.disease, Hepatitis C, Virology, Treatment Outcome, Infectious Diseases, Pharmaceutical Preparations, business, Direct acting
Abstract

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection carries substantial risk for all-cause mortality and liver-related morbidity and mortality, yet many persons coinfected with HIV/HCV remain untreated for HCV. We explored demographic, clinical, and sociodemographic factors among participants in routine HIV care associated with prescription of direct-acting antivirals (DAAs). The HIV Outpatient Study (HOPS) is an ongoing longitudinal cohort study of persons with HIV in care at participating clinics since 1993. There are currently eight study sites in six US cities. We analyzed medical records data of HOPS participants diagnosed with HCV since June 2010. Sustained virological response (SVR) was documented with first undetectable HCV viral load (VL). We assessed factors associated with being prescribed DAAs by multi-variable logistic regression and described the cumulative rate of SVR. Among 306 eligible participants, 131 (43%) were prescribed DAA therapy. Factors associated with greater odds of being prescribed DAA were older age, private health insurance, higher CD4 cell count, being a person who injects drugs, and receiving care at publicly funded sites (

Published
2021

20. An implantable restorative-neurostimulator for refractory mechanical chronic low back pain

Author

Marc Russo, ReActiv B investigators, Kristiaan Deckers, Jean-Pierre Van Buyten, Sam Eldabe, Jan Pieter Heemels, Eugene Mironer, Christopher J. Gilligan, Richard Rauck, Jonathan Gentile, Kris De Smedt, B. Mitchell, Vikas V. Patel, Matthew Green, Christopher A. Gilmore, Ganesan Baranidharan, Farshad M. Ahadian, Peter Georgius, Alexios G. Carayannopoulos, Antoine Tohmeh, Usman Latif, Jeffrey S. Fischgrund, Willem Volschenk, Salim M. Hayek, Robert Levy, Vivek Mehta, Shivanand P. Lad, James P. Rathmell, Timothy R. Deer, Ashish Gulve, William R. Klemme, Edgar L. Ross, Frank J P M Huygen, Meredith Langhorst, and Anesthesiology

Subjects
Visual analogue scale, business.industry, Chronic pain, Lumbosacral Region, medicine.disease, Neuromodulation (medicine), law.invention, Clinical trial, Anesthesiology and Pain Medicine, Treatment Outcome, Neurology, Randomized controlled trial, Double-Blind Method, law, Anesthesia, Cohort, Clinical endpoint, Medicine, Humans, Neurology (clinical), Chronic Pain, business, Adverse effect, Low Back Pain, Pain Measurement
Abstract

Chronic low back pain can be caused by impaired control and degeneration of the multifidus muscles and consequent functional instability of the lumbar spine. Available treatment options have limited effectiveness and prognosis is unfavorable. We conducted an international randomized, double-blind, sham-controlled trial at 26 multidisciplinary centers to determine safety and efficacy of an implantable, restorative neurostimulator designed to restore multifidus neuromuscular control and facilitate relief of symptoms (clinicaltrials.gov identifier: NCT02577354). Two hundred four eligible participants with refractory mechanical (musculoskeletal) chronic LBP and a positive prone instability test indicating impaired multifidus control were implanted and randomized to therapeutic (N = 102) or low-level sham (N = 102) stimulation of the medial branch of the dorsal ramus nerve (multifidus nerve supply) for 30 minutes twice daily. The primary endpoint was the comparison of responder proportions (≥30% relief on the LBP visual analogue scale without analgesics increase) at 120 days. After the primary endpoint assessment, participants in the sham-control group switched to therapeutic stimulation and the combined cohort was assessed through 1 year for long-term outcomes and adverse events. The primary endpoint was inconclusive in terms of treatment superiority (57.1% vs 46.6%; difference: 10.4%; 95% confidence interval, -3.3% to 24.1%, P = 0.138). Prespecified secondary outcomes and analyses were consistent with a modest but clinically meaningful treatment benefit at 120 days. Improvements from baseline, which continued to accrue in all outcome measures after conclusion of the double-blind phase, were clinically important at 1 year. The incidence of serious procedure- or device-related adverse events (3.9%) compared favorably with other neuromodulation therapies for chronic pain.

Published
2021

21. Conversations and Reactions Around Severe Hypoglycaemia (CRASH): Spanish results of a global survey of people with type 1 diabetes or insulin-treated type 2 diabetes and caregivers

Author

Mark Peyrot, Miriam Rubio, Frank J. Snoek, Robin Pokrzywinski, Esther Artime, Jesús Reviriego, F. Javier Ampudia-Blasco, Beth Mitchell, Erik Spaepen, Silvia Díaz, and Beatrice Osumili

Subjects
Adult, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, 030209 endocrinology & metabolism, Crash, Type 2 diabetes, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Diabetes mellitus, Health care, medicine, Humans, Insulin, 030212 general & internal medicine, media_common, Type 1 diabetes, Nutrition and Dietetics, business.industry, medicine.disease, Hypoglycemia, Layperson, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Feeling, Caregivers, Diabetes Mellitus, Type 2, Family medicine, Child, Preschool, business, Healthcare providers
Abstract

Introduction Information on experience/management of severe hypoglycaemic events (SHEs) among people with insulin-treated diabetes (PWD) and caregivers (CGs) providing care to PWD was sought. Materials and methods An online cross-sectional survey was conducted in eight countries. Inclusion criteria: PWD (aged ≥ 18 years; self-reported type 1 [T1D] or insulin-treated type 2 [T2D] diabetes; experienced ≥1 SHE [hypoglycaemia requiring external assistance] in past 3 years); CGs (layperson aged ≥18 years; caring for PWD meeting all criteria above except age [≥4 years]). This descriptive analysis provides data from Spain. SHE-associated data relate to the most recent SHE. Results Across all groups (T1D PWD, n = 106; T2D PWD, n = 88, T1D CG, n = 87; T2D CG, n = 96), 76–89% reported that the SHE occurred at home; most common cause was eating less than planned (38–53%). Most usual action during the SHE was to intake carbohydrates (67–84%); glucagon use was low (9–36%). Discussion of the SHE with their healthcare provider (HCP) was reported by 70–75% of PWD. During the SHE, 35–69% of PWD/CGs reported feeling scared, unprepared and/or helpless. Conclusions Most SHEs occurred outside the healthcare setting; treatment therefore depends greatly on CGs. SHEs have a negative emotional impact on PWD/CGs, underscoring the need for HCPs to discuss SHEs with PWD/CGs, and to provide tools and strategies to prevent and effectively manage SHEs.

Published
2021

22. Screening, Management, and Acceptance of Patients with Aorto-Iliac Vascular Disease for Kidney Transplantation: A Survey among 161 Transplant Surgeons

Author

Elsaline Rijkse, Robert C. Minnee, Hendrikus J. A. N. Kimenai, Jan N. M. IJzermans, and Frank J. M. F. Dor

Subjects
Surgeons, medicine.medical_specialty, business.industry, Vascular disease, General surgery, Second opinion, Psychological intervention, medicine.disease, Iliac Artery, Kidney Transplantation, Kidney transplant, Comorbidity, Transplantation, Risk Factors, Surveys and Questionnaires, Humans, Medicine, Surgery, Vascular Diseases, business, Kidney transplantation
Abstract

Introduction: Aorto-iliac vascular disease (AVD) is frequently found during the workup for kidney transplantation. However, recommendations on screening and management are lacking. We aimed to assess differences in screening, management, and acceptance of these patients for transplantation by performing a survey among transplant surgeons. Second, we aimed to identify center- and surgeon-related factors associated with decline or acceptance of kidney transplant candidates with AVD. Methods: A survey was sent to transplant surgeons and urologists. The survey contained general questions (part I) and 2 patient-based cases (part II) with Trans-Atlantic Inter-Society Consensus (TASC) D and B AVD supported with videos of their CT scans. Results: One hundred ninety-one (20.3%) participants responded; 171 were currently involved in kidney transplantation: 161 (94.2%) completed part I and 145 (84.8%) part II. Screening for AVD was often (38.5%) restricted to high-risk patients. The majority of respondents (67.7%) rated “technical problems” as the most important concern in case of AVD, followed by “increased mortality risk because of cardiovascular comorbidity” (29.8%). Pretransplant vascular interventions to facilitate transplantation were infrequently performed (71.4% mentioned Conclusion: There is no uniformity in the screening, management, and acceptance of patients with AVD for transplantation. If a center declines a patient with AVD because of technical concerns, the patient should be referred for a second opinion to a tertiary center with expertise in pretransplant vascular interventions. Multidisciplinary meetings including a vascular surgeon and a cardiologist could help optimize these patients for transplantation.

Published
2021

23. Kidney transplantation and patients who decline SARS‐CoV‐2 vaccination: an ethical framework

Author

Angela Jane Wood, Stephen Cass, Reza Motallebzadeh, Raj Thuraisingham, Adam McLean, Refik Gökmen, Frank J M F Dor, Ayo Samuel, Joyce Popoola, Jenny Johnson, Trish Longdon, Mohammad Ayaz Hossain, Antonia J. Cronin, Sue Lyon, Abbas Ghazanfar, and Wendy Brown

Subjects
Transplantation, medicine.medical_specialty, COVID-19 Vaccines, urogenital system, SARS-CoV-2, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Vaccination, COVID-19, medicine.disease, Kidney Transplantation, surgical procedures, operative, Vaccination status, View Point, Family medicine, Humans, Medicine, Clinical Ethics, Listing (finance), business, Ethical framework, Kidney transplantation
Abstract

As SARS-CoV-2 vaccines have started to be rolled out, a key question facing transplant units has been whether listing for transplantation should be contingent on recipients having received a vaccine. We aimed to provide an ethical framework when considering potential transplant candidates who decline vaccination. We convened a working group comprising transplant professionals, lay members and patients and undertook a literature review and consensus process. This group's work was also informed by discussions in two hospital clinical ethics committees. We have reviewed arguments for and against mandating vaccination prior to listing for kidney transplantation and considered some practical difficulties which may be associated with a policy of mandated vaccination. Rather than requiring that all patients must receive the SARS-CoV-2 vaccine prior to transplant listing, we recommend considering vaccination status as one of a number of SARS-CoV-2-related risk factors in relation to transplant listing. Transplant units should engage in individualised risk-benefit discussions with patients, avoid the language of mandated treatments and strongly encourage uptake of the vaccine in all patient groups, using tailor-made educational initiatives.

Published
2021

24. Insulin resistance as a marker for the immune-metabolic subtype of depression

Author

Femke Rutters, Aartjan T.F. Beekman, Marijke A. Bremmer, Daniël H. van Raalte, Annelies Brouwer, Femke Lamers, Eus J.W. Van Someren, Frank J. Snoek, Petra J. M. Elders, Netherlands Institute for Neuroscience (NIN), Clinical Psychology, Integrative Neurophysiology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Psychiatry, Internal medicine, ACS - Diabetes & metabolism, Amsterdam Gastroenterology Endocrinology Metabolism, APH - Mental Health, Epidemiology and Data Science, APH - Aging & Later Life, APH - Health Behaviors & Chronic Diseases, General practice, Amsterdam Neuroscience - Systems & Network Neuroscience, Medical psychology, Amsterdam Reproduction & Development (AR&D), APH - Digital Health, and Medical Psychology

Subjects
Light therapy, medicine.medical_specialty, medicine.medical_treatment, Subtype, Type 2 diabetes, Placebo, Irritability, Insulin resistance, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, Depression (differential diagnoses), business.industry, Depression, Diabetes, Anhedonia, medicine.disease, Antidepressive Agents, Psychiatry and Mental health, Clinical Psychology, Affect, Mood, Diabetes Mellitus, Type 2, medicine.symptom, Insulin Resistance, business
Abstract

Objective Insulin resistance (IR), a marker of metabolic dysregulation and pro-inflammatory state, moderates the antidepressant treatment effect in patients with type 2 diabetes (T2D) and is therefore a potential marker for personalized treatment. Based on data from a light therapy trial (NTR4942), we aimed to evaluate whether 1) depression symptoms differ according to the level of IR, and 2) improvement of specific depression symptoms drive the positive effects of light therapy in those with higher IR. Methods This secondary analysis in 59 individuals with depression and T2D explored differences in depressive symptom profile (30-item Inventory of Depressive Symptomatology (IDS)) at baseline and in response to light therapy (versus placebo), between lower and higher IR individuals, using Likelihood Ratio tests and Linear-by-linear association. IR was measured using the gold standard, a hyperinsulinemic-euglycaemic clamp. Results At baseline, higher IR individuals reported more symptoms of irritability (p=0.024) anhedonia (no interest in people and activities: p=0.011; absence of pleasure and enjoyment: p=0.021), fatigue (fatigue: p=0.036; physical fatigue: p=0.035) and hypersomnia (p=0.029) relative to persons with lower IR, who reported more insomnia (nightly awakening: p=0.041; early morning awakening: p=0.012). Light therapy led to an improvement across IDS symptoms in higher IR individuals, while in lower IR individuals, light therapy improved early morning awakening (p=0.005) and interest in people and activities (p=0.015), but worsened mood (feeling sad: p=0.001; feeling irritable: p=0.002; interpersonal sensitivity: p=0.014). Conclusions Results add to the hypothesis of an immune-metabolic subtype of depression, and suggest that IR might be a promising focus for precision medicine.

Published
2021

25. Bilateral supraclavicular abscesses following trigger point injections

Author

Frank J. Salamone, Joshua Sapire, Karthik Kanamalla, and Swachchhanda Songmen

Subjects
medicine.medical_specialty, Percutaneous, Percutaneous drainage, medicine.diagnostic_test, business.industry, Interventional pain, R895-920, Chronic pain, Early detection, Case Report, Computed tomography, Staphylococcus aureus bacteremia, Emergency department, medicine.disease, Complete resolution, Abscess, Medical physics. Medical radiology. Nuclear medicine, Trigger point injection, medicine, Radiology, Nuclear Medicine and imaging, Radiology, business
Abstract

A 54-year-old-woman presented to the emergency department with worsening bilateral shoulder pain six days after trigger point injections in the bilateral supraclavicular areas for chronic pain. A computed tomography scan of the neck revealed bilateral irregular rim enhancing fluid collections. Image-guided percutaneous drainage resulted in marked improvement and near complete resolution by 17 days post-drainage. This case demonstrates the need for early detection of soft-tissue infection and abscess formation related to interventional pain procedures to avoid potentially life-threatening complications, such as Staphylococcus aureus bacteremia.

