Adverse and serious adverse events incidence of pharmacological interventions for managing chronic and episodic migraine in adults: a systematic review.

Background: Migraine is the second most common prevalent disorder worldwide and is a top cause of disability with a substantial economic burden. Many preventive migraine medications have notable side effects that affect different body organs. Method: We systematically searched for published randomised controlled trials (RCTs) using terms for migraine/headache and preventive medications. Using eligibility criteria, two reviewers independently assessed the articles. Cochrane risk-of-bias tool was applied to assess the quality of the studies. Data were classified by system organ class (SOC). Results: Thirty-two RCTs with 21 780 participants met the eligibility criteria for the incidence of adverse events (AEs). Additionally, 33 RCTs with 22 615 participants were included to synthesise the incidence of serious AEs (SAEs). The percentage of attributed AEs and SAEs to each SOC for 10 preventive drugs with different dosing regimens was calculated. Amitriptyline and topiramate had a higher incidence of nervous system disorders; Topiramate was also associated with a higher incidence of psychiatric disorders. All drugs showed a certain incidence of infections and infestations, with Onabotulinumtoxin A (BTA) having the lowest rate. BTA had a higher incidence of musculoskeletal disorders than the other drugs. Calcitonin gene-related peptide (CGRP) monoclonal antibodies (MAbs) such as fremanezumab and galcanezumab were linked to more general disorders and administration site conditions than other drugs. Conclusion: Notably, the observed harm to SOCs varies among these preventive drugs. We suggest conducting head-to-head RCTs to evaluate the safety profile of oral medications, BTA, and CGRP MAbs in episodic and/or chronic migraine populations. PROSPERO registration number: CRD42021265993.

Clinical effectiveness of pharmacological interventions for managing chronic migraine in adults: a systematic review and network meta-analysis.

BACKGROUND: Chronic migraine can be a profoundly disabling disorder that may be treated with preventive medications. However, uncertainty remains as to which preventive medication is the most effective. We present a network meta-analysis to determine the effectiveness and rank of preventive drugs for chronic migraine in adults. METHODS: We identified, reviewed, and extracted data from randomised controlled trials (RCTs) of preventive drugs for chronic migraine with at least 200 participants. Data were analysed using network meta-analysis. FINDINGS: We included 12 RCTs of six medications (Eptinezumab, Erenumab, Fremanezumab, Galcanezumab, Onabotulinumtoxin A, and Topiramate) compared to placebo or each other. All drugs effectively reduced monthly headache and migraine days compared with placebo. The most effective drug for monthly headache days was Eptinezumab 300mg, with a mean difference of -2.46 days, 95% Credible Interval (CrI): -3.23 to -1.69. On the Surface Under the Cumulative Ranking Area (SUCRA) analysis, the probability that Eptinezumab 300mg was ranked highest was 0.82. For monthly migraine days, the most effective medication was Fremanezumab-monthly, with a mean difference: -2.77 days, 95% CrI: -3.36 to -2.17, and 0.98 probability of being ranked the highest. All included drugs, except Topiramate, improved headache-related quality of life. No eligible studies were identified for the other common preventive oral medications such as Amitriptyline, Candesartan, and Propranolol. The main reasons were that the studies did not define chronic migraine, were undertaken before the definition of chronic migraine, or were too small. INTERPRETATION: All six medications were more effective than the placebo on monthly headache and migraine days. The absolute differences in the number of headache/migraine days are, at best, modest. No evidence was found to determine the relative effectiveness of the six included drugs with other oral preventive medications. REGISTRATION: PROSPERO (number CRD42021265990).

Workplace wellbeing among health care workers providing HIV services in primary care in Johannesburg: a mixed methods study.

