Effectiveness and safety of COVID-19 vaccines on maternal and perinatal outcomes: a systematic review and meta-analysis.

OBJECTIVE: To assess the effects of COVID-19 vaccines in women before or during pregnancy on SARS-CoV-2 infection-related, pregnancy, offspring and reactogenicity outcomes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Major databases between December 2019 and January 2023. STUDY SELECTION: Nine pairs of reviewers contributed to study selection. We included test-negative designs, comparative cohorts and randomised trials on effects of COVID-19 vaccines on infection-related and pregnancy outcomes. Non-comparative cohort studies reporting reactogenicity outcomes were also included. QUALITY ASSESSMENT, DATA EXTRACTION AND ANALYSIS: Two reviewers independently assessed study quality and extracted data. We undertook random-effects meta-analysis and reported findings as HRs, risk ratios (RRs), ORs or rates with 95% CIs. RESULTS: Sixty-seven studies (1 813 947 women) were included. Overall, in test-negative design studies, pregnant women fully vaccinated with any COVID-19 vaccine had 61% reduced odds of SARS-CoV-2 infection during pregnancy (OR 0.39, 95% CI 0.21 to 0.75; 4 studies, 23 927 women; I2=87.2%) and 94% reduced odds of hospital admission (OR 0.06, 95% CI 0.01 to 0.71; 2 studies, 868 women; I2=92%). In adjusted cohort studies, the risk of hypertensive disorders in pregnancy was reduced by 12% (RR 0.88, 95% CI 0.82 to 0.92; 2 studies; 115 085 women), while caesarean section was reduced by 9% (OR 0.91, 95% CI 0.85 to 0.98; 6 studies; 30 192 women). We observed an 8% reduction in the risk of neonatal intensive care unit admission (RR 0.92, 95% CI 0.87 to 0.97; 2 studies; 54 569 women) in babies born to vaccinated versus not vaccinated women. In general, vaccination during pregnancy was not associated with increased risk of adverse pregnancy or perinatal outcomes. Pain at the injection site was the most common side effect reported (77%, 95% CI 52% to 94%; 11 studies; 27 195 women). CONCLUSION: COVID-19 vaccines are effective in preventing SARS-CoV-2 infection and related complications in pregnant women. PROSPERO REGISTRATION NUMBER: CRD42020178076.

Health and illness beliefs in adults with tuberculosis infection during the COVID-19 pandemic in the UK.

Background: COVID-19 disrupted the TB prevention programme in the UK, especially for TB infection (TBI) care. We explore whether experience of the COVID-19 pandemic impacted on patients' perceptions of TBI and its treatment. Methods: Semi-structured interviews were conducted as part of the Research to Improve Detection and Treatment of TBI (RID-TB) programme, exploring perceptual and practical barriers to TBI treatment. Nineteen people diagnosed with TBI were interviewed between August 2020 and April 2021. Recordings were transcribed and analysed using a constant comparative approach, allowing for a dynamic and iterative exploration of themes. Themes are organised using the Perceptions and Practicalities Approach. Findings: Some participants perceived TBI as a risk factor for increased susceptibility to COVID-19, while some thought that treatment for TBI might protect against COVID-19 or mitigate its effects. Adaptations to TB services (e.g., remote follow-up) and integrated practices during the COVID-19 restrictions (e.g., medication being posted) addressed some practical barriers to TBI treatment. However, we identified beliefs about TBI and COVID-19 that are likely to act as barriers to engagement with TBI treatment, including: interpreting service delays as an indication of TBI not being serious enough for treatment and concerns about contracting COVID-19 in TB clinics. Interpretation: COVID-19 and TBI service delays influence people's perceptions and practical barriers to TBI treatment adherence. Failure to address these beliefs may lead to people's concerns about their treatment not being fully addressed. Utilised service adaptations like remote consultations to address practical barriers may be relevant beyond COVID-19. Funding: NIHR RID-TB Program (RP-PG-0217-20009).

Extrapulmonary nontuberculous mycobacterial infections: a guide for the general physician.

Non-tuberculous mycobacteria (NTM) infections predominantly present as pulmonary disease. Although relatively rare, 20-30 % originate from extrapulmonary sites resulting in a wide range of clinical syndromes. Immunocompromised individuals are particularly susceptible. Clinical manifestations include skin and soft-tissue infections, lymphadenitis, musculoskeletal infections and disseminated disease. Diagnosing extrapulmonary NTM is challenging, and management is complex, often involving multiple radiological and microbiological investigations, long courses of combination antibiotic regimens and may require adjuvant surgical interventions. We highlight both the importance of involving NTM experts at an early stage and the role of a multidisciplinary approach in the diagnosis and management of these infections.