Published
2021

26. Sagittal age-adjusted score (SAAS) for adult spinal deformity (ASD) more effectively predicts surgical outcomes and proximal junctional kyphosis than previous classifications

Author

Christopher I. Shaffrey, Shay Bess, Douglas Burton, Richard A. Hostin, Christopher P. Ames, Gregory M. Mundis, Justin S. Smith, Han Jo Kim, Eric O. Klineberg, Virginie Lafage, Frank J. Schwab, Renaud Lafage, Jonathan Elysee, and Peter G. Passias

Subjects
medicine.medical_specialty, Sweet spot, business.industry, Age adjustment, Kyphosis, medicine.disease, Sagittal plane, medicine.anatomical_structure, Orthopedic surgery, medicine, Spinal deformity, Physical therapy, Sagittal alignment, Orthopedics and Sports Medicine, Lumbar spine, business
Abstract

Several methodologies have been proposed to determine ideal ASD sagittal spinopelvic alignment (SRS–Schwab classification) global alignment and proportion (GAP) score, patient age-adjusted alignment). A recent study revealed the ability and limitations of these methodologies to predict PJK. The aim of the study was to develop a new approach, inspired by SRS classification, GAP score, and age-alignment to improve the evaluation of the sagittal plane. A multi-center ASD database was retrospectively evaluated for surgically treated ASD patients with complete fusion of the lumbar spine, and minimum 2 year follow-up. The Sagittal age-adjusted score (SAAS) methodology was created by assigning numerical values to the difference between each patient’s postoperative sagittal alignment and ideal alignment defined by previously reported age generational norms for PI-LL, PT, and TPA. Postoperative HRQOL and PJK severity between each SAAS categories were evaluated. 409 of 667 (61.3%) patients meeting inclusion criteria were evaluated. At 2 year SAAS score showed that 27.0% of the patients were under-corrected, 51.7% over-corrected, and 21.3% matched their age-adjusted target. SAAS score increased as PJK worsened (from SAAS = 0.2 for no-PJK, to 4.0 for PJF, p

Published
2021

27. Duchenne muscular dystrophy patients: troponin leak in asymptomatic and implications for drug toxicity studies

Author

Kim Crum, William B. Burnette, Aryaz Sheybani, Jonathan H. Soslow, Larry W. Markham, and Frank J. Raucci

Subjects
musculoskeletal diseases, medicine.medical_specialty, biology, business.industry, Duchenne muscular dystrophy, Cardiomyopathy, macromolecular substances, musculoskeletal system, medicine.disease, Brain natriuretic peptide, Asymptomatic, Troponin, Heart failure, Internal medicine, Pediatrics, Perinatology and Child Health, Troponin I, cardiovascular system, medicine, biology.protein, Cardiology, Biomarker (medicine), cardiovascular diseases, medicine.symptom, business
Abstract

Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD), but studies suggest heart failure biomarkers correlate poorly with cardiomyopathy severity. DMD clinical trials have used troponin I (cTnI) as a biomarker of toxicity, but it is unclear if asymptomatic DMD patients have elevated cTnI. We longitudinally evaluated cTnI, brain natriuretic peptide (BNP), and N-terminal pro-BNP (NT-proBNP) in a DMD cohort. DMD patients were prospectively enrolled and followed for 3 years. Serum was drawn at the time of cardiac magnetic resonance (CMR). Normal biomarker values were derived from healthy subjects. Biomarkers were correlated with CMR markers. All subjects were asymptomatic at the time of enrollment. Several DMD subjects had transiently elevated cTnI. Those with elevated cTnI were more likely to have late gadolinium enhancement on baseline CMR. NT-proBNP correlated with indexed left ventricular end diastolic and maximum left atrial volumes. Otherwise, standard cardiac biomarkers did not correlate with CMR markers of cardiomyopathy. CTnI, BNP, and NT-proBNP do not correlate with CMR assessment of cardiomyopathy progression. A subset of DMD patients have asymptomatic cTnI leak of uncertain clinical significance, though of critical importance if cTnI is used to assess for cardiac toxicity in future drug trials.

Published
2021

29. Reduced pre-operative skin oxygen saturation predicts revision after open reduction and internal fixation in calcaneal fractures

Author

Frank Hildebrand, Kajetan Klos, Bryan J. M. van de Wall, Matthias Knobe, Philipp Lichte, Lukas Daniel Iselin, Reto Babst, Filippo Migliorini, Björn-Ch Link, Frank J. P. Beeres, Bergita Ganse, Sven Nebelung, Boyko Gueorguiev, and Pascal C Haefeli

Subjects
Adult, Male, Reoperation, medicine.medical_specialty, medicine.medical_treatment, Fracture Fixation, Internal, Fractures, Bone, Calcaneal fracture, Foot trauma, medicine, Humans, Internal fixation, Orthopedics and Sports Medicine, Reduction (orthopedic surgery), Retrospective Studies, Oxygen saturation (medicine), Receiver operating characteristic, Lateral extended approach, business.industry, Lasers, Microcirculation, Middle Aged, Laser Doppler velocimetry, medicine.disease, Surgery, Oxygen, Calcaneus, Pre-operative diagnostics, Spectrophotometry, Orthopedic surgery, Female, business, ORIF
Abstract

To assess which pre-operative parameters correlate with wound revisions after an extended lateral approach to the calcaneus. Pre-operative laser-Doppler spectrophotometry was applied in patients undergoing open reduction and internal fixation. The number of wound revisions was recorded during pos-toperative follow-up. Spearman rho analysis was used to identify factors associated with wound revision and receiver operator characteristics curves were calculated for the identified factors. Thirty-four patients (29 men, 5 women; 37 calcanei) with a mean patient age of 43 ± 14 years were analyzed. The minimal oxygen saturation value at the five measurement locations as well as the minimal value for flow correlated negatively with wound revisions (p value = 0.025 and 0.038, respectively). The area under the curve for the pre-operative minimal value of oxygen saturation was 0.841 (95%CI 0.64–1.00, p = 0.028), indicating a good accuracy as a test to predict wound revision. A pre-operative oxygen saturation of at least 20.5% across five measurement points along the anticipated incision identified all patients not needing a wound revision (negative predictive value 100%). On the other hand, patients with at least one measurement below 20.5% were at risk for wound revision surgery (sensitivity 100%, specificity 48.5%). ClinicalTrials.gov NCT01264146

Published
2021

30. Educational Outcomes of a Cohort of Children With Autism Who Received Early Intensive Behavioral Intervention

Author

Frank J. Symons, Adele F. Dimian, and Jason J. Wolff

Subjects
Autism spectrum disorder, Intervention (counseling), mental disorders, Rehabilitation, Cohort, medicine, Autism, Psychology, medicine.disease, behavioral disciplines and activities, Education, Clinical psychology, Dreyfus model of skill acquisition
Abstract

Early Intensive Behavioral Intervention (EIBI) can be effective for supporting skills acquisition among children with autism spectrum disorder (ASD). Few studies have followed children with ASD who received EIBI into schools. The purpose of this study was to investigate educational outcomes specific to instructional placement, standardized test proficiency, and special education eligibility under the ASD category for children who received EIBI. Medicaid records were utilized to create a cross-systems data set of 3- to 5-year-old children with ASD ( n = 667). Most students were placed in general education, and males and White students were more likely to receive special education services for ASD. Only half of the students participated in standardized testing and met proficiency standards. Implications for future research and advocacy for early intervention are discussed.

Published
2021

31. Proteolysis Targeting Chimera (PROTAC) for Macrophage Migration Inhibitory Factor (MIF) Has Anti-Proliferative Activity in Lung Cancer Cells

Author

Zhangping Xiao, Gerrit J. Poelarends, Wim J. Quax, Shanshan Song, Barbro N. Melgert, Frank J. Dekker, Robbert H. Cool, Deng Chen, Ronald van Merkerk, Petra E van der Wouden, Chemical and Pharmaceutical Biology, Molecular Pharmacology, Chemical and Pharmaceutical Biology (GRIP), Biopharmaceuticals, Discovery, Design and Delivery (BDDD), Nanotechnology and Biophysics in Medicine (NANOBIOMED), and Medicinal Chemistry and Bioanalysis (MCB)

Subjects
MAPK/ERK pathway, Cell cycle checkpoint, Macrophage migration inhibitory factor (MIF), 01 natural sciences, proteolysis targeting chimera (PROTACs), ACTIVATION, BINDING, A549 cells, Research Articles, Chemistry, General Medicine, respiratory system, Small molecule, Cell biology, G2 Phase Cell Cycle Checkpoints, Intramolecular Oxidoreductases, cell cycle arrest, Cancer Therapy | Hot Paper, medicine.symptom, Research Article, MAP Kinase Signaling System, PROTEINS, Ubiquitin-Protein Ligases, Inflammation, Antineoplastic Agents, Phthalimides, chemical and pharmacologic phenomena, TAUTOMERASE INHIBITORS, 010402 general chemistry, Mitogen-activated protein kinase (MAPK) pathway, Catalysis, PROBES, Spheroids, Cellular, medicine, otorhinolaryngologic diseases, Humans, CYCLE, Macrophage Migration-Inhibitory Factors, Adaptor Proteins, Signal Transducing, Cell Proliferation, A549 cell, COMPLEX, 010405 organic chemistry, POTENT, Proteolysis targeting chimera, Cancer, General Chemistry, medicine.disease, 0104 chemical sciences, Benzoxazines, DISCOVERY, Proteolysis, Macrophage migration inhibitory factor, Drug Screening Assays, Antitumor
Abstract

Macrophage migration inhibitory factor (MIF) is involved in protein‐protein interactions that play key roles in inflammation and cancer. Current strategies to develop small molecule modulators of MIF functions are mainly restricted to the MIF tautomerase active site. Here, we use this site to develop proteolysis targeting chimera (PROTAC) in order to eliminate MIF from its protein‐protein interaction network. We report the first potent MIF‐directed PROTAC, denoted MD13, which induced almost complete MIF degradation at low micromolar concentrations with a DC50 around 100 nM in A549 cells. MD13 suppresses the proliferation of A549 cells, which can be explained by deactivation of the MAPK pathway and subsequent induction of cell cycle arrest at the G2/M phase. MD13 also exhibits antiproliferative effect in a 3D tumor spheroid model. In conclusion, we describe the first MIF‐directed PROTAC (MD13) as a research tool, which also demonstrates the potential of PROTACs in cancer therapy., Targeting macrophage migration inhibitory factor (MIF) is challenging, as it is involved in diseases via protein‐protein interactions. Here, the first potent MIF‐directed PROTAC MD13 is reported, which eliminates MIF from its protein‐protein interaction network by inducing MIF degradation. MD13 suppresses the proliferation of A549 cells by reducing MIF protein levels and MIF‐related signaling, demonstrating the potential of PROTACs in cancer therapy.

Published
2021

32. Comparison of Outcomes for Open Popliteal Artery Aneurysm Repair Using Vein and Prosthetic Conduits

Author

Frank J. Veith, Heepeel Chang, Neal S. Cayne, Caron B. Rockman, Virendra I. Patel, Glenn R. Jacobowitz, Karan Garg, and Jeffrey J. Siracuse

Subjects
Male, medicine.medical_specialty, Time Factors, Databases, Factual, medicine.medical_treatment, Clinical Decision-Making, 030204 cardiovascular system & hematology, Prosthesis Design, Revascularization, Risk Assessment, Veins, 030218 nuclear medicine & medical imaging, Blood Vessel Prosthesis Implantation, 03 medical and health sciences, 0302 clinical medicine, Aneurysm, Hematoma, Risk Factors, medicine.artery, medicine, Humans, Popliteal Artery, Vein, Vascular Patency, Aged, Retrospective Studies, COPD, business.industry, Graft Occlusion, Vascular, General Medicine, Middle Aged, medicine.disease, Progression-Free Survival, Confidence interval, Popliteal artery, Blood Vessel Prosthesis, Surgery, medicine.anatomical_structure, Cohort, cardiovascular system, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Background Autologous vein is considered the preferred conduit for lower extremity bypass. There is, however, limited literature regarding conduit choice for open popliteal artery aneurysm (PAA) repair. We sought to compare outcomes of PAA repair using vein versus prosthetic conduits. Methods The Vascular Quality Initiative database (2003–2019) was queried for patients with PAAs undergoing elective conventional revascularization originating from the superficial femoral and popliteal arteries. Conduits were categorized as vein or prosthetic. Primary outcomes were primary graft patency, freedom from major adverse limb event (MALE) and MALE-free survival at 2-years. Kaplan-Meier method with log-rank tests was used for estimation and comparison of patency. Results A total of 1,146 limbs in 1,065 patients underwent elective open revascularization for PAA. Vein was used in 921 limbs (80%), and prosthetic in 225 (20%). Patients in the prosthetic cohort had a shorter procedure time, were older, and had a higher prevalence of COPD. Postoperatively, prosthetic patients were more likely to be started and maintained on anticoagulation without increased incidence of hematoma. There was no significant difference in the rate of surgical site infection (2% vs. 2%; P = 0.946). There was an increased tendency toward more symptomatic patients in the vein cohort although not statistically significant (49% vein vs. 41% prosthetic; P = 0.096). On a mean follow-up of 13 ± 5 months, the incidence of MALE and MALE-free survival were comparable between the two groups. The 2-year primary and secondary patency rates were similar, 87% and 96% in the vein, and 91% and 95% in the prosthetic groups, respectively. At multivariable analysis, outflow bypass targets to the infrapopliteal arteries (HR 2.05; 95% confidence interval (CI), 1.16–3.65; P = 0.014) and symptomatic aneurysm (HR 1.81; 95% CI, 1.04–3.15; P = 0.037) were independently associated with loss of primary patency. Conduit type did not make a difference in MALE-free survival, or primary graft patency at 2-years. Conclusion Our study demonstrates that conventional open PAA repair with prosthetic conduit yields results comparable to those with vein conduit with regard to primary and secondary patency and MALEs at 2-years for targets to the popliteal artery. However, when the distal target was infrapopliteal, worse outcomes were observed with prosthetic conduit. Our results suggest that vein conduit should be preferentially used for infrapopliteal targets, while prosthetic conduit confers comparable outcomes in a subset of patients who do not have suitable autologous vein conduits.