Background: Burnout among Health Care workers (HCWs) impacts on provider-patient relations and quality of care. Anova Health Institute (Anova) is a large South African non-profit organization and PEPFAR/USAID implementing partner. We conducted a study among HCWs providing HIV-related services in primary care settings in Johannesburg, South Africa, to examine levels of burnout, understand factors affecting workplace wellbeing, and explore strategies to prevent burnout. Methods: We used a sequential mixed-method approach. Data were collected between February and April 2022. The first phase consisted of a survey using the Maslach Burnout Inventory Human Services Survey (MBI-HSS) to measure levels of burnout. We then interviewed a subset of survey participants to understand the experiences that may affect wellbeing. We used descriptive statistics to quantify burnout rates for each MBI dimension (emotional exhaustion, personal accomplishment, and depersonalization). Qualitative data analysis was guided by the Job Demands-Resources Framework that explores the interactions between demands and resources in the workplace. Results: Survey findings (n = 194) revealed that although depersonalization rates were low at 6%, 21% of participants had high emotional exhaustion and 24% reported low professional accomplishment. Less than half (41%, n = 80) had scores in the high category for any one of the three MBI-HSS dimensions. The MBI-HSS dimensions differed significantly by type of work and job title. Roving positions (HCW working in more than one health facility) were more likely to experience higher emotional exhaustion and lower professional accomplishment. Qualitative findings (n = 25) indicate that a number of job demands, including high workload, inadequate mental health support, and challenging relationships with stakeholders, had a negative effect on HCWs' wellbeing. However, finding meaningfulness in their work, working as a team, and practicing autonomy were experienced as resources that reduced the negative effect of these demands. Conclusion: While measured burnout syndrome rates were low, various experiences negatively impacted at least one in five HCW. We identified key resources that provided buffering against workplace stressors. We recommend that as well as addressing key drivers of burnout, access to these resources should be fostered, for example by strengthening interventions that offer recognition, and promoting team interactions through social activities and support groups.

Evidence for stronger sexual selection in males than in females using an adapted method of Bateman's classic study of Drosophila melanogaster.

Bateman's principles, originally a test of Darwin's theoretical ideas, have since become fundamental to sexual selection theory and vital to contextualizing the role of anisogamy in sex differences of precopulatory sexual selection. Despite this, Bateman's principles have received substantial criticism, and researchers have highlighted both statistical and methodological errors, suggesting that Bateman's original experiment contains too much sampling bias for there to be any evidence of sexual selection. This study uses Bateman's original method as a template, accounting for two fundamental flaws in his original experiments, (a) viability effects and (b) a lack of mating behavior observation. Experimental populations of Drosophila melanogaster consisted of wild-type focal individuals and nonfocal individuals established by backcrossing the brown eye (bw-) eye-color marker-thereby avoiding viability effects. Mating assays included direct observation of mating behavior and total number of offspring, to obtain measures of mating success, reproductive success, and standardized variance measures based on Bateman's principles. The results provide observational support for Bateman's principles, particularly that (a) males had significantly more variation in number of mates compared with females and (b) males had significantly more individual variation in total number of offspring. We also find a significantly steeper Bateman gradient for males compared to females, suggesting that sexual selection is operating more intensely in males. However, female remating was limited, providing the opportunity for future study to further explore female reproductive success in correlation with higher levels of remating.

Outcomes of a model for re-testing HIV-negative index contacts in Sedibeng, South Africa.

Background: Index contact testing is an HIV case-finding approach that elicits sexual or needle-sharing partners, as well as biological children, of people living with HIV (PLHIV) and offers them HIV testing services. Objectives: We aim to describe the results of an innovative project in Sedibeng District that expanded index testing by retesting previously negative contacts and incorporating status-neutral testing. Method: We used registers to identify people who previously tested HIV-negative through index testing from March 2019 to September 2021. The individuals were telephonically traced and offered HIV retesting. Data were collected on a weekly basis using REDCap®. We monitored the number of individuals called, those who came back for retest, and their HIV results. Results: Fifteen counsellors contacted 968 people over 12 months. Forty-eight percent (462 out of 968) of those called returned for testing. Of those, 121 (26%) tested positive. Overall, 66 out of 276 (24%) men with HIV and 55 out of 186 (30%) women with HIV were identified and linked to antiretroviral treatment (ART). Fifty-seven percent (194 out of 341) of clients who tested HIV-negative were offered, and 124 out of 194 (64%) initiated, pre-exposure prophylaxis (PrEP). All individuals who retested HIV-positive had a new diagnosis; none reported having had another positive test result between the original negative and the positive retest. Conclusion: Revisiting index clients with a previous negative HIV test result is worthwhile, creating an opportunity to identify undiagnosed PLHIV and high-risk people for PrEP. The high positivity rate highlights the importance of providing a sero-neutral approach to HIV testing, including integrating prevention messaging and linkage to PrEP services.