COVID-19 in pregnant women: a systematic review and meta-analysis on the risk and prevalence of pregnancy loss.

BACKGROUND: Pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to experience preterm birth and their neonates are more likely to be stillborn or admitted to a neonatal unit. The World Health Organization declared in May 2023 an end to the coronavirus disease 2019 (COVID-19) pandemic as a global health emergency. However, pregnant women are still becoming infected with SARS-CoV-2 and there is limited information available regarding the effect of SARS-CoV-2 infection in early pregnancy on pregnancy outcomes. OBJECTIVE AND RATIONALE: We conducted this systematic review to determine the prevalence of early pregnancy loss in women with SARS-Cov-2 infection and compare the risk to pregnant women without SARS-CoV-2 infection. SEARCH METHODS: Our systematic review is based on a prospectively registered protocol. The search of PregCov19 consortium was supplemented with an extra electronic search specifically on pregnancy loss in pregnant women infected with SARS-CoV-2 up to 10 March 2023 in PubMed, Google Scholar, and LitCovid. We included retrospective and prospective studies of pregnant women with SARS-CoV-2 infection, provided that they contained information on pregnancy losses in the first and/or second trimester. Primary outcome was miscarriage defined as a pregnancy loss before 20 weeks of gestation, however, studies that reported loss up to 22 or 24 weeks were also included. Additionally, we report on studies that defined the pregnancy loss to occur at the first and/or second trimester of pregnancy without specifying gestational age, and for second trimester miscarriage only when the study presented stillbirths and/or foetal losses separately from miscarriages. Data were stratified into first and second trimester. Secondary outcomes were ectopic pregnancy (any extra-uterine pregnancy), and termination of pregnancy. At least three researchers independently extracted the data and assessed study quality. We calculated odds ratios (OR) and risk differences (RDs) with corresponding 95% CI and pooled the data using random effects meta-analysis. To estimate risk prevalence, we performed meta-analysis on proportions. Heterogeneity was assessed by I2. OUTCOMES: We included 120 studies comprising a total of 168 444 pregnant women with SARS-CoV-2 infection; of which 18 233 women were in their first or second trimester of pregnancy. Evidence level was considered to be of low to moderate certainty, mostly owing to selection bias. We did not find evidence of an association between SARS-CoV-2 infection and miscarriage (OR 1.10, 95% CI 0.81-1.48; I2 = 0.0%; RD 0.0012, 95% CI -0.0103 to 0.0127; I2 = 0%; 9 studies, 4439 women). Miscarriage occurred in 9.9% (95% CI 6.2-14.0%; I2 = 68%; 46 studies, 1797 women) of the women with SARS CoV-2 infection in their first trimester and in 1.2% (95% CI 0.3-2.4%; I2 = 34%; 33 studies; 3159 women) in the second trimester. The proportion of ectopic pregnancies in women with SARS-CoV-2 infection was 1.4% (95% CI 0.02-4.2%; I2 = 66%; 14 studies, 950 women). Termination of pregnancy occurred in 0.6% of the women (95% CI 0.01-1.6%; I2 = 79%; 39 studies; 1166 women). WIDER IMPLICATIONS: Our study found no indication that SARS-CoV-2 infection in the first or second trimester increases the risk of miscarriages. To provide better risk estimates, well-designed studies are needed that include pregnant women with and without SARS-CoV-2 infection at conception and early pregnancy and consider the association of clinical manifestation and severity of SARS-CoV-2 infection with pregnancy loss, as well as potential confounding factors such as previous pregnancy loss. For clinical practice, pregnant women should still be advised to take precautions to avoid risk of SARS-CoV-2 exposure and receive SARS-CoV-2 vaccination.

Tuberculosis incidence in foreign-born people residing in European countries in 2020.

