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Introduction: Verbal autopsy (VA) methods have emerged to estimate causes of death in populations lacking robust civil registration and vital statistics (CRVS) systems. Despite World Health Organization endorsement of routine VA use, cost and efficiency concerns persist. Telephonic verbal autopsies (teleVAs) can reduce cost. Physician coding offers a valuable approach, but the expertise required makes it resource-intensive, often involving multiple coders for consensus., Objective: To assess inter-coder agreement for cause of death (CoD) in South African teleVAs using Kappa statistics, evaluating if agreement surpasses a 0.8 cut-off (very high) potentially allowing single coders., Methods: A cross-sectional study employed telephonic VA interviews on non-facility deaths in Cape Town (December 2020-September 2021). Trained fieldworkers administered a standard VA questionnaire. Each case's VA responses were reviewed independently by two physicians, medically certifying the CoD. A panel was used to solve disagreements. Cohen's kappa-statistic ( k -statistic) tested agreement levels., Results: Decedents were aged between 18 and 98 years. In total, 228 teleVAs (16.6% response rate) were conducted. Physician coding agreement was good overall ( k -statistic: 0.63). Diabetes mellitus (47%) and other non-communicable disease (42%) had initial agreement between physician coders in less than 50% of cases in comparison to consensus totals. COVID-19 (89%) and acute cardiac disease (83%) showed initial agreement in more than 80% of cases compared to consensus totals. A chi-square test revealed a significant difference in the number of causes listed on death notification forms for cases with and without agreement in Part 1 (χ 2 = 14.71, p  < 0.01), but not in Part 2 (χ 2 = 4.97, p  = 0.17)., Conclusion: CoD agreement might not be high enough to infer that single coders can be used instead of multiple coders. Challenges with co-morbidities and specific CoDs with multiple sequelae highlight the need for further research and refinement of VA methodologies for reliable CoD determination in routine practice., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Verbal autopsy (VA), though imperfect, serves as a vital tool to determine cause-of-death, particularly for out-of-facility deaths, but challenges persist in integrating VA into Civil Registration and Vital Statistics systems., Objective: To describe the challenges and successes of collecting a national sample of verbal autopsy interviews in South Africa to obtain the cause of death profile in 2017/18., Methods: We recruited next of kin from 27 randomly selected sub-districts (10.5%) across South Africa between September 2017 and April 2018. Trained fieldworkers conducted face-to-face interviews using the WHO2016 VA instrument, with physicians certifying underlying causes of death. Feasibility was evaluated based on response rates, participation, and data quality., Results: Of the total 36,976 deaths registered, only 26% were identified during recruitment, with a 55% overall response rate for VA interviews. Physician-reviewed VA data were deemed of good quality for assigning underlying causes of death in 83% of cases. By comparing cause-specific mortality fractions, physician-reviewed VA identified 22.3% HIV/AIDS and InterVA-5 identified 18.5%, aligning with burden of disease estimates, while Statistics South Africa reported 4.9% HIV/AIDS., Conclusions: The study demonstrated the feasibility of using VA on a national scale, but immense challenges in identifying and recruiting next of kin highlight the importance of formalising VAs within the country's death notification system.

Vocal and swallowing deficits are common in Parkinson disease (PD). Because these impairments are resistant to dopamine replacement therapies, vocal and lingual exercise are the primary treatment, but not all individuals respond to exercise and neural mechanisms of treatment response are unclear. To explore putative mechanisms, we used the progressive Pink1-/- rat model of early to mid-stage PD and employed vocal and lingual exercises at 6- and 10-months of age in male Pink1-/- and wild type (WT) rats. We hypothesized that vocal and lingual exercise would improve vocal and tongue use dynamics and increase serotonin (5HT) immunoreactivity in related brainstem nuclei. Rats were tested at baseline and after 8 weeks of exercise or sham exercise. At early-stage PD (6 months), vocal exercise resulted in increased call complexity, but did not change intensity, while at mid-stage (10 months), vocal exercise no longer influenced vocalization complexity. Lingual exercise increased tongue force generation and reduced relative optical density of 5HT in the hypoglossal nucleus at both time points. The effects of vocal and lingual exercise at these time points are less robust than in prodromal stages observed in previous work, suggesting that early exercise interventions may yield greater benefit. Future work targeting optimization of exercise at later time points may facilitate clinical translation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: For high-risk patients receiving right-sided colectomy, stoma formation is a safety strategy. Options are anastomosis with loop ileostomy, end ileostomy, or split stoma. The aim is to compare the outcome of these three options., Methods: This retrospective cohort study included all patients who underwent right sided colectomy and stoma formation between January 2008 and December 2021 at two tertial referral centers in Switzerland. The primary outcome was the stoma associated complication rate within one year., Results: A total of 116 patients were included. A total of 20 patients (17%) underwent primary anastomosis with loop ileostomy (PA group), 29 (25%) received an end ileostomy (ES group) and 67 (58%) received a split stoma (SS group). Stoma associated complication rate was 43% (n = 21) in PA and in ES group and 50% (n = 34) in SS group (n.s.). A total of 30% (n = 6) of patients in PA group needed reoperations, whereas 59% (n = 17) in ES and 58% (n = 39) in SS group had reoperations (P = 0.07). Wound infections occurred in 15% (n = 3) in PA, in 10% (n = 3) in ES, and in 30% (n = 20) in SS group (P = 0.08). A total of 13 patients (65%) in PA, 7 (24%) in ES, and 29 (43%) in SS group achieved stoma closure (P = 0.02). A total of 5 patients (38%) in PA group, 2 (15%) in ES, and 22 patients (67%) in SS group had a stoma-associated rehospitalization (P < 0.01)., Conclusion: Primary anastomosis and loop ileostomy may be an option for selected patients. Patients with end ileostomies have fewer stoma-related readmissions than those with a split stoma, but they have a lower rate of stoma closure., Clinical Trial Registration: Trial not registered., (© 2024. The Author(s).)

Post-secondary education (PSE) plays an important role in preparing individuals with an intellectual and developmental disability (IDD) to gain employment and independent living. Despite the recent increase in PSE programs, however, there is a lack of research examining outcomes of individuals with IDD who have attended a PSE program. This study examined three years of data from students who participated in one PSE program that focuses on the acquisition of skills regarding self-determination, employment, and independent living. We analyzed the outcome data of program graduates regarding their acquisition of skills in employment and self-determination, as well as follow-up data on employment. It was found that participation in the program increased self-determination and post-secondary readiness. Our findings also indicated that the COVID-19 pandemic impacted the self-determination scores of participants and their employment outcomes.