Exploring healthcare workers' experiences of managing patients returning to HIV care in Johannesburg, South Africa.

BACKGROUND: Retention of patients in HIV care is a critical barrier to reaching the UNAIDS 90-90-90 goals in South Africa. In January 2019, Anova Health Institute launched a campaign to encourage patients who had interrupted antiretroviral therapy to return to care. The Welcome Back campaign included training of health care workers and implementation of Médecins Sans Frontiers Welcome Services principles. OBJECTIVE: The aim of this study was to explore the experiences of healthcare workers managing patients reinitiating antiretroviral therapy following training, including barriers and facilitators to implementation. METHODS: Data were collected from six clinics. This study consisted of three components: 1) surveys; 2) semi-structured interviews and 3) reflexive feedback sessions. Each component covered staff attitudes and facility management of patients reinitiating antiretroviral therapy. A descriptive analysis was conducted of survey responses. A thematic approach was used to analyze interviews. RESULTS: Thirty-six healthcare workers completed the survey and interview. Following analysis, feedback sessions were conducted with 99 healthcare workers. Twenty-two (61%) participants were lay counsellors. The majority of healthcare workers reported managing patients returning to care appropriately. However, barriers persisted: 9 (25%) responded that patients were sent to the back of the queue and that service providers continued to insist on transfer letters. Twenty-five (69%) responded they had seen/heard other healthcare workers act poorly towards returning patients after training. Many poor behaviours from healthcare workers stemmed from frustration with the clinical flow and their overburdened work environment. Many participants (78%) believed that the Welcome Back approach helped improve client-provider relationships. CONCLUSIONS: The Welcome Back approach supported healthcare workers to improve service provision for patients reinitiating antiretroviral therapy. Further support is needed to help providers consistently deliver services in line with the Welcome Back approach. Institutional level changes are required to implement patient-centred and trust-based models of care.

Why do patients interrupt and return to antiretroviral therapy? Retention in HIV care from the patient's perspective in Johannesburg, South Africa.

BACKGROUND: Retention in care is required for optimal clinical outcomes in people living with HIV (PLHIV). Although most PLHIV in South Africa know their HIV status, only 70% are on antiretroviral therapy (ART). Improved retention in care is needed to get closer to sustained ART for all. In January 2019, Anova Health Institute conducted a campaign to encourage patients who had interrupted ART to return to care. METHODS: Data collection was conducted in one region of Johannesburg. This mixed methods study consisted of two components: 1) healthcare providers entered data into a structured tool for all patients re-initiating ART at nine clinics over a nine-month period, 2) Semi-structured interviews were conducted with a sub-set of patients. Responses to the tool were analysed descriptively, we report frequencies, and percentages. A thematic approach was used to analyse participant experiences in-depth. RESULTS: 562 people re-initiated ART, 66% were women, 75% were 25-49 years old. The three most common reasons for disengagement from care were mobility (30%), ART related factors (15%), and time limitations due to work (10%). Reasons for returning included it becoming easier to attend the clinic (34%) and worry about not being on ART (19%). Mobile interview participants often forgot their medical files and expressed that managing their ART was difficult because they often needed a transfer letter to gain access to ART at another facility. On the other hand, clinics that had flexible and extended hours facilitated retention in care. CONCLUSION: In both the quantitative data, and the qualitative analysis, changing life circumstances was the most prominent reason for disengagement from care. Health services were not perceived to be responsive to life changes or mobility, leading to disengagement. More client-centred and responsive health services should improve retention on ART.

Community pharmacy advanced adherence services for children and young people with long-term conditions: A cross-sectional survey study.