BackgroundEuropean-specific policies for tuberculosis (TB) elimination require identification of key populations that benefit from TB screening.AimWe aimed to identify groups of foreign-born individuals residing in European countries that benefit most from targeted TB prevention screening.MethodsThe Tuberculosis Network European Trials group collected, by cross-sectional survey, numbers of foreign-born TB patients residing in European Union (EU) countries, Iceland, Norway, Switzerland and the United Kingdom (UK) in 2020 from the 10 highest ranked countries of origin in terms of TB cases in each country of residence. Tuberculosis incidence rates (IRs) in countries of residence were compared with countries of origin.ResultsData on 9,116 foreign-born TB patients in 30 countries of residence were collected. Main countries of origin were Eritrea, India, Pakistan, Morocco, Romania and Somalia. Tuberculosis IRs were highest in patients of Eritrean and Somali origin in Greece and Malta (both > 1,000/100,000) and lowest among Ukrainian patients in Poland (3.6/100,000). They were mainly lower in countries of residence than countries of origin. However, IRs among Eritreans and Somalis in Greece and Malta were five times higher than in Eritrea and Somalia. Similarly, IRs among Eritreans in Germany, the Netherlands and the UK were four times higher than in Eritrea.ConclusionsCountry of origin TB IR is an insufficient indicator when targeting foreign-born populations for active case finding or TB prevention policies in the countries covered here. Elimination strategies should be informed by regularly collected country-specific data to address rapidly changing epidemiology and associated risks.

A feasibility study evaluating the uptake, effectiveness and acceptability of routine screening of pregnant migrants for latent tuberculosis infection in antenatal care: a research protocol.

INTRODUCTION: Globally, tuberculosis (TB) is a leading cause of death in women of reproductive age and there is high risk of reactivation of latent tuberculosis infection (LTBI) in pregnancy. The uptake of routine screening of migrants for LTBI in the UK in primary care is low. Antenatal care is a novel setting which could improve uptake and can lend insight into the feasibility and acceptability of offering opt-out screening for LTBI. METHODS AND ANALYSIS: This is an observational feasibility study with a nested qualitative component. The setting will be the antenatal clinics in three hospitals in East London, UK . Inclusion criteria are pregnant migrant women aged 16-35 years attending antenatal clinics who are from countries with a TB incidence of greater than 150/100 000 including sub-Saharan Africa, and who have been in the UK for less than 5 years. Participants will be offered LTBI screening with an opt-out interferon gamma release assay blood test, and be invited to complete a questionnaire. Both participants and healthcare providers will be invited to participate in semistructured interviews or focus groups to evaluate understanding, feasibility and acceptability of routine opt-out LTBI screening. The primary analysis will focus on estimating the uptake of the screening programme along with the corresponding 95% CI. Secondary analysis will focus on estimating the test positivity. Qualitative analysis will evaluate the acceptability of offering routine opt-out LTBI screening to participants and healthcare providers. ETHICS AND DISSEMINATION: The study has received the following approvals: Health Research Authority (IRAS 247388) and National Health Service Ethics Committee (19/LO/0557). The results will be made available locally to antenatal clinics and primary care physicians, nationally to NHS England and Public Health England and internationally through conferences and journals. TRIAL REGISTRATION NUMBER: NCT04098341.

Country-specific lockdown measures in response to the COVID-19 pandemic and its impact on tuberculosis control: a global study.

The objective of this study was to describe country-specific lockdown measures and tuberculosis indicators collected during the first year of the COVID-19 pandemic. Data on lockdown/social restrictions (compulsory face masks and hand hygiene; international and local travel restrictions; restrictions to family visits, and school closures) were collected from 24 countries spanning five continents. The majority of the countries implemented multiple lockdowns with partial or full reopening. There was an overall decrease in active tuberculosis, drug-resistant tuberculosis, and latent tuberculosis cases. Although national lockdowns were effective in containing COVID-19 cases, several indicators of tuberculosis were affected during the pandemic.

SARS-CoV-2 positivity in offspring and timing of mother-to-child transmission: living systematic review and meta-analysis.

