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Frailty is associated with negative health outcomes, disability, and mortality. Physical activity is an effective intervention to improve functional health status. However, the effect of resistance training on multidimensional health in frail older adults remains unclear. This randomized controlled trial was conducted in a U.K. residential care home to assess feasibility with limited efficacy testing on health and functional outcomes and to inform a future definitive randomized controlled trial. Eleven frail older adults (>65 years) completed a 6-week machine-based resistance training protocol three times a week. Uptake and retention were greater than 80%. The measures and intervention were found to be acceptable and practicable. The analyses indicated large improvements in functional capacity, frailty, and strength in the intervention group compared with the controls. These findings support the feasibility of a definitive randomized controlled trial and reinforce the value of resistance training in this population. This trial was registered with ClinicalTrials.gov: NCT03141879.

The purpose of this study is to assess the impact of a germicidal ultraviolet light-emitting diode (LED) on the contamination level of a back table in the operating room (OR) during total joint arthroplasty procedures.Eight Tryptic Soy Agar petri plates were placed on a table located near the operative field and exposed to air. One plate was removed on the hour over an 8-hour time span. The back table had either an UV-LED for disinfection or a sham UV-LED. This process was repeated in 12 different ORs (6 with UV light, 6 with sham device). The plates were then incubated for 48 hours at 36°C ± 1°C . Colony forming units (CFU) were recorded 24 and 48 hours after incubation.There was a statistically significant difference in total CFUs between the intervention vs sham at 24-hours (27 vs 95, P = .0001) and 48-hours (38 vs 122, P.0001). The multivariate analysis revealed that the 24-hour and 48-hour count, the predictors UV light (P = .002) and hour of plate removal (P = .050) were statistically significantly associated with CFU counts. Together, the predictor variables explained 15.8% and 23.0% of the variance in CFU counts at 24- and 48-hours, respectively.A back table UV-LED may decrease environmental contamination near the operative field. This has potential to lead to a decrease in joint infection.

Inferring relationships that go beyond our direct experience is essential for understanding our environment. This capacity requires either building representations that directly reflect structure across experiences as we encounter them, or computing the indirect relationships across experiences as the need arises. Building structure directly into overlapping representations allows for powerful learning and generalization in neural network models, but building these so-calleddistributed representationsrequires inputs to be encountered in interleaved order. We test whether interleaving similarly facilitates the formation of representations that directly integrate related experiences in humans, and what advantages such integration may confer for behavior. In a series of behavioral experiments, we present evidence that interleaved learning indeed promotes the formation of representations that directly link across related experiences. As in neural network models, interleaved learning gives rise to fast and automatic recognition of item relatedness, affords efficient generalization, and is especially critical for inference when learning requires statistical integration of noisy information over time. We use the data to adjudicate between several existing computational models of human memory and inference. The results demonstrate the power of interleaved learning and implicate the formation of integrated, distributed representations that support generalization in humans.

Methicillin-Resistant Staphylococcus aureus (MRSA) is a major cause of healthcare-associated infections (HAI). Contact isolation has been traditionally implemented to stop transmission but its impact is increasingly questioned.A single center, retrospective, nonrandomized, observational, quasi-experimental study compared MRSA HAI rates between pre-/postdiscontinuation of MRSA contact isolation in a tertiary university hospital over 68 months. Data on primary outcomes, Central line-associated bloodstream infections and MRSA LabID bacteremia events, were analyzed by interrupted time series design using segmented Poisson regression modeling. As secondary outcomes catheter-associated urinary tract infections , ventilator-associated pneumonia , surgical site infections and hospital-associated pneumonia were compared using Fisher's exact tests. Current savings due to discontinuation were calculated based on gown use.Two hundred and ninty-five patients developed 399 HAIs. Infection rates between pre- and postinterventions were as follows: Central line-associated bloodstream infections: (0.02% vs 0.02%; P-value = .64), MRSA LabID events: (0.01% vs 0.02%; P-value = .32), hospital-associated pneumonia: (0.01% vs 0.01%; P-value = .64), catheter-associated urinary tract infections: (0% vs 0.01%; P-value = .56), ventilator-associated pneumonia: (0.01% vs 0.01%; P-value = .32), surgical site infections (0.55% vs 0.15%; P-value = .03). Savings amount to $139,228 annually.Discontinuing CP did not negatively impact endemic MRSA HAI rates between pre-postdiscontinuation periods and saved costs for isolation materials.

Purpose To evaluate whether intraoral devices reduce the adverse oral and dental effects of radiotherapy in head and neck cancer patients. Materials and methods A systematic search of the Medline and Embase databases for articles published before March 2019 was performed by two independent reviewers. Studies published in English that evaluated whether intraoral devices reduced the risk of radiotherapy-related complications in patients receiving radiotherapy to the head and neck region were included. The kappa statistic was used to calculate the level of inter-reviewer agreement. Results Five studies met the inclusion criteria, although only one was considered to be a low risk of bias. One study reported that intraoral devices did not reduce the severity of mucositis after 7 weeks. The remaining four studies reported that intraoral devices reduced the risk of xerostomia, mucositis, trismus, dysphagia, and dental caries over 2 to 6 months. Conclusion There are limited data to support the use of intraoral devices in head and neck cancer patients undergoing radiotherapy. Well-designed clinical studies that consider long-term outcomes are necessary to draw definitive conclusions.

Objective Delays in care for patients with acute cardiac complaints are associated with increased morbidity and mortality. The objective of this study was to quantify rural and urban differences in prehospital time intervals for patients with cardiac complaints. Methods The ESO Data Collaborative dataset consisting of records from 1332 EMS agencies was queried for 9–1-1 encounters with acute cardiac problems among adults (age ≥ 18) from 1/1/2013–6/1/2018. Location was classified as rural or urban using the 2010 United States Census. The primary outcome was total prehospital time. Generalized estimating equations evaluated differences in the average times between rural and urban encounters while controlling for age, sex, race, transport mode, loaded mileage, and patient stability. Results Among 428,054 encounters, the median age was 62 (IQR 50–75) years with 50.7% female, 75.3% white, and 10.3% rural. The median total prehospital, response, scene, and transport times were 37.0 (IQR 29.0–48.0), 6.0 (IQR 4.0–9.0), 16.0 (IQR 12.0–21.0), and 13.0 (IQR 8.0–21.0) minutes. Rural patients had an average total prehospital time that was 16.76 min (95%CI 15.15–18.38) longer than urban patients. After adjusting for covariates, average total time was 5.08 (95%CI 4.37–5.78) minutes longer for rural patients. Average response and transport time were 4.36 (95%CI 3.83–4.89) and 0.62 (95%CI 0.33–0.90) minutes longer for rural patients. Scene time was similar in rural and urban patients (0.09 min, 95%CI -0.15-0.33). Conclusion Rural patients with acute cardiac complaints experienced longer prehospital time than urban patients, even after accounting for other key variables, such as loaded mileage.

