Low CD4 counts predict excessive weight gains during first-line treatment for HIV.

BACKGROUND: Weight gain is common after antiretroviral initiation, especially among females, those of black race and lower baseline CD4, although this may potentially be due to lower baseline weight. Use of tenofovir disoproxil fumarate or efavirenz can suppress weight gain. METHODS: Data were pooled from the ADVANCE (n = 1053), NAMSAL (n = 613) and WHRI001 (n = 536) trials investigating first-line regimen. Week 96 weight and body mass index (BMI) was stratified by baseline CD4. Multivariable models of weight change and incident obesity (BMI ≥30 kg/m2) were adjusted for baseline CD4, age, sex, tenofovir disoproxil fumarate, efavirenz, baseline BMI and trial. RESULTS: Participants across all treatment arms experienced weight gain from baseline to week 96, with baseline CD4 count, baseline HIV RNA, tenofovir alafenamide and dolutegravir use, and female sex significant predictors. Mean unadjusted weight change was highest with CD4 < 100 (+8.6 kg; SD = 8.2) and lowest with CD4 ≥ 350 (+3.0 kg; SD = 6.5). This weight gain in CD4 < 100 was highest for participants on tenofovir alafenamide-inclusive treatment, such that absolute weight at week 96 was highest in the CD4 < 100 group. Although not statistically significant, obesity rate (BMI ≥ 30 kg/m2) in those taking TAF/FTC + DTG with CD4 < 100 overtook that seen in CD4 ≥ 350, despite lower baseline obesity prevalence. The unadjusted findings were corroborated in multivariable longitudinal models. CONCLUSIONS: Participants with low CD4 may demonstrate significant 'overshoot' weight gain, in addition to 'return to health', with a trend towards increased risk of obesity when initiated on TAF/FTC + DTG. Use of tenofovir disoproxil fumarate and efavirenz were associated with smaller weight gains. Effective weight management strategies are needed, especially for individuals with low baseline CD4.

Reply to: "The partner-an underutilized facilitator to support healthy gestational weight gain".

Facilitators and barriers influencing weight management behaviours were identified in our meta-synthesis of qualitative research entitled "Facilitators and barriers influencing weight management behaviours during pregnancy: a meta-synthesis of qualitative research". This manuscript is in response to the letter submitted by Sparks et al. regarding that work. The authors highlight the importance of including partners into intervention design when addressing weight management behaviours. We agree with the authors that it is important to include partners into intervention design and further research is granted to identify facilitators and barriers affecting their influence over women. As per our findings, the influence of the social context goes beyond the partner and we suggest that future interventions should address other relevant people in women's contexts such as parents, other relatives, and close friends.

Exploring first-time mothers' experiences and knowledge about behavioural risk factors for stillbirth.

BACKGROUND: Modifiable factors such as substance use, lack of attendance at antenatal care, overweight or obesity and sleeping position are associated with a higher risk of stillbirth. This qualitative study aimed to explore women's experiences of modifiable factors during pregnancy and their awareness of stillbirth. METHODS: Purposive sampling was implemented by hospital staff in a large tertiary maternity hospital in Ireland between November 2020 and March 2021. Women were approached during their stay in the hospital and were invited to participate in a semistructured interview 3-5 months later. Eligible women were primiparous, >18 years of age and had an uncomplicated pregnancy and delivery. Eighteen women who consented to be followed up were interviewed at 3-5 months postpartum. Thematic analysis was used to analyse the data. RESULTS: Four themes were identified: attitudes towards behaviour change, awareness regarding stillbirth and risk factors, the silence around stillbirth and risks, and attitudes towards receiving information about stillbirth. Women spoke about behaviour change in terms of outcomes, and most changes (e.g., ceasing alcohol consumption) were perceived as easy to manage. Awareness of stillbirth was limited among the women interviewed, and the association between risk behaviours and stillbirth was not known by any woman. Results suggest that there is a silence around stillbirth, including in antenatal care, which hinders information provision. However, most women highlighted the value of receiving information and extra education about modifiable risk factors and stillbirth. CONCLUSION: There is a general lack of understanding of the link between behavioural risk factors and potential pregnancy outcomes such as stillbirth. Providing further information to women about stillbirth and providing additional support with behaviour change might contribute to enhancing preventive efforts. PATIENT OR PUBLIC CONTRIBUTION: Patients were involved in this study by providing their experiences of antenatal care which were used as primary data.

Facilitators and barriers influencing weight management behaviours during pregnancy: a meta-synthesis of qualitative research.