OBJECTIVES: To assess the rates of SARS-CoV-2 positivity in babies born to mothers with SARS-CoV-2 infection, the timing of mother-to-child transmission and perinatal outcomes, and factors associated with SARS-CoV-2 status in offspring. DESIGN: Living systematic review and meta-analysis. DATA SOURCES: Major databases between 1 December 2019 and 3 August 2021. STUDY SELECTION: Cohort studies of pregnant and recently pregnant women (including after abortion or miscarriage) who sought hospital care for any reason and had a diagnosis of SARS-CoV-2 infection, and also provided data on offspring SARS-CoV-2 status and risk factors for positivity. Case series and case reports were also included to assess the timing and likelihood of mother-to-child transmission in SARS-CoV-2 positive babies. DATA EXTRACTION: Two reviewers independently extracted data and assessed study quality. A random effects model was used to synthesise data for rates, with associations reported using odds ratios and 95% confidence intervals. Narrative syntheses were performed when meta-analysis was inappropriate. The World Health Organization classification was used to categorise the timing of mother-to-child transmission (in utero, intrapartum, early postnatal). RESULTS: 472 studies (206 cohort studies, 266 case series and case reports; 28 952 mothers, 18 237 babies) were included. Overall, 1.8% (95% confidence interval 1.2% to 2.5%; 140 studies) of the 14 271 babies born to mothers with SARS-CoV-2 infection tested positive for the virus with reverse transcriptase polymerase chain reaction (RT-PCR). Of the 592 SARS-CoV-2 positive babies with data on the timing of exposure and type and timing of tests, 14 had confirmed mother-to-child transmission: seven in utero (448 assessed), two intrapartum (18 assessed), and five during the early postnatal period (70 assessed). Of the 800 SARS-CoV-2 positive babies with outcome data, 20 were stillbirths, 23 were neonatal deaths, and eight were early pregnancy losses; 749 babies were alive at the end of follow-up. Severe maternal covid-19 (odds ratio 2.4, 95% confidence interval 1.3 to 4.4), maternal death (14.1, 4.1 to 48.0), maternal admission to an intensive care unit (3.5, 1.7 to 6.9), and maternal postnatal infection (5.0, 1.2 to 20.1) were associated with SARS-CoV-2 positivity in offspring. Positivity rates using RT-PCR varied between regions, ranging from 0.1% (95% confidence interval 0.0% to 0.3%) in studies from North America to 5.7% (3.2% to 8.7%) in studies from Latin America and the Caribbean. CONCLUSION: SARS-CoV-2 positivity rates were found to be low in babies born to mothers with SARS-CoV-2 infection. Evidence suggests confirmed vertical transmission of SARS-CoV-2, although this is likely to be rare. Severity of maternal covid-19 appears to be associated with SARS-CoV-2 positivity in offspring. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178076. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Evaluating the effect of short-course rifapentine-based regimens with or without enhanced behaviour-targeted treatment support on adherence and completion of treatment for latent tuberculosis infection among adults in the UK (RID-TB: Treat): protocol for an open-label, multicentre, randomised controlled trial.

INTRODUCTION: The successful scale-up of a latent tuberculosis (TB) infection testing and treatment programme is essential to achieve TB elimination. However, poor adherence compromises its therapeutic effectiveness. Novel rifapentine-based regimens and treatment support based on behavioural science theory may improve treatment adherence and completion. METHODS AND ANALYSIS: A pragmatic multicentre, open-label, randomised controlled trial assessing the effect of novel short-course rifapentine-based regimens for TB prevention and additional theory-based treatment support on treatment adherence against standard-of-care. Participants aged between 16 and 65 who are eligible to start TB preventive therapy will be recruited in England. 920 participants will be randomised to one of six arms with allocation ratio of 5:5:6:6:6:6: daily isoniazid +rifampicin for 3 months (3HR), routine treatment support (control); 3HR, additional treatment support; weekly isoniazid +rifapentine for 3 months (3HP), routine treatment support; weekly 3HP, additional treatment support ; daily isoniazid +rifapentine for 1 month (1HP), routine treatment support; daily 1HP, additional treatment support. Additional treatment support comprises reminders using an electronic pillbox, a short animation, and leaflets based on the perceptions and practicalities approach. The primary outcome is adequate treatment adherence, defined as taking ≥90% of allocated doses within the pre-specified treatment period, measured by electronic pillboxes. Secondary outcomes include safety and TB incidence within 12 months. We will conduct process evaluation of the trial interventions and assess intervention acceptability and fidelity and mechanisms for effect and estimate the cost-effectiveness of novel regimens. The protocol was developed with patient and public involvement, which will continue throughout the trial. ETHICS AND DISSEMINATION: Ethics approval has been obtained from The National Health Service Health Research Authority (20/LO/1097). All participants will be required to provide written informed consent. We will share the results in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EudraCT 2020-004444-29.