Purpose: Late radiation toxicity is a major dose-limiting factor in curative cancer radiation therapy. Previous studies identified several risk factors for late radiation toxicity, including both dose-volume factors and genetic predisposition. Herein, we investigated the contribution of genetic predisposition, particularly compared with dose-volume factors, to the risk of late radiation toxicity in patients treated with highly conformal radiation therapy. Methods and Materials: We included 179 patients with prostate cancer who underwent treatment with curative external beam radiation therapy between 2009 and 2013. Toxicity was graded according to the Common Terminology Criteria for Adverse Events version 4.0. Transcriptional responsiveness of homologous recombination repair genes and γ-H2AX foci decay ratios (FDRs) were determined in ex vivo irradiated lymphocytes in a previous analysis. Dose-volume parameters were retrieved by delineating the organs at risk (OARs) on CT planning images. Associations between risk factors and grade ≥2 urinary and bowel late radiation toxicities were assessed using univariable and multivariable logistic regression analyses. The analyses were performed using the highest toxicity grade recorded during the follow-up per patient. Results: The median follow-up period was 31 months. One hundred and one patients (56%) developed grade ≥2 late radiation toxicity. Cumulative rates for urinary and bowel grade ≥2 late toxicities were 46% and 17%, respectively. In the multivariable analysis, factors significantly associated with grade ≥2 late toxicity were transurethral resection of the prostate (P = .013), γ-H2AX FDR 11.52% (P = .017). Conclusions: Our results suggest that impaired DNA double-strand break repair in lymphocytes, as quantified by γ-H2AX FDR, is the most critical determining factor of late radiation toxicity. The limited influence of dose-volume parameters could be due to the use of increasingly conformal techniques, leading to improved dose-volume parameters of the organs at risk.

Background Multidisciplinary Tumor Boards (MDT) are used to obtain input regarding cancer management. This study assessed the impact of our institutional Endocrine MDT. Methods MDT notes on patients with thyroid cancer treated during 2012–2018 were abstracted retrospectively from the electronic medical record. Management change (MC) was prospectively collected by the MDT coordinator. Biannual evaluations reviewed the impact of the MDT as observed by attendees. Results MC was recommended in 47 (15%) of 286 presentations, with additional imaging being the most frequent (43%). Presentation of recurrences were more likely to result in MC (24% vs. 13% initial, p = 0.03). Overall, 98% of attendees found the conference exceeded educational expectations. About 24% reported intending to use a more evidence/guideline-based approach after attending and this trend increased over time (p = 0.002). Conclusion MDT presentations led to a higher rate of MC particularly in recurrent TC patients and increased evidenced-based practice for attendees.

The literature, institutional reports, and market projections indicate considerable changes in work's nature, dynamics, and relationships. These changes are already influencing the offers of formal education and requiring new skills to keep people employable. Often, those skills training are not focused on the standard education system, being only targeted in corporate training programs. This study will investigate the affordances of Virtual Reality for training skills essential for work performance and employability in the context of the future of work. We will develop, implement and evaluate interactive VR experiences targeting soft skills crucial for teamwork and management.

Objectives It is generally held that exposure to both high-pressure and long-lasting contact with water makes diving a potentially hazardous sports activity as far as the ears are concerned. There is a number of research investigating the condition of the middle ear in a short period following diving; however, the knowledge regarding the long-term effects of regularly repeated diving remains limited. Material and methods The aim of this study is to evaluate the function of the middle ear after a diving season in a group of 31 adults diving regularly (1–17 years) by means of the following methods: 1) interview, 2) otoscopy, 3) pure tone audiometry, 4) classic tympanometry, and 5) wideband tympanometry. Results Periodic problems with pressure equalization in the middle ear were observed in 12 individuals (38.7%). In all the analyzed cases, the authors found a normal condition of the external auditory canal and the tympanic membrane in otoscopy, normal hearing in pure tone audiometry, curve type A, and normal gradient in both classic and wideband tympanometry. Conclusions Safe diving (according to safety precautions) does not have any long-term negative effects on the condition of the middle ear. However, these observations should be verified in a larger group of divers. Int J Occup Med Environ Health. 2021;34(6):779–88

Introduction: Kidney function declines with age, but its determinants in the general population remain incompletely understood. We investigated the rate and determinants of kidney function decline in the general population. Methods: Participants with information on kidney function were selected from a population-based cohort study. Joint models were used to investigate the evolution of the estimated glomerular filtration rate (eGFR, expressed in ml/min per 1.73 m2 per year) and the urine albumin-to-creatinine ratio (ACR, expressed in mg/g per year) with age. We stratified for 8 potential determinants of kidney function decline, including sex, cardiovascular risk factors, and cardiovascular disease. Results: We included 12,062 participants with 85,922 eGFR assessments (mean age 67.0 years, 58.7% women) and 3522 participants with 5995 ACR measurements. The annual eGFR decline was 0.82 and the ACR increase was 0.05. All determinants appeared detrimental for eGFR and ACR, except for prediabetes and higher body mass index which proved only detrimental for ACR. In participants without the determinants, eGFR decline was 0.75 and ACR increase was 0.002. Higher baseline eGFR but faster eGFR decline with age was detected in men (0.92 vs. 0.75), smokers (0.90 vs. 0.75), and participants with diabetes (1.07 vs. 0.78). Conclusion: We identify prediabetes, smoking, and blood pressure as modifiable risk factors for kidney function decline. As with diabetes, hyperfiltration seems important in accelerated kidney function decline in men and smokers. The interpretation of kidney function decline may require adjustment for age and sex to prevent overdiagnosis of chronic kidney disease in aging populations.

BACKGROUND Venous thrombosis (VT) and pulmonary embolism (PE), collectively venous thromboembolism (VTE), cause high mortality and morbidity. Factor XIII (FXIII) crosslinks fibrin to enhance thrombus stability and consequently may influence PE risk. Elucidating mechanisms contributing to PE is limited by a lack of models that recapitulate human PE characteristics. OBJECTIVE We aimed to develop a mouse model that permits embolization of red blood cell (RBC)- and fibrin-rich VT and determine the contribution of FXIII to PE risk. METHODS AND RESULTS In a thrombin-infusion PE model, F13a+/+ , F13a+/- , and F13a-/- mice had similar incidence of microthrombi in the lungs; however, thrombi were small, with low RBC content (≤7%), unlike human PEs (~70%). To identify a model producing PE consistent with histological characteristics of human PE, we compared mouse femoral vein electrolytic injury, femoral vein FeCl3 injury, and infrarenal vena cava (IVC) stasis models of VT. Electrolytic and FeCl3 models produced small thrombi with few RBCs (5% and 4%, respectively), whereas IVC stasis produced large thrombi with higher RBC content (68%) that was similar to human PEs. After IVC stasis and ligature removal (de-ligation) to permit thrombus embolization, compared to F13a+/+ mice, F13a+/- and F13a-/- mice had similar and increased PE incidence, respectively. CONCLUSIONS Compared to thrombin infusion-, electrolytic injury-, and FeCl3 -based models, IVC stasis produces thrombi that are more histologically similar to human thrombi. IVC stasis followed by de-ligation permits embolization of existing RBC- and fibrin-rich thrombi. Complete FXIII deficiency increases PE incidence, but partial deficiency does not.

