From symptom onset to treatment initiation: protocol for a narrative study exploring the journey of older adults with tuberculosis in the English Midlands, UK.

INTRODUCTION: Time from symptom onset to treatment initiation in tuberculosis (TB) remains stubbornly prolonged despite reductions in disease incidence. Delays may contribute to increased morbidity, mortality, onward spread of disease and poor patient experiences. Most delays occur prior to hospital referral. The average primary care healthcare provider in England is unlikely to see TB on a regular basis. Little is known about primary care diagnostic and referral challenges.Adults aged 65 years or older are more likely to experience delays. However, little is known about their journey from symptom onset to treatment initiation. METHODS AND ANALYSIS: We will carry out a narrative study including adults aged 65 years or older, living in the English Midlands and receiving treatment for active TB. Twelve English and 12 Urdu or Punjabi speakers will be recruited from TB clinics and interviewed. Their primary care records will be accessed, and the primary care story and secondary care letters will be extracted. Each of the data sources will be analysed using dialogical narrative analysis. Data will be triangulated within participants and across the data set. ETHICS AND DISSEMINATION: This study received approval from the Health Research Authority and the Research Ethics Committee in April 2022. Risk management and equity considerations have been made a priority. Findings will be disseminated through publication in open access peer-reviewed journals, presentations to policy makers, primary healthcare and secondary healthcare professionals, and through public facing materials developed in conjunction with patients, members of the pubic, TB services and charities.

A systematic review of the burden of, access to services for and perceptions of patients with overweight and obesity, in humanitarian crisis settings.

INTRODUCTION: Excess body weight causes 4 million deaths annually across the world. The number of people affected by humanitarian crises stands at a record high level with 1 in 95 people being forcibly displaced. These epidemics overlap. Addressing obesity is a post-acute phase activity in non-communicable disease management in humanitarian settings. Information is needed to inform guidelines and timing of interventions. The objective of this review was to explore the prevalence of overweight and obesity in populations directly affected by humanitarian crises; the cascade of care in these populations and perceptions of patients with overweight and obesity. METHODS: Literature searches were carried out in five databases. Grey literature was identified. The population of interest was non-pregnant, civilian adults who had experience of humanitarian crises (armed conflict, complex emergencies and natural disasters). All study types published from January 1st, 2011, were included. Screening, data extraction and quality appraisal were carried out in duplicate. A narrative synthesis is presented. RESULTS: Fifty-six reports from forty-five studies were included. Prevalence estimates varied widely across the studies and by subgroups. Estimates of overweight and obesity combined ranged from 6.4% to 82.8%. Studies were heterogenous. Global distribution was skewed. Increasing adiposity was seen over time, in older adults and in women. Only six studies were at low risk of bias. Body mass index was the predominant measure used. There were no studies reporting cascade of care. No qualitative studies were identified. CONCLUSION: Overweight and obesity varied in crisis affected populations but were rarely absent. Improved reporting of existing data could provide more accurate estimates. Worsening obesity may be prevented by acting earlier in long-term crises and targeting risk groups. The use of waist circumference would provide useful additional information. Gaps remain in understanding the existing cascade of care. Cultural norms around diet and ideal body size vary.

Safety and efficacy of tuberculosis vaccine candidates in low- and middle-income countries: a systematic review of randomised controlled clinical trials.

BACKGROUND: Tuberculosis (TB) remains a leading cause of death worldwide, with 98% of cases occurring in low- and middle-income countries (LMICs). The only vaccine licenced for the prevention of TB has limited protection for adolescents, adults and vulnerable populations. A safe and effective vaccine for all populations at risk is imperative to achieve global elimination of TB. We aimed to systematically review the efficacy and safety of TB vaccine candidates in late-phase clinical trials conducted in LMICs. METHODS: Medline, Embase, CENTRAL, PubMed, Clinicaltrials.gov and Greylit.org were searched in June 2021 to identify phase 2 or later clinical randomised controlled trials that report the efficacy or safety (adverse events) of TB vaccine candidates with participants of any age living in an LMIC. TB vaccine candidates listed in the 2020 WHO Global TB Report were eligible for inclusion aside from BCG revaccination. Trials were excluded if all participants had active TB at baseline. Two reviewers independently assessed papers for eligibility, and for bias and quality using the Risk of Bias 2 tool and GRADE guidelines, respectively. We report efficacy rates and frequencies of adverse events from each included trial where available and qualitatively synthesise the findings. RESULTS: Thirteen papers representing eleven trials met our inclusion criteria. Seven vaccine candidates were reviewed across seven countries: M72/AS01, RUTI, VPM1002, H56:IC31, MTBVAC, DAR-901 and ID93 + GLA-SE. Two trials reported on efficacy: an efficacy rate of 54% (95% CI 11.5, 76.2) was reported for M72/AS01 in adults with latent TB and 3% (95% CI -13.9, 17.7) for DAR-901 in healthy adolescents. However, the latter trial was underpowered. All vaccine candidates had comparable occurrences of adverse events between treatment arms and demonstrated acceptable safety profiles; though, RUTI resulted in one serious complication in a person living with HIV. M72/AS01 was the only vaccine considered safe across a diverse group of people including people living with HIV or latent TB and healthy infants and adolescents. CONCLUSION: Further efficacy trials for M72/AS01 are warranted to include additional populations at risk where safety has been demonstrated. Further safety trials are needed for the remaining vaccine candidates to confirm safety in vulnerable populations.