BACKGROUND: Obesity and overweight are considered risk factors for a range of adverse outcomes, including stillbirth. This study aims to identify factors reported by women influencing weight management behaviours during pregnancy. METHODS: A systematic search was conducted in five databases from inception to 2019 and updated in 2021. Qualitative studies involving pregnant or post-partum women, from high-income countries, examining women's experiences of weight management during pregnancy were included. Meta-ethnography was used to facilitate the meta-synthesis of 17 studies. RESULTS: Three themes were identified during the analysis: (1) Awareness and beliefs about weight gain and weight management, which included level of awareness and knowledge about dietary and exercise recommendations, risk perception and decision balance, perceived control over health and weight gain and personal insecurities. (2) Antenatal healthcare, women's experiences of their interactions with healthcare professionals during the antenatal period and the quality of the education received had an effect on women's behaviour. Further, our findings highlight the need for clear and direct information, and improved interactions with healthcare professionals, to better support women's weight management behaviours. (3) Social and environmental influence, the social judgement and stigmatization associated with overweight and obesity also acted as a negative influence in womens' engagement in weight management behaviours. CONCLUSION: Interventions developed to promote and maintain weight management behaviours during pregnancy should consider all levels of influence over women's behaviours, including women's level of awareness and beliefs, experiences in antenatal care, education provision and social influence.

Effect of anti-Ebola virus monoclonal antibodies on endogenous antibody production in survivors of Ebola virus disease in the Democratic Republic of the Congo: an observational cohort study.

BACKGROUND: The use of specific anti-Ebola virus therapy, especially monoclonal antibodies, has improved survival in patients with Ebola virus disease. We aimed to assess the effect of monoclonal antibodies on anti-Ebola virus antibody responses in survivors of the 2018-20 Ebola outbreak in the Democratic Republic of the Congo. METHODS: In this observational prospective cohort study, participants were enrolled at three Ebola survivor clinics in Beni, Mangina, and Butembo (Democratic Republic of the Congo). Eligible children and adults notified as survivors of Ebola virus disease (ie, who had confirmed Ebola virus disease [RT-PCR positive in blood sample] and were subsequently declared recovered from the virus [RT-PCR negative in blood sample] with a certificate of recovery from Ebola virus disease issued by an Ebola treatment centre) during the 2018-20 Ebola virus disease outbreak were invited to participate in the study. Participants were recruited on discharge from Ebola treatment centres and followed up for 12-18 months depending on recruitment date. Routine follow-up assessments were done at 1, 3, 6, and 12-18 months after inclusion. We collected sociodemographic (age, sex, visit site), clinical (anti-Ebola virus drugs), and laboratory data (RT-PCR and Ct values). The primary outcome was the antibody concentrations against Ebola virus glycoprotein, nucleoprotein, and 40-kDa viral protein antigens over time assessed in all participants. Antibody concentrations were measured by the multiplex immunoassay, and the association between anti-Ebola virus antibody levels and the relevant exposures, such as anti-Ebola virus disease drugs (ansuvimab, REGN-EB3, ZMapp, or remdesivir), was assessed using both linear and logistic mixed regression models. This study is registered at ClinicalTrials.gov, NCT04409405. FINDINGS: Between April 16, 2020, and Oct 18, 2021, 1168 survivors were invited to participate in the Les Vainqueurs d'Ebola cohort study. 787 survivors were included in the study, of whom 358 had data available for antibody responses. 85 (24%) of 358 were seronegative for at least two Ebola virus antigens on discharge from the Ebola treatment centre. The antibody response over time fluctuated but a continuous decrease in an overall linear evolution was observed. Quantitative modelling showed a decrease in nucleoprotein, glycoprotein, and VP-40 antibody concentrations over time (p<0·0001) with the fastest decrease observed for glycoprotein. The probability of being seropositive for at least two antigens after 36 months was 53·6% (95% CI 51·6-55·6) for participants who received ansuvimab, 73·5% (71·5-75·5) for participants who received REGN-EB3, 76·8% (74·8-78·8) for participants who received remdesivir, and 78·5% (76·5-80·5) for participants who received ZMapp. INTERPRETATION: Almost a quarter of survivors were seronegative on discharge from the Ebola treatment centre and antibody concentrations decreased rapidly over time. These results indicate that monoclonal antibodies might negatively affect the production of anti-Ebola virus antibodies in survivors of Ebola virus disease which could increase the risk of reinfection or reactivation. FUNDING: The French National Agency for AIDS Research-Emergent Infectious Diseases-The French National Institute of Health and Medical Research, the French National Research Institute for Development, and the European and Developing Countries Clinical Trials Partnership. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

[KRAS gene mutation in colorectal cancer]. / Mutación del gen KRAS en el cáncer de colon y recto.