Objectives: Adverse childhood experiences (ACEs; ie, exposure to abuse, neglect, household dysfunction in childhood) are associated with poor mental and physical health outcomes across the lifespan. Emerging research suggests parent ACEs also confer risk for poor child outcomes. The relation between parent ACEs and child pain in youth with chronic pain has not yet been examined. The aim of the current longitudinal study was to examine the associations among parent ACEs, parent health, and child pain, in a clinical sample of youth with chronic pain. Methods: In total, 192 youth (75.5% female, 10 to 18 y old) and one of their parents (92.2% female) were recruited from tertiary pediatric chronic pain clinics in Canada. At baseline, parents completed self-report measures of ACEs, chronic pain status, anxiety and depressive symptoms, and posttraumatic stress disorder symptoms. At a 3-month follow-up, youth completed self-report measures of pain intensity and pain interference. Results: Regression and mediation analyses revealed that parent ACEs significantly predicted parent chronic pain status and depressive symptoms, but not parent anxiety or posttraumatic stress disorder symptoms. Moreover, parent ACEs were not significantly related to youth pain, either directly or indirectly through parent health variables. Discussion: Findings suggest that an intergenerational cascade from parent ACEs to parent health to child pain was not present in the current sample. Further research that examines the role of parent ACEs in the development of child chronic pain, as well as other risk and resiliency factors that may mediate or moderate the association between parent ACEs and child chronic pain, is needed.

Background Malignant pleural effusions (MPEs) often cause symptoms, and guidelines recommend early definitive intervention. However, observational data suggest that systemic anticancer treatment (SACT) may control MPE because of certain pharmacologically sensitive tumors. Research Question Is SACT associated with higher rates of MPE resolution in people with pharmacologically sensitive tumors? Study Design and Methods This was a retrospective analysis of prospectively collected data from an observational cohort study of people diagnosed with MPE from lung, breast, ovarian, and hematologic malignancy between May 11, 2008, and August 6, 2017. MPE resolution (defined as radiologic resolution with removal of drain or catheter and cessation of interventions) was compared in pharmacologically sensitive (high-grade lymphoma, small cell or target-mutation-positive lung cancer, and hormone-receptor-positive breast or ovarian cancer) and nonsensitive (remainder of cohort) tumors, with and without SACT. Secondary outcomes included time to resolution, 3-month resolution rates, and total pleural interventions. Results Of 280 patients, 127 had sensitive and 153 had nonsensitive tumors. One hundred seventy-one received SACT, and 109 did not. More patients with sensitive tumors achieved MPE resolution than those with nonsensitive tumors (53/127 [41.7%] vs 42/153 [27.5%]; P = .01), and this occurred predominantly after receipt of SACT. However, hematologic malignancies were overrepresented in the sensitive group, with high rates of SACT use and MPE resolution. After adjustment for this and other confounders, no relationship was found among pharmacologic sensitivity, SACT, and MPE resolution (adjusted OR, 1.4; 95% CI, 0.5-4.1). The strongest predictor of MPE resolution was administration of chemical pleurodesis (adjusted OR, 6.2; 95% CI, 3.3-11.7). In sensitive tumors, MPE resolution occurred without chemical pleurodesis in 14 or 52 patients (26.9%; 95% CI, 15.6%-41.1%) after SACT and in 5 of 22 patients (22.7%; 95% CI, 8.2%-47.2%) without SACT. Interpretation In this observational study, SACT was not associated independently with MPE resolution in pharmacologically sensitive tumors. Randomized trials are required, but with current data, patients with symptomatic MPE should receive early definitive pleural intervention regardless of underlying tumor or intended treatment.

OBJECTIVES: To quantify the availability of authorised, age-appropriate paediatric medicines in clinical practice in the Netherlands and to identify gaps by assessing dispensing practice in a paediatric hospital. METHODS: The availability of age-appropriate formulations was assessed by conducting a survey on the use of pharmacy compounded medicines among the paediatric hospitals in the Netherlands, and by analysing dispensing data of oral medication from the inpatient pharmacy of the largest paediatric hospital in the Netherlands. The age-appropriateness of the dispensed formulations was assessed on two aspects: dose-capability and acceptability. Liquid drug products that are unsuitable due to the presence of potentially harmful excipients, were identified based on the dosage in clinical practice. RESULTS: For 129 out of 139 drug substances included in the survey (93%), at least one of the eight respondents stated to use a pharmacy compounded product to meet the needs of their paediatric patients. The age-appropriateness of medicines dispensed from the inpatient pharmacy increased with age, and was higher for non-intensive care unit (ICU) patients than for ICU patients. We identified 15 drug products causing excipient exposure above the European Medicines Agency-recommended values. CONCLUSIONS: This study confirms there is still a large need for age-appropriate formulations in daily clinical practice. Pharmacy compounding for paediatric patients remains essential for many indications. The need for potentially harmful excipients in compounded products should be critically assessed. ispartof: EUROPEAN JOURNAL OF HOSPITAL PHARMACY vol:28 issue:6 pages:306-312 ispartof: location:England status: published

Osteoporosis is a highly prevalent bone disease affecting more than 37.5 million individuals in the European Union (EU) and the United States of America (USA). It is characterized by low bone mineral density (BMD), impaired bone quality, and loss of structural and biomechanical properties, resulting in reduced bone strength. An increase in morbidity and mortality is seen in patients with osteoporosis, caused by the approximately 3.5 million new osteoporotic fractures occurring every year in the EU. Currently, different medications are available for the treatment of osteoporosis, including anti-resorptive and osteoanabolic medications. Bisphosphonates, which belong to the anti-resorptive medications, are the standard treatment for osteoporosis based on their positive effects on bone, long-term experience, and low costs. However, not only medications used for the treatment of osteoporosis can affect bone: several other medications are suggested to have an effect on bone as well, especially on fracture risk and BMD. Knowledge about the positive and negative effects of different medications on both fracture risk and BMD is important, as it can contribute to an improvement in osteoporosis prevention and treatment in general, and, even more importantly, to the individual’s health. In this review, we therefore discuss the effects of both osteoporotic and non-osteoporotic medications on fracture risk and BMD. In addition, we discuss the underlying mechanisms of action. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-021-01625-8.

Depending upon multiple factors, malignant solid tumors are conventionally treated by some combination of surgical resection, radiation, chemotherapy, and immunotherapy. Despite decades of research, therapeutic responses remain poor for many cancer indications. Further, many current therapies in our armamentarium are either invasive or accompanied by toxic side effects. In lieu of traditional pharmaceutics and invasive therapeutic interventions, gene therapies offer more flexible and potentially more durable approaches for new anti-cancer therapies. Nonetheless, many current gene delivery approaches suffer from low transfection efficiency due to physiological barriers limiting extravasation and uptake of genetic material. Additionally, systemically administered gene therapies may lack target-specificity, which can lead to off-target effects. To overcome these challenges, many preclinical studies have shown the utility of focused ultrasound (FUS) to increase macromolecule uptake in cells and tissue under image guidance, demonstrating promise for improved delivery of therapeutics to solid tumors. As FUS-based drug delivery is now being tested in several clinical trials around the world, FUS-targeted gene therapy for solid tumor therapy may not be far behind. In this review, we comprehensively cover the literature pertaining to preclinical attempts to more efficiently deliver therapeutic genetic material with FUS and offer perspectives for future studies and clinical translation.