Symptoms and risk factors for long COVID in non-hospitalized adults.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.

Associations between socioeconomic deprivation and pharmaceutical prescribing in primary care in England.

BACKGROUND: Socioeconomic deprivation is associated with health inequality. Previous studies have described associations between primary care prescribing rates and deprivation for individual drugs or drug classes. We explore the correlation between socioeconomic deprivation and the rate of prescribing of individual pharmaceutical drugs, and drug classes, in primary care in England, to identify prescribing inequalities that would require further investigation. METHODS: In this cross-sectional study, national primary care prescribing data, by primary care practice, were retrieved for the calendar year 2019 in England. Socioeconomic deprivation was quantified using the Index of Multiple Deprivation (IMD) score. Correlations were calculated using Spearman's rank correlation coefficient (ρ), adjusting for practice list size and demographics, with a Bonferroni-corrected p value threshold of 5×10-5. RESULTS: We included 1.05 billion prescription items dispensed from 6896 England practices. 142/206 (69%) drug classes and 505/774 (65%) drugs were significantly correlated with IMD score (p<5×10-5). Of the 774 included drugs, 31 (4%) were moderately positively associated with IMD score (ρ>0.4). Only one was moderately negatively correlated with IMD score (ρ<-0.4), suggesting higher prescribing rates in more affluent areas. The drug classes most strongly associated with IMD score included opioid and non-opioid analgesics, antipsychotics and reflux medications. Drug classes most strongly associated with affluence included epinephrine, combined oral contraceptives and hormone replacement therapy. CONCLUSION: We identify novel associations of prescribing with deprivation. Further work is required to identify the underlying reasons for these associations so that appropriate interventions can be formulated to address drivers of inequality.

A systematic review of the burden of hypertension, access to services and patient views of hypertension in humanitarian crisis settings.

INTRODUCTION: Globally, a record number of people are affected by humanitarian crises caused by conflict and natural disasters. Many such populations live in settings where epidemiological transition is underway. Following the United Nations high level meeting on non-communicable diseases, the global commitment to Universal Health Coverage and needs expressed by humanitarian agencies, there is increasing effort to develop guidelines for the management of hypertension in humanitarian settings. The objective was to investigate the prevalence and incidence of hypertension in populations directly affected by humanitarian crises; the cascade of care in these populations and patient knowledge of and attitude to hypertension. METHODS: A literature search was carried out in five databases. Grey literature was searched. The population of interest was adult, non-pregnant, civilians living in any country who were directly exposed to a crisis since 1999. Eligibility assessment, data extraction and quality appraisal were carried out in duplicate. RESULTS: Sixty-one studies were included in the narrative synthesis. They reported on a range of crises including the wars in Syria and Iraq, the Great East Japan Earthquake, Hurricane Katrina and Palestinian refugees. There were few studies from Africa or Asia (excluding Japan). The studies predominantly assessed prevalence of hypertension. This varied with geography and age of the population. Access to care, patient understanding and patient views on hypertension were poorly examined. Most of the studies had a high risk of bias due to methods used in the diagnosis of hypertension and in the selection of study populations. CONCLUSION: Hypertension is seen in a range of humanitarian settings and the burden can be considerable. Further studies are needed to accurately estimate prevalence of hypertension in crisis-affected populations throughout the world. An appreciation of patient knowledge and understanding of hypertension as well as the cascade of care would be invaluable in informing service provision.

Socioeconomic status and benzodiazepine and Z-drug prescribing: a cross-sectional study of practice-level data in England.