Country-specific lockdown measures in response to the COVID-19 pandemic and its impact on tuberculosis control: a global study / Medidas de confinamento específicas de cada país em resposta à pandemia de COVID-19 e seu impacto no controle da tuberculose: um estudo global

ABSTRACT The objective of this study was to describe country-specific lockdown measures and tuberculosis indicators collected during the first year of the COVID-19 pandemic. Data on lockdown/social restrictions (compulsory face masks and hand hygiene; international and local travel restrictions; restrictions to family visits, and school closures) were collected from 24 countries spanning five continents. The majority of the countries implemented multiple lockdowns with partial or full reopening. There was an overall decrease in active tuberculosis, drug-resistant tuberculosis, and latent tuberculosis cases. Although national lockdowns were effective in containing COVID-19 cases, several indicators of tuberculosis were affected during the pandemic.

RESUMO O objetivo deste estudo foi descrever as medidas de confinamento específicas de cada país e os indicadores de tuberculose coletados durante o primeiro ano da pandemia de COVID-19. Dados referentes a confinamento/restrições sociais (uso obrigatório de máscaras faciais e higiene obrigatória das mãos; restrições a viagens internacionais e locais; restrições a visitas familiares e fechamento das escolas) foram coletados de 24 países em cinco continentes. A maioria dos países implantou múltiplos confinamentos, com reabertura parcial ou total. Houve uma redução geral dos casos de tuberculose ativa, tuberculose resistente e tuberculose latente. Embora os confinamentos nacionais tenham sido eficazes na contenção dos casos de COVID-19, vários indicadores de tuberculose foram afetados durante a pandemia.

Treatment of COVID-19 in pregnant women: A systematic review and meta-analysis.

OBJECTIVE: Clinical trials evaluating pharmacological and non-pharmacological treatment of COVID-19, either excluded pregnant women or included very few women. Unlike the numerous systematic reviews on prevalence, symptoms and adverse outcomes of COVID-19 in pregnancy, there are very few on the effects of treatment on maternal and neonatal outcomes in pregnancy. We undertook a systematic review of all published and unpublished studies on the effects of pharmacological and non-pharmacological interventions for COVID-19 on maternal and neonatal pregnancy outcomes. DATA SOURCES: We performed a systematic literature search of the following databases: Medline, Embase, Cochrane database, WHO (World Health Organization) COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 1 December 2020. STUDY ELIGIBILITY CRITERIA: Studies were only included if they involved pregnant or postnatal women who were exposed to pregnancy specific interventions like the mode of delivery and type of anaesthesia, pharmacological or non-pharmacological interventions. STUDY APPRAISAL AND SYNTHESIS METHODS: We first screened the titles and abstracts of studies and then assessed the full text of the selected studies in detail for eligibility. Data on study design, population, type of screening for COVID-19, country, hospital, country status (high or low and middle income), treatment given (mode of delivery, type of anaesthesia, type of pharmacological and non-pharmacological treatment was extracted. The pre-defined maternal outcomes we collected were mode of delivery (vaginal or by caesarean section), severe or critical COVID-19 (as defined by the authors), symptomatic COVID-19, maternal death, maternal hospital admission, ICU admission, mechanical ventilation, ECMO and maternal pneumonia. The pre-defined neonatal outcomes we extracted were preterm birth (<37 weeks), stillbirth, neonatal death, NICU admission, neonatal COVID-19 positive, neonatal acidosis (pH < 7.0) and Apgar scores (<8 after 5 min). Study quality assessment was performed. RESULTS: From a total of 342 potential eligible studies, we included 27 studies in our systematic review, including 4943 pregnant women (appendix 3). Sixteen studies had a retrospective cohort design and 11 a prospective cohort design. There were no randomised controlled trials. There was a significant association between caesarean section and admission to ICU (OR 4.99, 95% CI 1.24 to 20.12; 4 studies, 153 women, I2 = 0%), and diagnosis of maternal COVID-19 pneumonia as defined by study authors (OR 3.09, 95% CI 1.52 to 6.28; 2 studies, 228 women, I2 = 0%). Women who had a preterm birth were more likely to have the baby via caesarean section (OR 3.03, 95% CI 1.71 to 5.36, 12 studies; 314 women, I2 = 0%). For pharmacological and non-pharmacological we provided estimates of the expected rates of outcomes in women exposed to various treatment of COVID-19. Comparative data for pregnant women, in particular for treatments proven to be effective in the general population, however, is lacking to provide clinically meaningful interpretation. CONCLUSIONS: We found associations for pregnancy specific interventions, like mode of delivery and outcomes of the disease, but there were too few data on pharmacological and non-pharmacological treatments in pregnant women with COVID-19. We report the rates of complications found in the literature. We encourage researchers to include pregnant women in their trials and report the data on pregnant women separately.