Enzymatic digestion of lignocellulosic plant biomass is a key step in bio-refinery approaches for the production of biofuels and other valuable chemicals. However, the recalcitrance of this material in conjunction with its variability and heterogeneity strongly hampers the economic viability and profitability of biofuel production. To complement both academic and industrial experimental research in the field, we designed an advanced web application that encapsulates our in-house developed complex biophysical model of enzymatic plant cell wall degradation. PREDIG (https://predig.cs.hhu.de/) is a user-friendly, free, and fully open-source web application that allows the user to perform in silico experiments. Specifically, it uses a Gillespie algorithm to run stochastic simulations of the enzymatic saccharification of a lignocellulose microfibril, at the mesoscale, in three dimensions. Such simulations can for instance be used to test the action of distinct enzyme cocktails on the substrate. Additionally, PREDIG can fit the model parameters to uploaded experimental time-course data, thereby returning values that are intrinsically difficult to measure experimentally. This gives the user the possibility to learn which factors quantitatively explain the recalcitrance to saccharification of their specific biomass material., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Contrary to the World Health Organization's internationally recommended medical certificate of cause of death, the South African (SA) death notification form (DNF) does not allow for the reporting of the manner of death to permit accurate coding of external causes of injury deaths., Objectives: To describe the injury cause-of-death profile from forensic pathology records collected for the National Cause-of-Death Validation (NCoDV) Project and compare it with profiles from other sources of injury mortality data. In particular, the recording of firearm use in homicides is compared between sources., Methods: The NCoDV Project was a cross-sectional study of deaths that occurred during a fixed period in 2017 and 2018, from a nationally representative sample of 27 health subdistricts in SA. Trained fieldworkers scanned forensic records for all deaths investigated at the forensic mortuaries serving the sampled subdistricts during the study period. Forensic practitioners reviewed the records and completed a medical certificate of cause of death for each decedent. Causes of death were coded to the International Statistical Classification of Diseases, 10th revision (ICD-10), using Iris automated coding software. Cause-specific mortality fractions for injury deaths were compared with Injury Mortality Survey 2017 (IMS 2017) and Statistics South Africa 2017 (Stats SA 2017) datasets. The cause profile for all firearm-related deaths was compared between the three datasets., Results: A total of 5 315 records were available for analysis. Males accounted for 77.6% of cases, and most decedents were aged between 25 and 44 years. Homicide was the leading cause of death (34.7%), followed by transport injuries (32.6%) and suicide (14.7%). This injury cause profile was similar to IMS 2017 but differed markedly from the official statistics, which showed markedly lower proportions of these three causes (15.0%, 11.6% and 0.7%, respectively), and a much higher proportion of other unintentional causes. Investigation of firearm-related deaths revealed that most were homicides in NCoDV 2017/18 (88.5%) and IMS 2017 (93.1%), while in the Stats SA 2017 data, 98.7% of firearm deaths were classified as accidental. Approximately 7% of firearm-related deaths were suicides in NCoDV 2017/18 and IMS 2017, with only 0.3% in Stats SA 2017., Conclusion: The official cause-of-death data for injuries in SA in 2017 differed substantially from findings from the NCoDV 2017/18 study and IMS 2017. Accurate data sources would ensure that public health interventions are designed to reduce the high injury burden. Inclusion of the manner of death on the DNF, as is recommended internationally, is critically important to enable more accurate, reliable and valid reporting of the injury profile.

Background: HIV-related stigma is a major barrier to the timely linkage and retention of patients in HIV care in sub-Saharan Africa, where most people living with HIV/AIDS reside. In this implementation study we aim to evaluate the effect of stigma-directed services on linkage to care and other health outcomes in newly diagnosed HIV-positive patients. Methods : In a nested project of the Kilombero and Ulanga Antiretroviral Cohort in rural Tanzania, we conduct a prospective observational pre-post study to assess the impact of a bundle of stigma-directed services for newly diagnosed HIV positive patients. Stigma-directed services, delivered by a lay person living with HIV, are i) post-test counseling, ii) post-test video-assisted teaching, iii) group support therapy and group health education, and iv) mobile health. Patients receiving stigma services (enrolled from 1 st February 2020 to 31 st August 2021) are compared to a historical control receiving the standard of care (enrolled from 1 st July 2017 to 1 st February 2019). The primary outcome is 'linkage to care'. Secondary endpoints are retention in care, viral suppression, death and clinical failure at 6-12 months (up to 31 st August 2022). Self-reported stigma and depression are assessed using the Berger Stigma scale and the PHQ-9 questionnaire, respectively. The sample size calculation was based on cohort data from 2018. Assuming a pre-intervention cohort of 511 newly diagnosed adults of whom 346 (68%) were in care and on antiretroviral treatment (ART) at 2 months, a 10% increase in linkage (from 70 to 80%), a two-sided type I error rate of 5%, and 90% power, 321 adults are required for the post-implementation group. Discussion: We expect that integration of stigma-directed services leads to an increase of proportions of patients in care and on ART. The findings will provide guidance on how to integrate stigma-directed services into routine care in rural sub-Saharan Africa., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Magnolini R et al.)

Purpose: The pre-interventional differentiation between complicated and uncomplicated appendicitis is decisive for treatment. In the context of conservative therapy, the definitive diagnosis of uncomplicated appendicitis is mandatory. This study investigates the ability of clinical scoring systems and imaging to differentiate between the two entities., Methods: This is a retrospective analysis of two cohorts from two tertiary referral centers in Switzerland and Germany. All consecutive patients underwent appendectomy between January 2008 and April 2013 (in the first cohort) or between January 2017 and June 2019 (the second cohort). Exclusion criteria did not apply as all patients found by the database search and received an appendectomy were included. Diagnostic testing and calculation of a receiver operating curve were performed to identify a cutoff for clinical scores that resulted in a minimum sensitivity of 90% to detect complicated appendicitis. The cutoff was combined with additional diagnostic imaging criteria to see if diagnostic properties could be improved., Results: Nine hundred fifty-six patients were included in the analysis. Two hundred twenty patients (23%) had complicated appendicitis, and 736 patients (77%) had uncomplicated appendicitis or no inflammation. The complicated appendicitis cohort had a mean Alvarado score of 7.03 and a mean AIR of 5.21. This compared to a mean Alvarado of 6.53 and a mean AIR of 4.07 for the uncomplicated appendicitis cohort. The highest Alvarado score with a sensitivity of > 90% to detect complicated appendicitis was ≧ 5 (sensitivity = 95%, specificity 8.99%). The highest AIR score with a sensitivity of > 90% to detect complicated appendicitis was ≧ 3 (sensitivity 91.82%, specificity 18.53). The analysis showed that additional CT information did not improve the sensitivity of the proposed cut-offs., Conclusion: AIR and Alvarado scores showed limited capability to distinguish between complicated and uncomplicated appendicitis even with additional imaging in this retrospective cohort. As conservative management of appendicitis needs to exclude patients with complicated disease reliably, appendectomy seems until now to remain the safest option to prevent undertreatment of this mostly benign disease., (© 2022. The Author(s).)

Background: HIV-related stigma is a major barrier to the timely linkage and retention of patients in HIV care in sub-Saharan Africa, where most people living with HIV/AIDS reside. In this implementation study we aim to evaluate the effect of stigma-directed services on linkage to care and other health outcomes in newly diagnosed HIV-positive patients. Methods : In a nested project of the Kilombero and Ulanga Antiretroviral Cohort in rural Tanzania, we conduct a prospective observational pre-post study to assess the impact of a bundle of stigma-directed services for newly diagnosed HIV positive patients. Stigma-directed services, delivered by a lay person living with HIV, are i) post-test counseling, ii) post-test video-assisted teaching, iii) group support therapy and group health education, and iv) mobile health. Patients receiving stigma services (enrolled from 1 st February 2020 to 31 st August 2021) are compared to a historical control receiving the standard of care (enrolled from 1 st July 2017 to 1 st February 2019). The primary outcome is 'linkage to care'. Secondary endpoints are retention in care, viral suppression, death and clinical failure at 6-12 months (up to 31 st August 2022). Self-reported stigma and depression are assessed using the Berger Stigma scale and the PHQ-9 questionnaire, respectively. The sample size calculation was based on cohort data from 2018. Assuming a pre-intervention cohort of 511 newly diagnosed adults of whom 346 (68%) were in care and on antiretroviral treatment (ART) at 2 months, a 10% increase in linkage (from 70 to 80%), a two-sided type I error rate of 5%, and 90% power, 321 adults are required for the post-implementation group. Discussion: We expect that integration of stigma-directed services leads to an increase of proportions of patients in care and on ART. The findings will provide guidance on how to integrate stigma-directed services into routine care in rural sub-Saharan Africa., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Magnolini R et al.)