BACKGROUND Scar severity and scar viewing are known to affect body image. The literature is lacking on the relationship between body image and surgical scar assessment. The aims of this study were to compare patients from 3 different surgical departments in terms of body image and scar assessment at discharge, in comparison with nurses' scar assessment, and 3 months post-surgery. In addition, the research examined age and gender in relation to the main variables. METHODS A longitudinal, comparative, correlational study was conducted using an instrument which included a health history, a nurses scar assessment tool and a patient scar assessment tool at hospital discharge, as well as a body image tool used both at discharge and at 3 months' post-surgery. The 10-item body image scale was comprised of affective items, behavioural items and cognitive items. The STROCSS 2019 checklist is used. RESULTS 75 patients were studied who were mostly male (68.0%) with a mean age of 59 and married (77.3%). The sample distribution of departments included 30.7% cardiothoracic, 29.3% neurosurgery and 40% urology. Cardiothoracic patients displayed a significant negative body image pre-surgery compared to post-surgery. Neurosurgical patients' scar assessments were significantly higher than nurses' assessments with no differences found in the other departments. CONCLUSIONS The healthcare team needs to consider engaging patients in post-surgery discussions concerning scarring and body image. The results of this study revealed that expectations in both clinician and patient participants need to be assessed and evaluated for congruency in order to offer a greater patient-focused peri-operative experience.

Purpose: When patients with advanced cancer have minor children (age < 18), their health-related quality of life is closely linked to their concerns about the impact of progressive illness and death on their children. The Parenting Concerns Questionnaire (PCQ), a validated measure for parents with cancer, does not capture the full range of concerns in advanced cancer. The aim of this was study was to adapt and establish psychometrics for the PCQ for advanced disease (PCQ-AD). Methods: After generating an initial item-bank, we conducted concept elicitation interviews with clinicians (n = 8) and cognitive interviews with patients (n = 23) for face validity. New items addressed concerns about impact of parental death, making every moment count, communication, and financial impact of cancer on children. We administered 21 candidate items to 151 parents with advanced cancer. We conducted confirmatory factor analysis (CFA), calculated internal consistency, and assessed convergent and known-groups validity. Results: We removed 8 redundant items due to residual covariation between items. CFA of the 13-item PCQ-AD demonstrated satisfactory fit (CFI = 0.971, TLI = 0.966, RMSEA = 0.081) and high internal consistency (Cronbach’s alpha = 0.94, composite reliability = 0.95). The PCQ-AD demonstrated convergent validity and known-groups validity; patients with poor functional status reported higher scores than patients with better functional status (Cohen’s d = 0.56, p = 0.002). Conclusion: Adaptation of the PCQ yielded the addition of constructs important in advanced cancer. The PCQ-AD appears to be a reliable and valid measure of parenting concerns in advanced cancer, but future studies are needed to examine measure performance in diverse populations and responsiveness of the PCQ-AD to interventions.

Aim To describe the evolution of electroencephalogram (EEG) characteristics in infants with tuberous sclerosis complex (TSC) and the relationship with neurodevelopmental outcome at 24 months. Method Eighty-three infants were enrolled in the EPISTOP trial and underwent serial EEG follow-up until the age of 24 months (males n=45, females n=37, median age at enrolment 28d, interquartile range 14-54d). Maturation of the EEG background and epileptiform discharges were compared between the TSC1 and TSC2 variants and between preventive and conventional groups respectively. Results Children with TSC2 more frequently had a slower posterior dominant rhythm (PDR) at 24 months (51% vs 11%, p=0.002), a higher number of epileptiform foci (median=8 vs 4, p=0.003), and a lower fraction of EEGs without epileptiform discharges (18% vs 61%, p=0.001) at follow-up. A slower PDR at 24 months was significantly associated with lower cognitive (median=70 vs 80, p=0.028) and motor developmental quotients (median=70 vs 79, p=0.008). A higher fraction of EEGs without epileptiform discharges was associated with a lower probability of autism spectrum disorder symptoms (odds ratio=0.092, 95% confidence interval=0.009-0.912, p=0.042) and higher cognitive (p=0.004), language (p=0.002), and motor (p=0.001) developmental quotients at 24 months. Interpretation TSC2 is associated with more abnormal EEG characteristics compared to TSC1, which are predictive for neurodevelopmental outcome.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that presents significant challenges to family communication. The investigators examined observations of communication between parents with HD and their offspring talking about the challenges of HD and explored potential correlates of their communication.The sample included parents with HD and their adolescent and young-adult offspring (N=64). Parent communication and chorea were independently coded from video recordings. Parents and offspring completed working memory assessments and self-reports of neuropsychiatric symptoms, stress, and coping.Evidence was found for the association of observed parent-offspring communication with disease markers, psychosocial characteristics, and neurocognitive function. For parents, disease markers and working memory were correlates of communication, whereas offspring's psychiatric symptoms, stress, and coping were associated with their communication.These findings have potential implications for clinical interventions to enhance communication and quality of life for HD families.

In the light of the urgency raised by the COVID-19 pandemic, global investment in wildlife virology is likely to increase, and new surveillance programmes will identify hundreds of novel viruses that might someday pose a threat to humans. To support the extensive task of laboratory characterization, scientists may increasingly rely on data-driven rubrics or machine learning models that learn from known zoonoses to identify which animal pathogens could someday pose a threat to global health. We synthesize the findings of an interdisciplinary workshop on zoonotic risk technologies to answer the following questions. What are the prerequisites, in terms of open data, equity and interdisciplinary collaboration, to the development and application of those tools? What effect could the technology have on global health? Who would control that technology, who would have access to it and who would benefit from it? Would it improve pandemic prevention? Could it create new challenges? This article is part of the theme issue ‘Infectious disease macroecology: parasite diversity and dynamics across the globe’.

We are developing an age-related macular degeneration (AMD) health-related quality of life (HRQoL) item bank, applicable to Western and Asian populations. We report primarily on content generation and refinement, but also compare the HRQoL issues reported in our study with Western studies and current AMD-HRQoL questionnaires. In this cross-sectional, qualitative study of AMD patients attending the Singapore National Eye Centre (May–December 2019), items/domains were generated from: (1) AMD-specific questionnaires; (2) published articles; (3) focus groups/semi-structured interviews with AMD patients (n = 27); and (4) written feedback from retinal experts. Following thematic analysis, items were systematically refined to a minimally representative set and pre-tested using cognitive interviews with 16 AMD patients. Of the 27 patients (mean ± standard deviation age 67.9 ± 7.0; 59.2% male), 18 (66.7%), two (7.4%), and seven (25.9%) had no, early-intermediate, and late/advanced AMD (better eye), respectively. Whilst some HRQoL issues, e.g. activity limitation, mobility, lighting, and concerns were similarly reported by Western patients and covered by other questionnaires, others like anxiety about intravitreal injections, work tasks, and financial dependency were novel. Overall, 462 items within seven independent HRQoL domains were identified: Activity limitation, Lighting, Mobility, Emotional, Concerns, AMD management, and Work. Following item refinement, items were reduced to 219, with 31 items undergoing amendment. Our 7-domain, 219-item AMD-specific HRQoL instrument will undergo psychometric testing and calibration for computerized adaptive testing. The future instrument will enable users to precisely, rapidly, and comprehensively quantify the HRQoL impact of AMD and associated treatments, with item coverage relevant across several populations.