Published
2021

33. CREB signaling activity correlates with differentiation and survival in medulloblastoma

Author

Walderik W. Zomerman, Sophia W.M. Bruggeman, Eduardo Sabino de Camargo Magalhães, Harm Jan Lourens, Frank J. G. Scherpen, Eveline S. J. M. de Bont, Tosca. E. I. Martini, Marlinde J. Smit, Shanna M. Hogeling, Tiny G. J. Meeuwsen-de Boer, Sabine L. A. Plasschaert, Geesina C. Rozema-Huizinga, Inna Armandari, and Stem Cell Aging Leukemia and Lymphoma (SALL)

Subjects
MAPK/ERK pathway, Male, Neurogenesis, Science, Developmental neurogenesis, CREB, Adult neurogenesis, Article, Mice, Neural Stem Cells, Cerebellum, TELOMERASE, medicine, FORSKOLIN, Animals, Humans, TRANSCRIPTION, Cerebellar Neoplasms, Cyclic AMP Response Element-Binding Protein, PHOSPHORYLATION, Transcription factor, Cells, Cultured, Progenitor, Cancer, Medulloblastoma, Neurons, Multidisciplinary, biology, PROLIFERATION, Cell Differentiation, medicine.disease, ELEMENT-BINDING PROTEIN, CNS cancer, Mice, Inbred C57BL, GDF7, CELLS, Cancer research, biology.protein, Phosphorylation, Medicine, Female, CAMP, Signal Transduction, Transcription Factors
Abstract

While there has been significant progress in the molecular characterization of the childhood brain cancer medulloblastoma, the tumor proteome remains less explored. However, it is important to obtain a complete understanding of medulloblastoma protein biology, since interactions between proteins represent potential new drug targets. Using previously generated phosphoprotein signaling-profiles of a large cohort of primary medulloblastoma, we discovered that phosphorylation of transcription factor CREB strongly correlates with medulloblastoma survival and associates with a differentiation phenotype. We further found that during normal cerebellar development, phosphorylated CREB was selectively expressed in differentiating cerebellar granule neuron progenitor (CGNP) cells. In line, we observed increased differentiation in CGNPs treated with Forskolin, Bmp6 and Bmp12 (Gdf7), which induce CREB phosphorylation. Lastly, we demonstrated that inducing CREB activation via PKA-mediated CREB signaling, but not Bmp/MEK/ERK mediated signalling, enhances medulloblastoma cell sensitivity to chemotherapy.

Published
2021

34. Patterns of recurrence following definitive chemoradiation for patients with proximal esophageal cancer

Author

Tom Rozema, Francine E.M. Voncken, Stefan A W Bouwense, L. Valkenburg-van Iersel, Vivianne C. G. Tjan-Heijnen, Paul M. Jeene, G.J. Blom, J.A. Bogers, Nicolien Kasperts, Pètra M. Braam, M.A. de Jong, Frank J. P. Hoebers, S. M. E. Geurts, Christina T. Muijs, J. de Vos-Geelen, G.A.P. Nieuwenhuijzen, Damage and Repair in Cancer Development and Cancer Treatment (DARE), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: MA Medische Oncologie (9), MUMC+: MA Heelkunde (9), and Radiotherapie

Subjects
Male, Time Factors, Esophageal Neoplasms, SURGERY, IMPACT, Kaplan-Meier Estimate, Gastroenterology, THERAPY, Carboplatin, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Upper thoracic, Cumulative incidence, Relapse, Complete response, Netherlands, Aged, 80 and over, General Medicine, Chemoradiotherapy, Middle Aged, Esophageal cancer, CHEMOTHERAPY, Progression-Free Survival, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Cervical, Esophageal Squamous Cell Carcinoma, SQUAMOUS-CELL CARCINOMA, After treatment, RADIOTHERAPY, Adult, medicine.medical_specialty, Paclitaxel, Antineoplastic Agents, CONCURRENT CHEMORADIATION, Disease-Free Survival, 03 medical and health sciences, CISPLATIN, Clinical complete response, Esophagus, Internal medicine, medicine, Humans, Aged, Retrospective Studies, Salvage Therapy, business.industry, Retrospective cohort study, medicine.disease, Esophagectomy, Squamous cell cancer, Neoplasm Recurrence, Local, business
Abstract

Introduction: The aim of this retrospective study was to determine the patterns of recurrence and overall survival (OS) in patients achieving clinical complete response after treatment with definitive chemoradiation (CRT) for proximal esophageal cancer.Materials and methods: Patients with proximal esophageal cancer treated with CRT between 2004 and 2014 in 11 centers in the Netherlands were included. OS and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Cumulative incidence of first recurrence (locoregional or distant) and locoregional recurrence (LRR) were assessed using competing risk analyses.Results: In 197 of the 200 identified patients, response was evaluated, 133 (68%) showed a complete response. In complete responders, median OS, three-year OS, and PFS were 45.0 months (95% CI 34.8-61.5 months), 58% (95% CI 48-66), and 49% (95% CI 40-57), respectively. Three- and five-year risk of recurrence were respectively 40% (95% CI 31-48), and 45% (95% CI 36-54). Three- and five-year risk of LRR were 26% (95% CI 19-33), and 30% (95% CI 22-38). Eight of 32 patients with an isolated LRR underwent salvage surgery, with a median OS of 32.0 months (95% CI 6.8-not reached).Conclusion: In patients with a complete response after definitive CRT for proximal esophageal cancer, most recurrences were locoregional and developed within the first three years after CRT. These findings suggest to shorten locoregional follow-up from five to three years. (C) 2021 The Authors. Published by Elsevier Ltd.

Published
2021

35. Effect of smoke-free policies in outdoor areas and private places on children's tobacco smoke exposure and respiratory health

Author

Famke J.M. Mölenberg, Márta K Radó, Alex Burdorf, Christopher Millett, Frank J. van Lenthe, Lauren E H Westenberg, Aziz Sheikh, Jasper V Been, Pediatrics, and Public Health

Subjects
Respiratory tract infections, Non-Randomized Controlled Trials as Topic, business.industry, Respiratory Tract Diseases, Public Health, Environmental and Occupational Health, MEDLINE, Attendance, Psychological intervention, Environmental Exposure, medicine.disease, Smoke-Free Policy, SDG 3 - Good Health and Well-being, Environmental health, Relative risk, Meta-analysis, medicine, Humans, Tobacco Smoke Pollution, Public aspects of medicine, RA1-1270, business, Child, Asthma, Randomized Controlled Trials as Topic
Abstract

Background: Smoke-free policies in outdoor areas and semi-private and private places (eg, cars) might reduce the health harms caused by tobacco smoke exposure (TSE). We aimed to investigate the effect of smoke-free policies covering outdoor areas or semi-private and private places on TSE and respiratory health in children, to inform policy. Methods: In this systematic review and meta-analysis, we searched 13 electronic databases from date of inception to Jan 29, 2021, for published studies that assessed the effects of smoke-free policies in outdoor areas or semi-private or private places on TSE, respiratory health outcomes, or both, in children. Non-randomised and randomised trials, interrupted time series, and controlled before–after studies, without restrictions to the observational period, publication date, or language, were eligible for the main analysis. Two reviewers independently extracted data, including adjusted test statistics from each study using a prespecified form, and assessed risk of bias for effect estimates from each study using the Risk of Bias in Non-Randomised Studies of Interventions tool. Primary outcomes were TSE in places covered by the policy, unplanned hospital attendance for wheezing or asthma, and unplanned hospital attendance for respiratory tract infections, in children younger than 17 years. Random-effects meta-analyses were done when at least two studies evaluated policies that regulated smoking in similar places and reported on the same outcome. This study is registered with PROSPERO, CRD42020190563. Findings: We identified 5745 records and assessed 204 full-text articles for eligibility, of which 11 studies met the inclusion criteria and were included in the qualitative synthesis. Of these studies, seven fit prespecified robustness criteria as recommended by the Cochrane Effective Practice and Organization of Care group, assessing smoke-free cars (n=5), schools (n=1), and a comprehensive policy covering multiple areas (n=1). Risk of bias was low in three studies, moderate in three, and critical in one. In the meta-analysis of ten effect estimates from four studies, smoke-free car policies were associated with an immediate TSE reduction in cars (risk ratio 0·69, 95% CI 0·55–0·87; 161 466 participants); heterogeneity was substantial (I2 80·7%; p

Published
2021

36. Difference in Pain, Complication Rates, and Clinical Outcomes After Suprapatellar Versus Infrapatellar Nailing for Tibia Fractures?

Author

Job N Doornberg, Inge H. F. Reininga, Ruurd L. Jaarsma, Laurent A. M. Hendrickx, Bryan J. M. van de Wall, Gino M. M. J. Kerkhoffs, Frank F A IJpma, Frank J. P. Beeres, Nils Jan Bleeker, and Kaj Ten Duis

Subjects
Chondropathy, medicine.medical_specialty, complications, Concordance, suprapatellar, Pain, Review Article, Bone Nails, anterior knee pain, law.invention, general quality of life, tibia fractures, Randomized controlled trial, Quality of life, law, medicine, physical functioning, Humans, Orthopedics and Sports Medicine, Prospective Studies, Retrospective Studies, intramedullary nailing, Tibia, business.industry, General Medicine, Evidence-based medicine, Patella, medicine.disease, Confidence interval, Fracture Fixation, Intramedullary, Tibial Fractures, Critical appraisal, Physical therapy, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Quality of Life, Surgery, Observational study, business, infrapatellar
Abstract

Supplemental Digital Content is Available in the Text., Objectives: To assess the effectiveness of suprapatellar (SP)-nailing versus infrapatellar (IP)-nailing of tibia fractures in anterior knee pain, complications (retropatellar chondropathy, infection, and malalignment) and physical functioning and quality of life. A clinical question-driven and thorough systematic review of current literature is provided. Data source: PubMed and Embase databases were searched for studies published between 2010 and 2020 relating to SP and IP-nailing of tibia fractures. The study is performed in concordance with PRISMA-guidelines. Study selection: Studies eligible for inclusion were randomized controlled trials, prospective and retrospective observational studies reporting on outcomes of interest. Data extraction: Data extraction was performed independently by 2 assessors. Methodological quality and risk of bias was assessed according to the guidelines of the McMaster Critical Appraisal. Data synthesis: Continuous variables are presented as means with SD and dichotomous variables as frequency and percentages. The weighted mean, standardized weighted mean differences, and 95% confidence interval were calculated. A pooled analysis could not be performed because of differences in outcome measures, time-points, and heterogeneity. Results: Fourteen studies with 1447 patients were analyzed. The weighted incidence of anterior knee pain was 29% after SP-nailing and 39% after IP-nailing, without reported significance. There was a significant lower rate of malalignment after the SP-approach (4% vs. 26%) with small absolute differences in all planes. No substantial differences were observed in retropatellar chondropathy, infection, physical functioning, and quality of life. Conclusions: This systematic review does not reveal superiority of either technique in any of the respective outcomes of interest. Definitive choice should depend on the surgeon's experience and available resources. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Published
2021

37. Intestinal MYC modulates obesity-related metabolic dysfunction

Author

Weiwei Liu, Yuhong Luo, Cen Xie, Frank J. Gonzalez, Oksana Gavrilova, Shoumei Yang, Henrique Bregolin Dias, Xuan Wu, Changtao Jiang, Xiaozhen Guo, Jie Cai, Kristopher W. Krausz, Shogo Takahashi, and Lulu Sun

Subjects
Ceramide, Endocrinology, Diabetes and Metabolism, Biology, Diet, High-Fat, Article, Ilium, Proto-Oncogene Proteins c-myc, Mice, chemistry.chemical_compound, Insulin resistance, Glucagon-Like Peptide 1, Non-alcoholic Fatty Liver Disease, Physiology (medical), Internal Medicine, medicine, Animals, Humans, Obesity, Intestinal Mucosa, Ceramide synthase, Transcription factor, Cell growth, Fatty liver, Cell Biology, medicine.disease, Disease Models, Animal, chemistry, Cancer research, Disease Susceptibility, Insulin Resistance, Steatosis, Steatohepatitis, Biomarkers
Abstract

MYC is a transcription factor with broad biological functions, notably in the control of cell proliferation. Here, we show that intestinal MYC regulates systemic metabolism. We find that MYC expression is increased in ileum biopsies from individuals with obesity and positively correlates with body mass index. Intestine-specific reduction of MYC in mice improves high-fat-diet-induced obesity, insulin resistance, hepatic steatosis and steatohepatitis. Mechanistically, reduced expression of MYC in the intestine promotes glucagon-like peptide-1 (GLP-1) production and secretion. Moreover, we identify Cers4, encoding ceramide synthase 4, catalysing de novo ceramide synthesis, as a MYC target gene. Finally, we show that administration of the MYC inhibitor 10058-F4 has beneficial effects on high-fat-diet-induced metabolic disorders, and is accompanied by increased GLP-1 and reduced ceramide levels in serum. This study positions intestinal MYC as a putative drug target against metabolic diseases, including non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.

Published
2021

38. Effects of web-based cognitive behavioral stress management and health promotion interventions on neuroendocrine and inflammatory markers in men with advanced prostate cancer: A randomized controlled trial

Author

Patricia I. Moreno, Ryne Estabrook, Rina S. Fox, Laura B. Oswald, Mark Begale, Robert T. Chatterton, Sarah C. Flury, Gregory E. Miller, David C. Mohr, Emily A. Walsh, Shilajit Kundu, Betina Yanez, Kent T. Perry, and Frank J. Penedo

Subjects
Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Evening, Hydrocortisone, Immunology, Psychological intervention, Health Promotion, Article, law.invention, Androgen deprivation therapy, 03 medical and health sciences, Behavioral Neuroscience, Prostate cancer, Cognition, 0302 clinical medicine, Randomized controlled trial, Quality of life, law, Internal medicine, medicine, Humans, Internet, Endocrine and Autonomic Systems, Prostatic Neoplasms, Cancer, Androgen Antagonists, medicine.disease, 030104 developmental biology, Health promotion, Quality of Life, Biomarkers, Stress, Psychological, 030217 neurology & neurosurgery
Abstract

Cognitive behavioral stress management (CBSM) improves quality of life and mitigates stress biology in patients with early-stage cancer, including men with localized prostate cancer. However, treatments for advanced prostate cancer like androgen deprivation therapy (ADT) can lead to significant symptom burden that may be further exacerbated by stress-induced inflammation and cortisol dysregulation. The aim of this study was to examine the effects of CBSM (versus an active health promotion control) on circulating inflammatory markers and cortisol in men with advanced prostate cancer. Methods: Men with stage III or IV prostate cancer (N = 192) who had undergone ADT within the last year were randomized to CBSM or health promotion. Both interventions were 10 weeks, group-based, and delivered online. Venous blood was drawn at baseline, 6 months, and 12 months to measure circulating levels of CRP, IL-6, IL8, IL-10, and TNF-α. Saliva samples were collected at awakening, 30 minutes after awakening, evening, and night for two consecutive days at baseline, 6-months, and 12-months to measure diurnal cortisol slopes. Results: Mixed modeling analyses demonstrated that changes in inflammatory markers and cortisol did not differ by intervention. Men in both CBSM and health promotion showed decreases in IL-10, IL-8, and TNF-α from baseline to 6 months (β=−3.85–5.04, p’s=.004–

Published
2021

39. Operative versus nonoperative treatment for adult symptomatic lumbar scoliosis at 5-year follow-up: durability of outcomes and impact of treatment-related serious adverse events