Polyamic acid (PAA) nanofibers produced by using the electrospinning method were fully characterized in terms of morphology and spectroscopy. A PAA nanofiber-modified screen-printed carbon electrode was applied to the detection of selected sulfonamides by following an electroanalytical protocol. The polyamic acid (PAA) nanofibers were characterized using Fourier transform infrared (FTIR) spectroscopy to study the integrity of polyamic acid functional groups as nanofibers by comparing them to chemically synthesized polyamic acid. A scanning electron microscope (SEM) was used to confirm the morphology of the produced nanofibers and 3D arrangement at the electrode interface. The Brunauer-Emmett-Teller (BET) method was used to determine the surface area of the nanofibers. Atomic force microscopy (AFM) was used to study the porosity and surface roughness of the nanofibers. Electrochemical evaluation based on diffusion-controlled kinetics was applied to determine the number of electrons transferred in the system, the surface concentration of the deposited PAA thin film (2.14 × 10 -6  mol/cm 2 ), and the diffusion coefficient (D e ) for the PAA nanofiber-modified screen-printed carbon electrode (9.43 × 10 -7  cm -2 /s). The reported LODs for sulfadiazine and sulfamethazine detection are consistent with requirements for trace-level monitoring by early warning diagnostic systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hamnca, Chamier, Grant, Glass, Iwuoha and Baker.)

Limited work to date has examined plastic ingestion in highly migratory seabirds like Great Shearwaters ( Ardenna gravis ) across the their entire migratory range, although this species is prone to ingest plastic as a wide-ranging procellariiform. We examined 217 Great Shearwaters obtained from 2008-2019 at multiple locations spanning their yearly migration cycle across the Northwest and South Atlantic to assess accumulation of ingested plastic as well as trends over time and between locations. A total of 2,328 plastic fragments were documented in the ventriculus portion of the gastrointestinal tract, with an average of 9 plastic fragments per bird. The mass, count, and frequency of plastic occurrence (FO) varied by location, with higher plastic burdens but lower FO in South Atlantic individuals from the breeding colonies. No fragments of the same size or morphology were found in the primary forage fish prey, the sand lance, ( Ammodytes spp. , n = 202) that supports Great Shearwaters in Massachusetts Bay, USA, suggesting the birds directly ingest the bulk of their plastic loads rather than accumulating via trophic transfer. Fourier-transform infrared spectroscopy indicated that low- and high-density polyethylene were the most common polymers ingested, within all years and locations. Individuals from the South Atlantic contained a higher proportion of larger plastic items and fragments compared to juveniles and non-breeding adults from the NW Atlantic, possibly due to increased use of remote, pelagic areas subject to reduced inputs of smaller, more diverse, and potentially less buoyant plastics found adjacent to coastal margins. Different signatures of polymer type, size, and category between similar life stages at different locations suggests rapid turnover of ingested plastics commensurate with migratory stage and location, though more empirical evidence is needed to ground-truth this hypothesis. This work is the first to comprehensively measure the accumulation of ingested plastics by Great Shearwaters over the last decade and across multiple locations spanning their yearly trans-equatorial migration cycle, and underscores their utility as sentinels of plastic pollution in Atlantic ecosystems., Competing Interests: 6 Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: The main indications for laparoscopic cholecystectomy are stone-related diseases in adults. With a normal abdominal ultrasound (US), a hepatobiliary iminodiacetic acid (HIDA) scan with ejection fraction (EF) is recommended to evaluate gallbladder function. Biliary dyskinesia or low gallbladder EF (EF < 35%) is a recognized indication for cholecystectomy. Recent articles report long-term resolution of symptoms in children with high EFs on the HIDA scan. The purpose of this study is to evaluate the response of patients with biliary colic and hyperkinetic gallbladder to cholecystectomy. We suggest that laparoscopic cholecystectomy might be a considerable surgical option in a subset of the adult population whose workup for food-related biliary abdominal pain is negative except for the high-value EF on HIDA scan., Methods: Data were consecutively collected from all patients who underwent laparoscopic cholecystectomy between June 2012 and June 2019 at a single institution. Cases were identified using Current Procedural Terminology codes. Patients older than 17 years of age with the negative US (no stone, no sludge, no gallbladder wall thickening) and EF greater than 80% on cholecystokinin (CCK)-HIDA scan were included in this study. All patients were seen at 2 weeks and 10-16 months after surgeries., Results: Over 7 years from June 2012 until June 2019, of 2116 patients who underwent laparoscopic cholecystectomy, 59 patients (2.78%) met study criteria. Postprandial abdominal pain was the most common symptom (43, 72.90%) followed by nausea/vomiting. Forty-seven patients (74.6%) had a reproduction of symptoms with CCK infusion. The average EF was 88.51%. Final pathology showed chronic cholecystitis in 41 (69.5%) patients, cholesterolosis in 13 (22%), polyp in 2 (3.4%). Thirty-six (61%) patients had complete resolution of symptoms, 9 (15%) patients had partial resolution, and 14 (24%) patients had no change. There was a complete resolution rate of 61% and an improvement rate of 76%., Conclusions: In patients with biliary symptoms, negative ultrasound, and elevated EF on HIDA scan (EF > 80%), laparoscopic cholecystectomy led to a significant rate of symptomatic relief. Interestingly, 94% also had unexpected pathologic findings. This disease process requires further analysis, but this could represent a new indication for laparoscopic cholecystectomy in the adult population.

This paper presents an autonomous method of collecting data for Visible Light Positioning (VLP) and a comprehensive investigation of VLP using a large set of experimental data. Received Signal Strength (RSS) data are efficiently collected using a novel method that utilizes consumer grade Virtual Reality (VR) tracking for accurate ground truth recording. An investigation into the accuracy of the ground truth system showed median and 90th percentile errors of 4.24 and 7.35 mm, respectively. Co-locating a VR tracker with a photodiode-equipped VLP receiver on a mobile robotic platform allows fingerprinting on a scale and accuracy that has not been possible with traditional manual collection methods. RSS data at 7344 locations within a 6.3 × 6.9 m test space fitted with 11 VLP luminaires is collected and has been made available for researchers. The quality and the volume of the data allow for a robust study of Machine Learning (ML)- and channel model-based positioning utilizing visible light. Among the ML-based techniques, ridge regression is found to be the most accurate, outperforming Weighted k Nearest Neighbor, Multilayer Perceptron, and random forest, among others. Model-based positioning is more accurate than ML techniques when a small data set is available for calibration and training. However, if a large data set is available for training, ML-based positioning outperforms its model-based counterparts in terms of localization accuracy.

Background : The Global Burden of Disease (GBD) approach estimates disease burden by combining fatal (years of life lost) and non-fatal burden prevalence-based years of life lived with disability (PYLDs) estimates. Although South Africa has data to estimate mortality, prevalence data to estimate non-fatal burden are sparse. PYLD estimates from the GBD study for South Africa can potentially be used. However, there is a divergence in mortality estimates for South Africa between the second South African National Burden of Disease (SANBD2) and 2013 GBD studies. Objective : We investigated the feasibility of utilising GBD PYLD estimates for stroke and diabetes by exploring different disease modelling scenarios. Method : DisMod II software-generated South African stroke and diabetes PYLDs for 2010 from models using local epidemiological parameters and demographic data for people 20-79 years old. We investigated the impact on PYLD estimates of 1) differences in the cause-of-death envelope, 2) differences in the cause-specific mortality estimates (increase/decrease by 15% for stroke and 30% for diabetes), and 3) difference using local disease parameters compared to other country or region parameters. Differences were expressed as ratios, average ratios and ratio ranges. Results : Using the GBD cause-of-death envelope (16% more deaths than SANBD2) and holding other parameters constant yielded age-specific ratios of PYLDs for stroke and diabetes ranging between 0.89 and 1.07 (average 0.98) for males. Similar results were observed for females. A 15% change in age-specific stroke mortality showed little difference in the ratio comparison of PYLDs (range 0.98-1.02) while a 30% change in age-specific diabetes mortality resulted in a ratio range of 0.96-1.07 for PYLDs depending on age. Conclusion : This study showed that GBD non-fatal burden estimates (PYLDs) can be used for stroke and diabetes non-fatal burden in the SANBD2 study.