OBJECTIVE: The aim of this study was to investigate the provision of community pharmacy services to children and young people with a focus on advanced services such as medicines use review. Perceptions and experiences of community pharmacists, pharmacy staff, young people and their parents or carers on the provision of such services were also explored. METHODS: Four different cross-sectional, self-administered questionnaires were distributed in parallel to pharmacists, pharmacy staff members, children and young people and parents in the United Kingdom. RESULTS: An outline of pharmacist's current involvement with children and young people was provided by 92 pharmacists. A different group of 38 community pharmacists and 40 non-pharmacist members of pharmacy staff from a total of 46 pharmacies provided information and views on the conduct of Medicines use review with children and young people. Experiences of advanced pharmacy service provision were collected from 51 children and young people and 18 parents. Most pharmacists offered public health advice to children and young people (73/92; 79.3%) and even more (83/92; 90.2%) reported that they often interacted with children and young people with long-term condition. Despite their high levels of interaction, and a majority opinion that medicines use reviews could benefit children (35/38; 92.1%), the number of pharmacies reporting to have conducted medicines use reviews with children was low (5/41). Pharmacists perceived the main barriers to recruitment as consent (17/29; 58.6%), guideline ambiguity (14/29; 48.3%) and training (13/29; 44.8%). A considerable proportion pharmacists (12/29; 41.4%) and other personnel (14/33; 42.4%) working in community pharmacies were unaware that children were potentially eligible for medicines use reviews. Only 29.4% of the 51 children and young people participants had received advice about their long-term condition from a pharmacist and the majority (46/51; 90.2%) had not taken part in an advanced service focused on adherence. CONCLUSIONS: While general engagement with children and young people appears high from the pharmacist's perspective, advice specific to children and young people with long-term conditions and the provision of advanced services in this group remains a challenge.

Community pharmacy advanced adherence services for children and young people with long-term conditions: a cross-sectional survey study

OBJECTIVE: The aim of this study was to investigate the provision of community pharmacy services to children and young people with a focus on advanced services such as medicines use review. Perceptions and experiences of community pharmacists, pharmacy staff, young people and their parents or carers on the provision of such services were also explored. METHODS: Four different cross-sectional, self-administered questionnaires were distributed in parallel to pharmacists, pharmacy staff members, children and young people and parents in the United Kingdom. RESULTS: An outline of pharmacist's current involvement with children and young people was provided by 92 pharmacists. A different group of 38 community pharmacists and 40 non-pharmacist members of pharmacy staff from a total of 46 pharmacies provided information and views on the conduct of Medicines use review with children and young people. Experiences of advanced pharmacy service provision were collected from 51 children and young people and 18 parents. Most pharmacists offered public health advice to children and young people (73/92; 79.3%) and even more (83/92; 90.2%) reported that they often interacted with children and young people with long-term condition. Despite their high levels of interaction, and a majority opinion that medicines use reviews could benefit children (35/38; 92.1%), the number of pharmacies reporting to have conducted medicines use reviews with children was low (5/41). Pharmacists perceived the main barriers to recruitment as consent (17/29; 58.6%), guideline ambiguity (14/29; 48.3%) and training (13/29; 44.8%). A considerable proportion pharmacists (12/29; 41.4%) and other personnel (14/33; 42.4%) working in community pharmacies were unaware that children were potentially eligible for medicines use reviews. Only 29.4% of the 51 children and young people participants had received advice about their long-term condition from a pharmacist and the majority (46/51; 90.2%) had not taken part in an advanced service focused on adherence. CONCLUSIONS: While general engagement with children and young people appears high from the pharmacist's perspective, advice specific to children and young people with long-term conditions and the provision of advanced services in this group remains a challenge

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CD4 testing after initiation of antiretroviral therapy: Analysis of routine data from the South African HIV programme.