Author

Stefan Parent, Christopher I. Shaffrey, Thomas J. Buell, Keith H. Bridwell, Michael P. Kelly, Tyler R. Koski, Lawrence G. Lenke, Charles H. Crawford, Thomas J. Errico, Shay Bess, Oheneba Boachie-Adjei, Charles C. Edwards, Christopher P. Ames, Christine R. Baldus, Stephen J. Lewis, Justin S. Smith, Virginie Lafage, Steven D. Glassman, Jacob M. Buchowski, Jon D. Lurie, Leah Y. Carreon, Han Jo Kim, Frank J. Schwab, and Elizabeth L. Yanik

Subjects
medicine.medical_specialty, Clinical Sciences, Scoliosis, outcomes, surgery, 03 medical and health sciences, nonoperative treatment, 0302 clinical medicine, Lumbar, Clinical Research, spine deformity, medicine, Prospective cohort study, Adverse effect, lumbar, scoliosis, Clinical Article, Cobb angle, business.industry, adult, Rehabilitation, Neurosciences, Evaluation of treatments and therapeutic interventions, General Medicine, medicine.disease, Surgery, Oswestry Disability Index, Orthopedics, 030220 oncology & carcinogenesis, Cohort, Patient Safety, Implant, business, 6.4 Surgery, 030217 neurology & neurosurgery
Abstract

OBJECTIVE Although short-term adult symptomatic lumbar scoliosis (ASLS) studies favor operative over nonoperative treatment, longer outcomes are critical for assessment of treatment durability, especially for operative treatment, because the majority of implant failures and nonunions present between 2 and 5 years after surgery. The objectives of this study were to assess the durability of treatment outcomes for operative versus nonoperative treatment of ASLS, to report the rates and types of associated serious adverse events (SAEs), and to determine the potential impact of treatment-related SAEs on outcomes. METHODS The ASLS-1 (Adult Symptomatic Lumbar Scoliosis–1) trial is an NIH-sponsored multicenter prospective study to assess operative versus nonoperative ASLS treatment. Patients were 40–80 years of age and had ASLS (Cobb angle ≥ 30° and Oswestry Disability Index [ODI] ≥ 20 or Scoliosis Research Society [SRS]–22 subscore ≤ 4.0 in the Pain, Function, and/or Self-Image domains). Patients receiving operative and nonoperative treatment were compared using as-treated analysis, and the impact of related SAEs was assessed. Primary outcome measures were ODI and SRS-22. RESULTS The 286 patients with ASLS (107 with nonoperative treatment, 179 with operative treatment) had 2-year and 5-year follow-up rates of 90% (n = 256) and 74% (n = 211), respectively. At 5 years, compared with patients treated nonoperatively, those who underwent surgery had greater improvement in ODI (mean difference −15.2 [95% CI −18.7 to −11.7]) and SRS-22 subscore (mean difference 0.63 [95% CI 0.48–0.78]) (p < 0.001), with treatment effects (TEs) exceeding the minimum detectable measurement difference (MDMD) for ODI (7) and SRS-22 subscore (0.4). TEs at 5 years remained as favorable as 2-year TEs (ODI −13.9, SRS-22 0.52). For patients in the operative group, the incidence rates of treatment-related SAEs during the first 2 years and 2–5 years after surgery were 22.38 and 8.17 per 100 person-years, respectively. At 5 years, patients in the operative group who had 1 treatment-related SAE still had significantly greater improvement, with TEs (ODI −12.2, SRS-22 0.53; p < 0.001) exceeding the MDMD. Twelve patients who received surgery and who had 2 or more treatment-related SAEs had greater improvement than nonsurgically treated patients based on ODI (TE −8.34, p = 0.017) and SRS-22 (TE 0.32, p = 0.029), but the SRS-22 TE did not exceed the MDMD. CONCLUSIONS The significantly greater improvement of operative versus nonoperative treatment for ASLS at 2 years was durably maintained at the 5-year follow-up. Patients in the operative cohort with a treatment-related SAE still had greater improvement than patients in the nonoperative cohort. These findings have important implications for patient counseling and future cost-effectiveness assessments.

Published
2021

40. A mixed‐methods study of cyclin‐dependent kinase 4 and 6 inhibitor symptom burden and quality of life among metastatic breast cancer patients and providers

Author

Hatem Soliman, Heather S.L. Jim, Michael H. Antoni, Frank J. Penedo, Cathy D. Meade, Mika Kadono, Brandy Arredondo, Dinorah Martinez-Tyson, Ricardo Costa, and Laura B. Oswald

Subjects
0301 basic medicine, Cancer Research, Psychological intervention, neoplasm metastasis, 0302 clinical medicine, polycyclic compounds, breast neoplasms, Medicine, Molecular Targeted Therapy, skin and connective tissue diseases, Fatigue, RC254-282, Original Research, Cyclin-Dependent Kinase Inhibitor Proteins, Oncologists, biology, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Middle Aged, Metastatic breast cancer, Oncology, 030220 oncology & carcinogenesis, patient‐reported outcomes measures, Female, Needs Assessment, Adult, medicine.medical_specialty, Psycho-oncology, 03 medical and health sciences, Quality of life (healthcare), Humans, Radiology, Nuclear Medicine and imaging, Patient Reported Outcome Measures, neoplasms, Aged, Cyclin-dependent kinase 4, business.industry, Symptom burden, Clinical Cancer Research, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, medicine.disease, Supportive interventions, 030104 developmental biology, quality of life, psycho‐oncology, Family medicine, biology.protein, business, qualitative research, Qualitative research
Abstract

Background Cyclin‐dependent kinase 4 and 6 (CDK4/6) inhibitor targeted therapies dramatically improve survival outcomes for metastatic breast cancer (MBC), but they are associated with significant symptom burden that can impact patients’ health‐related quality of life (HRQOL) and treatment outcomes. This study is the first to describe CDK4/6 inhibitor symptoms from the lived perspectives of MBC patients taking CDK4/6 inhibitors and healthcare providers involved in MBC care. This study also explored patients’ symptom management and HRQOL concerns, and gathered feedback about developing supportive interventions for MBC. Methods MBC patients taking CDK4/6 inhibitors (N = 20) and MBC healthcare providers (N = 12) participated in semi‐structured interviews that were analyzed for qualitative themes. MBC patients completed surveys about HRQOL, symptoms, and unmet needs. Results Patient and provider perceptions of CDK4/6 inhibitor symptoms did not align with patients perceiving symptoms as more burdensome. Patients reported that supportive resources (e.g., support groups, blogs) that are not specific to MBC do not adequately meet their needs. Patients and providers were enthusiastic about developing supportive interventions specifically for MBC and offered considerations for designing such interventions. Conclusions Findings highlight differences in perceptions of CDK4/6 inhibitor symptom burden between MBC patients and providers. Results will inform the development of supportive interventions to assist MBC patients in managing CDK4/6 inhibitor symptom burden and maintaining HRQOL. Such interventions could also improve treatment outcomes., Metastatic breast cancer (MBC) patient and provider perceptions of symptoms associated with CDK4/6 inhibitor did not align, with patients perceiving symptoms as more burdensome. Patients reported that supportive resources (e.g., support groups, blogs) that are not specific to MBC do not adequately meet their needs, however patients and providers were enthusiastic about developing supportive interventions specifically for MBC and offered considerations for designing such interventions. Results will inform the development of supportive interventions to assist MBC patients in managing CDK4/6 inhibitor symptom burden and maintaining health‐related quality of life.

Published
2021

41. Lower complexity and higher variability in beat-to-beat systolic blood pressure are associated with elevated long-term risk of dementia

Author

M. Arfan Ikram, Brad Manor, Jaap Goudsmit, Julia W Wu, Francesco U.S. Mattace-Raso, M. Kamran Ikram, Berend E. Westerhof, Maryam Kavousi, Frank J. Wolters, Albert Hofman, Lewis A. Lipsitz, Junhong Zhou, Yuan Ma, Epidemiology, Internal Medicine, and Neurology

Subjects
Male, medicine.medical_specialty, Epidemiology, Prodromal Symptoms, Blood Pressure, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Rotterdam Study, 0302 clinical medicine, Developmental Neuroscience, SDG 3 - Good Health and Well-being, Risk Factors, Internal medicine, Humans, Medicine, Dementia, Longitudinal Studies, Prospective Studies, Prospective cohort study, Aged, Netherlands, Subclinical infection, business.industry, Health Policy, Hazard ratio, Confounding, medicine.disease, Confidence interval, Psychiatry and Mental health, Blood pressure, Hypertension, Cardiology, Female, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Abstract

Introduction: We hypothesized that subclinical disruption in blood pressure (BP) dynamics, captured by lower complexity and higher variability, may contribute to dementia risk, above and beyond BP levels. Methods: This prospective cohort study followed 1835 older adults from 1997 to 2016, with BP complexity quantified by sample entropy and BP variability quantified by coefficient of variation using beat-to-beat BP measured at baseline. Results: Three hundred thirty-four participants developed dementia over 20 years. Reduced systolic BP (SBP) complexity was associated with a higher risk of dementia (hazard ratio [HR] comparing extreme quintiles: 1.55; 95% confidence interval [CI]: 1.09-2.20). Higher SBP variability was also associated with a higher risk of dementia (HR comparing extreme quintiles: 1.57; 95% CI: 1.11-2.22. These findings were observed after adjusting for age, sex, apolipoprotein E (APOE) genotype, mean SBP, and other confounding factors. Discussions: Our findings suggest that lower complexity and higher variability of beat-to-beat SBP are potential novel risk factors or biomarkers for dementia.

Published
2021

42. Safety and efficacy of occipital nerve stimulation for attack prevention in medically intractable chronic cluster headache (ICON)

Author

Joost Haan, P.G.G. Doesborg, Wim M Mulleners, Patty G.G. Doesborg, Onno P.M. Teernstra, Volker M. Tronnier, I.F. de Coo, Dirk Rasche, Katja Bürger, L.G. Eross, K. Burger, G.H. Spincemaille, Frank J P M Huygen, Wim M. Mulleners, Michel D. Ferrari, Erik W. van Zwet, E.W. van Zwet, Ilse F. de Coo, E.G.M. Couturier, Hartmut Göbel, F. Wille, F.J.P.M. Huygen, Frank Wille, E.C. Bartels, Geert H. Spincemaille, O.P.M. Teernstra, Delphine Magis, R.T.M. van Dongen, Jan Willem Kallewaard, Robert van Dongen, Eveline C Bartels, J. Afra, Jean Schoenen, M. D. Ferrari, Petrus H. Veltink, L.A. Wilbrink, Leopoldine A Wilbrink, E. Kurt, J. Haan, Axel Heinze, Erkan Kurt, Peter J. Koehler, RS: FHML non-thematic output, MUMC+: MA Med Staf Spec Neurochirurgie (9), Anesthesiology, TechMed Centre, and Biomedical Signals and Systems

Subjects
Adult, Male, medicine.medical_specialty, PATHOPHYSIOLOGY, TENS, Cluster Headache, Electric Stimulation Therapy, Placebo, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], law.invention, Double blind, 03 medical and health sciences, 0302 clinical medicine, Belgium, Double-Blind Method, Attack prevention, Randomized controlled trial, NOCEBO, law, Germany, Internal medicine, medicine, Health insurance, MANAGEMENT, Humans, 030212 general & internal medicine, Netherlands, Neurons, PLACEBO, business.industry, Cluster headache, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Cervical Cord, PAIN, Middle Aged, medicine.disease, Clinical trial, Treatment Outcome, CHRONIC MIGRAINE, Female, Occipital nerve stimulation, Occipital Lobe, Neurology (clinical), business, Head, 030217 neurology & neurosurgery
Abstract

Contains fulltext : 234463.pdf (Publisher’s version ) (Closed access) BACKGROUND: Occipital nerve stimulation (ONS) has shown promising results in small uncontrolled trials in patients with medically intractable chronic cluster headache (MICCH). We aimed to establish whether ONS could serve as an effective treatment for patients with MICCH. METHODS: The ONS in MICCH (ICON) study is an investigator-initiated, international, multicentre, randomised, double-blind, phase 3, electrical dose-controlled clinical trial. The study took place at four hospitals in the Netherlands, one hospital in Belgium, one in Germany, and one in Hungary. After 12 weeks' baseline observation, patients with MICCH, at least four attacks per week, and history of being non-responsive to at least three standard preventive drugs, were randomly allocated (at a 1:1 ratio using a computer-generated permuted block) to 24 weeks of occipital nerve stimulation at either 100% or 30% of the individually determined range between paraesthesia threshold and near-discomfort (double-blind study phase). Because ONS causes paraesthesia, preventing masked comparison versus placebo, we compared high-intensity versus low-intensity ONS, which are hypothesised to cause similar paraesthesia, but with different efficacy. In weeks 25-48, participants received individually optimised open-label ONS. The primary outcome was the weekly mean attack frequency in weeks 21-24 compared with baseline across all patients and, if a decrease was shown, to show a group-wise difference. The trial is closed to recruitment (ClinicalTrials.gov NCT01151631). FINDINGS: Patients were enrolled between Oct 12, 2010, and Dec 3, 2017. We enrolled 150 patients and randomly assigned 131 (87%) to treatment; 65 (50%) patients to 100% ONS and 66 (50%) to 30% ONS. One of the 66 patients assigned to 30% ONS was not implanted and was therefore excluded from the intention-to-treat analysis. Because the weekly mean attack frequencies at baseline were skewed (median 15·75; IQR 9·44 to 24·75) we used log transformation to analyse the data and medians to present the results. Median weekly mean attack frequencies in the total population decreased from baseline to 7·38 (2·50 to 18·50; p

Published
2021

43. Epigenetic regulation in macrophage migration inhibitory factor (MIF)-mediated signaling in cancer and inflammation

Author

Osipyan, Angelina, Chen, Deng, and Dekker, Frank J.

Subjects
0301 basic medicine, MAPK/ERK pathway, CD74, medicine.medical_treatment, Inflammation, Biology, Epigenesis, Genetic, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Drug Discovery, medicine, Animals, Humans, Macrophage Migration-Inhibitory Factors, PI3K/AKT/mTOR pathway, Pharmacology, Cancer, medicine.disease, 3. Good health, 030104 developmental biology, Cytokine, 030220 oncology & carcinogenesis, Cancer research, Macrophage migration inhibitory factor, Signal transduction, medicine.symptom, Signal Transduction
Abstract

Epigenetic mechanisms are important for the regular development and maintenance of the tissue-specific expression of cytokine genes. One of the crucial cytokines involved in cancer and inflammation is macrophage migration inhibitory factor (MIF), which triggers the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling pathways by binding to CD74 and other receptors. Altered expression of this cytokine and altered activity states of the connected pathways are linked to inflammatory disease and cancer. Therapeutic strategies based on epigenetic mechanisms have the potential to regulate MIF-mediated signaling in cancer and inflammation.