Background: Intensified viral load monitoring for pregnant and breastfeeding women has been proposed to help address concerns around antiretroviral therapy (ART) adherence, viraemia and transmission risk, but there have been no systematic evaluations of existing policies., Methods: We used an individual Monte Carlo simulation to describe longitudinal ART adherence and viral load from conception until 2 years' postpartum. We applied national and international guidelines for viral load monitoring to the simulated data. We compared guidelines on the percentage of women receiving viral load monitoring and the percentage of women monitored at the time of elevated viral load., Results: Coverage of viral load monitoring in pregnancy and breastfeeding varied markedly, with between 14% and 100% of women monitored antenatally and 38-98% monitored during breastfeeding. Specific recommendations for testing at either a fixed gestation or a short, fixed period after ART initiation achieved more than 95% testing in pregnancy but this was much lower (14-83%) among guidelines with no special stipulations. By the end of breastfeeding, only a small proportion of simulated episodes of elevated viral load more than 1000 copies/ml were successfully detected by monitoring (range, 20-50%)., Discussion: Although further research is needed to understand optimal viral load frequency and timing in this population, these results suggest that current policies yield suboptimal detection of elevated viral load in pregnant and breastfeeding women.

Introduction: HIV viral load (VL) is accepted as a key biomarker in HIV transmission and pathogenesis. This paper presents a review of the role of VL testing in mathematical models for HIV prevention and treatment., Methods: A search for simulation models of HIV was conducted in PubMed, yielding a total of 1210 studies. Publications before the year 2000, studies involving animals and analyses that did not use mathematical simulations were excluded. The full text of eligible articles was sourced and information about the intervention and population being modelled, type of modelling approach and disease monitoring strategy was extracted., Results and Discussion: A total of 279 studies related to HIV simulation models were included in the review, though only 17 (6%) included consideration of VL or VL testing and were evaluated in detail. Within the studies that included assessment of VL, routine monitoring was the focus, and usually in comparison to alternate monitoring strategies such as clinical or CD4 count-based monitoring. The majority of remaining models focus on the impact or delivery of antiretroviral therapy (n=68; 27%), pre-exposure prophylaxis (n=28; 11%) and/or HIV testing (n=24; 9%) on population estimates of HIV epidemiology and exclude consideration of VL. Few studies investigate or compare alternate VL monitoring frequencies, and only a small number of studies overall (3%) include consideration of vulnerable population groups such as pregnant women or infants., Conclusions: There are very few simulations of HIV treatment or prevention that include VL measures, despite VL being recognised as the key determinant of both transmission and treatment outcomes. With growing emphasis on VL monitoring as key tool for population-level HIV control, there is a clear need for simulations of HIV epidemiology based on VL., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Widespread access to antiretroviral therapy (ART) has substantially increased life expectancy in sub-Saharan African countries. As a result, the rates of comorbidities and use of co-medications among people living with HIV are increasing, necessitating a sound understanding of drug-drug interactions (DDIs). We aimed to assess the prevalence and management of DDIs with ART in a rural Tanzanian setting., Methods: We included consenting HIV-positive adults initiating ART in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) between January 2013 and December 2016. DDIs were classified using www.hiv-druginteractions.org as red (contra-indicated), amber (potential clinical relevance requiring dosage adjustment/monitoring), yellow (weak clinical significance unlikely to require further management) or green (no interaction). We assessed management of amber DDIs by evaluating monitoring of laboratory or clinical parameters, or changes in drug dosages., Results: Of 2069 participants, 1945 (94%) were prescribed at least one co-medication during a median follow-up of 1.8 years. Of these, 645 (33%) had at least one potentially clinically relevant DDI, with the highest grade being red in nine (< 1%) and amber in 636 (33%) participants. Of the 23 283 prescriptions, 19 (< 1%) and 1745 (7%) were classified as red and amber DDIs, respectively. Overall, 351 (2%) prescriptions were red DDIs or not appropriately managed amber DDIs., Conclusions: Co-medication use was common in this rural sub-Saharan cohort. A third of participants had DDIs requiring further management. Of the 9% of participants with not appropriately managed DDIs, most were with cardiovascular and analgesic drugs. This highlights the importance of physicians' awareness of DDIs for their recognition and management., (© 2019 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Purpose: The use of cumulative measures of exposure to raised HIV viral load (viremia copy-years) is increasingly common in HIV prevention and treatment epidemiology due to the association of long-term elevated viral load with more rapid progression to disease. We sought to estimate the magnitude and direction of bias in a cumulative measure of viremia caused by different frequency of sampling and duration of follow-up., Methods: We simulated longitudinal viral load measures and reanalyzed cohort study data sets with longitudinal viral load measurements under different sampling strategies to estimate cumulative viremia., Results: In both simulated and observed data, estimates of cumulative viremia by the trapezoidal rule show systematic upward bias when there are fewer sampling time points and/or increased duration between sampling time points, compared with estimation of full time series. Absolute values of cumulative viremia vary appreciably by the patterns of viral load over time, even after adjustment for total duration of follow-up., Conclusions: Sampling bias due to differential frequency of sampling appears extensive and of meaningful magnitude in measures of cumulative viremia. Cumulative measures of viremia should be used only in studies with sufficient frequency of viral load measures and always as relative measures., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To present our technique of robotic retrorectus parastomal hernia repair., Background: Parastomal hernias represent a significant problem with high recurrence and long-term complications. An estimated of 120,000 new stomas are created per year with a prevalence of up to 800,000 patients in the U.S. 40-60% of these ostomies will never be reversed. Parastomal hernias cause skin breakdown and make adherence of ostomy appliances difficult, creating the need for frequent bag exchanges. They can also cause pain, bowel obstruction and bowel incarceration or strangulation. All of these factors affect quality of life and represent a significant burden to our health care system. There is no definitive gold-standard technique to repair parastomal hernias. The use of prosthesis decreases the recurrence rates, yet using prosthetic material can result in long-term complications. Surgeons have developed techniques of pre-peritoneal mesh placement to provide long-lasting repairs and at the same time prevent complications associated with the mesh. We believe that a robotic retro-rectus approach provides a secure repair and avoids leaving prosthetic material in the abdominal cavity at the same time., Methods: A three-arm technique is used, inserting ports opposite to the target anatomy. Hernia contents are reduced protecting the ostomy loop and mesentery. The contralateral retro-rectus space is entered and this space is developed extensively across the midline and around the ostomy. The hernia defect is approximated. Concomitant ventral hernias are also repaired. A polypropylene mesh with a keyhole is used and wide coverage is ensured in all directions. The leaflets of the mesh are stitched together and the mesh is sutured to the abdominal wall. Finally, the retro-rectus space is closed., Results: We have performed this technique in two patients safely and at 1-year follow-up there were no recurrences in either. On conclusion, this is a novel minimally invasive technique to repair parastomal hernias that provides wide coverage of the defect and avoids leaving mesh intraperitoneally.