BACKGROUND: KRAS oncogene is involved in colorectal carcinogenesis in 22 to 45% of cases. AIM: To determine the frequency, types and distribution of KRAS mutations in colorectal cancer. MATERIAL AND METHODS: KRAS mutations studies were carried out in primary tumors and metastases of colo-rectal cancer from 56 women aged 60 ± 14 years and 53 men aged 61 ± 11 years. Formalin fixed and paraffin embedded tissue samples were evaluated using RFLP (Restriction Fragment Length Polymorphism) and direct sequencing. RESULTS: Primary tumors were located in the colon and rectum in 82 (75.2%) and 24 cases (20%), respectively. In three cases the extraction site of the tumor sample was unknown. In 46 cases (42.2%) KRAS mutations were demonstrated. The main point mutations were located in codon 12 (80.4%), G12D (39.1%), G12V (24.2%), G12S (6.5%), G12A (4.3%); G12C (4.3%), G12R (2.1%) and 19.6% at codon 13 (G13D). No differences were demonstrated in the frequency and distribution of mutations by gender, age, primary versus metastatic tumors or tumor location. CONCLUSIONS: In this series, 42% of colorectal cancer tissue samples had KRAS mutations. Their frequency and distribution are similar to those reported in the literature, except for G12C mutation.

[Quality of DNA from archival pathological samples of gallbladder cancer]. / ¿Es posible utilizar las muestras de colecistectomías con cáncer en investigación?: Calidad del ADN de muestras obtenidas del sistema público y privado de salud.

BACKGROUND: The quality of the archival samples stored at pathology services could be a limiting factor for molecular biology studies. AIM: To determine the quality of DNA extracted from gallbladder cancer samples at different institutions. MATERIAL AND METHODS: One hundred ninety four samples coming from five medical centers in Chile, were analyzed. DNA extraction was quantified determining genomic DNA concentration. The integrity of DNA was determined by polymerase chain reaction amplification of different length fragments of a constitutive gene (ß-globin products of 110, 268 and 501 base pairs). RESULTS: The mean DNA concentration obtained in 194 gallbladder cancer samples was 48 ± 43.1 ng/µl. In 22% of samples, no amplification was achieved despite obtaining a mean DNA concentration of 58.3 ng/ul. In 81, 67 and 22% of samples, a DNA amplification of at least 110, 268 or 501 base pairs was obtained, respectively. No differences in DNA concentration according to the source of the samples were demonstrated. However, there were marked differences in DNA integrity among participating centers. Samples from public hospitals were of lower quality than those from private clinics. CONCLUSIONS: Despite some limitations, in 80% of cases, the integrity of DNA in archival samples from pathology services in our country would allow the use of molecular biology techniques.

A systematic review of behaviour change techniques used in the context of stillbirth prevention.

BACKGROUND: Stillbirth is one of the most devastating pregnancy outcomes that families can experience. Previous research has associated a wide range of risk factors with stillbirth, including maternal behaviours such as substance use, sleep position and attendance and engagement with antenatal care. Hence, some preventive efforts have been focused on tackling the behavioural risk factors for stillbirth. This study aimed to identify the Behaviour Change Techniques (BCTs) used in behaviour change interventions tacking behavioural risk factors for stillbirth such as substance use, sleep position, unattendance to antenatal care and weight management. STUDY DESIGN: A systematic review of the literature was conducted in June 2021 and updated in November 2022 in five databases: CINHAL, Psyhinfo, SociIndex, PubMed and Web of Science. Studies published in high-income countries describing interventions designed in the context of stillbirth prevention, reporting stillbirth rates and changes in behaviour were eligible for inclusion. BCTs were identified using the Behaviour Change Technique Taxonomy v1. RESULTS: Nine interventions were included in this review identified in 16 different publications. Of these, 4 interventions focused on more than one behaviour (smoking, monitoring fetal movements, sleep position, care-seeking behaviours), one focused on smoking, three on monitoring fetal movements and one on sleep position. Twenty-seven BCTs were identified across all interventions. The most commonly used was "Information about health consequences" (n = 7/9) followed by "Adding objects to the environment" (n = 6/9). One of the interventions included in this review has not been assessed for efficacy yet, of the remaining eight, three showed results in the reduction of stillbirth rates. and four interventions produced behaviour change (smoking reductions, increased knowledge, reduced supine sleeping time). CONCLUSIONS: Our findings suggest that interventions designed to date have limited effects on the rates of stillbirth and utilise a limited number of BCTs which are mostly focused on information provision. Further research is necessary to design evidence base behaviour change interventions with a greater focus to tackle all the other factors influencing behaviour change during pregnancy (e.g.: social influence, environmental barriers).

