A Community-Driven Framework to Prioritize the Use of Donated Human Biological Materials in the Context of HIV Cure-Related Research at the End of Life

Initiated in 2017 after extensive community engagement, the Last Gift program enrolls altruistic volunteers willing to donate their cells and tissues at the end of life to allow studies on HIV reservoir dynamics across anatomical sites. As the Last Gift team received tissue requests outside the scope of HIV cure research, we noticed the absence of guiding frameworks to help prioritize the use of altruistically donated human biological materials. In this commentary, we present a proposed framework for prioritizing the use of donated human biological materials within and outside the end-of-life (EOL) HIV cure research context, using the Last Gift study as an example. First, we discuss regulatory and policy considerations, and highlight key ethical values to guide prioritization decisions. Second, we present our prioritization framework and share some of our experiences prioritizing requests for donated human biological materials within and outside EOL HIV cure research.

Prepregnancy obesity is associated with cognitive outcomes in boys in a low-income, multiethnic birth cohort

Background Maternal obesity and high gestational weight gain (GWG) disproportionally affect low-income populations and may be associated with child neurodevelopment in a sex-specific manner. We examined sex-specific associations between prepregnancy BMI, GWG, and child neurodevelopment at age 7. Methods Data are from a prospective low-income cohort of African American and Dominican women (n = 368; 44.8% male offspring) enrolled during the second half of pregnancy from 1998 to 2006. Neurodevelopment was measured using the Wechsler Intelligence Scale for Children (WISC-IV) at approximately child age 7. Linear regression estimated associations between prepregnancy BMI, GWG, and child outcomes, adjusting for race/ethnicity, marital status, gestational age at delivery, maternal education, maternal IQ and child age. Results Overweight affected 23.9% of mothers and obesity affected 22.6%. At age 7, full-scale IQ was higher among girls (99.7 ± 11.6) compared to boys (96.9 ± 13.3). Among boys, but not girls, prepregnancy overweight and obesity were associated with lower full-scale IQ scores [overweight β: − 7.1, 95% CI: (− 12.1, − 2.0); obesity β: − 5.7, 95% CI: (− 10.7, − 0.7)]. GWG was not associated with full-scale IQ in either sex. Conclusions Prepregnancy overweight and obesity were associated with lower IQ among boys, but not girls, at 7 years. These findings are important considering overweight and obesity prevalence and the long-term implications of early cognitive development

Suicide attempts and related factors in patients admitted to a general hospital: a ten-year cross-sectional study (1997-2007)

[Abstract] Background: Suicide and suicide attempts represent a severe problem for public health services. The aim of this study is to determine the socio-demographic and psychopathological variables associated with suicide attempts in the population admitted to a General Hospital. Methods: An observational-descriptive study of patients admitted to the A Coruña University Hospital (Spain) during the period 1997-2007, assessed by the Consultation and Liaison Psychiatric Unit. We include n = 5,234 admissions from 4,509 patients. Among these admissions, n = 361 (6.9%) were subsequent to a suicide attempt. Admissions arising from a suicide attempt were compared with admissions occurring due to other reasons.Multivariate generalised estimating equation logistic regression models were used to examine factors associated with suicide attempts. Results: Adjusting by age, gender, educational level, cohabitation status, being employed or unemployed, the psychiatric diagnosis at the time of the interview and the information on previous suicide attempts, we found that the variables associated with the risk of a suicide attempt were: age, psychiatric diagnosis and previous suicide attempts. The risk of suicide attempts decreases with age (OR = 0.969). Psychiatric diagnosis was associated with a higher risk of suicide attempts, with the highest risk being found for Mood or Affective Disorders (OR = 7.49), followed by Personality Disorders (OR = 7.31), and Schizophrenia and Other Psychotic Disorders (OR = 5.03).The strongest single predictive factor for suicide attempts was a prior history of attempts (OR = 23.63). Conclusions: Age, psychopathological diagnosis and previous suicide attempts are determinants of suicide attempts

Target product profiles for neonatal care devices: systematic development and outcomes with NEST360 and UNICEF.

BACKGROUND: Medical devices are critical to providing high-quality, hospital-based newborn care, yet many of these devices are unavailable in low- and middle-income countries (LMIC) and are not designed to be suitable for these settings. Target Product Profiles (TPPs) are often utilised at an early stage in the medical device development process to enable user-defined performance characteristics for a given setting. TPPs can also be applied to assess the profile and match of existing devices for a given context. METHODS: We developed initial TPPs for 15 newborn product categories for LMIC settings. A Delphi-like process was used to develop the TPPs. Respondents completed an online survey where they scored their level of agreement with each of the proposed performance characteristics for each of the 15 devices. Characteristics with  75% agreement. Areas of disagreement were voted on by 69 participants at an in-person consensus meeting, with consensus achieved for 648 (97%) performance characteristics. Only 20 (3%) performance characteristics did not achieve consensus, most (15/20) relating to quality management systems. UNICEF published the 15 TPPs in April 2020, accompanied by a report detailing the online survey results and consensus meeting discussion, which has been viewed 7,039 times (as of January 2023). CONCLUSIONS: These 15 TPPs can inform developers and enable implementers to select neonatal care products for LMIC. Over 2,400 medical devices and diagnostics meeting these TPPs have been installed in 65 hospitals in Nigeria, Tanzania, Kenya, and Malawi through the NEST360 Alliance. Twenty-three medical devices identified and qualified by NEST360 meet nearly all performance characteristics across 11 of the 15 TPPs. Eight of the 23 qualified medical devices are available in the UNICEF Supply Catalogue. Some developers have adjusted their technologies to meet these TPPs. There is potential to adapt the TPP process beyond newborn care

