Diabetes care in a complex humanitarian emergency setting: a qualitative evaluation.

BACKGROUND: Evidence is urgently needed from complex emergency settings to support efforts to respond to the increasing burden of diabetes mellitus (DM). We conducted a qualitative study of a new model of DM health care (Integrated Diabetic Clinic within an Outpatient Department [IDC-OPD]) implemented by Médecins Sans Frontières (MSF) in Mweso Hospital in eastern Democratic Republic of Congo (DRC). We aimed to explore patient and provider perspectives on the model in order to identify factors that may support or impede it. METHODS: We used focus group discussions (FGDs; two discussions, each with eight participants) and individual semi-structured qualitative interviews (seven patients and 10 staff) to explore experience of and perspectives on the IDC-OPD. Participants were recruited purposively to represent a range of DM disease severity and staff functions respectively, and to ensure the age and gender distribution was representative of the population of DM patients registered in the clinic. Data were coded in NVivo10© and analysed using an inductive thematic approach. RESULTS: There appears to be little awareness surrounding DM in patient communities, resulting in delays presenting to hospital. Patients describe their first reactions to symptoms as fear and confusion, often assuming symptoms are of another disease (e.g. HIV/AIDS). They often express disbelief that they could have DM (e.g. stating DM is a 'rich man's disease') and lack acceptance that there is no cure. Patients experienced difficulty travelling to appointments, exacerbated by flare-ups in the conflict. Providing psycho-social and sensitisation activities in a group setting appears to offer an opportunity for patients to support each other in their effort to adhere to drug treatment and follow-up appointments. All patients reported great difficulty in adhering to the recommended diet, which was viewed as unaffordable and unavailable, and fear that this would be the biggest obstacle to maintaining their drug treatment (as treatment must be taken with food). CONCLUSION: Our findings emphasize the importance of community awareness of DM and the value of treatment support, including psychosocial and educational support to DM patients and their families, and culturally sensitive, low-cost dietary advice, to ensuring the adoption and maintenance of DM treatment

Capturing patient-reported and quality of life outcomes with use of shorter regimens for drug-resistant tuberculosis: mixed-methods substudy protocol, TB PRACTECAL-PRO

Introduction- People living with multidrug-resistant tuberculosis currently have few options for effective treatment and cure. Regimens that are available are toxic, may involve injections and take up to 2 years to complete treatment, with success rates as low as 50%. The TB-PRACTECAL trial is evaluating shorter, more tolerable regimens of oral drugs; we detail the substudy within this trial, PRACTECAL-PRO, which aims to evaluate patient experiences and perspectives on treatment, to understand outcomes more fully. Methods and analysis- We are conducting a mixed-methods evaluation within both investigational and standard of care arms within the TB-PRACTECAL trial, using sequential quality of life (QoL) surveys and in-depth interviews. Data collection involves the Short Form 12 (SF-12) and St George’s Respiratory Questionnaire (SGRQ), collected at up to four fixed timepoints, from baseline, to up to 12 months later. Healthy volunteers will be surveyed to establish locally relevant controls. We will also purposively sample participants for qualitative data collection and analysis, to provide rich explanation of QoL scores. The study will be implemented in all six TB-PRACTECAL study sites in Uzbekistan, South Africa and Belarus. QoL surveys will be scored and analysed according to SF-12 and SGRQ developers’ manuals. Differences between scores at baseline and later timepoints will be evaluated as well as graphical exploration of group score trajectories of investigational and standard of care arms. Ethics and dissemination- Ethics approval was obtained from the Médecins Sans Frontières Ethics Review Board. Local ethics approval has been obtained in Uzbekistan, Belarus and South Africa. Results of the substudy will be shared with local health authorities, the WHO and submitted for publication in a peer-reviewed journal. Trial- registration number NCT03942354; Pre-results

‘They prefer hidden treatment': anti-tuberculosis drug-taking practices and drug regulation in Karakalpakstan

