Developing a Complex Understanding of Physical Activity in Cardiometabolic Disease from Low-to-Middle-Income Countries—A Qualitative Systematic Review with Meta-Synthesis

Physical activity behaviour is complex, particularly in low-resource settings, while existing behavioural models of physical activity behaviour are often linear and deterministic. The objective of this review was to (i) synthesise the wide scope of factors that affect physical activity and thereby (ii) underpin the complexity of physical activity in low-resource settings through a qualitative meta-synthesis of studies conducted among patients with cardiometabolic disease living in low-to-middle income countries (LMIC). A total of 41 studies were included from 1200 unique citations (up to 15 March 2021). Using a hybrid form of content analysis, unique factors (n = 208) that inform physical activity were identified, and, through qualitative meta-synthesis, these codes were aggregated into categories (n = 61) and synthesised findings (n = 26). An additional five findings were added through deliberation within the review team. Collectively, the 31 synthesised findings highlight the complexity of physical activity behaviour, and the connectedness between person, social context, healthcare system, and built and natural environment. Existing behavioural and ecological models are inadequate in fully understanding physical activity participation in patients with cardiometabolic disease living in LMIC. Future research, building on complexity science and systems thinking, is needed to identify key mechanisms of action applicable to the local context

A position statement and practical guide to the use of particulate filtering facepiece respirators (N95, FFP2, or equivalent) for South African health workers exposed to respiratory pathogens including Mycobacterium tuberculosis and SARS-CoV-2

Summary Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is transmitted mainly by aerosol in particles <10 µm that can remain suspended for hours before being inhaled. Because particulate filtering facepiece respirators (‘respirators’; e.g. N95 masks) are more effective than surgical masks against bio-aerosols, many international organisations now recommend that health workers (HWs) wear a respirator when caring for individuals who may have COVID-19. In South Africa (SA), however, surgical masks are still recommended for the routine care of individuals with possible or confirmed COVID-19, with respirators reserved for so-called aerosol-generating procedures. In contrast, SA guidelines do recommend respirators for routine care of individuals with possible or confirmed tuberculosis (TB), which is also transmitted via aerosol. In health facilities in SA, distinguishing between TB and COVID-19 is challenging without examination and investigation, both of which may expose HWs to potentially infectious individuals. Symptom-based triage has limited utility in defining risk. Indeed, significant proportions of individuals with COVID-19 and/or pulmonary TB may not have symptoms and/or test negative. The prevalence of undiagnosed respiratory disease is therefore likely significant in many general clinical areas (e.g. waiting areas). Moreover, a proportion of HWs are HIV-positive and are at increased risk of severe COVID-19 and death. Recommendations Sustained improvements in infection prevention and control (IPC) require reorganisation of systems to prioritise HW and patient safety. While this will take time, it is unacceptable to leave HWs exposed until such changes are made. We propose that the SA health system adopts a target of ‘zero harm’, aiming to eliminate transmission of respiratory pathogens to all individuals in every healthcare setting. Accordingly, we recommend: 1. the use of respirators by all staff (clinical and non-clinical) during activities that involve contact or sharing air in indoor spaces with individuals who: (i) have not yet been clinically evaluated; or (ii) are thought or known to have TB and/or COVID-19 or other potentially harmful respiratory infections; 2. the use of respirators that meet national and international manufacturing standards; 3. evaluation of all respirators, at the least, by qualitative fit testing; and 4. the use of respirators as part of a ‘package of care’ in line with international IPC recommendations. We recognise that this will be challenging, not least due to global and national shortages of personal protective equipment (PPE). SA national policy around respiratory protective equipment enables a robust framework for manufacture and quality control and has been supported by local manufacturers and the Department of Trade, Industry and Competition. Respirator manufacturers should explore adaptations to improve comfort and reduce barriers to communication. Structural changes are needed urgently to improve the safety of health facilities: persistent advocacy and research around potential systems change remain essential