Published
2021

44. National protocol for model-based selection for proton therapy in head and neck cancer

Author

Johannes A. Langendijk, Chris H.J. Terhaard, Patricia Doornaert, Liesbeth J. Boersma, Olga Hamming-Vrieze, Arjen van der Schaaf, Roel J H M Steenbakkers, Frank J. P. Hoebers, Wilko F.A.R. Verbakel, Martin A. de Jong, Fatma Keskin-Cambay, Johannes B. Reitsma, Jeroen B. van de Kamer, Ewoud Schuit, Radiotherapie, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Radiotherapy, Radiation Oncology, CCA - Cancer Treatment and quality of life, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Damage and Repair in Cancer Development and Cancer Treatment (DARE), and ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)

Subjects
medicine.medical_specialty, model-based selection, PATIENT-RATED XEROSTOMIA, R895-920, QC770-798, 3-DIMENSIONAL CONFORMAL RADIOTHERAPY, STICKY SALIVA, VALIDATION, 030218 nuclear medicine & medical imaging, Medical physics. Medical radiology. Nuclear medicine, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, QUALITY-OF-LIFE, Nuclear and particle physics. Atomic energy. Radioactivity, Health care, medicine, proton therapy, Radiology, Nuclear Medicine and imaging, Routine clinical practice, Medical physics, Proton therapy, Selection (genetic algorithm), Protocol (science), radiation-induced side effects, business.industry, NTCP MODELS, Health Policy, Head and neck cancer, CHEMOTHERAPY, medicine.disease, national indication protocol, Atomic and Molecular Physics, and Optics, INTENSITY-MODULATED RADIOTHERAPY, DELINEATION, 030220 oncology & carcinogenesis, Photon therapy, head and neck cancer, GASTROSTOMY, business
Abstract

In the Netherlands, the model-based approach is used to identify patients with head and neck cancer who may benefit most from proton therapy in terms of prevention of late radiation-induced side effects in comparison with photon therapy. To this purpose, a National Indication Protocol Proton therapy for Head and Neck Cancer patients (NIPP-HNC) was developed, which has been approved by the health care authorities. When patients qualify according to the guidelines of the NIPP-HNC, proton therapy is fully reimbursed. This article describes the procedures that were followed to develop this NIPP-HNC and provides all necessary information to introduce model-based selection for patients with head and neck cancer into routine clinical practice.

Published
2021

45. Admission to the Regular Ward is Safe Following Uncomplicated Craniosynostosis Surgery: A Retrospective Study

Author

Frank J Walch, Sarah Graber, Deseray Sileo, Ken R. Winston, Allyson Alexander, C Corbett Wilkinson, Krista Greenan, Maureen Andrews, Brooke French, Aaron Mason, and Thanh Hung Nguyen

Subjects
03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, 030220 oncology & carcinogenesis, medicine, Retrospective cohort study, medicine.disease, business, 030217 neurology & neurosurgery, Craniosynostosis, Surgery
Abstract

Background: At our craniofacial center patients are routinely admitted to a regular ward, or floor, rather an intensive care unit (ICU) after uncomplicated craniosynostosis surgery. In this study, we review the safety of our postoperative placement policy, examining the rate of transfer from floor to ICU. Methods: The charts of patients who underwent craniosynostosis surgery from 2009 through 2017 at a single children’s hospital were reviewed. Postoperative hospital courses were characterized as preoperatively-planned ICU admission, perioperatively-planned ICU admission, or primary floor admission. The primary outcome was transfer from floor to ICU. Secondary outcomes included duration of hospitalization. Results: Chart review yielded 420 patients. Three hundred sixty-eight (88%) were admitted directly to the floor and 52 (12.0%) directly to an ICU. Of patients admitted to the floor, 2 (0.5%) were transferred to an ICU. Twenty-four patients with syndromic and 20 patients with multisutural craniosynostosis were admitted to the floor. Only 1 patient from each group (the same patient; 4.2% and 5.0%, respectively), was transferred to an ICU. Thirty-two ICU admissions were preoperatively planned and 20 were perioperatively planned. Reasons for preoperatively planned ICU admission included significant comorbidities and type of surgery. Reasons for perioperatively planned ICU admissions included significant intraoperative adverse events, excessive blood loss, and failure of clearance from the post-anesthesia care unit (PACU). Patients admitted to the ICU had a statistically significant longer mean length of hospitalization (4.8 days vs 2.7 days) than did patients admitted to the floor. Conclusions: Most postoperative craniosynostosis surgery patients—including patients with syndromic and/or multisutural synostosis—are managed safely on the floor at our center. Some patients still need postoperative ICU admission, but are easily identified preoperatively, intraoperatively, or in the PACU. Our findings should be applicable to other large craniofacial centers.

Published
2021

46. Lipid-rich Plaques Detected by Near-infrared Spectroscopy Are More Frequently Exposed to High Shear Stress

Author

Frits Mastik, Jolanda J. Wentzel, Giuseppe De Nisco, Annette M. Kok, Joost Daemen, Koen Nieman, Eline M J Hartman, Frank J. H. Gijsen, Adriaan Coenen, Ayla Hoogendoorn, Suze-Anne Korteland, Anton F. W. van der Steen, Cardiology, and Radiology & Nuclear Medicine

Subjects
Male, Patient-Specific Modeling, Pharmaceutical Science, 030204 cardiovascular system & hematology, Coronary artery disease, Vulnerable plaques, Wall shear stress, 0302 clinical medicine, Intravascular ultrasound, Prospective Studies, 030212 general & internal medicine, Genetics (clinical), Lipid-rich plaques, Spectroscopy, Near-Infrared, medicine.diagnostic_test, Models, Cardiovascular, Middle Aged, Coronary Vessels, Lipids, Plaque, Atherosclerotic, surgical procedures, operative, medicine.anatomical_structure, cardiovascular system, Cardiology, Molecular Medicine, Female, Original Article, lipids (amino acids, peptides, and proteins), Cardiology and Cardiovascular Medicine, circulatory and respiratory physiology, Artery, medicine.medical_specialty, Acute coronary syndrome, 03 medical and health sciences, Imaging, Three-Dimensional, Near-infrared spectroscopy, Predictive Value of Tests, Coronary Circulation, Internal medicine, Genetics, medicine, Humans, Acute Coronary Syndrome, High shear stress, Ultrasonography, Interventional, Aged, Rupture, Spontaneous, business.industry, Hemodynamics, equipment and supplies, medicine.disease, Coronary arteries, Lipid content, Hydrodynamics, Stress, Mechanical, business
Abstract

High wall shear stress (WSS) and near-infrared spectroscopy (NIRS) detected lipid-rich plaque (LRP) are both known to be associated with plaque destabilization and future adverse cardiovascular events. However, knowledge of spatial co-localization of LRP and high WSS is lacking. This study investigated the co-localization of LRP based on NIRS and high WSS. Fifty-three patients presenting acute coronary syndrome underwent NIRS-intravascular-ultrasound (NIRS-IVUS) imaging of a non-culprit coronary artery. WSS was obtained using WSS profiling in 3D-reconstructions of the coronary arteries based on fusion of IVUS-segmented lumen and CT-derived 3D-centerline. Thirty-eight vessels were available for final analysis and divided into 0.5 mm/45° sectors. LRP sectors, as identified by NIRS, were more often colocalized with high WSS than sectors without LRP. Moreover, there was a dose-dependent relationship between lipid content and high WSS exposure. This study is a first step in understanding the evolution of LRPs to vulnerable plaques. Graphical Abstract Electronic supplementary material The online version of this article (10.1007/s12265-020-10072-x) contains supplementary material, which is available to authorized users.

Published
2021

47. PTCOG Head and Neck Subcommittee Consensus Guidelines on Particle Therapy for the Management of Head and Neck Tumors

Author

Alexander Lin, MD, John H. C. Chang, MD, Ryan S. Grover, MD, Frank J. P. Hoebers, MD, PhD, Upendra Parvathaneni, MBBS, FRANZCR, Samir H. Patel, MD, Juliette Thariat, MD, PhD, David J. Thomson, MA, MD, FACR, Johannes A. Langendijk, MD, PhD, Steven J. Frank, MD, on behalf of the International Particle Therapy Co-operative Group (PTCOG) Head and Neck Subcommittee, Radiotherapie, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
OROPHARYNGEAL CANCER, medicine.medical_specialty, medicine.medical_treatment, R895-920, PROTON-BEAM THERAPY, QC770-798, 030218 nuclear medicine & medical imaging, Medical physics. Medical radiology. Nuclear medicine, Clinical, 03 medical and health sciences, 0302 clinical medicine, QUALITY-OF-LIFE, Nuclear and particle physics. Atomic energy. Radioactivity, RADIATION-THERAPY, NASOPHARYNGEAL CARCINOMA, medicine, proton therapy, Radiology, Nuclear Medicine and imaging, MULTIFIELD OPTIMIZATION, Head and neck, Proton therapy, Task group, Particle therapy, business.industry, Head and neck tumors, Head and neck cancer, HUMAN-PAPILLOMAVIRUS, medicine.disease, 2ND PRIMARY HEAD, Atomic and Molecular Physics, and Optics, Radiation therapy, Clinical trial, INTENSITY-MODULATED RADIOTHERAPY, 030220 oncology & carcinogenesis, head and neck cancer, Radiology, business, LOCALLY ADVANCED HEAD
Abstract

Purpose: Radiation therapy is a standard modality in the treatment for cancers of the head and neck, but is associated with significant short- and long-term side effects. Proton therapy, with its unique physical characteristics, can deliver less dose to normal tissues, resulting in fewer side effects. Proton therapy is currently being used for the treatment of head and neck cancer, with increasing clinical evidence supporting its use. However, barriers to wider adoption include access, cost, and the need for higher-level evidence. Methods: The clinical evidence for the use of proton therapy in the treatment of head and neck cancer are reviewed here, including indications, advantages, and challenges. Results: The Particle Therapy Cooperative Group Head and Neck Subcommittee task group provides consensus guidelines for the use of proton therapy for head and neck cancer. Conclusion: This report can be used as a guide for clinical use, to understand clinical trials, and to inform future research efforts.

Published
2021

48. How to Identify Responders and Nonresponders to Dorsal Root Ganglion-Stimulation Aimed at Eliciting Motor Responses in Chronic Spinal Cord Injury

Author

Judith Drenthen, Rutger Osterthun, Frank J P M Huygen, Cecile C de Vos, Chris I. De Zeeuw, Biswadjiet S. Harhangi, Sadaf Soloukey, Neurosciences, Neurosurgery, Neurology, Rehabilitation Medicine, Anesthesiology, and Netherlands Institute for Neuroscience (NIN)

Subjects
Epidural Space, Male, medicine.medical_specialty, dorsal root ganglion, responder, Clinical neurophysiology, DORSAL ROOT GANGLION STIMULATION, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Dorsal root ganglion, Clinical Research, nonresponder, peripheral nervous system, Ganglia, Spinal, Reflex, medicine, Humans, Spasticity, Spinal cord injury, Spinal Cord Injuries, business.industry, General Medicine, medicine.disease, Neuromodulation (medicine), spinal cord injury, Anesthesiology and Pain Medicine, medicine.anatomical_structure, Neurology, Muscle Spasticity, Peripheral nervous system, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, Sensory nerve, DRG‐stimulation
Abstract

Objective: While integrity of spinal pathways below injury is generally thought to be an important factor in the success-rate of neuromodulation strategies for spinal cord injury (SCI), it is still unclear how the integrity of these pathways conveying the effects of stimulation should be assessed. In one of our institutional case series of five patients receiving dorsal root ganglion (DRG)-stimulation for elicitation of immediate motor response in motor complete SCI, only two out of five patients presented as responders, showing immediate muscle activation upon DRG-stimulation. The current study focuses on post hoc clinical-neurophysiological tests performed within this patient series to illustrate their use for prediction of spinal pathway integrity, and presumably, responder-status. Materials and Methods: In a series of three nonresponders and two responders (all male, American Spinal Injury Association [ASIA] impairment scale [AIS] A/B), a test-battery consisting of questionnaires, clinical measurements, as well as a series of neurophysiological measurements was performed less than eight months after participation in the initial study. Results: Nonresponders presented with a complete absence of spasticity and absence of leg reflexes. Additionally, nonresponders presented with close to no compound muscle action potentials (CMAPs) or Hofmann(H)-reflexes. In contrast, both responders presented with clear spasticity, elicitable leg reflexes, CMAPs, H-reflexes, and sensory nerve action potentials, although not always consistent for all tested muscles. Conclusions: Post hoc neurophysiological measurements were limited in clearly separating responders from nonresponders. Clinically, complete absence of spasticity-related complaints in the nonresponders was a distinguishing factor between responders and nonresponders in this case series, which mimics prior reports of epidural electrical stimulation, potentially illustrating similarities in mechanisms of action between the two techniques. However, the problem remains that explicit use and report of preinclusion clinical-neurophysiological measurements is missing in SCI literature. Identifying proper ways to assess these criteria might therefore be unnecessarily difficult, especially for nonestablished neuromodulation techniques.