Importance: Studies of socioeconomic status and neurodevelopmental outcome in very preterm neonates have not sensitively accounted for brain injury., Objective: To determine the association of brain injury and maternal education with motor and cognitive outcomes at age 4.5 years in very preterm neonates., Design, Setting, and Participants: Prospective cohort study of preterm neonates (24-32 weeks' gestation) recruited August 16, 2006, to September 9, 2013, at British Columbia Women's Hospital in Vancouver, Canada. Analysis of 4.5-year outcome was performed in 2018., Main Outcomes and Measures: At age 4.5 years, full-scale IQ assessed using the Wechsler Primary and Preschool Scale of Intelligence, Fourth Edition, and motor outcome by the percentile score on the Movement Assessment Battery for Children, Second Edition., Results: Of 226 survivors, neurodevelopmental outcome was assessed in 170 (80 [47.1%] female). Based on the best model to assess full-scale IQ accounting for gestational age, standardized β coefficients demonstrated the effect size of maternal education (standardized β = 0.21) was similar to that of white matter injury volume (standardized β = 0.23) and intraventricular hemorrhage (standardized β = 0.23). The observed and predicted cognitive scores in preterm children born to mothers with postgraduate education did not differ in those with and without brain injury. The best-performing model to assess for motor outcome accounting for gestational age included being small for gestational age, severe intraventricular hemorrhage, white matter injury volume, and chronic lung disease., Conclusions and Relevance: At preschool age, cognitive outcome was comparably associated with maternal education and neonatal brain injury. The association of brain injury with poorer cognition was attenuated in children born to mothers of higher education level, suggesting opportunities to promote optimal outcomes.

Background: Reviews on alcohol use in transplant recipients focus on liver recipients and their risk of post-transplant rejection, but do not assess alcohol use in kidney, heart, or lung transplant recipients. This systematic review and meta-analysis aims to synthesize the evidence on correlates and outcomes of any alcohol use and at-risk drinking after solid organ transplantation (Tx)., Methods: We searched 4 databases for quantitative studies in adult heart, liver, kidney and lung Tx recipients, investigating associations between post-Tx alcohol use and correlates and/or clinical, economic or quality of life outcomes. Paper selection, data extraction and quality assessment were performed by 2 reviewers independently. A pooled odds ratio (OR) was computed for each correlate/outcome reported ≥5 times., Results: Of the 5331 studies identified, 76 were included in this systematic review (93.3% on liver Tx; mean sample size 148.9 (SD = 160.2); 71.9% male; mean age 48.9 years (SD = 6.5); mean time post-Tx 57.7 months (SD = 23.1)). On average, 23.6% of patients studied used alcohol post-transplant. Ninety-three correlates of any post-Tx alcohol use were identified, and 9 of the 19 pooled ORs were significantly associated with a higher odds for any post-Tx alcohol use: male gender, being employed post-transplant, smoking pre-transplant, smoking post-transplant, a history of illicit drug use, having first-degree relatives who have alcohol-related problems, sobriety <6 months prior to transplant, a history of psychiatric illness, and having received treatment for alcohol-related problems pre-transplant. On average 15.1% of patients had at-risk drinking. A pooled OR was calculated for 6 of the 47 correlates of post-Tx at risk drinking investigated, of which pre-transplant smoking was the only correlate being significantly associated with this behavior. None of the outcomes investigated were significantly associated with any use or at-risk drinking., Conclusion: Correlates of alcohol use remain under-investigated in solid organ transplant recipients other than liver transplantation. Further research is needed to determine whether any alcohol use or at-risk drinking is associated with poorer post-transplant outcomes. Our meta-analysis highlights avenues for future research of higher methodological quality and improved clinical care., Protocol Registration: PROSPERO protocol CRD42015003333., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Previous epidemiological studies investigating modification of organophosphate (OP) neurotoxicity by xenobiotic metabolizing enzymes (XMEs) polymorphisms have produced inconsistent results., Methods: A cross-sectional study of 301 emerging farmers was conducted. Neurotoxicity testing included forward and backward recall, digit span, and vibration sensitivity testing. Questionnaire data included demography, potential confounders, and work history of pesticide exposures. Genomic DNA was analyzed from study participants for DNA variants of two glutathione S-transferases (GSTM1 and GSTT1), N-acetyltransferase 2 (NAT2), and Paraoxonase 1 (PON1)., Results: There was evidence of OP pesticide neurotoxicity modification by rs1799931 (NAT2), rs662 (PON1), and the null allele of GSTM1 in multivariate analysis. The strongest evidence of modification was observed for rs1799931 (NAT2) on the relationship between pesticide poisoning and impaired vibration sense., Conclusions: DNA variants of NAT2, PON1, and GSTM1 may modify OP neurotoxicity, and this requires further exploration., (© 2017 Wiley Periodicals, Inc.)

Introduction: HIV viral load (VL) monitoring is a central tool to evaluate ART effectiveness and transmission risk. There is a global movement to expand VL monitoring following recent recommendations from the World Health Organization (WHO), but there has been little research into VL monitoring in pregnant women. We investigated one important question in this area: when and how frequently VL should be monitored in women initiating ART during pregnancy to predict VL at the time of delivery in a simulated South African population., Methods: We developed a mathematical model simulating VL from conception through delivery using VL data from the Maternal and Child Health - Antiretroviral Therapy (MCH-ART) cohort. VL was modelled based on three major compartments: pre-ART VL, viral decay immediately after ART initiation and viral maintenance (including viral suppression and viraemic episodes). Using this simulation, we examined the performance of various VL monitoring schema in predicting elevated VL at delivery., Results and Discussion: If WHO guidelines for non-pregnant adults were used, the majority of HIV-infected pregnant women (69%) would not receive a VL test during pregnancy. Most models that based VL monitoring in pregnancy on the time elapsed since ART initiation (regardless of gestation) performed poorly (sensitivity <50%); models that based VL measures in pregnancy on the woman's gestation (regardless of time on ART) appeared to perform better overall (sensitivity >60%). Across all permutations, inclusion of pre-ART VL values had a negligible impact on predictive performance (improving test sensitivity and specificity <6%). Performance of VL monitoring in predicting VL at delivery generally improved at later gestations, with the best performing option a single VL measure at 36 weeks' gestation., Conclusions: Development and evaluation of a novel simulation model suggests that strategies to measure VL relative to gestational age may be more useful than strategies relative to duration on ART, in women initiating ART during pregnancy, supporting better integration of maternal and HIV health services. Testing turnaround times require careful consideration, and point-of-care VL testing may be the best approach for measuring VL at delivery. Broadening the scope of this simulation model in the light of current scale up of VL monitoring in high burden countries is important., (© 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Objectives: Self-reported adherence assessment in HIV-infected patients on antiretroviral therapy (ART) is challenging and may overestimate adherence. The aim of this study was to improve the ability of health care providers to elicit patients' reports of nonadherence using a "patient-centred" approach in a rural sub-Saharan African setting., Methods: A prospective interventional cohort study of HIV-infected patients on ART for ≥ 6 months attending an HIV clinic in rural Tanzania was carried out. The intervention consisted of a 2-day workshop for health care providers on patient-centred communication and the provision of an adherence assessment checklist for use in the consultations. Patients' self-reports of nonadherence (≥ 1 missed ART dose/4 weeks), subtherapeutic plasma ART concentrations (< 2.5th percentile of published population-based pharmacokinetic models), and virological and immunological failure according to the World Health Organization definition were assessed before and after (1-3 and 6-9 months after) the intervention., Results: Before the intervention, only 3.3% of 299 patients included in the study reported nonadherence. Subtherapeutic plasma ART drug concentrations and virological and immunological failure were recorded in 6.5%, 7.7% and 14.5% of the patients, respectively. Two months after the intervention, health care providers detected significantly more patients reporting nonadherence compared with baseline (10.7 vs. 3.3%, respectively; P < 0.001), decreasing to 5.7% after 6-9 months. A time trend towards higher drug concentrations was observed for efavirenz but not for other drugs. The virological failure rate remained unchanged whereas the immunological failure rate decreased from 14.4 to 8.7% at the last visit (P = 0.002)., Conclusions: Patient-centred communication can successfully be implemented with a simple intervention in rural Africa. It increases the likelihood of HIV-infected patients reporting problems with adherence to ART; however, sustainability remains a challenge., (© 2017 The Authors HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: Antibiotic use in early life has been linked to disruptions in the microbiome. Such changes can disturb immune system development. Differences have been observed in the microbiota of children with and without allergies, but there have been few studies on antibiotic use and allergic disease., Objective: We evaluated associations of early-life antibiotic use with subsequent occurrence of food allergy and other allergies in childhood using electronic health record data., Methods: We used longitudinal data on 30 060 children up to age 7 years from Geisinger Clinic's electronic health record to conduct a sex- and age-matched case-control study to evaluate the association between antibiotic use and milk allergy, non-milk food allergies, and other allergies. For each outcome, we estimated conditional logistic regression models adjusting for race/ethnicity, history of Medical Assistance, and mode of birth delivery. Models were repeated separately for penicillins, cephalosporins and macrolides., Results: There were 484 milk allergy cases, 598 non-milk food allergy cases and 3652 other allergy cases. Children with three or more antibiotic orders had a greater odds of milk allergy (Odds Ratio; 95% Confidence interval) (1.78; 1.28-2.48), non-milk food allergy (1.65; 1.27-2.14), and other allergies (3.07; 2.72-3.46) compared with children with no antibiotic orders. Associations were strongest at younger ages and differed by antibiotic class., Conclusions and Clinical Relevance: We observed associations between antibiotic orders and allergic diseases, providing evidence of a potentially modifiable clinical practice associated with paediatric allergic disease. Differences by antibiotic class should be further explored, as this knowledge could inform paediatric treatment decisions., (© 2016 John Wiley & Sons Ltd.)