Therapeutic hypothermia (TH) has applications dating back millennia. In modern history, however, TH saw its importation into medical practice where investigations have demonstrated that TH is efficacious in ischemic insults, notably cardiac arrest and hypoxic-ischemic encephalopathy. As well, studies have been undertaken to investigate whether TH can provide benefit in focal stroke (i.e., focal ischemia and intracerebral hemorrhage). However, clinical studies have encountered various challenges with induction and maintenance of post-stroke TH. Most clinical studies have attempted to use body-wide cooling protocols, commonly hindered by side effects that can worsen post-stroke outcomes. Some of the complications and difficulties with systemic TH can be circumvented by using local hypothermia (LH) methods. Additional advantages include the potential for lower target temperatures to be achieved, and faster TH induction rates with LH. This systematic review summarizes the body of clinical and preclinical LH focal stroke studies, and raises key points to consider for future LH research. We conclude with an overview of LH neuroprotective mechanisms and a comparison of LH mechanisms with those observed with systemic TH. Overall, whereas many LH studies have been conducted preclinically in the context of focal ischemia, insufficient work has been done in intracerebral hemorrhage. Furthermore, key translational studies have yet to be done in either stroke subtype (e.g., varied models and time-to-treat, studies considering aged animals or animals with comorbidities). Few clinical LH investigations have been performed and the optimal LH parameters to achieve neuroprotection are unknown.

Objective:To characterise the prevalence and persistence of anaemia among Samoan children over a 2–3-year period.Design:Data were from two consecutive waves (2015 and 2017–2018) of the Ola Tuputupua’e ‘Growing up’ study. Anaemia (Hb < 11·0 or 11·5 g/dl for 2–4 and ≥ 5 years old, respectively) was considered ‘transient’ when it occurred at only one wave or ‘persistent’ if it was present at two consecutive waves. Child, maternal and household correlates of anaemia were examined using log-binomial and modified Poisson regressions.Setting:Eleven Samoan villages.Participants:Mother–child pairs (n 257) recruited in 2015 and reassessed in 2017–2018.Results:Anaemia prevalence was 33·9 % in 2015 and 28·0 % in 2017–2018; 35·6 % of cases identified in 2015 were persistent. Risk of anaemia at only one wave was lower among children who were older in 2015 (age 4 v. 2 years, adjusted relative risk (aRR) = 0·54, (95 % CI 0·35, 0·84), P = 0·007), had older mothers (≥ 40 v. 18–29 years, aRR = 0·61, (95 % CI 0·39, 0·95), P = 0·029) and had higher daily sodium intake (for every 100 mg/d, aRR = 0·97, (95 % CI 0·95, 0·99), P = 0·003) than children with no anaemia. Children whose anaemia persisted were more likely to have had a mother with anaemia (aRR = 2·13, (95 % CI 1·17, 3·89), P = 0·013) and had higher daily dietary iron intake (for every 10 mg/d, aRR = 4·69, (95 % CI 1·33, 16·49), P = 0·016) than those with no anaemia.Conclusions:Alongside broadly targeted prevention efforts, which are warranted given the moderate-high anaemia prevalence observed, specific attention should be paid to children with risk factors for persistent anaemia. Routine screening of children whose mothers have anaemia should be encouraged.

Burnout in the social work field receives significant attention, yet existing literature has disregarded social work educators as an affected population. This research utilized Bronfenbrenner’s eco...

Background Expediting the measurement of serum troponin by leveraging EMS blood collection could reduce the diagnostic time for patients with acute chest pain and help address Emergency Department (ED) overcrowding. However, this practice has not been examined among an ED chest pain patient population in the United States. Methods A prospective observational cohort study of adults with non-traumatic chest pain without ST-segment elevation myocardial infarction was conducted in three EMS agencies between 12/2016–4/2018. During transport, paramedics obtained a patient blood sample that was sent directly to the hospital core lab for troponin measurement. On ED arrival HEART Pathway assessments were completed by ED providers as part of standard care. ED providers were blinded to troponin results from EMS blood samples. To evaluate the potential impact on length of stay (LOS), the time difference between EMS blood draw and first clinical ED draw was calculated. To determine the safety of using troponin measures from EMS blood samples, the diagnostic performance of the HEART Pathway for 30-day major adverse cardiac events (MACE: composite of cardiac death, myocardial infarction (MI), coronary revascularization) was determined using EMS troponin plus arrival ED troponin and EMS troponin plus a serial 3-h ED troponin. Results The use of EMS blood samples for troponin measures among 401 patients presenting with acute chest pain resulted in a mean potential reduction in LOS of 72.5 ± SD 35.7 min. MACE at 30 days occurred in 21.0% (84/401), with 1 cardiac death, 78 MIs, and 5 revascularizations without MI. Use of the HEART Pathway with EMS and ED arrival troponin measures yielded a NPV of 98.0% (95% CI: 89.6–100). NPV improved to 100% (95% CI: 92.9–100) when using the EMS and 3-h ED troponin measures. Conclusions EMS blood collection used for core lab ED troponin measures could significantly reduce ED LOS and appears safe when integrated into the HEART Pathway.

Purpose This study aims to evaluate the reach, usefulness, acceptability, and factors influencing engagement with a lifestyle-focused text message intervention to support women’s mental and physical health after breast cancer treatment. Methods This study uses a mixed-methods process evaluation nested in the EMPOWER-SMS randomised controlled trial (n = 160; intervention n = 80, wait-list control n = 80). Data sources included screening logs, text message delivery software analytics, intervention feedback survey, and focus groups (n = 16), which were summarised thematically based on the framework approach. Results A total of 387 women met the inclusion criteria (meanage ± SD = 59.3 ± 11.6 years). Participants who declined (n = 227) were significantly older than those who enrolled (n = 160; 62.2 ± 11.1 vs 55.1 ± 11.1 years, respectively, p

Patients who have total knee arthroplasty (TKA) likely suffer from decreased postural stability because of postoperative changes in musculoskeletal structure and loss of proprioception. The purpose of this experimental biomechanical study was to determine if patients who have TKA improve their dynamic postural control during walking after TKA as compared with before TKA. The secondary purpose was to assess changes in postural control between post-TKA patients and healthy controls.Twenty-three patients who had primary knee osteoarthritis scheduled to undergo unilateral or bilateral TKA were prospectively enrolled. Each patient was tested at 3 months, 6 months, and 12 months after TKA. Ten healthy controls matched for age, sex, and body mass index were selected from a database of previous healthy volunteers without knee osteoarthritis. Ten Vicon cameras and four AMTI force platforms were used to collect the marker and center of pressure (COP) data while participants performed gait.Initial improvement in the double stance ratio was found by 6 months after TKA compared with before TKA. Patients showed improved postural control as evidenced by a faster mediolateral COP velocity and decreased double stance ratio at 12-month post-TKA compared with pre-TKA (P.05). However, patients who underwent TKA exhibited limited ability to maintain consistent COP movement during walking with increased variability in COP parameters as compared with controls (P.05).Patients exhibited improvement in dynamic postural control after TKA with time, but had higher variability in COP parameters during gait than controls. It is possible that therapy aimed to improve proprioceptive balance after TKA may improve dynamic postural control.