Referrals for positive tuberculin tests in new health care workers and students: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Documentation of test results for latent tuberculosis (TB) infection is important for health care workers and students before they begin work. A negative result provides a baseline for comparison with future tests. A positive result affords a potential opportunity for treatment of latent infection when appropriate. We sought to evaluate the yield of the referral process for positive baseline tuberculin tests, among persons beginning health care work or studies.</p> <p>Methods</p> <p>Retrospective cohort study. We reviewed the charts of all new health care students and workers referred to the Montreal Chest Institute in 2006 for positive baseline tuberculin skin tests (≥10 mm). Health care workers and students evaluated for reasons other than positive baseline test results were excluded.</p> <p>Results</p> <p>630 health care students and workers were evaluated. 546 (87%) were foreign-born, and 443 (70%) reported previous Bacille Calmette-Guérin (BCG) vaccination. 420 (67%) were discharged after their first evaluation without further treatment. 210 (33%) were recommended treatment for latent TB infection, of whom 165 (79%) began it; of these, 115 (70%) completed adequate treatment with isoniazid or rifampin. Treatment discontinuation or interruption occurred in a third of treated subjects, and most often reflected loss to follow-up, or abdominal discomfort. No worker or student had active TB.</p> <p>Conclusions</p> <p>Only a small proportion of health care workers and students with positive baseline tuberculin tests were eligible for, and completed treatment for latent TB infection. We discuss recommendations for improving the referral process, so as to better target workers and students who require specialist evaluation and treatment for latent TB infection. Treatment adherence also needs improvement.</p

A position statement and practical guide to the use of particulate filtering facepiece respirators (N95, FFP2, or equivalent) for South African health workers exposed to respiratory pathogens including Mycobacterium tuberculosis and SARS-CoV-2.

SUMMARY: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is transmitted mainly by aerosol in particles <10 µm that can remain suspended for hours before being inhaled. Because particulate filtering facepiece respirators ('respirators'; e.g. N95 masks) are more effective than surgical masks against bio-aerosols, many international organisations now recommend that health workers (HWs) wear a respirator when caring for individuals who may have COVID-19. In South Africa (SA), however, surgical masks are still recommended for the routine care of individuals with possible or confirmed COVID-19, with respirators reserved for so-called aerosol-generating procedures. In contrast, SA guidelines do recommend respirators for routine care of individuals with possible or confirmed tuberculosis (TB), which is also transmitted via aerosol. In health facilities in SA, distinguishing between TB and COVID-19 is challenging without examination and investigation, both of which may expose HWs to potentially infectious individuals. Symptom-based triage has limited utility in defining risk. Indeed, significant proportions of individuals with COVID-19 and/or pulmonary TB may not have symptoms and/or test negative. The prevalence of undiagnosed respiratory disease is therefore likely significant in many general clinical areas (e.g. waiting areas). Moreover, a proportion of HWs are HIV-positive and are at increased risk of severe COVID-19 and death. RECOMMENDATIONS: Sustained improvements in infection prevention and control (IPC) require reorganisation of systems to prioritise HW and patient safety. While this will take time, it is unacceptable to leave HWs exposed until such changes are made. We propose that the SA health system adopts a target of 'zero harm', aiming to eliminate transmission of respiratory pathogens to all individuals in every healthcare setting. Accordingly, we recommend: the use of respirators by all staff (clinical and non-clinical) during activities that involve contact or sharing air in indoor spaces with individuals who: (i) have not yet been clinically evaluated; or (ii) are thought or known to have TB and/or COVID-19 or other potentially harmful respiratory infections;the use of respirators that meet national and international manufacturing standards;evaluation of all respirators, at the least, by qualitative fit testing; andthe use of respirators as part of a 'package of care' in line with international IPC recommendations. We recognise that this will be challenging, not least due to global and national shortages of personal protective equipment (PPE). SA national policy around respiratory protective equipment enables a robust framework for manufacture and quality control and has been supported by local manufacturers and the Department of Trade, Industry and Competition. Respirator manufacturers should explore adaptations to improve comfort and reduce barriers to communication. Structural changes are needed urgently to improve the safety of health facilities: persistent advocacy and research around potential systems change remain essential

Processing Parameter Effects on Residual Stress and Mechanical Properties of Selective Laser Melted Ti6Al4V