Insect chaperones Hsp70 and Hsp90 cooperatively enhance toxicity of Bacillus thuringiensis Cry1A toxins and counteract insect resistance.

Bacillus thuringiensis (Bt) produces different insecticidal proteins effective for pest control. Among them, Cry insecticidal proteins have been used in transgenic plants for the control of insect pests. However, evolution of resistance by insects endangers this technology. Previous work showed that the lepidopteran insect Plutella xylostella PxHsp90 chaperone enhanced the toxicity of Bt Cry1A protoxins by protecting them from degradation by the larval gut proteases and by enhancing binding of the protoxin to its receptors present in larval midgut cells. In this work, we show that PxHsp70 chaperone also protects Cry1Ab protoxin from gut proteases degradation, enhancing Cry1Ab toxicity. We also show that both PxHsp70 and PxHsp90 chaperones act cooperatively, increasing toxicity and the binding of Cry1Ab439D mutant, affected in binding to midgut receptors, to cadherin receptor. Also, insect chaperones recovered toxicity of Cry1Ac protein to a Cry1Ac-highly resistant P. xylostella population, NO-QAGE, that has a disruptive mutation in an ABCC2 transporter linked to Cry1Ac resistance. These data show that Bt hijacked an important cellular function for enhancing its infection capability, making use of insect cellular chaperones for enhancing Cry toxicity and for lowering the evolution of insect resistance to these toxins.

Risks of metabolic syndrome in the ADVANCE and NAMSAL trials.

Introduction: The ADVANCE and NAMSAL trials evaluating antiretroviral drugs have both reported substantial levels of clinical obesity in participants. As one of the main risk factors for metabolic syndrome, growing rates of obesity may drive metabolic syndrome development. This study aims to evaluate the risk of metabolic syndrome in the ADVANCE and NAMSAL trials. Methods: The number of participants with metabolic syndrome was calculated at baseline and week 192 as central obesity and any of the following two factors: raised triglycerides, reduced HDL-cholesterol, raised blood pressure and raised fasting glucose. Differences between the treatment arms were calculated using the χ2 test. Results: Across all visits to week 192, treatment-emergent metabolic syndrome was 15% (TAF/FTC + DTG), 10% (TDF/FTC + DTG) and 7% (TDF/FTC/EFV) in ADVANCE. The results were significantly higher in the TAF/FTC + DTG arm compared to the TDF/FTC/EFV arm (p < 0.001), and the TDF/FTC + DTG vs. the TDF/FTC/EFV arms (p < 0.05) in all patients, and in females. In NAMSAL, the incidence of treatment-emergent metabolic syndrome at any time point was 14% (TDF/3TC + DTG) and 5% (TDF/3TC + EFV) (p < 0.001). This incidence was significantly greater in the TDF/3TC/DTG arm compared to the TDF/3TC/EFV arm in all patients (p < 0.001), and in males (p < 0.001). Conclusion: In this analysis, we highlight treatment-emergent metabolic syndrome associated with dolutegravir, likely driven by obesity. Clinicians initiating or monitoring patients on INSTI-based ART must counsel for lifestyle optimisation to prevent these effects.

Durability of the Efficacy and Safety of Dolutegravir-Based and Low-Dose Efavirenz-Based Regimens for the Initial Treatment of Human Immunodeficiency Virus Type 1 Infection in Cameroon: Week 192 Data of the NAMSAL-ANRS-12313 Study.

