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Background\ud Good patient adherence to antiretroviral (ART) medication determines effective HIV viral suppression, and thus reduces the risk of progression and transmission of HIV. With accurate methods to monitor treatment adherence, we could use simple triage to target adherence support interventions that could help in the community or at health centres in resource‐limited settings.\ud \ud Objectives\ud To determine the accuracy of simple measures of ART adherence (including patient self‐report, tablet counts, pharmacy records, electronic monitoring, or composite methods) for detecting non‐suppressed viral load in people living with HIV and receiving ART treatment.\ud \ud Search methods\ud The Cochrane Infectious Diseases Group Information Specialists searched CENTRAL, MEDLINE, Embase, LILACS, CINAHL, African‐Wide information, and Web of Science up to 22 April 2021. They also searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing studies. No restrictions were placed on the language or date of publication when searching the electronic databases.\ud \ud Selection criteria\ud We included studies of all designs that evaluated a simple measure of adherence (index test) such as self‐report, tablet counts, pharmacy records or secondary database analysis, or both, electronic monitoring or composite measures of any of those tests, in people living with HIV and receiving ART treatment. We used a viral load assay with a limit of detection ranging from 10 copies/mL to 400 copies/mL as the reference standard. We created 2 × 2 tables to calculate sensitivity and specificity.\ud \ud Data collection and analysis\ud We screened studies, extracted data, and assessed risk of bias using QUADAS‐2 independently and in duplicate. We assessed the certainty of evidence using the GRADE method. The results of estimated sensitivity and specificity were presented using paired forest plots and tabulated summaries. We encountered a high level of variation among studies which precluded a meaningful meta‐analysis or comparison of adherence measures. We explored heterogeneity using pre‐defined subgroup analysis.\ud \ud Main results\ud We included 51 studies involving children and adults with HIV, mostly living in low‐ and middle‐income settings, conducted between 2003 and 2021. Several studies assessed more than one index test, and the most common measure of adherence to ART was self‐report.\ud \ud ‐ Self‐report questionnaires (25 studies, 9211 participants; very low‐certainty): sensitivity ranged from 10% to 85% and specificity ranged from 10% to 99%.\ud \ud ‐ Self‐report using a visual analogue scale (VAS) (11 studies, 4235 participants; very low‐certainty): sensitivity ranged from 0% to 58% and specificity ranged from 55% to 100%.\ud \ud ‐ Tablet counts (12 studies, 3466 participants; very low‐certainty): sensitivity ranged from 0% to 100% and specificity ranged from 5% to 99%.\ud \ud ‐ Electronic monitoring devices (3 studies, 186 participants; very low‐certainty): sensitivity ranged from 60% to 88% and the specificity ranged from 27% to 67%.\ud \ud ‐ Pharmacy records or secondary databases (6 studies, 2254 participants; very low‐certainty): sensitivity ranged from 17% to 88% and the specificity ranged from 9% to 95%.\ud \ud ‐ Composite measures (9 studies, 1513 participants; very low‐certainty): sensitivity ranged from 10% to 100% and specificity ranged from 49% to 100%.\ud \ud Across all included studies, the ability of adherence measures to detect viral non‐suppression showed a large variation in both sensitivity and specificity that could not be explained by subgroup analysis. We assessed the overall certainty of the evidence as very low due to risk of bias, indirectness, inconsistency, and imprecision.\ud \ud The risk of bias and the applicability concerns for patient selection, index test, and reference standard domains were generally low or unclear due to unclear reporting. The main methodological issues identified were related to flow and timing due to high numbers of missing data. For all index tests, we assessed the certainty of the evidence as very low due to limitations in the design and conduct of the studies, applicability concerns and inconsistency of results.\ud \ud Authors' conclusions\ud We encountered high variability for all index tests, and the overall certainty of evidence in all areas was very low. No measure consistently offered either a sufficiently high sensitivity or specificity to detect viral non‐suppression. These concerns limit their value in triaging patients for viral load monitoring or enhanced adherence support interventions.

Chronic pain in childhood is an international public health problem. We conducted a systematic review and meta-analysis to provide a summary of the published evidence of pharmacological, physical, and psychological therapies for children with chronic pain conditions. We searched CENTRAL, MEDLINE, EMBASE, and PsycINFO from inception to April 2020; clinical trial registries; and other sources for randomised controlled trials or comparative observational trials. We extracted critical outcomes of pain intensity, quality of life, physical functioning, role functioning, emotional functioning, sleep, and adverse events. We assessed studies for risk of bias and certainty of the evidence using GRADE. We included 34 pharmacological (4091 participants), 25 physical therapy (1470 participants), and 63 psychological trials (5025 participants). Participants reported a range of chronic pain conditions. Most studies were assessed to have unclear or high risk of bias across multiple domains. Pharmacological, physical, and psychological therapies showed some benefit for reducing pain, posttreatment, but only physical and psychological therapies improved physical functioning. We found no benefit of any treatment modality for health-related quality of life, role functioning, emotional functioning, or sleep. Adverse events were poorly reported, particularly for psychological and physical interventions. The largest evidence base for the management of chronic pain in children supports the use of psychological therapies, followed by pharmacological and physical therapies. However, we rated most outcomes as low or very low certainty, meaning further evidence is likely to change our confidence in the estimates of effects. This protocol was registered on PROSPERO (CRD42020172451).