BACKGROUND: Benzodiazepines and Z-drugs (such as zopiclone) are widely prescribed in primary care. Given their association with addiction and dependence, understanding where and for whom these medications are being prescribed is a necessary step in addressing potentially harmful prescribing. OBJECTIVE: To determine whether there is an association between primary care practice benzodiazepine and Z-drug prescribing and practice population socioeconomic status in England. METHODS: This was a cross-sectional study. An aggregated data set was created to include primary care prescribing data for 2017, practice age and sex profiles and practice Index of Multiple Deprivation (IMD) scores-a marker of socioeconomic status. Drug doses were converted to their milligram-equivalent of diazepam to allow comparison. Multiple linear regression was used to examine the association between IMD and prescribing (for all benzodiazepines and Z-drugs in total, and individually), adjusting for practice sex (% male) and older age (>65 years) distribution (%). RESULTS: Benzodiazepine and Z-drug prescribing overall was positively associated with practice-level IMD score, with more prescribing in practices with more underserved patients, after adjusting for age and sex (P < 0.001), although the strength of the association varied by individual drug. Overall, however, IMD score, age and sex only explained a small proportion of the overall variation in prescribing across GP practices. CONCLUSION: Our findings may, in part, be a reflection of an underlying association between the indications for benzodiazepine and Z-drug prescribing and socioeconomic status. Further work is required to more accurately define the major contributors of prescribing variation.

Associations Between Anthropometric Measurements and Cardiometabolic Risk Factors in White European and South Asian Adults in the United Kingdom.

OBJECTIVE: To investigate the association of 4 anthropometric measurements with cardiometabolic risk factors in a UK biethnic sample of South Asians (SAs) and white Europeans (WEs). PATIENTS AND METHODS: Baseline data were collected from adults of WE and SA origin participating in the Leicester arm of the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care (ADDITION-Leicester) study between August 2004 and December 2007. Overall, 6268 WE and SA adults had measures of body mass index, waist circumference, waist-to-hip ratio, and waist-to-height ratio assessed between June 18, 2004, and December 4, 2007. Hypertension, dyslipidemia, and dysglycemia were established from venous blood samples using standard definitions. Crude and adjusted (covariates used were age, sex, ethnicity, smoking, and alcohol consumption) odds ratios were calculated using multivariate logistic regression. Receiver operating characteristic curves and the area under the curve were used to calculate optimal cut points for the whole cohort and for both ethnic groups. RESULTS: Increases in all anthropometric measurements resulted in a higher odds ratio for each of the risk factors in both the crude and adjusted models (P<.001). The adjusted odds ratios for dyslipidemia, hypertension, and dysglygemia ranged from 1.30 to 1.35, from 1.36 to 1.52, and from 1.62 to 1.75 (P<.001 for all), respectively, in WEs. The adjusted odds ratio for dyslipidemia, hypertension, and dysglygemia ranged from 1.50 to 1.65 (P<.01), from 1.40 to 1.60 (P<.01), and from 1.96 to 2.11 (P<.001 for all), respectively, in SAs. The areas under the receiver operating characteristic curves for all the anthropometric measurements had low accuracy (P<.70) for the whole cohort and when stratified by ethnicity and sex. CONCLUSION: There is insufficient evidence to recommend replacing body mass index with another anthropometric measurement for the ethnically diverse population in the United Kingdom. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00318032.

Blood pressure in primary school children in Uganda: a cross-sectional survey.

BACKGROUND: Non-communicable diseases are an emerging concern in sub-Saharan Africa, and risks for these conditions are often based on exposures in early life, with premonitory signs developing during childhood. The prevalence of hypertension has been reported to be high in African adults, but little is known about blood pressure in African children. We studied prevalence and risk factors for high blood pressure (HBP) among school children in central Uganda. METHODS: Two urban and five rural schools were randomly selected from government schools in Wakiso district, Uganda. Questionnaires were administered and anthropometric measures taken. Blood pressure (BP) was measured three times in one sitting (on day 1) and the average compared to internationally-used normograms. Children with BP >95th percentile were re-tested at two additional sittings (day 2 and day 3) within one week, and at two further follow up visits over a period of six months. Those with sustained HBP were referred for further investigation. RESULTS: Of 552 students included, 539 completed the initial assessments (days 1-3) of whom 92 (17.1%) had HBP at the initial sitting. Age (adjusted odds ratio (aOR) 1.29 (95% confidence interval 1.14, 1.47), p< 0.001), body mass index (1.70 (1.25-2.31) p = 0.001) and soil-transmitted helminths (2.52 (1.04-6.11), 0.04) were associated with increased prevalence of HBP at the initial sitting. After further investigation, sustained HBP was seen in 14 children, yielding an estimated prevalence of 3.8% allowing for losses to follow up. Four children required treatment. CONCLUSION: It is feasible to measure blood pressure accurately in the school setting. A high HBP prevalence on initial readings gave cause for concern, but follow up suggested a true HBP prevalence commensurate with international normograms. Extended follow up is important for accurate assessment of blood pressure among African children.