Background: A prospective study was extended to the new antiretroviral and monitoring strategies in HIV-infected adults in low-income countries (NAMSAL-ANRS)-12313 trial, a 96-week open-label, multicenter, randomized phase 3 trial comparing dolutegravir (DTG) 50 mg with efavirenz 400 mg (EFV400), both administered with tenofovir disoproxil fumarate and lamivudine (TDF/3TC) as first-line treatment for antiretroviral therapy (ART)-naive people living with human immunodeficiency virus type 1 (HIV). Noninferiority of DTG to EFV400 was demonstrated at 48-week and sustained at 96 weeks. Here, we present results at 192-week. Methods: Previous trial participants were reconsented and followed up on their initial randomization arm (1:1 DTG/TDF/3TC:EFV400/TDF/3TC). Assessments included changes in viral suppression, biological parameters, and new serious adverse events (SAEs). Results: Among the participants enrolled in the trial, 81% (499/613) were analyzed at week 192: 84% (261/310) on DTG/TDF/3TC and 78% (238/303) on EFV400/TDF/3TC. HIV RNA suppression was maintained in 69% (214/310) on DTG/TDF/3TC-based and 62% (187/303) on EFV400/TDF/3TC-based regimens (difference, 7.3% [95% confidence interval, -.20 to 14.83]; P = .057). Five (DTG/TDF/3TC = 2; EFV400/TDF/3TC = 3) new viral failures (World Health Organization definition) without related resistance DTG mutations and 24 new SAEs were observed (DTG/TDF/3TC = 13; EFV400/TDF/3TC = 11). Mean weight gain was +9.4 kg on DTG/TDF/3TC and +5.9 kg on EFV400/TDF/3TC. The percentage of participants with obesity increased from 6.9% to 27.7% on DTG/TDF/3TC (P < .0001) and from 8.3% to 16.7% on EFV400/TDF/3TC (P = .0033). Conclusions: Four-year follow-up of people with HIV on DTG- and EFV400-based regimens showed long-term efficacy and safety of both ARTs, markedly among participants on DTG/TDF/3TC with high baseline viral load. However, unexpected substantial weight gain over time was prominent among participants on DTG/TDF/3TC, which should be closely monitored. Clinical Trials Registration. NCT02777229.

Improvements in Patient-Reported Outcomes Following Initiation of Dolutegravir-Based or Low-Dose Efavirenz-Based First-Line Antiretroviral Therapy: A Four-Year Longitudinal Analysis in Cameroon (NAMSAL ANRS 12313 Trial).

BACKGROUND: We provide new and comprehensive evidence on the evolution of a wide range of patient-reported outcomes (PROs) in the NAMSAL ANRS 12313 trial in Cameroon (2016-2021)-the first randomized comparison of dolutegravir 50 mg (DTG) and low-dose efavirenz (ie, 400 mg; EFV400) in treatment-naive adults living with HIV-1 in sub-Saharan Africa. METHODS: We first described the evolution of PROs between baseline and week 192. Then, we used random-effects models to measure the effect of time since the initiation of antiretroviral therapy and the differential effect of DTG versus EFV400 on each PRO, adjusting for clinical, demographic, and socioeconomic factors, while accounting for unobserved heterogeneity and missing data. RESULTS: Among the 613 patients randomized (DTG arm, n = 310; EFV400 arm, n = 303), (1) physical and mental health-related quality of life improved by 13.3% and 6.8%, respectively, (2) the percentage of patients with depression, anxiety, and stress decreased from 23.3%, 23.0%, and 7.7% to 3.1%, 3.5%, and 0.4%, respectively, and (3) the mean number of HIV-related symptoms decreased from 7.2 to 3.0 ( P < 0.001). For most PROs, no significant difference was found between both arms, even when accounting for the effect of DTG on weight gain. Nevertheless, our results suggest smaller improvements in mental health outcomes in the DTG arm, with a 5 percentage point higher adjusted probability of having anxiety at week 192 ( P < 0.01). CONCLUSIONS: Although supporting the current World Health Organization guidelines recommending DTG-based and EFV400-based regimens as preferred and alternative first-line antiretroviral therapy, further studies should investigate medium-term mental health outcomes in patients on DTG. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02777229.

Facilitators and barriers to seeking and engaging with antenatal care in high-income countries: A meta-synthesis of qualitative research.

Inadequate attendance to antenatal care has been associated with negative maternal and fetal outcomes, including stillbirth. This study aimed to identify facilitators and barriers to antenatal care attendance. A systematic search was conducted in March 2019 and updated in January 2021. Qualitative studies involving pregnant or post-partum women up to 12 months from high-income countries that provided data about facilitators and barriers to antenatal care attendance were sought. Meta-ethnography was used to inform this meta-synthesis. Fifteen studies were included in the analysis. Findings indicate that inadequate antenatal care attendance is influenced at different levels. Aspects like sociodemographic factors, difficulties navigating the health system, administrative delays, lack of flexibility and tailored care, constant change of carer and communication issues also act as barriers. These issues affect women's access to knowledge and the formation of women's beliefs and feelings towards seeking care. On the contrary, having a positive attitude towards the pregnancy, encountering empathetic healthcare professionals and availing of social support acted as facilitators. The reasons why women seek or delay attending antenatal care are multifactorial and can be explained using the Social Determinants of Health Framework. Any response needs to be taken across all levels of influence and not just focused on the individual. A better understanding of the barriers and facilitators to antenatal care might contribute to informing intervention or policy development addressing this issue.

