Prognosis of patients with post-Covid-19 condition: Prospective cohort cluster analysis at one year.

OBJECTIVE: We aimed to identify clinically relevant clusters among patients with post-Covid-19 condition (PCC) and assess prognosis overall and within clusters. METHODS: Prospective cohort study of patients with PCC attending a rehabilitation clinic. We monitored patient reported outcome measures (PROMs): EuroHIS quality of life and symptoms. Unsupervised hierarchical cluster analyses were performed to identify clusters of patients with different quantity of symptoms, and symptoms presenting together. Preliminary findings on symptom prevalence and quality of life at 12 months are reported. RESULTS: Among 409 patients, 70.4% were women, with an average baseline of 20.3 (SD 6.8) symptoms. Three clusters emerged based on symptom quantity, labelled by the average number of symptoms at baseline: Cluster-11 (17% of all patients), Cluster-17 (35%), and Cluster-25 (48%). Multinomial logistic regression showed female sex, multiple comorbidities predicting more symptoms. Four symptom-based clusters were defined: fatigue and cognitive complaints; pain, trouble sleeping, palpitations and other symptoms; gastrointestinal symptoms; and emotion-related symptoms. Linear regression models showed that female sex, multiple comorbidities, anxiety, use of antidepressants, BMI and smoking were among the determinants of symptom clusters. In 12-month follow-up, symptom count decreased, and quality of life improved across all clusters, with 9% having good quality of life at baseline and 33% at 12 months. CONCLUSION: Four patient clusters based on symptoms were identified in the PCC cohort. Prognosis was favorable across all clusters, with symptom reduction and improved quality of life observed. Female sex, comorbidities, BMI, and mental-health related variables predicted higher symptom burden, suggesting multifactorial origins of PCC.

Chronic fatigue syndromes: real illnesses that people can recover from.

The 'Oslo Chronic Fatigue Consortium' consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brain's response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation.Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them.

Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.

Deaths and parasuicides associated with mefloquine chemoprophylaxis: A systematic review.

BACKGROUND: Mefloquine is recommended in international health guidelines for preventing malaria in travellers. Reports of psychosis and suicide are often alluded to but are not clearly established. METHODS: We carried out a systematic review of the literature to identify and critically appraise any reported death or parasuicide associated with mefloquine prophylaxis. We developed a comprehensive search that included publications up to 11 July 2017. We included case studies but excluded newspaper reports. Two authors independently appraised each death or parasuicide against a standardised causality assessment tool. The protocol was registered on PROSPERO (CRD42016041988). RESULTS: We identified 527 articles that required full-text retrieval; of these 17 were unique publications that reported deaths or parasuicide. Eight unique publications had sufficient detail to be included in causality assessment. We identified 2 deaths with a probable association that appeared to be idiosyncratic drug reactions; we categorised the remaining 8 deaths as "unlikely" to be related to mefloquine, or "unclassifiable". There was one parasuicide with a possible causal association. There were 9 additional publications that searched spontaneous drug reporting databases; none provided sufficient detail to perform a causality assessment. CONCLUSIONS: Overall, the number of deaths that we could reliably attribute to the prophylactic use of mefloquine is very low.

Decentralising HIV treatment in lower- and middle-income countries

BACKGROUND: Policy makers, health staff and communities recognise that health services in lower- and middle-income countries need to improve people's access to HIV treatment and retention to treatment programmes. One strategy is to move antiretroviral delivery from hospitals to more peripheral health facilities or even beyond health facilities. This could increase the number of people with access to care, improve health outcomes, and enhance retention in treatment programmes. On the other hand, providing care at less sophisticated levels in the health service or at community-level may decrease quality of care and result in worse health outcomes. To address these uncertainties, we summarised the research studies examining the risks and benefits of decentralising antiretroviral therapy service delivery. OBJECTIVES: To assess the effects of various models that decentralised HIV treatment and care to more basic levels in the health system for initiating and maintaining antiretroviral therapy. METHODS: Search methods: We conducted a comprehensive search to identify all relevant studies regardless of language or publication status (published, unpublished, in press, and in progress) from 1 January 1996 to 31 March 2013, and contacted relevant organisations and researchers. The search terms included "decentralisation", "down referral", "delivery of health care", and "health services accessibility". Selection criteria: Our inclusion criteria were controlled trials (randomised and non-randomised), controlled-before and after studies, and cohorts (prospective and retrospective) in which HIV-infected people were either initiated on antiretroviral therapy or maintained on therapy in a decentralised setting in lower- and middle-income countries. We define decentralisation as providing treatment at a more basic level in the health system to the comparator. Data collection and analysis: Two authors applied the inclusion criteria and extracted ...

Drugs for preventing malaria in pregnant women in endemic areas: any drug regimen versus placebo or no treatment.