PURPOSEEffective treatment options are limited for patients with advanced (metastatic or unresectable) melanoma who progress after immune checkpoint inhibitors and targeted therapies. Adoptive cell therapy using tumor-infiltrating lymphocytes has demonstrated efficacy in advanced melanoma. Lifileucel is an autologous, centrally manufactured tumor-infiltrating lymphocyte product.METHODSWe conducted a phase II open-label, single-arm, multicenter study in patients with advanced melanoma who had been previously treated with checkpoint inhibitor(s) and BRAF ± MEK targeted agents. Lifileucel was produced from harvested tumor specimens in central Good Manufacturing Practice facilities using a streamlined 22-day process. Patients received a nonmyeloablative lymphodepletion regimen, a single infusion of lifileucel, and up to six doses of high-dose interleukin-2. The primary end point was investigator-assessed objective response rate (ORR) per RECIST, version 1.1.RESULTSSixty-six patients received a mean of 3.3 prior therapies (anti–programmed death 1 [PD-1] or programmed death ligand 1 [PD-L1]: 100%; anticytotoxic T-lymphocyte-associated protein-4: 80%; BRAF ± MEK inhibitor: 23%). The ORR was 36% (95% CI, 25 to 49), with two complete responses and 22 partial responses. Disease control rate was 80% (95% CI, 69 to 89). Median duration of response was not reached after 18.7-month median study follow-up (range, 0.2-34.1 months). In the primary refractory to anti–PD-1 or PD-L1 therapy subset, the ORR and disease control rate were 41% (95% CI, 26 to 57) and 81% (95% CI, 66 to 91), respectively. Safety profile was consistent with known adverse events associated with nonmyeloablative lymphodepletion and interleukin-2.CONCLUSIONLifileucel demonstrated durable responses and addresses a major unmet need in patients with metastatic melanoma with limited treatment options after approved therapy, including the primary refractory to anti–PD-1 or PD-L1 therapy subset.

PURPOSE Patients with cancer experience high rates of morbidity and unplanned health care utilization and may benefit from new models of care. We evaluated an adult oncology hospital at home program's rate of unplanned hospitalizations and health care costs and secondarily, emergency department (ED) use, length of hospital stays, and intensive care unit (ICU) admissions during the 30 days after enrollment. METHODS We conducted a prospective, nonrandomized, real-world cohort comparison of 367 hospitalized patients with cancer—169 patients consecutively admitted after hospital discharge to Huntsman at Home (HH), a hospital-at-home program, compared with 198 usual care patients concurrently identified at hospital discharge. All patients met clinical criteria for HH admission, but those in usual care lived outside the HH service area. Primary outcomes were the number of unplanned hospitalizations and costs during the 30 days after enrollment. Secondary outcomes included length of hospital stays, ICU admissions, and ED visits during the 30 days after enrollment. RESULTS Groups were comparable except that more women received HH care. In propensity-weighted analyses, the odds of unplanned hospitalizations was reduced in the HH group by 55% (odds ratio, 0.45, 95% CI, 0.29 to 0.70; P < .001) and health care costs were 47% lower (mean cost ratio, 0.53; 95% CI, 0.39 to 0.72; P < .001) over the 30-day period. Secondary outcomes also favored HH. Total hospital stay days were reduced by 1.1 days ( P = .004) and ED visits were reduced by 45% (odds ratio, 0.55; 95% CI, 0.33 to 0.92; P = .022). There was no evidence of a difference in ICU admissions ( P = .972). CONCLUSION This oncology hospital at home program shows initial promise as a model for oncology care that may lower unplanned health care utilization and health care costs.

Objective To evaluate physician perceptions and attitudes toward telemedicine use at a tertiary care academic institution in northeast Florida during the coronavirus disease 2019 pandemic. Patients and Methods An anonymous 38-question cross-sectional survey was developed using Qualtrics survey software (Qualtrics) and e-mailed to all staff physicians from all specialty disciplines at Mayo Clinic in Florida. The survey was open from August 17, 2020, through September 1, 2020. Collected data included general demographic characteristics and employment information, attitude and experience with telemedicine use before and during the coronavirus disease 2019 pandemic, perception of patients’ experience, and the effect of telemedicine on burnout. Results The survey was distributed to 529 eligible physicians at our institution, with 103 physicians responding (20%). The distribution of specialties was 22% primary care specialties, 41% other internal medicine subspecialties, and 18% surgical specialties. Collectively, 63% found comparable quality of care when provided virtually (vs in-person) whereas 80% perceived telemedicine as cost-effective. A total of 76% of physicians felt that telemedicine increased flexibility and control over patient care activities, with 36% reporting improved work-life balance and 30% reporting improved burnout symptoms. Overall, 42% preferred using telemedicine over in-person visits when possible. Conclusion Physicians generally had positive attitudes regarding the adoption of telemedicine and perceived that the quality of health care delivery as generally comparable to in-person care. Future studies are needed to explore attitudes regarding telemedicine after the pandemic and how this virtual technology may be further used to improve physicians’ professional and personal well-being.

How targeted therapies and immunotherapies shape tumors, and thereby influence subsequent therapeutic responses, is poorly understood. In the present study, we show, in melanoma patients and mouse models, that when tumors relapse after targeted therapy with MAPK pathway inhibitors, they are cross-resistant to immunotherapies, despite the different modes of action of these therapies. We find that cross-resistance is mediated by a cancer cell–instructed, immunosuppressive tumor microenvironment that lacks functional CD103+ dendritic cells, precluding an effective T cell response. Restoring the numbers and functionality of CD103+ dendritic cells can re-sensitize cross-resistant tumors to immunotherapy. Cross-resistance does not arise from selective pressure of an immune response during evolution of resistance, but from the MAPK pathway, which not only is reactivated, but also exhibits an increased transcriptional output that drives immune evasion. Our work provides mechanistic evidence for cross-resistance between two unrelated therapies, and a scientific rationale for treating patients with immunotherapy before they acquire resistance to targeted therapy. Obenauf and colleagues report that acquired resistance to BRAF and MEK inhibitors in melanoma confers cross-resistance to immune checkpoint blockade by fostering a cancer cell–instructed, immune-evasive tumor microenvironment.