Facilitators and barriers to substance-free pregnancies in high-income countries: A meta-synthesis of qualitative research.

BACKGROUND: Previous studies have associated substance use (alcohol, illicit drugs and smoking) to negative pregnancy outcomes, including higher risk of stillbirth. AIM: This study aims to identify facilitators and barriers reported by women to remain substance free during pregnancy. METHODS: A systematic search was conducted in six databases from inception to March 2019 and updated in November 2020. Qualitative studies involving pregnant or post-partum women, from high-income countries, examining women's experiences of substance use during pregnancy were eligible. Meta-ethnography was used to facilitate this meta-synthesis. FINDINGS: Twenty-two studies were included for analysis. Internal barriers included the perceived emotional and social benefits of using substances such as stress coping, and the associated feelings of shame and guilt. Finding insensitive professionals, the lack of information and discussion about risks, and lack of social support were identified as external barriers. Furthermore, the social stigma and fear of prosecution associated with substance use led some women to conceal their use. Facilitators included awareness of the health risks of substance use, having intrinsic incentives and finding support in family, friends and professionals. DISCUSSION: Perceived benefits, knowledge, experiences in health care settings, and social factors all play important roles in women's behaviours. These factors can co-occur and must be considered together to be able to understand the complexity of prenatal substance use. CONCLUSION: Increased clinical and community awareness of the modifiable risk factors associated with substance use during pregnancy presented in this study, is necessary to inform future prevention efforts.

A protocol for a systematic review of behaviour change techniques used in the context of stillbirth prevention.

Background: Stillbirth is a devastating pregnancy outcome that affects approximately 3.5 per 1000 births in high-income countries. Previous research has highlighted the importance of focusing prevention efforts on targeting risk factors and vulnerable groups. A wide range of risk factors has been associated with stillbirth before, including maternal behaviours such as back sleep position, smoking, alcohol intake, illicit drug use, and inadequate attendance at antenatal care. Given the modifiable nature of these risk factors, there has been an increase in the design of behaviour change interventions targeting such behaviours to reduce the risk of stillbirth. Objectives: The aim of this study is to identify all behavioural interventions with a behavioural component designed and trialled for the prevention of stillbirth in high-income countries, and to identify the behaviour change techniques (BCTs) used in such interventions using the Behaviour Change Techniques Taxonomy V1 (BCTTv1). Inclusion criteria: Interventions will be included in this review if they (1) have the objective of reducing stillbirth rates with a focus on behavioural risk factors; (2) are implemented in high-income countries; (3) target pregnant women or women of childbearing age; and (4) are published in research articles. Methods: A systematic search of the literature will be conducted. The results of the search will be screened against our inclusion criteria by two authors. The following data items will be extracted from the selected papers: general information, study characteristics, participant and intervention/approach details. The Cochrane Effective Practice and Organization of Care (EPOC) risk of bias criteria will be used to assess the methodological quality of included studies. Intervention content will be coded for BCTs as present (+) or absent (-) by two authors using the BCTTv1, discrepancies will be discussed with a third author. A narrative synthesis approach will be used to present the results of this systematic review.

Satisfaction with Self and External Regulation of Learning in Higher Education Students in Brazil.

The satisfaction of university students with the variables that regulate their learning provides very valuable information to improve the quality of teaching processes. The main objective of this study was to evaluate the learning of Brazilian university students, exploring both self-regulation variables, such as study techniques; and more external regulation variables, namely, satisfaction with the teaching-learning process and with the infrastructure, based on three variables: gender, the institution of higher education and the academic year of the students. To achieve this, 560 students of the Pedagogy degree were evaluated with two questionnaires: a questionnaire of satisfaction with the educational infrastructure and the teaching-learning process and a questionnaire on study techniques. Statistically significant differences were obtained, especially depending on the type of institution and the academic year. The students of private schools and earlier academic years were the ones who obtained the most satisfaction with the study techniques and with the infrastructure. Those from private centers also expressed more satisfaction with the teaching-learning processes. These results provide greater knowledge about the processes of self-regulation and external regulation of university learning and of their satisfaction with them, which can contribute to improving educational policies in Brazil.