Background: The poor health of South Africans is known to be associated with a quadruple disease burden. In the second National Burden of Disease (NBD) study, we aimed to analyse cause of death data for 1997-2012 and develop national, population group, and provincial estimates of the levels and causes of mortality., Method: We used underlying cause of death data from death notifications for 1997-2012 obtained from Statistics South Africa. These data were adjusted for completeness using indirect demographic techniques for adults and comparison with survey and census estimates for child mortality. A regression approach was used to estimate misclassified HIV/AIDS deaths and so-called garbage codes were proportionally redistributed by age, sex, and population group population group (black African, Indian or Asian descent, white [European descent], and coloured [of mixed ancestry according to the preceding categories]). Injury deaths were estimated from additional data sources. Age-standardised death rates were calculated with mid-year population estimates and the WHO age standard. Institute of Health Metrics and Evaluation Global Burden of Disease (IHME GBD) estimates for South Africa were obtained from the IHME GHDx website for comparison., Findings: All-cause age-standardised death rates increased rapidly since 1997, peaked in 2006 and then declined, driven by changes in HIV/AIDS. Mortality from tuberculosis, non-communicable diseases, and injuries decreased slightly. In 2012, HIV/AIDS caused the most deaths (29·1%) followed by cerebrovascular disease (7·5%) and lower respiratory infections (4·9%). All-cause age-standardised death rates were 1·7 times higher in the province with the highest death rate compared to the province with the lowest death rate, 2·2 times higher in black Africans compared to whites, and 1·4 times higher in males compared with females. Comparison with the IHME GBD estimates for South Africa revealed substantial differences for estimated deaths from all causes, particularly HIV/AIDS and interpersonal violence., Interpretation: This study shows the reversal of HIV/AIDS, non-communicable disease, and injury mortality trends in South Africa during the study period. Mortality differentials show the importance of social determinants, raise concerns about the quality of health services, and provide relevant information to policy makers for addressing inequalities. Differences between GBD estimates for South Africa and this study emphasise the need for more careful calibration of global models with local data., Funding: South African Medical Research Council's Flagships Awards Project., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

Places where we buy food influence dietary patterns, making local food environments a good example of a mass influence on population diets. Cross-cultural studies, using reliable methods, may help understanding the relationship between food environments and diet-related health outcomes. We aimed to understand cross-national differences in the local food environment between Madrid and Baltimore by comparing an average neighborhood in each city in terms of food store types, healthy food availability, and residents' pedestrian access. During 2012-2013, we assessed one neighborhood (~15,000 residents) in each city selecting median areas in terms of socio-demographic characteristics (segregation, education, aging, and population density). We collected on-field data on (a) number and types of all food stores, (b) overall healthy food availability and (c) specific availability of fruits & vegetables. Throughout a street network analysis (200m, 400m and 800m) of food stores with high healthy food availability, we estimated residents' pedestrian accessibility. We found 40 stores in Madrid and 14 in Baltimore. Small food stores carrying fresh foods in Madrid contrasted with the high presence of corner and chain convenience stores in Baltimore. In Madrid, 77% of the residents lived within less than 200m from a food store with high healthy food availability. In contrast, 95% of Baltimore's residents lived further than 400m from these stores. Our results may help promoting interventions from local city agencies to allocate resources to existing small-sized food stores, and to improve walkable urban environments. These actions may influence food choices, especially for those residents lacking access to private vehicles., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: The epidemiological and clinical determinants of hepatitis delta virus (HDV) infection in Sub-Saharan Africa are ill-defined. The prevalence of HDV infection was determined in HIV/hepatitis B virus (HBV) co-infected individuals in rural Tanzania., Methods: All HBV-infected adults under active follow-up in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) were screened for anti-HDV antibodies. For positive samples, a second serological test and nucleic acid amplification were performed. Demographic and clinical characteristics at initiation of antiretroviral therapy (ART) were compared between anti-HDV-negative and -positive patients., Results: Among 222 HIV/HBV co-infected patients on ART, 219 (98.6%) had a stored serum sample available and were included in the study. Median age was 37 years, 55% were female, 46% had World Health Organization stage III/IV HIV disease, and the median CD4 count was 179 cells/μl. The prevalence of anti-HDV positivity was 5.0% (95% confidence interval 2.8-8.9%). There was no significant predictor of anti-HDV positivity. HDV could not be amplified in any of the anti-HDV-positive patients and the second serological test was negative in all of them., Conclusions: No confirmed case of HDV infection was found among over 200 HIV/HBV co-infected patients in Tanzania. As false-positive serology results are common, screening results should be confirmed with a second test., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background/objectives: Antibiotics are commonly prescribed for children. Use of antibiotics early in life has been linked to weight gain but there are no large-scale, population-based, longitudinal studies of the full age range among mainly healthy children., Subjects/methods: We used electronic health record data on 163 820 children aged 3-18 years and mixed effects linear regression to model associations of antibiotic orders with growth curve trajectories of annual body mass index (BMI) controlling for confounders. Models evaluated three kinds of antibiotic associations-reversible (time-varying indicator for an order in year before each BMI), persistent (time-varying cumulative orders up to BMIj) and progressive (cumulative orders up to prior BMI (BMIj-1))-and whether these varied by age., Results: Among 142 824 children under care in the prior year, a reversible association was observed and this short-term BMI gain was modified by age (P<0.001); effect size peaked in mid-teen years. A persistent association was observed and this association was stronger with increasing age (P<0.001). The addition of the progressive association among children with at least three BMIs (n=79 752) revealed that higher cumulative orders were associated with progressive weight gain; this did not vary by age. Among children with an antibiotic order in the prior year and at least seven lifetime orders, antibiotics (all classes combined) were associated with an average weight gain of approximately 1.4 kg at age 15 years. When antibiotic classes were evaluated separately, the largest weight gain at 15 years was associated with macrolide use., Conclusions: We found evidence of reversible, persistent and progressive effects of antibiotic use on BMI trajectories, with different effects by age, among mainly healthy children. The results suggest that antibiotic use may influence weight gain throughout childhood and not just during the earliest years as has been the primary focus of most prior studies.