BACKGROUND: People living with HIV (PLHIV) who have low CD4 counts require advanced clinical care (ACC) to minimise morbidity and mortality risk. These patients include immunological non-responders (INRs) with low CD4 counts despite a suppressed viral load. OBJECTIVES: To determine the proportion of patients with low CD4 counts after antiretroviral therapy (ART) initiation and to describe INRs within that group. METHODS: Routine Three Interlinked Electronic Registers.Net (TIER.Net) data from four South African districts were analysed for adult PLHIV on ART > 12 months. Immunological non-responders were defined as patients on ART > 4 years who were virally suppressed (viral load < 1000 copies/mL) with a CD4 count ≤ 350 cell/mm3. RESULTS: Baseline CD4 was recorded for 80.9% of the 869 571 patients newly initiating ART, with 37.2% of those starting ART since 2017 having baseline counts ≤ 200 cells/mm3. Amongst all 1 178 190 patients on ART, only 46.5% had a CD4 test after ART initiation and of these, 14.3% had CD4 ≤ 200 cells/mm3. This proportion was highest amongst patients on ART ≤ 2 years (19.7%) (p < 0.001). Amongst virally suppressed patients, 20.0% were INRs. Immunological non-response was significantly more likely amongst patients on second-line ART (adjusted odds ratio [aOR] 1.79), those aged 35-45 and ≥ 45 years (aOR 1.15 and 1.50, respectively), males (aOR 2.28) and patients with confirmed TB (aOR 2.49), and was significantly less likely in cases with higher baseline CD4 count (aOR 0.35). CONCLUSION: CD4 testing subsequent to ART initiation is poorly implemented and there is a notable proportion of patients with low CD4 counts. Guidelines regarding CD4 testing and ACC need to be more widely implemented to identify patients with low CD4 counts and improve their outcomes.

Seasonal variation in exploitative competition between honeybees and bumblebees.

Honeybees (Apis mellifera) and bumblebees (Bombus spp.) often undergo exploitative competition for shared floral resources, which can alter their foraging behaviour and flower choice, even causing competitive exclusion. This may be strongest in summer, when foraging conditions are most challenging for bees, compared to other times of the year. However, the seasonal dynamics of competition between these major pollinator groups are not well understood. Here, we investigate whether the strength of exploitative competition for nectar between honeybees and bumblebees varies seasonally, and whether competitive pressure is greatest in summer months. We carried out experimental bee exclusion trials from May to late September, using experimental patches of lavender, variety Grosso, in full bloom. In each trial, we compared the numbers of honeybees (HB) foraging on patches from which bumblebees had been manually excluded (bumblebee excluded, BBE) versus control (CON) patches, HB(BBE-CON). This measure of exploitative competition varied significantly with season. As expected, mean HB(BBE-CON) was significantly greater in summer trials than in spring or autumn trials. This was despite high nectar standing crop volumes in BBE patch flowers in spring and autumn trials. Mean HB(BBE-CON) was not different between spring and autumn trials. Our results show that nectar competition between honeybees and bumblebees varies seasonally and is stronger in summer than spring or autumn, adding to current understanding of the seasonality of resource demand and competition between bee species. This information may also help to inform conservation programs aiming to increase floral resources for bees by showing when these resources are most needed.

Clients' experiences utilizing a safer conception service for HIV affected individuals: implications for differentiated care service delivery models.

BACKGROUND: Safer conception services promote the reproductive health and rights of families, while minimizing HIV transmission risks between partners trying to conceive, as well vertical transmission risks. Implementation data, including clients' experiences utilizing safer conception services in sub-Saharan Africa are limited. METHODS: Hillbrow Community Health Centre began offering safer conception services for individuals and couples affected by HIV in Johannesburg, South Africa in June 2015. A stratified sub-sample of safer conception clients were consecutively recruited from April 2016-August 2017 for a cross-sectional interview assessing clients' perceptions of service acceptability and value, as well as perceived safer conception knowledge and self-efficacy. Visual analog scales from 0 to 100 were used to measure clients' experiences; scores were classified as low, moderate and high acceptance/value/knowledge/self-efficacy if they were < 50, 50-79 and ≥ 80 respectively. Comparisons of scores were made across safer conception visits attended. RESULTS: Among 692 clients utilizing safer conception services, 120 (17%) were sampled for the process evaluation; sub-sample participant characteristics were similar to the overall cohort. Clients gave a mean score of ≥90-points for each question assessing service acceptability and 96% (114/119) indicated a high perceived value (scores ≥80) for regular safer conception attendance until conception. Fifty-eight percent (n = 70) of clients reported learning something new during the visit completed the day of the survey, though acquisition of new information tended to decrease as visits increased (p = 0.09). In terms of safer conception strategies, 80% of clients reported high levels of knowledge on the impact of antiretroviral treatment (ART) and viral suppression on HIV transmission, 67% reported high levels of knowledge of the importance of STI screening and 56% regarding limiting condomless sex to days of peak fertility; 34% in sero-different relationships reported high pre-exposure prophylaxis (PrEP) knowledge. Self-efficacy varied by safer conception methods and was similar across study visits. CONCLUSIONS: Clients perceived high value from their safer conception visits and preferred regular attendance until conception, however we observed a plateau in knowledge and self-efficacy across subsequent visits after initially attending safer conception care. More intensive services may be appropriate for certain clients based on clinical circumstances, but many couples may potentially receive a 'lighter touch' approach while still minimizing HIV transmission risks.