This paper establishes the potential of the recently introduced ABX3 metal-free perovskite structures for third-order nonlinear optical processes. The base unit in this family of materials is an ammonium halide octahedra, and it incorporates a large aromatic cation spacer forming the classic perovskite structure. This work shows that the choice of cation is key to the resulting third-order nonlinearity, where the incorporation of "MDABCO"into the structure, a very polar cation, results in a third-order nonlinear refractive index on the order of 10-17 m2 W-1 and high laser damage threshold of 0.8 J cm-2. Owing to its very wide band gap of ∼5.12 eV, this material exhibits a high nonlinear figure of merit across the visible and near-infrared transmission windows. These results show that the metal-free family of perovskite materials is an excellent candidate for nonlinear optics in the important visible and near-infrared wavelength regimes.

Objective To examine the relationship between COVID-19-related distress and mental health among first-year college students. Participants Data for this longitudinal study (n = 727) were collected before the school year (August 2019), end of fall semester (December 2019), and soon after the university suspended in-person instruction (April 2020). Methods We used multivariable log-linear and logistic regressions to examine continuous and dichotomous outcomes on the 9-item Patient Health Questionnaire and the 7-item Generalized Anxiety Disorder scale. Results The most consistent predictor of during-pandemic mental health was feeling extremely isolated (versus not at all), which was associated with increased symptom severity of depression (proportional change[95% CI] = 2.43[1.87, 3.15]) and anxiety (2.02[1.50, 2.73]) and greater odds of new moderate depression (OR[95% CI] = 14.83[3.00, 73.41]) and anxiety (24.74[2.91, 210.00]). Greater COVID-19-related concern was also related to increased mental health symptoms. Conclusions Results highlight the need for mental health services during crises that lead to social isolation.

Palliative care has evolved to be an integral part of comprehensive cancer care with the goal of early intervention to improve quality of life and patient outcomes. The NCCN Guidelines for Palliative Care provide recommendations to help the primary oncology team promote the best quality of life possible throughout the illness trajectory for each patient with cancer. The NCCN Palliative Care Panel meets annually to evaluate and update recommendations based on panel members’ clinical expertise and emerging scientific data. These NCCN Guidelines Insights summarize the panel’s recent discussions and highlights updates on the importance of fostering adaptive coping strategies for patients and families, and on the role of pharmacologic and nonpharmacologic interventions to optimize symptom management.

Background Patients with a preoperative varus deformity >8 degrees are at increased risk of aseptic loosening after total knee arthroplasty. This study analyzes the effect of a tibial stem on the rate of aseptic loosening in patients with a severe preoperative varus deformity. Methods Patients with a preoperative varus deformity of >8 degrees and 2-year minimum follow-up with a stemmed tibial component (n = 67) were matched 1:2 to patients with a similar preoperative varus deformity with a standard tibial component (n = 134). Radiolucent lines were measured on the tibia at 6 weeks, 1 year, and 2 years postoperatively using the Knee Society Radiographic Evaluation System. Failure was defined as revision due to aseptic loosening of the tibial component. Outcomes were evaluated using Student’s t-tests and log-rank tests. Results Patients with tibial stems had greater preoperative deformity (12.9 vs 11.3 degrees, P = .004). There was no difference in postoperative alignment (1.7 vs 2.1 degrees varus, P = .25) or tibial component angle (1.8 vs 2.1 degrees varus, P = .33). Patients with stems were more likely to have more constraint (44.8% vs 1.5%, P 2 mm was observed in 17.6% (23/134) vs 5.97% (4/67) of patients in the stem group (P = .03). Rates of aseptic loosening were lower in the stem group (0% vs 5.15%, P = .05). Conclusion Despite worse preoperative deformity and higher utilization of constraint, tibial stem use in patients with severe preoperative varus deformity resulted in lower rates of aseptic loosening. Prophylactic use of stems in these patients may help increase implant survival.

Irritability is a common reason why children and adolescents are brought for psychiatric care. Although research is advancing what is known about the underlying brain and behavior mechanisms of irritability, clinicians often are shut out of that research. This article explains some of these research methods, providing brief summaries of what is known about brain/behavior mechanisms in disorders involving irritability, including bipolar disorder, disruptive mood dysregulation disorder, attention-deficit/hyperactivity disorder, and autism spectrum disorder. Greater access to these methods may help clinicians now and in the future, with such mechanisms translated into improved care, as occurs in the treatment of childhood leukemia.

Objective:To explore the promotion of discretionary foods/beverages and marketing strategies employed by the top three online food delivery services’ (OFDS) Instagram accounts in three countries before and during the coronavirus disease 2019 (COVID-19) pandemic.Design:Publicly available data were extracted for the top three OFDS Instagram accounts for Australia, United Kingdom (UK) and the United States of America (USA) from March to May 2019 and 2020. Food/beverage items from posts were classified as ‘discretionary’ or from the five food groups (FFG) according to the Australian Dietary Guidelines. Marketing strategies were coded using an existing framework. Posts referring to COVID-19 were coded under four marketing strategies: (i) appropriating frontline workers; (ii) combatting the pandemic; (iii) selling social distancing; and (iv) accelerating digitalisation.Results:From 581 posts, 618 food/beverage items were shown, of which 69 % (427/618) were classified as discretionary. In 2019, the most used marketing strategies were product imagery (unbranded) (137/195, 70 %), links (111/195, 57 %) and sponsorships/partnerships (58/195, 30 %). In 2020, the most used were links (252/386, 68 %), product imagery (unbranded) (179/386, 49 %) and branding elements (175/386, 45 %). The most common COVID-19 marketing strategy was combatting the pandemic (76/123, 62 %) followed by selling social distancing (53/123, 43 %), appropriating frontline workers (34/123, 28 %) and accelerating digitalisation (32/123, 26 %).Conclusions:Following the COVID-19 pandemic, OFDS adapted their marketing, creating content with the theme of ‘combatting the pandemic’. Due to the growing number of discretionary foods/beverages promoted on Instagram, this highlights the need for policy action to counter the potential influence social media platforms have on dietary behaviours.

PURPOSE To determine whether the age-adjusted Charlson comorbidity index (age-CCI) in sino-orbital fungal disease patients correlates with disease-specific mortality. METHODS Hospital billing systems at 2 academic institutions were queried for patients with ICD-9, ICD-10, and CPT codes used in fungal disease who also had orbital disease and significant visual loss. Thirty-two patients at Institution A and 18 patients at Institution B met the inclusion criteria of microbiologic or pathologic confirmation of fungal infection and completion of inpatient ophthalmology evaluation. Patients without radiographic abnormality in the sinus or orbit were excluded. Demographic, diagnostic, treatment, and outcome variables were recorded. Our primary outcome was death due to fungal disease. RESULTS Of the 50 medical records examined, 44 patients met the criteria for fungal-related death outcome on multivariate analysis. The regression coefficient for age-CCI and fungal-related mortality was 0.242 (95% CI, 0.012-0.779) with a p value of 0.038. CONCLUSIONS Age-CCI is significantly associated with fungal-related mortality. This relationship remains significant when controlling for 5 covariates of fungal organism phylum, presence or absence of CNS disease, exenteration, local treatment use, and presence or absence of an immunosuppressive diagnosis. Age-CCI shows promise as a clinical and research tool in the evaluation of invasive fungal disease involving the orbit.

