Treading the thin line: pharmacy workers’ perspectives on medication abortion provision in Lusaka, Zambia

Context: Despite liberal abortion laws, safe abortion access in Zambia is impeded by limited legal awareness, lack of services, and restrictive clinical policies. As in many countries with restricted abortion access, women frequently seek abortions informally from pharmacies. Methods: We conducted 16 in-depth interviews in 2019 to understand the experiences and motivations of pharmacy workers who sell medication abortion (MA) drugs in Lusaka. Results: We found that pharmacy staff reluctantly assume a gatekeeper role for MA due to competing pressures from clients and from regulatory constraints. Pharmacy staff often decide to provide MA, motivated by their duty of care and desire to help clients, as well as financial interests. However, pharmacy workers’ motivation to protect themselves from legal and business risk perpetuates inequalities in abortion access, as pharmacy workers improvise additional eligibility criteria based on personal risk and values such as age, partner approval, reason for abortion and level of desperation. Conclusion: These findings highlight how pharmacy staff informally determine women’s abortion access when laws and policies prevent comprehensive access to safe abortion. Reform of clinical guidelines, public education, strengthened public sector availability, task-sharing, and improved access to prescription services are needed to ensure women can legally access safe abortion

Safety, Quality, and Acceptability of Contraceptive Subdermal Implant Provision by Community Health Extension Workers Versus Nurses and Midwives in Nigeria: Protocol for a Quasi-Experimental, Noninferiority Study.

BACKGROUND: As part of its Family Planning 2020 commitment, the Nigerian government is aiming for a contraceptive prevalence rate of 36% by 2018, and in 2014, approved a policy to allow community health extension workers (CHEWs), in addition to doctors, nurses, and midwives, to provide contraceptive subdermal implants. There is a lack of rigorous evidence on the safety of long-acting reversible contraceptive provision, such as implants, among lower cadres of health providers. OBJECTIVE: This study aimed to compare implant provision by CHEWs versus nurses and midwives up to 14 days post insertion. METHODS: The quasi-experimental, noninferiority study will take place in public sector facilities in Kaduna and Ondo States. In each state, we will select 60 facilities, and from these, we will select a total of 30 nurses and midwives and 30 CHEWs to participate. Selected providers will be trained to provide implant services. Once trained, providers will recruit a minimum of 8125 women aged between 18 and 49 years who request and are eligible for an implant, following comprehensive family planning counseling. During implant insertion, providers will record data about the process and any adverse events, and 14 days post insertion, providers will ask 4410 clients about adverse events arising from the implant. Supervisors will observe 792 implant insertions to assess service provision quality and ask clients about their satisfaction with the procedure. We will conclude noninferiority if the CI for the difference in the proportion of adverse events between CHEWs and nurses and midwives on the day of insertion or 14 days post insertion lies to the right of -2%. RESULTS: In September and October 2015, we trained 60 CHEWs and a total of 60 nurses and midwives from 12 local government areas (LGAs) in Kaduna and 23 LGAs in Ondo. Recruitment took place between November 2015 and December 2016. Data analysis is being finalized, and results are expected in March 2018. CONCLUSIONS: The strength of this study is having a standard care (nurse and midwife provision) group with which CHEW provision can be compared. The intervention builds on existing training and supervision procedures, which increases the sustainability and scalability of CHEW implant provision. Important limitations include the lack of randomization due to nurses and midwives in Nigeria working in separate types of health care facilities compared with CHEWs, and that providers self-assess their own practices. It is unfeasible to observe all procedures independently, and observation may change practice. Although providers will be trained to conduct implant removals, the study time will be too short to reach the sample size required to make noninferiority comparisons for removals. TRIAL REGISTRATION: ClinicalTrials.gov NCT03088722; https://clinicaltrials.gov/ct2/show/NCT03088722 (Archived by WebCite at http://www.webcitation.org/6xIHImWvu)

Safety, Quality, and Acceptability of Contraceptive Implant Provision by Community Health Extension Workers versus Nurses and Midwives in Two States in Nigeria.

Task sharing is a strategy with potential to increase access to effective modern contraceptive methods. This study examines whether community health extension workers (CHEWs) can insert contraceptive implants to the same safety and quality standards as nurse/midwives. We analyze data from 7,691 clients of CHEWs and nurse/midwives who participated in a noninferiority study conducted in Kaduna and Ondo States, Nigeria. Adverse events (AEs) following implant insertions were compared. On the day of insertion AEs were similar among CHEW and nurse/midwife clients-0.5 percent and 0.4 percent, adjusted odds ratio (aOR) 0.92 (95 percent CI 0.38-2.23)-but noninferiority could not be established. At follow-up 6.6 percent of CHEW clients and 2.1 percent of nurse/midwife clients experienced AEs. There was strong evidence of effect modification by State. In the final adjusted model, odds of AEs for CHEW clients in Kaduna was 3.34 (95 percent CI 1.53-7.33) compared to nurse/midwife clients, and 0.72 (95 percent CI 0.19-2.72]) in Ondo. Noninferiority could not be established in either State. Implant expulsions were higher among CHEW clients (142/2987) compared to nurse/midwives (40/3517). Results show the feasibility of training CHEWs to deliver implants in remote rural settings but attention must be given to provider selection, training, supervision, and follow-up to ensure safety and quality of provision