Cost-Utility Analysis of a Dolutegravir-Based Versus Low-Dose Efavirenz-Based Regimen for the Initial Treatment of HIV-Infected Patients in Cameroon (NAMSAL ANRS 12313 Trial).

OBJECTIVES: Evidence comparing the economic and patient values of the World Health Organization's preferred (dolutegravir 50 mg [DTG]-based) and alternative (low-dose [400 mg] efavirenz [EFV400]-based) first-line antiretroviral regimens is limited. We compared patient-reported outcomes (PROs), costs, and the cost-utility of DTG- versus EFV400-based regimens in treatment-naive HIV-1 adults in the randomised NAMSAL ANRS 12313 trial in Yaoundé, Cameroon. METHODS: We used clinical data, PROs, and health resource use data collected in the trial's first 96 weeks (2016-2019). Quality-adjusted life-years (QALYs) were computed using utility scores obtained from the 12-item Short Form (SF-12) generic health scale. Other PROs included perceived symptoms, depression, anxiety, and stress. In the 96-week base-case analysis, we estimated the unadjusted and multivariate-adjusted (1) mean costs (in US$, 2016 values) and QALYs/patient, (2) incremental costs and QALYs/patient, and (3) net health benefit (NHB). Outcomes were extrapolated over 5 and 10 years. Uncertainty was assessed using the cost-effectiveness acceptability curve and scenario and cost-effective price threshold analyses. RESULTS: In the base-case analysis, the NHB (95% confidence interval) for the DTG-based regimen relative to the EFV400-based regimen was 0.056 (- 0.037 to 0.153), corresponding to an 88% probability of DTG being cost-effective. A 10% decrease in this regimen's price (from $5.2 to $4.7/month) would increase its cost-effectiveness probability to 95%. When extrapolating outcomes over 5 and 10 years, the DTG-based regimen had a 100% probability of being cost-effective for a large range of cost-effectiveness thresholds. CONCLUSIONS: At 2020 antiretroviral drug prices, a DTG-based first-line regimen should be preferred over an EFV400-based regimen in sub-Saharan Africa. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02777229.

Dolutegravir-based and low-dose efavirenz-based regimen for the initial treatment of HIV-1 infection (NAMSAL): week 96 results from a two-group, multicentre, randomised, open label, phase 3 non-inferiority trial in Cameroon.

BACKGROUND: Updated WHO guidelines recommend a dolutegravir-based regimen as the preferred first-line treatment for HIV infection and low-dose efavirenz (400 mg) as an alternative. We aimed to report the non-inferior efficacy of dolutegravir compared with efavirenz 400 mg at week 96. METHODS: We did a multicentre, randomised, open label, phase 3 trial in in three hospitals in Yaoundé, Cameroon, in HIV-1 infected antiretroviral-naive adults with an HIV RNA viral load of greater than 1000 copies per mL to compare dolutegravir 50 mg with efavirenz 400 mg (reference treatment), both combined with lamivudine and tenofovir disoproxil fumarate. The primary endpoint was the proportion with a viral load of less than 50 copies per mL at week 48 (10% non-inferiority margin). The study is registered with ClinicalTrials.gov, NCT02777229 and is ongoing. FINDINGS: Between July, 2016, and August, 2019, of 820 patients assessed, 613 were randomly assigned to receive at least one dose of study medication, with 310 in the dolutegravir group and 303 in the efavirenz 400 mg group. At week 96 in the intention-to-treat analysis, 229 (74%) of 310 patients receiving dolutegravir and 219 (72%) of 303 patients receiving efavirenz, achieved plasma HIV-1 RNA less than 50 copies per mL (difference 1·6%, 95% CI -5·4 to 8·6; p=0.66). Viral load suppression was reached significantly more rapidly in the dolutegravir group (p<0·001). Virological failure (>1000 copies per mL) was observed in 27 patients (eight in the dolutegravir group, among which, three women switched to efavirenz 600 mg because of the dolutegravir teratogeneicity signal, and 19 in the efavirenz 400 mg group). No acquired resistance mutations to dolutegravir were observed against 17 mutations to efavirenz with or without mutations to lamivudine and tenofovir disoproxil fumarate among the 19 efavirenz 400 mg participants with virological failure. Weight gain was greater in the dolutegravir group (median weight gain, 5·0 kg in the dolutegravir group and 3·0 kg in the efavirenz 400 mg group, p<0·001, and incidence of obesity, 22% in the dolutegravir group and 16% in the efavirenz 400 mg group, p=0·043). The incidence of new WHO HIV-related stage 3 and 4 events was similar in each group (12 [4%] in each group). The two groups had similar rates of serious adverse events (28 [9%] of 310 in the dolutegravir group and 21 [7%] of 303 in the efavirenz 400 mg group). 18 deaths were observed during the 96-week follow-up (eight in the dolutegravir group and ten in the efavirenz 400 mg group). INTERPRETATION: The non-inferior efficacy of the dolutegravir-based regimen and non-emergence of dolutegravir resistance at 96 weeks supports its use as a first-line regimen for antiretroviral-naive adults with HIV-1 infection. Viral load suppression was reached more quickly in the dolutegravir group and weight gain was significantly higher. FUNDING: UNITAID and the French National Agency for AIDS Research.