Background: Childhood sports-related head trauma is common, frequently leading to emergency department (ED) visits. We describe the spectrum of these injuries and trends in computed tomography (CT) use in the Pediatric Emergency Care Applied Research Network., Methods: This was a secondary analysis of a large prospective cohort of children with head trauma in 25 Pediatric Emergency Care Applied Research Network EDs between 2004 and 2006. We described and compared children 5 to 18 years old by CT rate, traumatic brain injury (TBI) on CT, and clinically important TBI (ciTBI). We used multi-variable logistic regression to compare CT rates, adjusting for clinical severity. Outcomes included frequency of CT, TBIs on CT, and ciTBIs (defined by [a] death, [b] neurosurgery, [c] intubation>24 hours, or [d] hospitalization for ≥2 nights)., Findings: A total of 3289 (14%) of 23082 children had sports-related head trauma. Two percent had Glasgow Coma Scale scores less than 14. 53% received ED CTs, 4% had TBIs on CT, and 1% had ciTBIs. Equestrians had increased adjusted odds (1.8; 95% confidence interval [CI], 1.0-3.0]) of CTs; the rate of TBI on CT was 4% (95% CI, 3%-5%). Compared with team sports, snow (adjusted odds ratio, 4.1; 95% CI 1.5-11.4) and nonmotorized wheeled (adjusted odds ratio, 12.8; 95% CI, 5.5-32.4) sports had increased adjusted odds of ciTBIs., Conclusions: Children with sports-related head trauma commonly undergo CT. Only 4% of those imaged had TBIs on CT. Clinically important TBIs occurred in 1%, with significant variation by sport. There is an opportunity for injury prevention efforts in high-risk sports and opportunities to reduce CT use in general by use of evidence-based prediction rules. What is known about this subject: Pediatric sports-related head injuries are a common and increasingly frequent ED presentation, as is the use of CT in their evaluation. Little is known about TBIs resulting from different types of sports activities in children. What this study adds to existing knowledge: This study broadens the understanding of the epidemiology of Pediatric TBIs resulting from different sports activities through a prospective assessment of frequency and severity of ciTBIs and ED CT use in a large cohort of head-injured children in a network of pediatric EDs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background and Objective: Children and adolescents with minor blunt head trauma and isolated skull fractures are often admitted to the hospital. The objective of this study was to describe the injury circumstances and frequency of clinically important neurologic complications among children with minor blunt head trauma and isolated linear skull fractures., Methods: This study was a planned secondary analysis of a large prospective cohort study in children <18 years old with blunt head trauma. Data were collected in 25 emergency departments. We analyzed patients with Glasgow Coma Scale scores of 14 or 15 and isolated linear skull fractures. We ascertained acute neurologic outcomes through clinical information collected during admission or via telephone or mail at least 1 week after the emergency department visit., Results: In the parent study, we enrolled 43,904 children (11,035 [25%] <2 years old). Of those with imaging studies, 350 had isolated linear skull fractures. Falls were the most common injury mechanism, accounting for 70% (81% for ages <2 years old). Of 201 hospitalized children, 42 had computed tomography or MRI repeated; 5 had new findings but none required neurosurgical intervention. Of 149 patients discharged from the hospital, 20 had repeated imaging, and none had new findings., Conclusions: Children with minor blunt head trauma and isolated linear skull fractures are at very low risk of evolving other traumatic findings noted in subsequent imaging studies or requiring neurosurgical intervention. Hospital admission for neurologically normal children with isolated linear skull fractures after minor blunt head trauma for monitoring is typically unnecessary., (Copyright © 2015 by the American Academy of Pediatrics.)

In the era of antiretroviral therapy (ART) as prevention for transmission of HIV as well as treatment for HIV-positive individuals irrespective of CD4 cell counts, the importance of adherence has grown. Although adherence is not the only determinant of treatment success, it is one of the only modifiable risk factors. Treatment failure reduces future treatment options and therefore long-term clinical success as well as increases the possibility of developing drug resistant mutations. Drug-resistant strains of HIV can then be transmitted to uninfected or drug-naïve individuals limiting their future treatment options, making adherence an important public-health topic, especially in resource-limited settings. Adherence should be monitored as a part of routine clinical care; however, no gold standard for assessment of adherence exists. For use in daily clinical practice, self-report is the most likely candidate for widespread use due to its many advantages over other measurement methods, such as low cost and ease of administration. Asking individuals about their adherence behaviour has been shown to yield valid and predictive data - well beyond the mere flip of a coin. However, there is still work to be done. This article reviews the literature and evidence on self-reported adherence, identifies gaps in adherence research, and makes recommendations for clinicians on how to best utilise self-reported adherence data to support patients in daily clinical practice.

Purpose: About 5% of pediatric intracranial germ cell tumors and 20% of non-germinomatous germ cell tumors (NGGCT) progress to growing teratoma syndrome (GTS) following chemoradiotherapy. The growing teratoma is thought to arise from the chemotherapy-resistant, teratomatous portion of a germ cell tumor and is commonly benign but may undergo malignant transformation., Methods: Two pediatric patients whose intracranial NGGCTs progressed to growing teratomas during chemotherapy and later transformed to secondary malignant tumors after partial resection and radiation therapy (RT)., Results: Both tumors were diagnosed by MRI scans and elevated serum and CSF markers. Following normalization of tumor markers with chemotherapy and initial decrease in tumor volume, subsequent imaging showed regrowth during chemotherapy with pathology revealing benign teratoma. RT was administered. Several years following this treatment, further growth was seen with pathology indicating malignant carcinoma in one patient and malignant rhabdomyosarcoma in the other. The patient with carcinoma received palliative care while the patient with the sarcoma received further resection, intensive chemotherapy, and an autologous stem cell transplant and is currently in remission, 36 months since malignant transformation., Conclusion: Malignant transformation of presumed residual teratoma has been seldom reported. Treatment of NGGCT involves platinum-based chemotherapy with craniospinal RT and boost to the primary site, with cure rates of around 80%. Teratomas are characteristically chemotherapy and RT resistant and are treated surgically. In the event that residual or growing teratoma is suspected, a complete resection should be considered early in the management as there is a risk of malignant transformation of residual teratoma.

Induced abortion is a controversial topic among obstetricians. "100 Professors" extolled the benefits of elective abortion in a Clinical Opinion published in AJOG. However, scientific balance requires the consideration of a second opinion from practitioners who care for both patients, and who recognize the humanity of both. Alternative approaches to the management of a problem pregnancy, as well as short and long term risks to women as published in the peer reviewed medical literature are discussed. Maintaining a position of "pro-choice" requires that practitioners also be given a right to exercise Hippocratic principles in accordance with their conscience.

Purpose: Little is known about what triggers an episode of low back pain (LBP) in those presenting to primary care. Previous studies of risk factors have focused on specific occupational settings and work conditions. No study has asked primary care clinicians to consider what triggers an episode of sudden-onset LBP in patients presenting to them for care. The purpose of this study, therefore, was to describe the short- and long-term factors that primary care clinicians consider important in triggering a sudden episode of acute LBP., Methods: One hundred and thirty-one primary care clinicians who were recruiting patients with LBP to a large observational study were invited to participate. A questionnaire was designed to obtain information about the clinician's characteristics, profession and clinical experience. We also asked clinicians to nominate the five short- and five long-term exposure factors, most likely to trigger a sudden episode of acute LBP, based on their experience. Descriptive statistics and frequency distributions were used to describe clinician's characteristics and the frequencies of the main risk factor categories were reported., Results: Based on the views of 103 primary care clinicians, biomechanical risk factors appear to be the most important short-term triggers (endorsed by 89.3% of clinicians) and long-term triggers (endorsed by 54.2% of clinicians) for a sudden episode of acute LBP. Individual risk factors were endorsed by 39% of clinicians as important long-term triggers, while only 6.4% of clinicians considered them important short-term triggers. Other risk factors, such as psychological/psychosocial and genetic factors, were not commonly endorsed as risk factors for an episode of LBP by primary care clinicians., Conclusions: This study shows that primary care clinicians believe that biomechanical risk factors are the most important short-term triggers, while biomechanical and individual risk factors are the most important long-term triggers for a sudden onset of LBP. However, other risk factors, such as psychological/psychosocial and genetic, were not commonly endorsed as risk factors for an episode of LBP by primary care clinicians. Results of this study are based on primary care clinicians' views and further investigation is needed to test the validity of these suggested risk factors.