Setting: The joint Médecins Sans Frontières/Ministry of Health multidrug-resistant tuberculosis (MDR-TB) programme; Karakalpakstan, Uzbekistan. Objective: Uzbekistan has high rates of MDR-TB. We aimed to understand patients’ and prescribers’ attitudes to TB drug prescription, regulation, and drug-taking behaviour. Methods: Participants (12 patients, 12 practitioners) were recruited purposively. Data were gathered qualitatively using field notes and in-depth interviews and analysed thematically. Findings: Our analysis highlighted two main themes. First, shame and stigma were reported to increase the likelihood of self-treatment and incorrect use of TB drugs, most commonly at initial stages of illness. A health system failure to promote health information was perceived, leading to wrong diagnoses and inappropriate therapies. Motivated by shame, patients hid their condition by resorting to drug-treatment options outside the programme, compounding the risk of chaotic management and dissemination of erroneous information through lay networks. Second, positive influences on treatment were reported through patients, practitioners and peers working effectively together to deliver the correct information and support, which acted to normalise TB, reduce stigma and prevent misuse of TB drugs. Conclusion: Effective case finding, patient support and community education strategies are essential. Patients, practitioners and peers working together can help reduce stigma and prevent misuse of TB drugs

"Life is so easy on ART, once you accept it": Acceptance, denial and linkage to HIV care in Shiselweni, Swaziland.

BACKGROUND: Timely uptake of antiretroviral therapy, adherence and retention in care for people living with HIV (PLHIV) can improve health outcomes and reduce transmission. Médecins Sans Frontières and the Swaziland Ministry of Health provide community-based HIV testing services (HTS) in Shiselweni, Swaziland, with high HTS coverage but sub-optimal linkage to HIV care. This qualitative study examined factors influencing linkage to HIV care for PLHIV diagnosed by community-based HTS. METHODS: Participants were sampled purposively, exploring linkage experiences among both genders and different age groups. Interviews were conducted with 28 PLHIV (linked and not linked) and 11 health practitioners. Data were thematically analysed to identify emergent patterns and categories using NVivo 10. Principles of grounded theory were applied, including constant comparison of findings, raising codes to a conceptual level, and inductively generating theory from participant accounts. RESULTS: The process of HIV status acceptance or denial influenced the accounts of patients' health seeking and linkage to care. This process was non-linear and varied temporally, with some experiencing non-acceptance for an extended period of time. Non-acceptance was linked to perceptions of HIV risk, with those not identifying as at risk less likely to expect and therefore be prepared for a positive result. Status disclosure was seen to support linkage, reportedly occurring after the acceptance of HIV status. HIV status acceptance motivated health seeking and tended to be accompanied by a perceived need for, and positive value placed on, HIV health care. CONCLUSIONS: The manner in which PLHIV process a positive result can influence their engagement with HIV treatment and care. Thus, there is a need for individually tailored approaches to HTS, including the potential for counselling over multiple sessions if required, supporting status acceptance, and disclosure. This is particularly relevant considering 90-90-90 targets and the need to better support PLHIV to engage with HIV treatment and care following diagnosis

The factors affecting household transmission dynamics and community compliance with Ebola control measures: a mixed-methods study in a rural village in Sierra Leone.

BACKGROUND: Little is understood of Ebola virus disease (EVD) transmission dynamics and community compliance with control measures over time. Understanding these interactions is essential if interventions are to be effective in future outbreaks. We conducted a mixed-methods study to explore these factors in a rural village that experienced sustained EVD transmission in Kailahun District, Sierra Leone. METHODS: We reconstructed transmission dynamics using a cross-sectional survey conducted in April 2015, and cross-referenced our results with surveillance, burial, and Ebola Management Centre (EMC) data. Factors associated with EVD transmission were assessed with Cox proportional hazards regression. Following the survey, qualitative semi-structured interviews explored views of community informants and households. RESULTS: All households (n = 240; 1161 individuals) participated in the survey. 29 of 31 EVD probable/confirmed cases died (93·5% case fatality rate); six deaths (20·6%) had been missed by other surveillance systems. Transmission over five generations lasted 16 weeks. Although most households had ≤5 members there was a significant increase in risk of Ebola in households with > 5 members. Risk of EVD was also associated with older age. Cases were spatially clustered; all occurred in 15 households. EVD transmission was better understood when the community experience started to concord with public health messages being given. Perceptions of contact tracing changed from invading privacy and selling people to ensuring community safety. Burials in plastic bags, without female attendants or prayer, were perceived as dishonourable. Further reasons for low compliance were low EMC survival rates, family perceptions of a moral duty to provide care to relatives, poor communication with the EMC, and loss of livelihoods due to quarantine. Compliance with response measures increased only after the second generation, coinciding with the implementation of restrictive by-laws, return of the first survivor, reduced contact with dead bodies, and admission of patients to the EMC. CONCLUSIONS: Transmission occurred primarily in a few large households, with prolonged transmission and a high death toll. Return of a survivor to the village and more effective implementation of control strategies coincided with increased compliance to control measures, with few subsequent cases. We propose key recommendations for management of EVD outbreaks based on this experience

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society