Leptin Administration Favors Muscle Mass Accretion by Decreasing FoxO3a and Increasing PGC-1α in ob/ob Mice

Absence of leptin has been associated with reduced skeletal muscle mass in leptin-deficient ob/ob mice. The aim of our study was to examine the effect of leptin on the catabolic and anabolic pathways regulating muscle mass. Gastrocnemius, extensor digitorum longus and soleus muscle mass as well as fiber size were significantly lower in ob/ob mice compared to wild type littermates, being significantly increased by leptin administration (P<0.001). This effect was associated with an inactivation of the muscle atrophy-related transcription factor forkhead box class O3 (FoxO3a) (P<0.05), and with a decrease in the protein expression levels of the E3 ubiquitin-ligases muscle atrophy F-box (MAFbx) (P<0.05) and muscle RING finger 1 (MuRF1) (P<0.05). Moreover, leptin increased (P<0.01) protein expression levels of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a regulator of muscle fiber type, and decreased (P<0.05) myostatin protein, a negative regulator of muscle growth. Leptin administration also activated (P<0.01) the regulators of cell cycle progression proliferating cell nuclear antigen (PCNA) and cyclin D1, and increased (P<0.01) myofibrillar protein troponin T. The present study provides evidence that leptin treatment may increase muscle mass of ob/ob mice by inhibiting myofibrillar protein degradation as well as enhancing muscle cell proliferation

An Integrated Approach for a Structural and Functional Evaluation of Biosimilars: Implications for Erythropoietin

BACKGROUND: Authorization to market a biosimilar product by the appropriate institutions is expected based on biosimilarity with its originator product. The analogy between the originator and its biosimilar(s) is assessed through safety, purity, and potency analyses. OBJECTIVE: In this study, we proposed a useful quality control system for rapid and economic primary screening of potential biosimilar drugs. For this purpose, chemical and functional characterization of the originator rhEPO alfa and two of its biosimilars was discussed. METHODS: Qualitative and quantitative analyses of the originator rhEPO alfa and its biosimilars were performed using reversed-phase high-performance liquid chromatography (RP-HPLC). The identification of proteins and the separation of isoforms were studied using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF–MS) and two-dimensional gel electrophoresis (2D-PAGE), respectively. Furthermore, the biological activity of these drugs was measured both in vitro, evaluating the TF-1 cell proliferation rate, and in vivo, using the innovative experimental animal model of the zebrafish embryos. RESULTS: Chemical analyses showed that the quantitative concentrations of rhEPO alfa were in agreement with the labeled claims by the corresponding manufacturers. The qualitative analyses performed demonstrated that the three drugs were pure and that they had the same amino acid sequence. Chemical differences were found only at the level of isoforms containing N-glycosylation; however, functional in vitro and in vivo studies did not show any significant differences from a biosimilar point of view. CONCLUSION: These rapid and economic structural and functional analyses were effective in the evaluation of the biosimilarity between the originator rhEPO alfa and the biosimilars analyzed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40259-015-0136-3) contains supplementary material, which is available to authorized users

Excellent adherence and no contamination by physiotherapists involved in a randomized controlled trial on reactivation of COPD patients: a qualitative process evaluation study

Contains fulltext : 107813.pdf (publisher's version ) (Open Access)OBJECTIVE: To assess the adherence of physiotherapists to the study protocol and the occurrence of contamination bias during the course of a randomized controlled trial with a recruitment period of 2 years and a 1-year follow-up (COPE-II study). STUDY DESIGN AND SETTING: In the COPE-II study, intervention patients received a standardized physiotherapeutic reactivation intervention (COPE-active) and control patients received usual care. The latter could include regular physiotherapy treatment. Information about the adherence of physiotherapists with the study protocol was collected by performing a single interview with both intervention and control patients. Patients were only interviewed when they were currently receiving physiotherapy. Interviews were performed during two separate time periods, 10 months apart. Nine characteristics of the COPE-active intervention were scored. Scores were converted into percentages (0%, no aspects of COPE-active; 100%, full implementation of COPE-active). RESULTS: Fifty-one patients were interviewed (first period: intervention n = 14 and control n = 10; second period: intervention n = 18 and control n = 9). Adherence with the COPE-active protocol was high (median scores: period 1, 96.8%; period 2, 92.1%), and large contrasts in scores between the intervention and control group were found (period 1: 96.8% versus 22.7%; period 2: 92.1% versus 25.0%). The scores of patients treated by seven physiotherapists who trained patients of both study groups were similar to the scores of patients treated by physiotherapists who only trained patients of one study group. CONCLUSION: The adherence of physiotherapists with the COPE-active protocol was high, remained unchanged over time, and no obvious contamination bias occurred

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030