Published
2021

49. Cervical deformity patients with baseline hyperlordosis or hyperkyphosis differ in surgical treatment and radiographic outcomes

Author

Christopher I. Shaffrey, Cole Bortz, Frank J. Schwab, Avery E. Brown, Juan S. Uribe, Peter G. Passias, Virginie Lafage, Gregory M. Mundis, Themistocles S. Protopsaltis, Justin S. Smith, Haddy Alas, Han Jo Kim, Eric O. Klineberg, Christopher P. Ames, Katherine E. Pierce, Renaud Lafage, Shay Bess, Alan H. Daniels, Douglas C. Burton, Breton Line, and Bassel G Diebo

Subjects
medicine.medical_specialty, Lordosis, hyperlordosis, Radiography, Clinical Sciences, Hyperlordosis, Diseases of the musculoskeletal system, spine surgery, cervical deformity, Clinical Research, Cervical deformity, medicine, Surgical treatment, cervical lordosis, business.industry, Neurosciences, medicine.disease, Sagittal plane, Surgery, Cervical lordosis, medicine.anatomical_structure, RC925-935, Etiology, Original Article, Neurology (clinical), Patient Safety, business
Abstract

BackgroundPatients with symptomatic cervical deformity (CD) requiring surgical correction often present with hyperkyphosis (HK), although patients with hyperlordotic curves may require surgery as well. Few studies have investigated differences in CD corrective surgery with regard to HK and hyperlordosis (HL).ObjectiveThe objective of the study is to evaluate patterns in treatment for CD patients with baseline (BL) HK and HL and understand how extreme curvature of the spine may influence surgical outcomes.Materials and methodsOperative CD patients with BL and 1-year (1Y) radiographic data were included in the study. Patients were stratified based on BL C2-C7 lordosis (CL) angle: those >1 standard deviation (SD) from the mean (-6.96 ± 21.47°) were hyperlordotic (>14.51°) or hyperkyphotic (