Modifiable risk factors for stillbirth: a literature review.

A stillbirth is defined as an infant born weighing 500 g and/or more or at a gestational age of 24 weeks who shows no signs of life. Having a stillborn baby has a wide range of consequences that can affect parents, family and the healthcare professionals involved. Several risk factors have been associated with an increased risk of stillbirth: including maternal medical factors, maternal characteristics, fetal factors, sociodemographic factors and behavioral factors. The aim of this work is to review the literature on risk factors that have a behavioral component. The main behaviors modulating the risk of stillbirth that have been more widely studied in the literature include use of substances (smoking, alcohol, illicit drugs and medical drugs), weight management, attendance at antenatal care and sleeping position. There is evidence in the literature that supports that all those behaviors have an impact on the risk of stillbirth, especially in the cases of smoking and drugs consumption during the pregnancy. Hence, more research is needed to establish interventions targeting these behaviors as preventive measures to reduce the risk of adverse obstetric outcomes.

Intervención educativa sobre la COVID-19 en los trabajadores del Centro de Investigaciones Científicas de la Defensa Civil / Educational intervention on COVID-19 in the personnel of the Civil Defense Scientific Research Center

Introducción: La COVID-19 creó desafíos sin precedentes para la comunidad y los trabajadores de la salud, por lo que contribuir a incrementar la percepción del riesgo mediante la capacitación fue una premisa elemental en tiempos de la pandemia. Objetivo: La investigación tuvo la finalidad de contribuir a incrementar el conocimiento en aspectos importantes sobre la COVID-19 en los trabajadores del Centro de Investigaciones Científicas de la Defensa Civil. Métodos: Se realizó una evaluación antes y después de la intervención en el período de febrero a abril de 2021. La muestra estuvo conformada por 50 trabajadores divididos en dos grupos: 1) investigadores y técnicos; 2) personal de apoyo. La investigación se desarrolló en tres etapas: diagnóstico, intervención y evaluación. Se conformó una base de datos con la información recopilada y para su análisis se empleó el método de comparación de proporciones de las respuestas entre los grupos, antes y después de la evaluación. Se calculó el porcentaje de apropiación de conocimientos con nivel de significación (p < 0,05) y se aplicó el t-Student para muestras dependientes. Resultados: De 50 trabajadores 35 (70 %) eran del sexo femenino; predominó el nivel escolar universitario con un total de 33 (66 %). Se observó un incremento estadísticamente significativo, tanto en la apropiación del conocimiento en ambos grupos, como en las preguntas adecuadas, después de la intervención (p < 0,05); siendo superior en el grupo del personal de apoyo. Conclusiones: La intervención educativa contribuyó a incrementar los conocimientos acerca de la COVID-19 en los trabajadores del centro, lo que tuvo un impacto favorable.

Introduction: COVID-19 created unprecedented challenges for the community and health workers; therefore, contributing to increase risk perception through training was an elementary premise in times of the pandemic. Objective: The research aimed at increasing the knowledge of important aspects of COVID-19 among the personnel of the Civil Defense Scientific Research Center. Methods: An evaluation was carried out before and after the intervention from February to April 2021. The sample consisted of 50 workers divided into two groups: 1) researchers and technicians; 2) support personnel. The research comprised three stages: diagnosis, intervention, and evaluation. A database was created with the information collected. For its analysis, the compare proportions test of responses between the groups, before and after the evaluation, was used. The percentage of knowledge appropriation was calculated with significance level (p < 0.05), and the t-Student was applied for dependent samples. Results: Out of 50 workers, 35 (70%) were female; 33 (66%) had a university education level. A statistically significant increase in both knowledge acquisition and appropriate questions was observed in the groups after the intervention (p < 0.05), which was higher in the support staff group. Conclusions: The educational intervention contributed to increasing knowledge about COVID-19 among the workers of the center, which had a favorable impact.