Collapsed structures, typically as a result of earthquakes, may result in individuals entrapped by their limbs under heavy structural elements. In addition, access to living persons may be blocked by the deceased. Individuals are often critically ill by the time they are found, and rapid extrication is warranted. This and other factors may necessitate field amputation of an extremity on a living person or dismemberment of the deceased to achieve a rescue. Although case reports have described industrial, mining, and transportation accidents, few discuss this potential in collapsed structures. Also, few specifically outline the indications or the decision process and associated administrative procedures that should be addressed before conducting these procedures. This report presents a review of the literature along with a limited case series. A discussion regarding relevant decision making is provided to encourage the development of protocols. An international consensus statement on these procedures is provided.

Genetic factors, other exposures, individual disease states and allostatic load, psychosocial stress, and socioeconomic position all have the potential to modify the response to environmental exposures. Moreover, many of these modifiers covary with the exposure, leading to much higher risks in some subgroups. These are not theoretical concerns; rather, all these patterns have already been demonstrated in studies of the effects of lead and air pollution. However, recent regulatory impact assessments for these exposures have generally not incorporated these findings. Therefore, differential risk and vulnerability is a critically important but neglected area within risk assessment, and should be incorporated in the future.

Several methodological issues have been identified in analysis of epidemiological data to better assess the distributional effects of exposures and hypotheses about effect modification. We discuss the hierarchical mixed model and some more complex methods. Methods of capturing inequality are a second dimension of risk assessment, and simulation studies are important because plausible choices for air pollution effects and effect modifiers could result in extremely high risks in a small subset of the population. Future epidemiological studies should explore contextual and individual-level factors that might modify these relationships. The Environmental Protection Agency should make this a standard part of their risk assessments whenever the necessary information is available.

The central paradigm of the Environmental Protection Agency is risk assessment. We examined how differential responses across population groups could be better integrated into the environmental risk assessment process, providing tools to achieve greater equity in health status in addition to risk reduction. Such integration was difficult with paradigms like reference dose and was easier with consideration of dose-response curves, which incorporated nontrivial effects observed at low doses for common exposures. We identified 6 assumptions implicit in standard chemical risk assessments that should changed: (1) risk independence, (2) risk averaging, (3) risk nontransferability, (4) risk synchrony, (5) risk accumulation and chaining, and (6) quantification of numbers of persons above certain thresholds or limit values sufficient to characterize risk.

Intramural pregnancies are a rare form of ectopic pregnancy located within the myometrium separate from the endometrial cavity. In an effort to prevent potential complications, diagnosis should be made early when more conservative approaches can be performed to preserve reproductive potential. The diagnosis of ectopic pregnancies can be successfully accomplished through sonography; however, intramural pregnancies may be difficult to diagnose as they can appear similar to other etiologies. We present a unique case of a ruptured intramural pregnancy diagnosed with sonography and pelvic MRI in a patient with tuberous sclerosis. Surgical enucleation of the intramural pregnancy was successfully performed with postoperative resolution of beta hCG levels.

Objectives: A population-based sexual network study was used to identify sexual network structures associated with sexually transmitted infection (STI) risk, and to evaluate the degree to which the use of network-level data furthers the understanding of STI risk., Methods: Participants (n = 655) were from the baseline and 12-month follow-up waves of a 2001-2 population-based longitudinal study of sexual networks among urban African-American adolescents. Sexual network position was characterised as the interaction between degree (number of partners) and two-reach centrality (number of partners' partners), resulting in the following five positions: confirmed dyad, unconfirmed dyad, periphery of non-dyadic component, centre of star-like component and interior of non-star component. STI risk was measured as laboratory-confirmed infection with gonorrhoea and/or chlamydia., Results: Results of logistic regression models with generalised estimating equations showed that being in the centre of a sexual network component increased the odds of infection at least sixfold compared with being in a confirmed dyad. Individuals on the periphery of non-dyadic components were nearly five times more likely to be infected than individuals in confirmed dyads, despite having only one partner. Measuring network position using only individual-based information led to twofold underestimates of the associations between STI risk and network position., Conclusions: These results demonstrate the importance of measuring sexual network structure using network data to fully capture the probability of exposure to an infected partner.

Background: Inadequate availability of healthy foods may be a barrier to achieving recommended diets., Objective: The objective was to study the association between the directly measured availability of healthy foods and diet quality., Design: We conducted a cross-sectional study of 759 participants from the Baltimore site of the Multi-Ethnic Study of Atherosclerosis. Diet was characterized by using a food-frequency questionnaire and summarized by using 2 empirically derived dietary patterns reflecting low- and high-quality diets. For each participant, the availability of healthy foods was directly assessed by using 3 measures: in all food stores within their census tract, in their closest food store, and in all food stores within 1 mile (1.6 km) of their residence., Results: Twenty-four percent of the black participants lived in neighborhoods with a low availability of healthy food compared with 5% of white participants (P < 0.01). After adjustment for age, sex, income, and education, a lower availability of healthy foods in the tract of residence or in the closest store was associated with higher scores on the low-quality dietary pattern (P < 0.05). Less consistent associations were observed for the high-quality dietary pattern., Conclusions: Healthy foods were less available for black participants. Low availability of healthy foods was associated with a lower-quality diet. The extent to which improvements in the availability of healthy foods results in higher-quality diets deserves further investigation.

Uterine perforation by a contraceptive intrauterine device (IUD) is a relatively rare event. These events may result secondary to mechanical force applied during placement (primary perforation) or migration by uterine contractions or surgical manipulation after placement (secondary perforation). A 33-year-old woman with an IUD placed 9 years before admission visited the emergency department with an early pregnancy and a 3-day history of vaginal bleeding. Vaginal examination revealed IUD strings visible at the cervical os, and transvaginal ultrasound confirmed the presence of an IUD in the lower uterine segment and upper cervix. The IUD migrated spontaneously to the fundal myometrium at 15 weeks' gestation. Premature rupture of membranes ensued at 20 weeks' gestation, and, at delivery, the IUD could not be retrieved. Subsequent computed tomography confirmed that the IUD was incompletely embedded in the fundal myometrium and partially extending into the peritoneal cavity. At laparoscopic sterilization 6 weeks later, the IUD had perforated the small bowel, and the device was removed with concomitant bowel repair. This case documents spontaneous migration of a copper IUD from the lower uterine segment through the fundus during early pregnancy and supports removal of asymptomatic ectopic IUDs whenever possible.

In order to develop a rapid inexpensive test for cadmium in rice, we identified an antibody specific for cadmium-EDTA complexes; this antibody binds to cadmium-EDTA with a Kd of approximately 10(-8) M. Although the antibody's cross reactivity to magnesium was minimal (Kd approximately 10(-5) M), the high toxicity of cadmium coupled with the high natural occurrence of magnesium in rice resulted in a situation where magnesium interfered with cadmium determination and resulted in falsely elevated estimates of cadmium. Fortunately, the formation constant of EDTA for cadmium is approximately 5 x 10(7) times higher (at pH 7) than the formation constant of EDTA for magnesium, and we were able to eliminate the magnesium interference by judicious selection of the EDTA concentration used in the assay. The resulting equilibria are complex, but we show that a relatively simple two-step model in which cadmium and magnesium compete for EDTA followed by cadmium-EDTA and magnesium-EDTA competing for antibody provided a good fit to the measured data. These analyses enabled appropriate selection of the optimum EDTA concentration for an immunoassay with improved selectivity.