Published
2022

50. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author

Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Luxia Zhang, Young-Ho Khang, Ellina Rakhimova, Kairit Mikkel, Tiina Vlasoff, Eruke E. Egbagbe, Sidsel Graff-Iversen, Ilona Nenko, Magdalena Klimek, Mathilde Savy, Sanjib Kumar Sharma, Alfonso Siani, Luís Lopes, Vanina Bongard, Gregor Jurak, Jacqueline F. Price, Christina-Paulina Lambrinou, Maria Lc Iurilli, Rainford J. Wilks, Bontha V. Babu, Fereidoun Azizi, Harunobu Nakamura, Marialaura Bonaccio, Angela Döring, Zhenyu Zhang, Naser Ahmadi, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Clive Osmond, Thirunavukkarasu Sathish, Robert J. Adams, Themistoklis Tzotzas, Reina Engle-Stone, Atul Trivedi, Shoichiro Tsugane, Niels Møller, Jorge Bezerra, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Badreya Al-Lahou, J. Jaime Miranda, Bahram Mohajer, Sigmund A. Anderssen, Lital Keinan Boker, Eero Kajantie, Martin Gulliford, Maties Torrent, Sumit Bharadwaj, Toshiharu Ninomiya, Zbigniew Gaciong, Nayu Ikeda, Li Juan Wu, Adrian Richter, Licia Iacoviello, Marc J. Gunter, Wenbin Wei, Norsyamlina Che Abdul Rahim, Eman Aly, Ambady Ramachandran, Nils Lehmann, Soile E. Puhakka, Giovanni Veronesi, Hongsheng Bi, Eiji Oda, Jia Li Duan, Per Tynelius, José María Huerta, Janne Schurmann Tolstrup, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Hanno Ulmer, Shukri F. Mohamed, Anthony Kafatos, Suyeon Park, Mohsen Ibrahim, Hamed Pouraram, Bin Zhou, May Soe Aung, Lars Bo Andersen, Erfan Ghasemi, René Charles Sylva, Himanshu K. Chaturvedi, Luc Dauchet, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Valérie Deschamps, Ko Ko Zaw, Peter Vollenweider, Tomas Vega, Yves Martin-Prével, Mahfuzar Rahman, Dorja Vočanec, Roman Topor-Madry, Vinay Nangia, Herculina S. Kruger, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Aleksander Giwercman, Elżbieta Dziankowska-Zaborszczyk, Cecilia Björkelund, Tatjana Hejgaard, Maria Puiu, Maria Benedetta Donati, Andrew Wong, Carlos P. Boissonnet, Santosh K. Bhargava, Patrick Kolsteren, Dermot O'Reilly, Bahareh Kheiri, Wolfgang Kratzer, Susanne R. de Rooij, H. Bas Bueno-de-Mesquita, Günther Fink, José R. Banegas, Michele Monroy-Valle, Drude Molbo, Mahmudur Rahman, Hynek Pikhart, Rafael N. Pichardo, Massimo Salvetti, Hui Cai, Sarah Filippi, Georg Posch, Hung-Kwan So, Yonghua Hu, Katsuyasu Kouda, Joana Carvalho, Gailute Bernotiene, Hannu Uusitalo, Thein Thein Htay, Felix Kaducu, Maigeng Zhou, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Michel Joffres, Sabina Zambon, Ronald D. 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Duante, Sheikh Mohammed Shariful Islam, Quang Ngoc La, Ricky Eddie, Petra Rust, Daniela Rodrigues, Dirk De Bacquer, Karen Sparrenberger, Agneta Sjöberg, Thet Thet Mu, Katarzyna Dereń, Cora L. Craig, Jorge Motta, Janina Petkeviciene, Boyd Swinburn, Paibul Suriyawongpaisal, Visnja Djordjic, Ramón Alberto Rascón-Pacheco, Pradeep Joshi, Daan Kromhout, Marius B. Bjertness, Stefano Marventano, Juel Jarani, Alireza Khosravi, Eva Martos, David De Ridder, Lizzy M. Brewster, Nico Dragano, Liam Smeeth, Kenji Shibuya, Emma Ruiz Moreno, Hashem Jaddou, Grzegorz Sobek, Dimitrios Trichopoulos, Marvin Cervantes-Loaiza, Abu Am Hanif, Elaine M. Murtagh, Carlos A. Aguilar-Salinas, Graziella D'Arrigo, Kyungwon Oh, Heiner Boeing, Regina Heidinger-Felso, André Luiz Sena Guimarães, Balkish M. Naidu, Avula Laxmaiah, Ana M. B. Menezes, Marie Eliasen, Francesco Pistelli, Yuan He, Dusko Bjelica, José A. Casajús, Guang Ning, Lutgart Braeckman, Dirk Vanderschueren, Jochanan Stessman, Ivana Radic, Yi Zeng, Hans Concin, Damaskini Valvi, Sari Hantunen, Catherine Kyobutungi, Diego Augusto Santos Silva, Wenhua Zhao, Sok King Ong, Anne W. Taylor, Iraj Nabipour, Justyna Godos, Cyrus Cooper, Mattias Johansson, Samuel C. Dumith, Magdalena Muc, Sabine Schipf, Idowu O Senbanjo, Jim Mann, Rajaa Al-Raddadi, Yih Chung Tham, Kay-Tee Khaw, Joseph Cacciottolo, Ana Henriques, Sahar Saeedi Moghaddam, Reza Mohammadpourhodki, Bernhard O. Boehm, Songhomitra Panda-Jonas, Iveta Pudule, Elisabete Ramos, Lacramioara Aurelia Brinduse, Paul H. Lee, Terence W O'Neill, Javad Aghazadeh-Attari, Margus Punab, Bojan Jelaković, Camilla T. Damsgaard, Takafumi Ishida, Ekaterina Chikova-Iscener, Mirjam M. Heinen, Tazeen H. Jafar, Semánová Csilla, Constance Schultsz, Santiago F. Gomez, Raija Korpelainen, Edward W. Gregg, Laura Gutierrez, Pierre Traissac, Victor M. Herrera, Aristides M. 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Cyril and Methodius University, University of Leuven, Lamprecht und Stamm Sozialforschung und Beratung AG, Bonn University, National Institute of Public Health - National Institute of Hygiene, Kalina Malina Kindergarten, The Jikei University School of Medicine, Fu Jen Catholic University, National Statistical Office, Scientific Research Institute of Maternal and Child Health, University of Lincoln, Central University of Kerala, Amsterdam Public Health Research Institute, Health Service of Murcia, Institut d’Investigacio Sanitaria Illes Balears, University of Bologna, Hellenic Health Foundation, Government Medical College, Sefako Makgatho Health Science University, Addis Ababa University, Universidad Centro-Occidental Lisandro Alvarado, Meharry Medical College, Dokuz Eylul University, University of Tampere Tays Eye Center, Sabiha Gokcen Ilkokulu, Polytechnic Institute of Porto, Icahn School of Medicine at Mount Sinai, Universidad CEU San Pablo, University Miguel Hernandez, Vrije Universiteit Amsterdam, Sunflower Nursery School, North Karelia Center for Public Health, University of the Witwatersrand, Medical University of Vienna, Cork Institute of Technology, Institute for Medical Research, Xinjiang Medical University, Shanghai Educational Development Co. Ltd, Orebro University, University of London, Universitas Indonesia, Institute of Food and Nutrition Development of Ministry of Agriculture and Rural Affairs, Children’s Hospital of Fudan University, University of Cyprus, Niigata University, International Medical University, Iran University of Medical Sciences, Center for Diabetes and Endocrine Care, Peking University First Hospital, Jiangsu Provincial Center for Disease Control and Prevention, Sun Yat-sen University, West Kazakhstan Medical University, Inner Mongolia Medical University, University of Ghana, Maria Lc Iurilli , Bin Zhou , James E Bennett , Rodrigo M Carrillo-Larco , Marisa K Sophiea , Andrea Rodriguez-Martinez , Honor Bixby , Bethlehem D Solomon , Cristina Taddei , Goodarz Danaei , Mariachiara Di Cesare , Gretchen A Stevens , Leanne M Riley , Stefan Savin , Melanie J Cowan , Pascal Bovet , Albertino Damasceno , Adela Chirita-Emandi , Alison J Hayes , Nayu Ikeda , Rod T Jackson , Young-Ho Khang , Avula Laxmaiah , Jing Liu , J Jaime Miranda , Olfa Saidi , Sylvain Sebert , Maroje Sorić , Gregor Starc , Edward W Gregg , Leandra Abarca-Gómez , Ziad A Abdeen , Shynar Abdrakhmanova , Suhaila Abdul Ghaffar , Hanan F Abdul Rahim , Niveen M Abu-Rmeileh , Jamila Abubakar Garba , Benjamin Acosta-Cazares , Robert J Adams , Wichai Aekplakorn , Kaosar Afsana , Shoaib Afzal , Imelda A Agdeppa , Javad Aghazadeh-Attari , Carlos A Aguilar-Salinas , Charles Agyemang , Mohamad Hasnan Ahmad , Noor Ani Ahmad , Ali Ahmadi , Naser Ahmadi , Soheir H Ahmed , Wolfgang Ahrens , Gulmira Aitmurzaeva , Kamel Ajlouni , Hazzaa M Al-Hazzaa , Badreya Al-Lahou , Rajaa Al-Raddadi , Monira Alarouj , Fadia AlBuhairan , Shahla AlDhukair , Mohamed M Ali , Abdullah Alkandari , Ala'a Alkerwi , Kristine Allin , Mar Alvarez-Pedrerol , Eman Aly , Deepak N Amarapurkar , Parisa Amiri , Norbert Amougou , Philippe Amouyel , Lars Bo Andersen , Sigmund A Anderssen , Lars Ängquist , Ranjit Mohan Anjana , Alireza Ansari-Moghaddam , Hajer Aounallah-Skhiri , Joana Araújo , Inger Ariansen , Tahir Aris , Raphael E Arku , Nimmathota Arlappa , Krishna K Aryal , Thor Aspelund , Felix K Assah , Maria Cecília F Assunção , May Soe Aung , Juha Auvinen , Mária Avdicová , Shina Avi , Ana Azevedo , Mohsen Azimi-Nezhad , Fereidoun Azizi , Mehrdad Azmin , Bontha V Babu , Maja Bæksgaard Jørgensen , Azli Baharudin , Suhad Bahijri , Jennifer L Baker , Nagalla Balakrishna , Mohamed Bamoshmoosh , Maciej Banach , Piotr Bandosz , José R Banegas , Joanna Baran , Barbagallo CM, Alberto Barceló , Amina Barkat , Aluisio Jd Barros , Mauro Virgílio Gomes Barros , Abdul Basit , Joao Luiz D Bastos , Iqbal Bata , Anwar M Batieha , Rosangela L Batista , Zhamilya Battakova , Assembekov Batyrbek , Louise A Baur , Robert Beaglehole , Silvia Bel-Serrat , Antonisamy Belavendra , Habiba Ben Romdhane , Judith Benedics , Mikhail Benet , Ingunn Holden Bergh , Salim Berkinbayev , Antonio Bernabe-Ortiz , Gailute Bernotiene , Heloísa Bettiol , Jorge Bezerra , Aroor Bhagyalaxmi , Sumit Bharadwaj , Santosh K Bhargava , Zulfiqar A Bhutta , Hongsheng Bi , Yufang Bi , Daniel Bia , Elysée Claude Bika Lele, Mukharram M Bikbov , Bihungum Bista , Dusko J Bjelica , Peter Bjerregaard , Espen Bjertness , Marius B Bjertness , Cecilia Björkelund , Katia V Bloch , Anneke Blokstra , Simona Bo , Martin Bobak , Lynne M Boddy , Bernhard O Boehm , Heiner Boeing , Jose G Boggia , Elena Bogova , Carlos P Boissonnet , Stig E Bojesen , Marialaura Bonaccio , Vanina Bongard , Alice Bonilla-Vargas , Matthias Bopp , Herman Borghs , Lien Braeckevelt , Lutgart Braeckman , Marjolijn Ce Bragt , Imperia Brajkovich , Francesco Branca , Juergen Breckenkamp , João Breda , Hermann Brenner , Lizzy M Brewster , Garry R Brian , Lacramioara Brinduse , Sinead Brophy , Graziella Bruno , H Bas Bueno-de-Mesquita , Anna Bugge , Marta Buoncristiano , Genc Burazeri , Con Burns , Antonio Cabrera de León , Joseph Cacciottolo , Hui Cai , Tilema Cama , Christine Cameron , José Camolas , Günay Can , Ana Paula C Cândido , Felicia Cañete , Mario V Capanzana , Nadežda Capková , Eduardo Capuano , Vincenzo Capuano , Marloes Cardol , Viviane C Cardoso , Axel C Carlsson , Esteban Carmuega , Joana Carvalho , José A Casajús , Felipe F Casanueva , Ertugrul Celikcan , Laura Censi , Marvin Cervantes-Loaiza , Juraci A Cesar , Snehalatha Chamukuttan , Angelique W Chan , Queenie Chan , Himanshu K Chaturvedi , Nish Chaturvedi , Norsyamlina Che Abdul Rahim , Miao Li Chee , Chien-Jen Chen , Fangfang Chen , Huashuai Chen , Shuohua Chen , Zhengming Chen , Ching-Yu Cheng , Bahman Cheraghian , Angela Chetrit , Ekaterina Chikova-Iscener , Arnaud Chiolero , Shu-Ti Chiou , María-Dolores Chirlaque , Belong Cho , Kaare Christensen , Diego G Christofaro , Jerzy Chudek , Renata Cifkova , Michelle Cilia , Eliza Cinteza , Frank Claessens , Janine Clarke , Els Clays , Emmanuel Cohen , Hans Concin , Susana C Confortin , Cyrus Cooper , Tara C Coppinger , Eva Corpeleijn , Simona Costanzo , Dominique Cottel , Chris Cowell , Cora L Craig , Amelia C Crampin , Ana B Crujeiras , Semánová Csilla , Alexandra M Cucu , Liufu Cui , Felipe V Cureau , Ewelina Czenczek-Lewandowska , Graziella D'Arrigo , Eleonora d'Orsi , Liliana Dacica , María Ángeles Dal Re Saavedra , Jean Dallongeville , Camilla T Damsgaard , Rachel Dankner , Thomas M Dantoft , Parasmani Dasgupta , Saeed Dastgiri , Luc Dauchet , Kairat Davletov , Guy De Backer , Dirk De Bacquer , Giovanni de Gaetano , Stefaan De Henauw , Paula Duarte de Oliveira , David De Ridder , Karin De Ridder , Susanne R de Rooij , Delphine De Smedt , Mohan Deepa , Alexander D Deev , Vincent Jr DeGennaro , Abbas Dehghan , Hélène Delisle , Francis Delpeuch , Stefaan Demarest , Elaine Dennison , Katarzyna Dereń , Valérie Deschamps , Meghnath Dhimal , Augusto F Di Castelnuovo , Juvenal Soares Dias-da-Costa , María Elena Díaz-Sánchez , Alejandro Diaz , Zivka Dika , Shirin Djalalinia , Visnja Djordjic , Ha Tp Do , Annette J Dobson , Maria Benedetta Donati , Chiara Donfrancesco , Silvana P Donoso , Angela Döring , Maria Dorobantu , Ahmad Reza Dorosty , Kouamelan Doua , Nico Dragano , Wojciech Drygas , Jia Li Duan , Charmaine A Duante , Priscilla Duboz , Rosemary B Duda , Vesselka Duleva , Virginija Dulskiene , Samuel C Dumith , Anar Dushpanova , Vilnis Dzerve , Elzbieta Dziankowska-Zaborszczyk , Ricky Eddie , Ebrahim Eftekhar , Eruke E Egbagbe , Robert Eggertsen , Sareh Eghtesad , Gabriele Eiben , Ulf Ekelund , Mohammad El-Khateeb , Jalila El Ati , Denise Eldemire-Shearer , Marie Eliasen , Paul Elliott , Reina Engle-Stone , Macia Enguerran , Rajiv T Erasmus , Raimund Erbel , Cihangir Erem , Louise Eriksen , Johan G Eriksson , Jorge Escobedo-de la Peña , Saeid Eslami , Ali Esmaeili , Alun Evans , David Faeh , Albina A Fakhretdinova , Caroline H Fall , Elnaz Faramarzi , Mojtaba Farjam , Victoria Farrugia Sant'Angelo , Farshad Farzadfar , Mohammad Reza Fattahi , Asher Fawwad , Francisco J Felix-Redondo , Trevor S Ferguson , Romulo A Fernandes , Daniel Fernández-Bergés , Daniel Ferrante , Thomas Ferrao , Marika Ferrari , Marco M Ferrario , Catterina Ferreccio , Eldridge Ferrer , Jean Ferrieres , Thamara Hubler Figueiró , Anna Fijalkowska , Günther Fink , Krista Fischer , Leng Huat Foo , Maria Forsner , Heba M Fouad , Damian K Francis , Maria do Carmo Franco , Ruth Frikke-Schmidt , Guillermo Frontera , Flavio D Fuchs , Sandra C Fuchs , Isti I Fujiati , Yuki Fujita , Matsuda Fumihiko , Takuro Furusawa , Zbigniew Gaciong , Mihai Gafencu , Andrzej Galbarczyk , Henrike Galenkamp , Daniela Galeone , Myriam Galfo , Fabio Galvano , Jingli Gao , Manoli Garcia-de-la-Hera , Marta García-Solano , Dickman Gareta , Sarah P Garnett , Jean-Michel Gaspoz , Magda Gasull , Adroaldo Cesar Araujo Gaya , Anelise Reis Gaya , Andrea Gazzinelli , Ulrike Gehring , Harald Geiger , Johanna M Geleijnse , Ali Ghanbari , Erfan Ghasemi , Oana-Florentina Gheorghe-Fronea , Simona Giampaoli , Francesco Gianfagna , Tiffany K Gill , Jonathan Giovannelli , Glen Gironella , Aleksander Giwercman , Konstantinos Gkiouras , Justyna Godos , Sibel Gogen , Marcel Goldberg , Rebecca A Goldsmith , David Goltzman , Santiago F Gómez , Aleksandra Gomula , Bruna Goncalves Cordeiro da Silva , Helen Gonçalves , David A Gonzalez-Chica , Marcela Gonzalez-Gross , Margot González-Leon , Juan P González-Rivas , Clicerio González-Villalpando , María-Elena González-Villalpando , Angel R Gonzalez , Frederic Gottrand , Antonio Pedro Graça , Sidsel Graff-Iversen , Dušan Grafnetter , Aneta Grajda , Maria G Grammatikopoulou , Ronald D Gregor , Tomasz Grodzicki , Else Karin Grøholt , Anders Grøntved , Giuseppe Grosso , Gabriella Gruden , Dongfeng Gu , Emanuela Gualdi-Russo , Pilar Guallar-Castillón , Andrea Gualtieri , Elias F Gudmundsson , Vilmundur Gudnason , Ramiro Guerrero , Idris Guessous , Andre L Guimaraes , Martin C Gulliford , Johanna Gunnlaugsdottir , Marc J Gunter , Xiu-Hua Guo , Yin Guo , Prakash C Gupta , Rajeev Gupta , Oye Gureje , Beata Gurzkowska , Enrique Gutiérrez-González , Laura Gutierrez , Felix Gutzwiller , Seongjun Ha , Farzad Hadaegh , Charalambos A Hadjigeorgiou , Rosa Haghshenas , Hamid Hakimi , Jytte Halkjær , Ian R Hambleton , Behrooz Hamzeh , Dominique Hange , Abu Am Hanif , Sari Hantunen , Jie Hao , Rachakulla Hari Kumar , Seyed Mohammad Hashemi-Shahri , Maria Hassapidou , Jun Hata , Teresa Haugsgjerd , Jiang He , Yuan He , Yuna He , Regina Heidinger-Felso , Mirjam Heinen , Tatjana Hejgaard , Marleen Elisabeth Hendriks , Rafael Dos Santos Henrique , Ana Henriques , Leticia Hernandez Cadena , Sauli Herrala , Victor M Herrera , Isabelle Herter-Aeberli , Ramin Heshmat , Allan G Hill , Sai Yin Ho , Suzanne C Ho , Michael Hobbs , Michelle Holdsworth , Reza Homayounfar , Clara Homs , Wilma M Hopman , Andrea Rvr Horimoto , Claudia M Hormiga , Bernardo L Horta , Leila Houti , Christina Howitt , Thein Thein Htay , Aung Soe Htet , Maung Maung Than Htike , Yonghua Hu , José María Huerta , Ilpo Tapani Huhtaniemi , Laetitia Huiart , Constanta Huidumac Petrescu , Martijn Huisman , Abdullatif Husseini , Chinh Nguyen Huu , Inge Huybrechts , Nahla Hwalla , Jolanda Hyska , Licia Iacoviello , Jesús M Ibarluzea , Mohsen M Ibrahim , Norazizah Ibrahim Wong , M Arfan Ikram , Violeta Iotova , Vilma E Irazola , Takafumi Ishida , Muhammad Islam , Sheikh Mohammed Shariful Islam , Masanori Iwasaki , Jeremy M Jacobs , Hashem Y Jaddou , Tazeen Jafar , Kenneth James , Kazi M Jamil , Konrad Jamrozik , Imre Janszky , Edward Janus , Juel Jarani , Marjo-Riitta Jarvelin , Grazyna Jasienska , Ana Jelakovic , Bojan Jelakovic , Garry Jennings , Anjani Kumar Jha , Chao Qiang Jiang , Ramon O Jimenez , Karl-Heinz Jöckel , Michel Joffres , Mattias Johansson , Jari J Jokelainen , Jost B Jonas , Jitendra Jonnagaddala , Torben Jørgensen , Pradeep Joshi , Farahnaz Joukar , Dragana P Jovic , Jacek J Jóźwiak , Anne Juolevi , Gregor Jurak , Iulia Jurca Simina , Vesna Juresa , Rudolf Kaaks , Felix O Kaducu , Anthony Kafatos , Eero O Kajantie , Zhanna Kalmatayeva , Ofra Kalter-Leibovici , Yves Kameli , Freja B Kampmann , Kodanda R Kanala , Srinivasan Kannan , Efthymios Kapantais , Argyro Karakosta , Line L Kårhus , Khem B Karki , Marzieh Katibeh , Joanne Katz , Peter T Katzmarzyk , Jussi Kauhanen , Prabhdeep Kaur , Maryam Kavousi , Gyulli M Kazakbaeva , Ulrich Keil , Lital Keinan Boker , Sirkka Keinänen-Kiukaanniemi , Roya Kelishadi , Cecily Kelleher , Han Cg Kemper , Andre P Kengne , Maryam Keramati , Alina Kerimkulova , Mathilde Kersting , Timothy Key , Yousef Saleh Khader , Davood Khalili , Kay-Tee Khaw , Bahareh Kheiri , Motahareh Kheradmand , Alireza Khosravi , Ilse Msl Khouw , Ursula Kiechl-Kohlendorfer , Stefan Kiechl , Japhet Killewo , Dong Wook Kim , Hyeon Chang Kim , Jeongseon Kim , Jenny M Kindblom , Heidi Klakk , Magdalena Klimek , Jeannette Klimont , Jurate Klumbiene , Michael Knoflach , Bhawesh Koirala , Elin Kolle , Patrick Kolsteren , Jürgen König , Raija Korpelainen , Paul Korrovits , Magdalena Korzycka , Jelena Kos , Seppo Koskinen , Katsuyasu Kouda , Viktoria A Kovacs , Sudhir Kowlessur , Slawomir Koziel , Jana Kratenova , Wolfgang Kratzer , Susi Kriemler , Peter Lund Kristensen , Steinar Krokstad , Daan Kromhout , Herculina S Kruger , Ruzena Kubinova , Renata Kuciene , Urho M Kujala , Enisa Kujundzic , Zbigniew Kulaga , R Krishna Kumar , Marie Kunešová , Pawel Kurjata , Yadlapalli S Kusuma , Kari Kuulasmaa , Catherine Kyobutungi , Quang Ngoc La , Fatima Zahra Laamiri , Tiina Laatikainen , Carl Lachat , Youcef Laid , Tai Hing Lam , Christina-Paulina Lambrinou , Edwige Landais , Vera Lanska , Georg Lappas , Bagher Larijani , Tint Swe Latt , Laura Lauria , Maria Lazo-Porras , Gwenaëlle Le Coroller , Khanh Le Nguyen Bao , Agnès Le Port , Tuyen D Le , Jeannette Lee , Jeonghee Lee , Paul H Lee , Nils Lehmann , Terho Lehtimäki , Daniel Lemogoum , Naomi S Levitt , Yanping Li , Merike Liivak , Christa L Lilly , Wei-Yen Lim , M Fernanda Lima-Costa , Hsien-Ho Lin , Xu Lin , Yi-Ting Lin , Lars Lind , Allan Linneberg , Lauren Lissner , Mieczyslaw Litwin , Lijuan Liu , Wei-Cheng Lo , Helle-Mai Loit , Khuong Quynh Long , Luis Lopes , Oscar Lopes , Esther Lopez-Garcia , Tania Lopez , Paulo A Lotufo , José Eugenio Lozano , Janice L Lukrafka , Dalia Luksiene , Annamari Lundqvist , Robert Lundqvist , Nuno Lunet , Charles Lunogelo , Michala Lustigová , Edyta Łuszczki , Guansheng Ma , Jun Ma , Xu Ma , George Ll Machado-Coelho , Aristides M Machado-Rodrigues , Luisa M Macieira , Ahmed A Madar , Stefania Maggi , Dianna J Magliano , Sara Magnacca , Emmanuella Magriplis , Gowri Mahasampath , Bernard Maire , Marjeta Majer , Marcia Makdisse , Päivi Mäki , Fatemeh Malekzadeh , Reza Malekzadeh , Rahul Malhotra , Kodavanti Mallikharjuna Rao , Sofia K Malyutina , Lynell V Maniego , Yannis Manios , Jim I Mann , Fariborz Mansour-Ghanaei , Enzo Manzato , Paula Margozzini , Anastasia Markaki , Oonagh Markey , Eliza Markidou Ioannidou , Pedro Marques-Vidal , Larissa Pruner Marques , Jaume Marrugat , Yves Martin-Prevel , Rosemarie Martin , Reynaldo Martorell , Eva Martos , Katharina Maruszczak , Stefano Marventano , Luis P Mascarenhas , Shariq R Masoodi , Ellisiv B Mathiesen , Prashant Mathur , Alicia Matijasevich , Tandi E Matsha , Christina Mavrogianni , Artur Mazur , Jean Claude N Mbanya , Shelly R McFarlane , Stephen T McGarvey , Martin McKee , Stela McLachlan , Rachael M McLean , Scott B McLean , Breige A McNulty , Sounnia Mediene Benchekor , Jurate Medzioniene , Parinaz Mehdipour , Kirsten Mehlig , Amir Houshang Mehrparvar , Aline Meirhaeghe , Jørgen Meisfjord , Christa Meisinger , Ana Maria B Menezes , Geetha R Menon , Gert Bm Mensink , Maria Teresa Menzano , Alibek Mereke , Indrapal I Meshram , Andres Metspalu , Haakon E Meyer , Jie Mi , Kim F Michaelsen , Nathalie Michels , Kairit Mikkel , Karolina Milkowska , Jody C Miller , Cláudia S Minderico , G K Mini , Juan Francisco Miquel , Mohammad Reza Mirjalili , Daphne Mirkopoulou , Erkin Mirrakhimov , Marjeta Mišigoj-Durakovic , Antonio Mistretta , Veronica Mocanu , Pietro A Modesti , Sahar Saeedi Moghaddam , Bahram Mohajer , Mostafa K Mohamed , Shukri F Mohamed , Kazem Mohammad , Zahra Mohammadi , Noushin Mohammadifard , Reza Mohammadpourhodki , Viswanathan Mohan , Salim Mohanna , Muhammad Fadhli Mohd Yusoff , Iraj Mohebbi , Farnam Mohebi , Marie Moitry , Drude Molbo , Line T Møllehave , Niels C Møller , Dénes Molnár , Amirabbas Momenan , Charles K Mondo , Michele Monroy-Valle , Eric Monterrubio-Flores , Kotsedi Daniel K Monyeki , Jin Soo Moon , Mahmood Moosazadeh , Leila B Moreira , Alain Morejon , Luis A Moreno , Karen Morgan , Suzanne N Morin , Erik Lykke Mortensen , George Moschonis , Malgorzata Mossakowska , Aya Mostafa , Anabela Mota-Pinto , Jorge Mota , Mohammad Esmaeel Motlagh , Jorge Motta , Marcos André Moura-Dos-Santos , Malay K Mridha , Kelias P Msyamboza , Thet Thet Mu , Magdalena Muc , Boban Mugoša , Maria L Muiesan , Parvina Mukhtorova , Martina Müller-Nurasyid , Neil Murphy , Jaakko Mursu , Elaine M Murtagh , Kamarul Imran Musa , Sanja Music Milanovic , Vera Musil , Norlaila Mustafa , Iraj Nabipour , Shohreh Naderimagham , Gabriele Nagel , Balkish M Naidu , Farid Najafi , Harunobu Nakamura , Jana Námešná , Ei Ei K Nang , Vinay B Nangia , Martin Nankap , Sameer Narake , Paola Nardone , Matthias Nauck , William A Neal , Azim Nejatizadeh , Chandini Nekkantti , Keiu Nelis , Liis Nelis , Ilona Nenko , Martin Neovius , Flavio Nervi , Chung T Nguyen , Nguyen D Nguyen , Quang Ngoc Nguyen , Ramfis E Nieto-Martínez , Yury P Nikitin , Guang Ning , Toshiharu Ninomiya , Sania Nishtar , Marianna Noale , Oscar A Noboa , Helena Nogueira , Teresa Norat , Maria Nordendahl , Børge G Nordestgaard , Davide Noto , Natalia Nowak-Szczepanska , Mohannad Al Nsour , Irfan Nuhoglu , Eha Nurk , Terence W O'Neill , Dermot O'Reilly , Galina Obreja , Caleb Ochimana , Angélica M Ochoa-Avilés , Eiji Oda , Kyungwon Oh , Kumiko Ohara , Claes Ohlsson , Ryutaro Ohtsuka , Örn Olafsson , Maria Teresa A Olinto , Isabel O Oliveira , Mohd Azahadi Omar , Altan Onat , Sok King Ong , Lariane M Ono , Pedro Ordunez , Rui Ornelas , Ana P Ortiz , Pedro J Ortiz , Merete Osler , Clive Osmond , Sergej M Ostojic , Afshin Ostovar , Johanna A Otero , Kim Overvad , Ellis Owusu-Dabo , Fred Michel Paccaud , Cristina Padez , Ioannis Pagkalos , Elena Pahomova , Karina Mary de Paiva , Andrzej Pajak , Domenico Palli , Alberto Palloni , Luigi Palmieri , Wen-Harn Pan , Songhomitra Panda-Jonas , Arvind Pandey , Francesco Panza , Dimitrios Papandreou , Soon-Woo Park , Suyeon Park , Winsome R Parnell , Mahboubeh Parsaeian , Ionela M Pascanu , Patrick Pasquet , Nikhil D Patel , Ivan Pecin , Mangesh S Pednekar , Nasheeta Peer , Gao Pei , Sergio Viana Peixoto , Markku Peltonen , Alexandre C Pereira , Marco A Peres , Napoleón Pérez-Farinós , Cynthia M Pérez , Valentina Peterkova , Annette Peters , Astrid Petersmann , Janina Petkeviciene , Ausra Petrauskiene , Emanuela Pettenuzzo , Niloofar Peykari , Son Thai Pham , Rafael N Pichardo , Daniela Pierannunzio , Iris Pigeot , Hynek Pikhart , Aida Pilav , Lorenza Pilotto , Francesco Pistelli , Freda Pitakaka , Aleksandra Piwonska , Andreia N Pizarro , Pedro Plans-Rubió , Bee Koon Poh , Hermann Pohlabeln , Raluca M Pop , Stevo R Popovic , Miquel Porta , Georg Posch , Anil Poudyal , Dimitrios Poulimeneas , Hamed Pouraram , Farhad Pourfarzi , Akram Pourshams , Hossein Poustchi , Rajendra Pradeepa , Alison J Price , Jacqueline F Price , Rui Providencia , Jardena J Puder , Iveta Pudule , Soile E Puhakka , Maria Puiu , Margus Punab , Radwan F Qasrawi , Mostafa Qorbani , Tran Quoc Bao , Ivana Radic , Ricardas Radisauskas , Salar Rahimikazerooni , Mahfuzar Rahman , Mahmudur Rahman , Olli Raitakari , Manu Raj , Ellina Rakhimova , Sherali Rakhmatulloev , Ivo Rakovac , Sudha Ramachandra Rao , Ambady Ramachandran , Jacqueline Ramke , Elisabete Ramos , Rafel Ramos , Lekhraj Rampal , Sanjay Rampal , Vayia Rarra , Ramon A Rascon-Pacheco , Mette Rasmussen , Cassiano Ricardo Rech , Josep Redon , Paul Ferdinand M Reganit , Valéria Regecová , Luis Revilla , Abbas Rezaianzadeh , Lourdes Ribas-Barba , Robespierre Ribeiro , Elio Riboli , Adrian Richter , Fernando Rigo , Natascia Rinaldo , Tobias F Rinke de Wit , Ana Rito , Raphael M Ritti-Dias , Juan A Rivera , Cynthia Robitaille , Romana Roccaldo , Daniela Rodrigues , Fernando Rodríguez-Artalejo , María Del Cristo Rodriguez-Perez , Laura A Rodríguez-Villamizar , Ulla Roggenbuck , Rosalba Rojas-Martinez , Nipa Rojroongwasinkul , Dora Romaguera , Elisabetta L Romeo , Rafaela V Rosario , Annika Rosengren , Ian Rouse , Joel Gr Roy , Adolfo Rubinstein , Frank J Rühli , Jean-Bernard Ruidavets , Blanca Sandra Ruiz-Betancourt , Maria Ruiz-Castell , Emma Ruiz Moreno , Iuliia A Rusakova , Kenisha Russell Jonsson , Paola Russo , Petra Rust , Marcin Rutkowski , Charumathi Sabanayagam , Elena Sacchini , Harshpal S Sachdev , Alireza Sadjadi , Ali Reza Safarpour , Saeid Safiri , Nader Saki , Benoit Salanave , Eduardo Salazar Martinez , Diego Salmerón , Veikko Salomaa , Jukka T Salonen , Massimo Salvetti , Margarita Samoutian , Jose Sánchez-Abanto , Sandjaja , Susana Sans , Loreto Santa Marina , Diana A Santos , Ina S Santos , Lèlita C Santos , Maria Paula Santos , Osvaldo Santos , Rute Santos , Sara Santos Sanz , Jouko L Saramies , Luis B Sardinha , Nizal Sarrafzadegan , Thirunavukkarasu Sathish , Kai-Uwe Saum , Savvas Savva , Mathilde Savy , Norie Sawada , Mariana Sbaraini , Marcia Scazufca , Beatriz D Schaan , Angelika Schaffrath Rosario , Herman Schargrodsky , Anja Schienkiewitz , Sabine Schipf , Carsten O Schmidt , Ida Maria Schmidt , Peter Schnohr , Ben Schöttker , Sara Schramm , Stine Schramm , Helmut Schröder , Constance Schultsz , Aletta E Schutte , Aye Aye Sein , Rusidah Selamat , Vedrana Sember , Abhijit Sen , Idowu O Senbanjo , Sadaf G Sepanlou , Victor Sequera , Luis Serra-Majem , Jennifer Servais , Ludmila Ševcíková , Svetlana A Shalnova , Teresa Shamah-Levy , Morteza Shamshirgaran , Coimbatore Subramaniam Shanthirani , Maryam Sharafkhah , Sanjib K Sharma , Jonathan E Shaw , Amaneh Shayanrad , Ali Akbar Shayesteh , Lela Shengelia , Zumin Shi , Kenji Shibuya , Hana Shimizu-Furusawa , Dong Wook Shin , Majid Shirani , Rahman Shiri , Namuna Shrestha , Khairil Si-Ramlee , Alfonso Siani , Rosalynn Siantar , Abla M Sibai , Antonio M Silva , Diego Augusto Santos Silva , Mary Simon , Judith Simons , Leon A Simons , Agneta Sjöberg , Michael Sjöström , Gry Skodje , Jolanta Slowikowska-Hilczer , Przemyslaw Slusarczyk , Liam Smeeth , Hung-Kwan So , Fernanda Cunha Soares , Grzegorz Sobek , Eugène Sobngwi , Morten Sodemann , Stefan Söderberg , Moesijanti Ye Soekatri , Agustinus Soemantri , Reecha Sofat , Vincenzo Solfrizzi , Mohammad Hossein Somi , Emily Sonestedt , Yi Song , Thorkild Ia Sørensen , Elin P Sørgjerd , Charles Sossa Jérome , Victoria E Soto-Rojas , Aïcha Soumaré , Slavica Sovic , Bente Sparboe-Nilsen , Karen Sparrenberger , Angela Spinelli , Igor Spiroski , Jan A Staessen , Hanspeter Stamm , Maria G Stathopoulou , Kaspar Staub , Bill Stavreski , Jostein Steene-Johannessen , Peter Stehle , Aryeh D Stein , George S Stergiou , Jochanan Stessman , Ranko Stevanovic , Jutta Stieber , Doris Stöckl , Tanja Stocks , Jakub Stokwiszewski , Ekaterina Stoyanova , Gareth Stratton , Karien Stronks , Maria Wany Strufaldi , Lela Sturua , Ramón Suárez-Medina , Machi Suka , Chien-An Sun , Johan Sundström , Yn-Tz Sung , Jordi Sunyer , Paibul Suriyawongpaisal , Boyd A Swinburn , Rody G Sy , Holly E Syddall , René Charles Sylva , Moyses Szklo , Lucjan Szponar , E Shyong Tai , Mari-Liis Tammesoo , Abdonas Tamosiunas , Eng Joo Tan , Xun Tang , Maya Tanrygulyyeva , Frank Tanser , Yong Tao , Mohammed Rasoul Tarawneh , Jakob Tarp , Carolina B Tarqui-Mamani , Radka Taxová Braunerová , Anne Taylor , Julie Taylor , Félicité Tchibindat , William R Tebar , Grethe S Tell , Tania Tello , Yih Chung Tham , K R Thankappan , Holger Theobald , Xenophon Theodoridis , Lutgarde Thijs , Nihal Thomas , Betina H Thuesen , Lubica Tichá , Erik J Timmermans , Anne Tjonneland , Hanna K Tolonen , Janne S Tolstrup , Murat Topbas , Roman Topór-Madry , Liv Elin Torheim , María José Tormo , Michael J Tornaritis , Maties Torrent , Laura Torres-Collado , Stefania Toselli , Giota Touloumi , Pierre Traissac , Thi Tuyet-Hanh Tran , Dimitrios Trichopoulos , Antonia Trichopoulou , Oanh Th Trinh , Atul Trivedi , Lechaba Tshepo , Maria Tsigga , Shoichiro Tsugane , Azaliia M Tuliakova , Marshall K Tulloch-Reid , Fikru Tullu , Tomi-Pekka Tuomainen , Jaakko Tuomilehto , Maria L Turley , Gilad Twig , Per Tynelius , Themistoklis Tzotzas , Christophe Tzourio , Peter Ueda , Eunice Ugel , Flora Am Ukoli , Hanno Ulmer , Belgin Unal , Zhamyila Usupova , Hannu Mt Uusitalo , Nalan Uysal , Justina Vaitkeviciute , Gonzalo Valdivia , Susana Vale , Damaskini Valvi , Rob M van Dam , Johan Van der Heyden , Yvonne T van der Schouw , Koen Van Herck , Hoang Van Minh , Natasja M 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Weghuber , Wenbin Wei , Aneta Weres , Bo Werner , Peter H Whincup , Kurt Widhalm , Indah S Widyahening , Andrzej Wiecek , Rainford J Wilks , Johann Willeit , Peter Willeit , Julianne Williams , Tom Wilsgaard , Bogdan Wojtyniak , Roy A Wong-McClure , Andrew Wong , Jyh Eiin Wong , Tien Yin Wong , Jean Woo , Mark Woodward , Frederick C Wu , Jianfeng Wu , Li Juan Wu , Shouling Wu , Haiquan Xu , Liang Xu , Nor Azwany Yaacob , Uruwan Yamborisut , Weili Yan , Ling Yang , Xiaoguang Yang , Yang Yang , Nazan Yardim , Mehdi Yaseri , Tabara Yasuharu , Xingwang Ye , Panayiotis K Yiallouros , Moein Yoosefi , Akihiro Yoshihara , Qi Sheng You , San-Lin You , Novie O Younger-Coleman , Safiah Md Yusof , Ahmad Faudzi Yusoff , Luciana Zaccagni , Vassilis Zafiropulos , Ahmad A Zainuddin , Seyed Rasoul Zakavi , Farhad Zamani , Sabina Zambon , Antonis Zampelas , Hana Zamrazilová , Maria Elisa Zapata , Abdul Hamid Zargar , Ko Ko Zaw , Tomasz Zdrojewski , Kristyna Zejglicova , Tajana Zeljkovic Vrkic , Yi Zeng 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Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