While the impact of livestock grazing has been frequently assessed for grasses, little is known about how livestock affects tree seedlings and saplings. We explored the effects of goat, cattle and ...

BACKGROUND: Interventions to support patients with complex needs have proliferated in recent years, but the question of how to identify patients with complex needs has received relatively little attention. There are innumerable ways to structure inclusion and exclusion criteria for complex care interventions, and little is known about the implications of choices made in designing patient selection criteria. OBJECTIVE: To provide insights into the design of patient selection criteria for interventions, by implementing criteria sets within a large health plan member population and comparing the characteristics of the resulting complex patient cohorts. DESIGN: Retrospective observational descriptive study. SUBJECTS: Patients identified as having complex needs, within the membership population of Kaiser Permanente Southern California, a large, population-based health plan with more than 4 million members. We characterize five commonly used archetypes of complex needs: high-cost patients, patients with multiple chronic conditions, frail elders, emergency department high-utilizers, and inpatient high-utilizers. MEASURES: We selected an initial set of criteria for identifying patients in each of the archetypical complex populations, based on available administrative data. We then tested multiple variants of each definition. We compared the resulting patient cohorts using univariate and bivariate descriptive statistics. KEY RESULTS: Overall, 32.7% of the 3,112,797 adults in our population-based sample were selected by at least one of the 25 definitions of complexity we tested. Across definitions the total number of patients identified as complex ranged from 622,560 to 1583 and complex patient cohorts varied widely in demographic characteristics, chronic conditions, healthcare utilization, spending, and survival. CONCLUSIONS: Choice of patient population is critical to the design of complex care programs. Exploratory analyses of population criteria can provide useful information for program planning in the setting of limited resources for interventions. Data such as these should be generated as a key step in program design. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-021-06815-4.

BackgroundInternet cognitive behavioural therapy (iCBT) is a viable delivery format of CBT for depression. However, iCBT programmes include training in a wide array of cognitive and behavioural skills via different delivery methods, and it remains unclear which of these components are more efficacious and for whom.MethodsWe did a systematic review and individual participant data component network meta-analysis (cNMA) of iCBT trials for depression. We searched PubMed, PsycINFO, Embase, and the Cochrane Library for randomised controlled trials (RCTs) published from database inception to Jan 1, 2019, that compared any form of iCBT against another or a control condition in the acute treatment of adults (aged ≥18 years) with depression. Studies with inpatients or patients with bipolar depression were excluded. We sought individual participant data from the original authors. When these data were unavailable, we used aggregate data. Two independent researchers identified the included components. The primary outcome was depression severity, expressed as incremental mean difference (iMD) in the Patient Health Questionnaire-9 (PHQ-9) scores when a component is added to a treatment. We developed a web app that estimates relative efficacies between any two combinations of components, given baseline patient characteristics. This study is registered in PROSPERO, CRD42018104683.FindingsWe identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42·0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD −1·83 [95% credible interval (CrI) −2·90 to −0·80]) and that relaxation might be harmful (1·20 [95% CrI 0·17 to 2·27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0·32 [95% CrI 0·13 to 0·93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components.InterpretationThe individual patient data cNMA revealed potentially helpful, less helpful, or harmful components and delivery formats for iCBT packages. iCBT packages aiming to be effective and efficient might choose to include beneficial components and exclude ones that are potentially detrimental. Our web app can facilitate shared decision making by therapist and patient in choosing their preferred iCBT package.FundingJapan Society for the Promotion of Science.

Interventions to support patients with complex needs are proliferating. However, little attention has been paid to methods for identifying complex patients. This study aims to summarize approaches used to define populations with complex needs in practice, by cataloging specific population criteria and organizing them into a taxonomy. The authors conducted a pragmatic review of literature published January 2000-December 2018 using PubMed. Search results were limited to English-language studies of adults that specified a set of objective criteria to identify a population with complex needs. The authors abstracted data from each article on population parameters, and conducted thematic analysis guided by deductive coding. The review identified 70 studies reflecting 90 unique complex population definitions. Complex populations criteria reflected 3 approaches: stratification, segmentation, and targeting. Six domains of population criteria were found within, including age-based criteria (59 populations); income (12); health care costs (45); health care utilization (39); health conditions (35); and subjective criteria (15). Criteria from multiple domains were frequently used in combination, and exact specifications were highly variable within each domain. Overall, 83% of the 90 population definitions included at least 1 cost- or utilization-based criterion. Nearly every study in the review presented a unique approach to identifying patients with complex needs but a limited number of "schools of thought" were found. Variability in definitions and inconsistent terminology are potential sources of ambiguity between stakeholders. Greater specificity and transparency in complex population definition would be a substantial contribution to the emerging field of complex care.

Aim: We aimed to determine the reasons for hospitalizations and factors of mortality of Filipino Parkinson's disease (PD) patients in a tertiary hospital. Methods: We conducted a retrospective review of medical records of PD patients admitted to our institution between 2016 and 2018. Demographic and clinical data were analyzed. Results: We included 166 PD patients. The most common cause of admission was infectious (pneumonia, urinary tract, and skin-soft tissue infections) (n = 65, 39.2%). The most common cause of mortality was sepsis (n = 9, 5.4%). Renal comorbidity was a significant factor of mortality (OR: 3.67, 95% CI: 1.11–12.12; p = 0.033). Conclusion: Interventions designed to reduce the risk of complications in PD patients should be prioritized to potentially decrease the probability of eventual hospitalization.

Background Synovial fluid alpha-defensin (AD) may improve diagnostic accuracy of periprosthetic joint infection (PJI) following total knee (TKA) and hip (THA) arthroplasty but is only available as send-out test. This study evaluated laboratory result accuracy between send-out test vs hospital labs and if AD made a difference in treatment plan. Methods A retrospective review was performed of 152 consecutive patients with a TKA or THA joint aspiration for painful or clinically concerning joint. Synovial fluid was sent to our institution (hospital-based labs, HBL) and send-out immunoassay laboratory (Synovasure). Patients were scored with specific criteria from validated scoring system for PJI using HBL and Synovasure results. The score with and without AD test was compared to determine if AD impacted patient management. Results Overall, there was strong agreement between institutions for PJI diagnosis (Cohen’s kappa score 0.96). Twenty-nine patients had PJI diagnosis (score ≥6), of which 28 (97%) had positive AD with 1 false-negative result. Sixty-three patients had inconclusive score (between 2 and 5) and 60 patients had negative PJI diagnosis (score ≤1). Of these patients, 5 underwent surgery for infection. Two patients had surgery for positive AD, 2 for positive culture, and 1 because of elevated HBL results. The AD test changed the PJI diagnosis and influenced decision for surgery in only 1.3% (2/152) of patients. Conclusion Minimal differences were found in laboratory values between institutions. The addition of AD may be useful in cases of equivocal laboratory results but does not appear to be necessary for routine diagnosis of PJI after TKA/THA. Level Evidence Level III.