Exploring a combined biomarker for tuberculosis treatment response: protocol for a prospective observational cohort study.

INTRODUCTION: An improved understanding of factors explaining tuberculosis (TB) treatment response is urgently needed to help clinicians optimise and personalise treatment and assist scientists undertaking novel treatment regimen trials. Promising outcome proxy measures, including sputum bacillary load and host immune response, are widely reported with variable results. However, they have not been studied together in combination with antibiotic exposure. The aim of this observational cohort study is to investigate which antibiotic exposures correlate with sputum bacillary load and which with the host immune response. Subsequently, we will explore if these correlations can be used to inform a candidate combined biomarker predicting cure. METHODS AND ANALYSIS: All patients aged ≥ 18, diagnosed with drug-sensitive pulmonary TB (culture or molecular test), eligible for standard anti-TB treatment, at selected London, UK TB Services, will be invited to participate in this observational cohort study (target sample size=210). Patients will be asked to give blood for host transcriptomics and antibiotic plasma exposure, in addition to standard of care sputum samples for bacillary load. Antibiotic plasma concentrations will be quantified using a validated liquid chromatograph triple quadrupole mass spectrometer (LC-MS/MS) assay and sputum bacillary load by mycobacterial growth incubator tube time to positivity. Expression from a total of 35 prespecified host blood genes will be quantified using NanoString®. Antibiotic exposure, sputum bacillary load and host blood transcriptomic time series data will be analysed using nonlinear mixed-effects models. Correlations between combinations of longitudinal biomarkers and microbiological cure at the end of treatment and remaining relapse free for 1 year thereafter will be analysed using logistic regression and Cox proportional hazard models. ETHICS AND DISSEMINATION: The observational cohort study has been approved by the UK's HRA REC (20/SW/0007). Written informed consent will be obtained. Results will be disseminated via publication, presentation and through engagement with institutes/companies developing novel anti-TB treatment combinations.

"You have to change your whole life": A qualitative study of the dynamics of treatment adherence among adults with tuberculosis in the United Kingdom.

Maintaining adherence to treatment for tuberculosis (TB) is essential if the disease is to be eliminated. As part of formative research to develop an intervention to improve adherence, we documented the lived experiences of adults receiving anti-TB treatment (ATT) in three UK cities and examined how personal, social, and structural circumstances interacted to impact on individuals' adherence to treatment. Using a topic guide that explored social circumstances and experiences of TB care, we conducted in-depth interviews with 18 adults (six women) who were being or had been treated for TB (patients) and four adults (all women) who were caring for a friend, relative, or partner being treated for TB (caregivers). We analysed transcripts using an adapted framework method that classified factors affecting adherence as personal, social, structural, health systems, or treatment-related. Eleven of 18 patients were born outside the UK (in South, Central, and East Asia, and Eastern and Southern Africa); among the seven who were UK-born, four were Black, Asian, or Minority Ethnic and three were White British. TB and its treatment were often disruptive: in addition to debilitating symptoms and side effects of ATT, participants faced job insecurity, unstable housing, stigma, social isolation, worsening mental health, and damaged relationships. Those who had a strong support network, stable employment, a routine that could easily be adapted, a trusting relationship with their TB team, and clear understanding of the need for treatment reported finding it easier to adhere to ATT. Changes in circumstances sometimes had dramatic effects on an individual's ability to take ATT; participants described how the impact of certain acute events (e.g., the onset of side effects or fatigue, episodes of stigmatisation, loss of income) were amplified by their timing or through their interaction with other elements of the individual's life. We suggest that the dynamic and fluctuating nature of these factors necessitates comprehensive and regular review of needs and potential problems, conducted before and during ATT; this, coupled with supportive measures that consider (and seek to mitigate) the influence of social and structural factors, may help improve adherence.

Diagnostic pitfalls of urogenital tuberculosis.