Integrating Cervical Cancer Screening Into Safer Conception Services to Improve Women's Health Outcomes: A Pilot Study at a Primary Care Clinic in South Africa.

BACKGROUND: Sub-optimal cervical cancer screening in low- and middle-income countries contributes to preventable cervical cancer deaths, particularly among human immunodeficiency virus (HIV)-positive women. We assessed feasibility and outcomes of integrating cervical cancer screening into safer conception services for HIV-affected women. METHODS: At a safer conception service in Johannesburg, South Africa, HIV-affected women desiring pregnancy received a standard package of care designed to minimize HIV transmission risks while optimizing prepregnancy health. All eligible women were offered Papanicolaou smear, and those with significant pathology were referred for colposcopy before attempting pregnancy. Multivariable analyses identified associations between patient characteristics and abnormal pathology. RESULTS: In total, 454 women were enrolled between June 2015 and April 2017. At enrolment, 91% were HIV-positive, 92% were on antiretroviral therapy (ART) and 82% virally suppressed. Eighty-three percent (376 of 454) of clients were eligible for cervical cancer screening and 85% (321 of 376) of these completed screening. More than half had abnormal cervical pathology (185 of 321) and 20% required colposcopy for possible high-grade or persistently atypical lesions (64 of 321). Compared with HIV-negative women, abnormal pathology was more likely among HIV-positive women, both those on ART <2 years (adjusted prevalence ratio, 2.5; 95% confidence interval, 1.2-5.0) and those on ART 2 years or longer (adjusted prevalence ratio, 2.1; 95% confidence interval, 1.0-4.2). CONCLUSIONS: Integrating cervical cancer screening into safer conception care was feasible with high coverage, including for HIV-positive women. Significant pathology, requiring colposcopy, was common, even among healthy women on ART. Safer conception services present an opportunity for integration of cervical cancer screening to avert preventable cancer-related deaths among HIV-affected women planning pregnancy.

Global and national guidance for the use of pre-exposure prophylaxis during peri-conception, pregnancy and breastfeeding.

Pre-exposure prophylaxis (PrEP) is a well-established biomedical HIV prevention strategy and recommended to reduce HIV risk during peri-conception, pregnancy and breastfeeding. Efforts are needed to translate global recommendations into national guidelines and implementation strategies. This article presents the current status of policy guidance for the use of PrEP during peri-conception, pregnancy and breastfeeding, with a particular focus on high prevalence countries, including those in sub-Saharan Africa. PrEP clinical guidelines released by ministries of health or other national-level health bodies, with a particular focus on recommendations for PrEP use during peri-conception, pregnancy and breastfeeding, were reviewed and summarised. Among countries with PrEP guidelines and/or policy, pregnancy is recognised as a period with increased HIV vulnerability, and some recommend PrEP use specifically during pregnancy. Only one country notes that PrEP is contraindicated during pregnancy, recognising a gap in complete safety data from women using PrEP throughout pregnancy. PrEP is not contraindicated as a peri-conception HIV prevention strategy in any country, but only three countries have specific guidance for peri-conception HIV prevention. Multiple barriers to the implementation of PrEP during pregnancy and breastfeeding are discussed, including barriers at the policy, health systems, social and personal levels. Although pregnancy is a period of heightened risk and fertility rates are high in many settings with high HIV burden, few PrEP policies have included guidance for PrEP use specific to peri-conception, pregnancy and breastfeeding periods. This gap can be overcome by the development or adoption of national clinical guidelines and implementation strategies from exemplary countries.