Unintended consequences of mHealth interactive voice messages promoting contraceptive use after menstrual regulation in Bangladesh : intimate partner violence results from a randomized controlled trial

This study is funded by UK aid from the UK government. It was part-funded through the Strengthening Evidence for Programming on Unintended Pregnancy (STEP-UP) Research Consortium, managed by the Population Council. KR was funded by an ESRC PhD fellowship.Background: Mobile phones for health (mHealth) hold promise for delivering behavioral interventions. We evaluated the effect of automated interactive voice messages promoting contraceptive use with a focus on long-acting reversible contraceptives (LARCs) among women in Bangladesh who had undergone menstrual regulation (MR), a procedure to “regulate the menstrual cycle when menstruation is absent for a short duration.” Methods: We recruited MR clients from 41 public- and private-sector clinics immediately after MR. Eligibility criteria included having a personal mobile phone and consenting to receive messages about family planning by phone. We randomized participants remotely to an intervention group that received at least 11 voice messages about contraception over 4 months or to a control group (no messages). The primary outcome was LARC use at 4 months. Adverse events measured included experience of intimate partner violence (IPV). Researchers recruiting participants and 1 analyst were blinded to allocation groups. All analyses were intention to treat. The trial is registered with ClinicalTrials.gov (NCT02579785). Results: Between December 2015 and March 2016, 485 women were allocated to the intervention group and 484 to the control group. We completed follow-up on 389 intervention and 383 control participants. Forty-eight (12%) participants in the intervention group and 59 (15%) in the control group reported using a LARC method at 4 months (adjusted odds ratio [aOR] using multiple imputation=0.95; 95% confidence interval [CI]=0.49 to 1.83; P=.22). Reported physical IPV was higher in the intervention group: 42 (11%) intervention versus 25 (7%) control (aOR=1.97; 95% CI=1.12 to 3.46; P=.03) when measured using a closed question naming acts of violence. No violence was reported in response to an open question about effects of being in the study. Conclusions: The intervention did not increase LARC use but had an unintended consequence of increasing self-reported IPV. Researchers and health program designers should consider possible negative impacts when designing and evaluating mHealth and other reproductive health interventions. IPV must be measured using closed questions naming acts of violence.Publisher PDFPeer reviewe

Procalcitonin Is Not a Reliable Biomarker of Bacterial Coinfection in People With Coronavirus Disease 2019 Undergoing Microbiological Investigation at the Time of Hospital Admission

Abstract Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in bacterial coinfection, this was neither clinically significant (median [IQR], 0.33 [0.11–1.70] ng/mL vs 0.24 [0.10–0.90] ng/mL) nor diagnostically useful (area under the receiver operating characteristic curve, 0.56 [95% confidence interval, .51–.60]).</jats:p

Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study

BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study.

Background: Early in the pandemic it was suggested that pre-existing use of non-steroidal anti-inflammatory drugs (NSAIDs) could lead to increased disease severity in patients with COVID-19. NSAIDs are an important analgesic, particularly in those with rheumatological disease, and are widely available to the general public without prescription. Evidence from community studies, administrative data, and small studies of hospitalised patients suggest NSAIDs are not associated with poorer COVID-19 outcomes. We aimed to characterise the safety of NSAIDs and identify whether pre-existing NSAID use was associated with increased severity of COVID-19 disease. Methods: This prospective, multicentre cohort study included patients of any age admitted to hospital with a confirmed or highly suspected SARS-CoV-2 infection leading to COVID-19 between Jan 17 and Aug 10, 2020. The primary outcome was in-hospital mortality, and secondary outcomes were disease severity at presentation, admission to critical care, receipt of invasive ventilation, receipt of non-invasive ventilation, use of supplementary oxygen, and acute kidney injury. NSAID use was required to be within the 2 weeks before hospital admission. We used logistic regression to estimate the effects of NSAIDs and adjust for confounding variables. We used propensity score matching to further estimate effects of NSAIDS while accounting for covariate differences in populations. Results: Between Jan 17 and Aug 10, 2020, we enrolled 78 674 patients across 255 health-care facilities in England, Scotland, and Wales. 72 179 patients had death outcomes available for matching; 40 406 (56·2%) of 71 915 were men, 31 509 (43·8%) were women. In this cohort, 4211 (5·8%) patients were recorded as taking systemic NSAIDs before admission to hospital. Following propensity score matching, balanced groups of NSAIDs users and NSAIDs non-users were obtained (4205 patients in each group). At hospital admission, we observed no significant differences in severity between exposure groups. After adjusting for explanatory variables, NSAID use was not associated with worse in-hospital mortality (matched OR 0·95, 95% CI 0·84–1·07; p=0·35), critical care admission (1·01, 0·87–1·17; p=0·89), requirement for invasive ventilation (0·96, 0·80–1·17; p=0·69), requirement for non-invasive ventilation (1·12, 0·96–1·32; p=0·14), requirement for oxygen (1·00, 0·89–1·12; p=0·97), or occurrence of acute kidney injury (1·08, 0·92–1·26; p=0·33). Interpretation: NSAID use is not associated with higher mortality or increased severity of COVID-19. Policy makers should consider reviewing issued advice around NSAID prescribing and COVID-19 severity. Funding: National Institute for Health Research and Medical Research Council

Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study

Background: Microbiological characterisation of co-infections and secondary infections in patients with COVID-19 is lacking, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and secondary infections, and antimicrobial use, in patients admitted to hospital with COVID-19. Methods: The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study is an ongoing, prospective cohort study recruiting inpatients from 260 hospitals in England, Scotland, and Wales, conducted by the ISARIC Coronavirus Clinical Characterisation Consortium. Patients with a confirmed or clinician-defined high likelihood of SARS-CoV-2 infection were eligible for inclusion in the ISARIC WHO CCP-UK study. For this specific study, we excluded patients with a recorded negative SARS-CoV-2 test result and those without a recorded outcome at 28 days after admission. Demographic, clinical, laboratory, therapeutic, and outcome data were collected using a prespecified case report form. Organisms considered clinically insignificant were excluded. Findings: We analysed data from 48 902 patients admitted to hospital between Feb 6 and June 8, 2020. The median patient age was 74 years (IQR 59–84) and 20 786 (42·6%) of 48 765 patients were female. Microbiological investigations were recorded for 8649 (17·7%) of 48 902 patients, with clinically significant COVID-19-related respiratory or bloodstream culture results recorded for 1107 patients. 762 (70·6%) of 1080 infections were secondary, occurring more than 2 days after hospital admission. Staphylococcus aureus and Haemophilus influenzae were the most common pathogens causing respiratory co-infections (diagnosed ≤2 days after admission), with Enterobacteriaceae and S aureus most common in secondary respiratory infections. Bloodstream infections were most frequently caused by Escherichia coli and S aureus. Among patients with available data, 13 390 (37·0%) of 36 145 had received antimicrobials in the community for this illness episode before hospital admission and 39 258 (85·2%) of 46 061 patients with inpatient antimicrobial data received one or more antimicrobials at some point during their admission (highest for patients in critical care). We identified frequent use of broad-spectrum agents and use of carbapenems rather than carbapenem-sparing alternatives. Interpretation: In patients admitted to hospital with COVID-19, microbiologically confirmed bacterial infections are rare, and more likely to be secondary infections. Gram-negative organisms and S aureus are the predominant pathogens. The frequency and nature of antimicrobial use are concerning, but tractable targets for stewardship interventions exist. Funding: National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, UK Department for International Development, Bill &amp; Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, and NIHR HPRU in Respiratory Infections at Imperial College London

Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study

Background: Microbiological characterisation of co-infections and secondary infections in patients with COVID-19 is lacking, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and secondary infections, and antimicrobial use, in patients admitted to hospital with COVID-19. Methods: The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study is an ongoing, prospective cohort study recruiting inpatients from 260 hospitals in England, Scotland, and Wales, conducted by the ISARIC Coronavirus Clinical Characterisation Consortium. Patients with a confirmed or clinician-defined high likelihood of SARS-CoV-2 infection were eligible for inclusion in the ISARIC WHO CCP-UK study. For this specific study, we excluded patients with a recorded negative SARS-CoV-2 test result and those without a recorded outcome at 28 days after admission. Demographic, clinical, laboratory, therapeutic, and outcome data were collected using a prespecified case report form. Organisms considered clinically insignificant were excluded. Findings: We analysed data from 48 902 patients admitted to hospital between Feb 6 and June 8, 2020. The median patient age was 74 years (IQR 59–84) and 20 786 (42·6%) of 48 765 patients were female. Microbiological investigations were recorded for 8649 (17·7%) of 48 902 patients, with clinically significant COVID-19-related respiratory or bloodstream culture results recorded for 1107 patients. 762 (70·6%) of 1080 infections were secondary, occurring more than 2 days after hospital admission. Staphylococcus aureus and Haemophilus influenzae were the most common pathogens causing respiratory co-infections (diagnosed ≤2 days after admission), with Enterobacteriaceae and S aureus most common in secondary respiratory infections. Bloodstream infections were most frequently caused by Escherichia coli and S aureus. Among patients with available data, 13 390 (37·0%) of 36 145 had received antimicrobials in the community for this illness episode before hospital admission and 39 258 (85·2%) of 46 061 patients with inpatient antimicrobial data received one or more antimicrobials at some point during their admission (highest for patients in critical care). We identified frequent use of broad-spectrum agents and use of carbapenems rather than carbapenem-sparing alternatives. Interpretation: In patients admitted to hospital with COVID-19, microbiologically confirmed bacterial infections are rare, and more likely to be secondary infections. Gram-negative organisms and S aureus are the predominant pathogens. The frequency and nature of antimicrobial use are concerning, but tractable targets for stewardship interventions exist. Funding: National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, UK Department for International Development, Bill &amp; Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, and NIHR HPRU in Respiratory Infections at Imperial College London