Subjects
Population -- Health aspects, Leanness, Baixo peso/Underweight, none, Double burden, alipainoisuus, tulotaso, global health, systematic analysis, Sedentary behaviors, RC1200, Prospective associations, 0302 clinical medicine, underweight, nälänhätä, Biology (General), skin and connective tissue diseases, Children, ComputingMilieux_MISCELLANEOUS, Body mass index, Human Nutrition & Health, education.field_of_study, Humane Voeding & Gezondheid, ylipaino, General Medicine, kansainvälinen vertailu, 3. Good health, World health, Medicine, A100 Pre-clinical Medicine, Population distribution, medicine.medical_specialty, QH301-705.5, Science, Socio-culturale, Nursing, Social sciences, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Thinness, SDG 3 - Good Health and Well-being, BMI, epidemiology, obesity, None, Humans, Obesidade/Obesity, SDG 2 - Zero Hunger, education, VLAG, US adults, Omvårdnad, body mass index, malnutrition, obesity, underweight, nutritional and metabolic diseases, medicine.disease, terveellisyys, Obesity, Faculdade de Ciências Sociais, Body Mass Index, Prevalence, Risk Factors, General Biochemistry, WIAS, lihavuus, RA, Demography, N.A, double burden, Settore MED/09 - Medicina Interna, alueelliset erot, Nutrition and Disease, Animal Nutrition, [SDV]Life Sciences [q-bio], Medizin, 030204 cardiovascular system & hematology, 0601 Biochemistry and Cell Biology, Change distribution of body mass index, RA0421, Voeding en Ziekte, Epidemiology, Medicine and Health Sciences, Global health, Índice de massa corporal/Body Mass Index, 030212 general & internal medicine, Underweight, painoindeksi, 2. Zero hunger, General Neuroscience, aliravitsemus, elintarvikkeet, health, Public Health, Global Health, Social Medicine and Epidemiology, Diervoeding, 3142 Public health care science, environmental and occupational health, purl.org/pe-repo/ocde/ford#3.01.03 [https], Chinese adults, pooled analysis, medicine.symptom, Diet quality, B120 Physiology, Research Article, trends, purl.org/pe-repo/ocde/ford#1.06.03 [https], prevalence, Population, Mothers, Genetics and Molecular Biology, 3121 Internal medicine, medicine, Life Science, ddc:610, 3125 Otorhinolaryngology, ophthalmology, kehonkoostumus, Nutrition, Australian adults, General Immunology and Microbiology, purl.org/pe-repo/ocde/ford#3.01.04 [https], Ciências sociais, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Malnutrition, Epidemiology and Global Health, sense organs, Estilos de Vida e Impacto na Saúde
Abstract

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions., Wellcome Trust, Medical Research Council, peer-reviewed

Published
2021

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