Selective laser melting (SLM) process is characterized by large temperature gradients resulting in high levels of residual stress within the additively manufactured metallic structure. SLM-processed Ti6Al4V yields a martensitic microstructure due to the rapid solidification and results in a ductility generally lower than a hot working equivalent. Post-process heat treatments can be applied to SLM components to remove in-built residual stress and improve ductility. Residual stress buildup and the mechanical properties of SLM parts can be controlled by varying the SLM process parameters. This investigation studies the effect of layer thickness on residual stress and mechanical properties of SLM Ti6Al4V parts. This is the first-of-its kind study on the effect of varying power and exposure in conjunction with keeping the energy density constant on residual stress and mechanical properties of SLM Ti6Al4V components. It was found that decreasing power and increasing exposure for the same energy density lowered the residual stress and improved the % elongation of SLM Ti6Al4V parts. Increasing layer thickness resulted in lowering the residual stress at the detriment of mechanical properties. The study is based on detailed experimental analysis along with finite element simulation of the process using ABAQUS to understand the underlying physics of the process

Seasonal Patterns of Body Temperature Daily Rhythms in Group-Living Cape Ground Squirrels Xerus inauris

Organisms respond to cyclical environmental conditions by entraining their endogenous biological rhythms. Such physiological responses are expected to be substantial for species inhabiting arid environments which incur large variations in daily and seasonal ambient temperature (Ta). We measured core body temperature (Tb) daily rhythms of Cape ground squirrels Xerus inauris inhabiting an area of Kalahari grassland for six months from the Austral winter through to the summer. Squirrels inhabited two different areas: an exposed flood plain and a nearby wooded, shady area, and occurred in different social group sizes, defined by the number of individuals that shared a sleeping burrow. Of a suite of environmental variables measured, maximal daily Ta provided the greatest explanatory power for mean Tb whereas sunrise had greatest power for Tb acrophase. There were significant changes in mean Tb and Tb acrophase over time with mean Tb increasing and Tb acrophase becoming earlier as the season progressed. Squirrels also emerged from their burrows earlier and returned to them later over the measurement period. Greater increases in Tb, sometimes in excess of 5°C, were noted during the first hour post emergence, after which Tb remained relatively constant. This is consistent with observations that squirrels entered their burrows during the day to ‘offload’ heat. In addition, greater Tb amplitude values were noted in individuals inhabiting the flood plain compared with the woodland suggesting that squirrels dealt with increased environmental variability by attempting to reduce their Ta-Tb gradient. Finally, there were significant effects of age and group size on Tb with a lower and less variable Tb in younger individuals and those from larger group sizes. These data indicate that Cape ground squirrels have a labile Tb which is sensitive to a number of abiotic and biotic factors and which enables them to be active in a harsh and variable environment

Phosphorylation Provides a Negative Mode of Regulation for the Yeast Rab GTPase Sec4p

The Rab family of Ras-related GTPases are part of a complex signaling circuitry in eukaryotic cells, yet we understand little about the mechanisms that underlie Rab protein participation in such signal transduction networks, or how these networks are integrated at the physiological level. Reversible protein phosphorylation is widely used by cells as a signaling mechanism. Several phospho-Rabs have been identified, however the functional consequences of the modification appear to be diverse and need to be evaluated on an individual basis. In this study we demonstrate a role for phosphorylation as a negative regulatory event for the action of the yeast Rab GTPase Sec4p in regulating polarized growth. Our data suggest that the phosphorylation of the Rab Sec4p prevents interactions with its effector, the exocyst component Sec15p, and that the inhibition may be relieved by a PP2A phosphatase complex containing the regulatory subunit Cdc55p

ISSN exercise & sport nutrition review: research & recommendations

Sports nutrition is a constantly evolving field with hundreds of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper is a five year update of the sports nutrition review article published as the lead paper to launch the JISSN in 2004 and presents a well-referenced overview of the current state of the science related to how to optimize training and athletic performance through nutrition. More specifically, this paper provides an overview of: 1.) The definitional category of ergogenic aids and dietary supplements; 2.) How dietary supplements are legally regulated; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of the ergogenic value of nutrition and dietary supplementation in regards to weight gain, weight loss, and performance enhancement. Our hope is that ISSN members and individuals interested in sports nutrition find this review useful in their daily practice and consultation with their clients

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.

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