OBJECTIVES: To describe characteristics, details of diagnosis and outcomes of urogenital tuberculosis (UGTB) in a low-prevalence country. METHODS: We conducted a retrospective observational study of 37 consecutive patients diagnosed with UGTB between 1st January 2014 and 31st October 2019 in an East London hospital. RESULTS: 68% (25/37) of patients were male and the median age was 42 years (IQR 34-55). 89% (33/37) of patients were born outside the United Kingdom with 65% (24/37) born in the South Asian region. Renal (32.4%), epididymal (24.3%) and endometrial TB (21.6%) were the most prevalent forms of UGTB. Only 13.5% of UGTB patients had concurrent pulmonary TB. The median length of time from symptom onset to treatment was 163 days, while endometrial TB had an average delay to diagnosis of 564 days. Approximately half of patients with UGTB were culture positive (51.4%). However, 70% of early morning urines (EMUs) sent in urinary TB were culture positive. 11 patients (30.6%) underwent two or more invasive procedures, such as biopsy to obtain specimen samples. The mean treatment length for all UGTB cases was 7.3 months (SD 3.1). Notably, 25% of patients with endometrial TB required surgery despite antituberculous treatment. CONCLUSIONS: UGTB is challenging to diagnose as early disease is often asymptomatic. Clinicians faced with non-specific symptoms, or features suggestive of urogenital malignancy amongst patients from TB-endemic areas, should maintain a high suspicion of UGTB.

Non tuberculous mycobacteria pulmonary disease: patients and clinicians working together to improve the evidence base for care.

Non-tuberculous mycobacterial pulmonary disease is on the rise globally. It is often missed, and causes significant morbidity and even mortality. Here, members of a clinical research network and a patient support group discuss some of the current key issues in NTM management. In addition to the need for research into epidemiology, immunology and treatment, we recommend greater use of patient and clinician networks to: (i) educate primary and secondary care clinicians to develop a high index of suspicion when investigating and treating at risk populations. (ii) promote a multidisciplinary team. (iii) promote shared patient-clinician decision making throughout care. (iv) incorporate use of patient self-report measures to assess progress and outcomes. (v) increase education of patients on their illness and its management. (vi) recruit patients into research projects and registries to improve the clinical evidence base. (vii) increase co-production of research with key stakeholders such as patients and their families, using expert patients and patient groups. (viii) understand more about the psychological, social and economic consequences of the disease.

Clinical manifestations, prevalence, risk factors, outcomes, transmission, diagnosis and treatment of COVID-19 in pregnancy and postpartum: a living systematic review protocol.

INTRODUCTION: Rapid, robust and continually updated evidence synthesis is required to inform management of COVID-19 in pregnant and postpartum women and to keep pace with the emerging evidence during the pandemic. METHODS AND ANALYSIS: We plan to undertake a living systematic review to assess the prevalence, clinical manifestations, risk factors, rates of maternal and perinatal complications, potential for mother-to-child transmission, accuracy of diagnostic tests and effectiveness of treatment for COVID-19 in pregnant and postpartum women (including after miscarriage or abortion). We will search Medline, Embase, WHO COVID-19 database, preprint servers, the China National Knowledge Infrastructure system and Wanfang databases from 1 December 2019. We will supplement our search with studies mapped by Cochrane Fertility and Gynaecology group, Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre), COVID-19 study repositories, reference lists and social media blogs. The search will be updated every week and not be restricted by language. We will include observational cohort (≥10 participants) and randomised studies reporting on prevalence of COVID-19 in pregnant and postpartum women, the rates of clinical manifestations and outcomes, risk factors in pregnant and postpartum women alone or in comparison with non-pregnant women with COVID-19 or pregnant women without COVID-19 and studies on tests and treatments for COVID-19. We will additionally include case reports and series with evidence on mother-to-child transmission of SARS-CoV-2 in utero, intrapartum or postpartum. We will appraise the quality of the included studies using appropriate tools to assess the risk of bias. At least two independent reviewers will undertake study selection, quality assessment and data extraction every 2 weeks. We will synthesise the findings using quantitative random effects meta-analysis and report OR or proportions with 95% CIs and prediction intervals. Case reports and series will be reported as qualitative narrative synthesis. Heterogeneity will be reported as I2 and τ2 statistics. ETHICS AND DISSEMINATION: Ethical approval is not required as this is a synthesis of primary data. Regular updates of the results will be published on a dedicated website (https://www.birmingham.ac.uk/research/who-collaborating-centre/pregcov/index.aspx) and disseminated through publications, social media and webinars. PROSPERO REGISTRATION NUMBER: CRD42020178076.