BACKGROUND: Pregnancy increases the risk of malaria and this is associated with poor health outcomes for both the mother and the infant, especially during the first or second pregnancy. To reduce these effects, the World Health Organization recommends that pregnant women living in malaria endemic areas sleep under insecticide-treated bednets, are treated for malaria illness and anaemia, and receive chemoprevention with an effective antimalarial drug during the second and third trimesters. OBJECTIVES: To assess the effects of malaria chemoprevention given to pregnant women living in malaria endemic areas on substantive maternal and infant health outcomes. We also summarised the effects of intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) alone, and preventive regimens for Plasmodium vivax. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and reference lists up to 1 June 2014. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs of any antimalarial drug regimen for preventing malaria in pregnant women living in malaria-endemic areas compared to placebo or no intervention. In the mother, we sought outcomes that included mortality, severe anaemia, and severe malaria; anaemia, haemoglobin values, and malaria episodes; indicators of malaria infection, and adverse events. In the baby, we sought foetal loss, perinatal, neonatal and infant mortality; preterm birth and birthweight measures; and indicators of malaria infection. We included regimens that were known to be effective against the malaria parasite at the time but may no longer be used because of parasite drug resistance. DATA COLLECTION AND ANALYSIS: Two review authors applied inclusion criteria, assessed risk of bias and extracted data. Dichotomous outcomes were compared using risk ratios (RR), and continuous outcomes using mean differences (MD); both are presented with 95% confidence intervals (CI). We assessed the quality of evidence using the GRADE approach. MAIN RESULTS: Seventeen trials enrolling 14,481 pregnant women met our inclusion criteria. These trials were conducted between 1957 and 2008, in Nigeria (three trials), The Gambia (three trials), Kenya (three trials), Mozambique (two trials), Uganda (two trials), Cameroon (one trial), Burkina Faso (one trial), and Thailand (two trials). Six different antimalarials were evaluated against placebo or no intervention; chloroquine (given weekly), pyrimethamine (weekly or monthly), proguanil (daily), pyrimethamine-dapsone (weekly or fortnightly), and mefloquine (weekly), or intermittent preventive therapy with SP (given twice, three times or monthly). Trials recruited women in their first or second pregnancy (eight trials); only multigravid women (one trial); or all women (eight trials). Only six trials had adequate allocation concealment.For women in their first or second pregnancy, malaria chemoprevention reduces the risk of moderate to severe anaemia by around 40% (RR 0.60, 95% CI 0.47 to 0.75; three trials, 2503 participants, high quality evidence), and the risk of any anaemia by around 17% (RR 0.83, 95% CI 0.74 to 0.93; five trials,, 3662 participants, high quality evidence). Malaria chemoprevention reduces the risk of antenatal parasitaemia by around 61% (RR 0.39, 95% CI 0.26 to 0.58; seven trials, 3663 participants, high quality evidence), and two trials reported a reduction in febrile illness (low quality evidence). There were only 16 maternal deaths and these trials were underpowered to detect an effect on maternal mortality (very low quality evidence).For infants of women in their first and second pregnancies, malaria chemoprevention probably increases mean birthweight by around 93 g (MD 92.72 g, 95% CI 62.05 to 123.39; nine trials, 3936 participants, moderate quality evidence), reduces low birthweight by around 27% (RR 0.73, 95% CI 0.61 to 0.87; eight trials, 3619 participants, moderate quality evidence), and reduces placental parasitaemia by around 46% (RR 0.54, 95% CI 0.43 to 0.69; seven trials, 2830 participants, high quality evidence). Fewer trials evaluated spontaneous abortions, still births, perinatal deaths, or neonatal deaths, and these analyses were underpowered to detect clinically important differences.In multigravid women, chemoprevention has similar effects on antenatal parasitaemia (RR 0.38, 95% CI 0.28 to 0.50; three trials, 977 participants, high quality evidence)but there are too few trials to evaluate effects on other outcomes.In trials giving chemoprevention to all pregnant women irrespective of parity, the average effects of chemoprevention measured in all women indicated it may prevent severe anaemia (defined by authors, but at least < 8 g/L: RR 0.19, 95% CI 0.05 to 0.75; two trials, 1327 participants, low quality evidence), but consistent benefits have not been shown for other outcomes.In an analysis confined only to intermittent preventive therapy with SP, the estimates of effect and the quality of the evidence were similar.A summary of a single trial in Thailand of prophylaxis against P. vivax showed chloroquine prevented vivax infection (RR 0.01, 95% CI 0.00 to 0.20; one trial, 942 participants). AUTHORS' CONCLUSIONS: Routine chemoprevention to prevent malaria and its consequences has been extensively tested in RCTs, with clinically important benefits on anaemia and parasitaemia in the mother, and on birthweight in infants.

Access to electronic health knowledge in five countries in Africa: a descriptive study.

BACKGROUND: Access to medical literature in developing countries is helped by open access publishing and initiatives to allow free access to subscription only journals. The effectiveness of these initiatives in Africa has not been assessed. This study describes awareness, reported use and factors influencing use of on-line medical literature via free access initiatives. METHODS: Descriptive study in four teaching hospitals in Cameroon, Nigeria, Tanzania and Uganda plus one externally funded research institution in The Gambia. Survey with postgraduate doctors and research scientists to determine Internet access patterns, reported awareness of on-line medical information and free access initiatives; semi structured interviews with a sub-sample of survey participants to explore factors influencing use. RESULTS: In the four African teaching hospitals, 70% of the 305 postgraduate doctors reported textbooks as their main source of information; 66% had used the Internet for health information in the last week. In two hospitals, Internet cafés were the main Internet access point. For researchers at the externally-funded research institution, electronic resources were their main source, and almost all had used the Internet in the last week. Across all 333 respondents, 90% had heard of PubMed, 78% of BMJ on line, 49% the Cochrane Library, 47% HINARI, and 19% BioMedCentral. HINARI use correlates with accessing the Internet on computers located in institutions. Qualitative data suggested there are difficulties logging into HINARI and that sometimes it is librarians that limit access to passwords. CONCLUSION: Text books remain an important resource for postgraduate doctors in training. Internet use is common, but awareness of free-access initiatives is limited. HINARI and other initiatives could be more effective with strong institutional endorsement and management to promote and ensure access.