Background Human African trypanosomiasis, or sleeping sickness, is a severe disease affecting people in the poorest parts of Africa. It is usually fatal without treatment. Conventional treatments require days of intravenous infusion, but a recently developed drug, fexinidazole, can be given orally. Another oral drug candidate, acoziborole, is undergoing clinical development and will be considered in subsequent editions. Objectives To evaluate the effectiveness and safety of currently used drugs for treating second‐stage Trypanosoma brucei gambiense trypanosomiasis (gambiense human African trypanosomiasis, g‐HAT). Search methods On 14 May 2021, we searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Latin American and Caribbean Health Science Information database, BIOSIS, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. We also searched reference lists of included studies, contacted researchers working in the field, and contacted relevant organizations. Selection criteria Eligible studies were randomized controlled trials that included adults and children with second‐stage g‐HAT, treated with anti‐trypanosomal drugs currently in use. Data collection and analysis Two review authors extracted data and assessed risk of bias; a third review author acted as an arbitrator if needed. The included trial only reported dichotomous outcomes, which we presented as risk ratio (RR) or risk difference (RD) with 95% confidence intervals (CI). Main results We included one trial comparing fexinidazole to nifurtimox combined with eflornithine (NECT). This trial was conducted between October 2012 and November 2016 in the Democratic Republic of the Congo and the Central African Republic, and included 394 participants. The study reported on efficacy and safety, with up to 24 months' follow‐up. We judged the study to be at low risk of bias in all domains except blinding; as the route of administration and dosing regimens differed between treatment groups, participants and personnel were not blinded, resulting in a high risk of performance bias. Mortality with fexinidazole may be higher at 24 months compared to NECT. There were 9/264 deaths in the fexinidazole group and 2/130 deaths in the NECT group (RR 2.22, 95% CI 0.49 to 10.11; 394 participants; low‐certainty evidence). None of the deaths were related to treatment. Fexinidazole likely results in an increase in the number of people relapsing during follow‐up, with 14 participants in the fexinidazole group (14/264) and none in the NECT group (0/130) relapsing at 24 months (RD 0.05, 95% CI 0.02 to 0.08; 394 participants; moderate‐certainty evidence). We are uncertain whether there is any difference between the drugs regarding the incidence of serious adverse events at 24 months. (31/264 with fexinidazole and 13/130 with NECT group at 24 months). Adverse events were common with both drugs (247/264 with fexinidazole versus 121/130 with NECT), with no difference between groups (RR 1.01, 95% CI 0.95 to 1.06; 394 participants; moderate‐certainty evidence). Authors' conclusions Oral treatment with fexinidazole is much easier to administer than conventional treatment, but deaths and relapse appear to be more common. However, the advantages or an oral option are considerable, in terms of convenience, avoiding hospitalisation and multiple intravenous infusions, thus increasing adherence., Plain language summary Medicines for second‐stage human African trypanosomiasis What is the aim of this review? Gambiense human African trypanosomiasis (g‐HAT), or sleeping sickness, is a severe disease transmitted through the bite of infected tsetse flies found in rural parts of sub‐Saharan Africa. Sleeping sickness has two clinical stages. This review only examines treating the second‐stage, where people develop symptoms caused by invasion of the central nervous system (CNS), resulting in changes in the nervous system. Death is inevitable without treatment. Drugs for treatment are few, often require intravenous infusion every day over several weeks, and have serious side effects. In this review we aimed to compare the effects of current drugs for gambiense sleeping sickness and we examined nifurtimox‐eflornithine combination (NECT) with a new drug, fexinidazole, that can be taken orally. Key messages Whilst fexinidazole cures some people, deaths from any cause and treatment failure rates are higher than with conventional treatment. Adverse events were common in both groups. Fexinidazole is more practical to give, and means less time in hospital for intravenous treatment infusion. What was studied in this review? We looked at the evidence about the benefits and harms of current drugs used in people with second stage g‐HAT. We searched for randomized trials, which provide robust evidence about the various treatments. We aimed to determine whether any drug provides a definite advantage over the other, measured in terms of clinical outcomes and in relation to the severity of adverse effects. What are the main results of the review? We only identified one suitable trial, which included 394 people and was conducted in the Democratic Republic of the Congo and the Central African Republic. The trial showed that deaths from any cause at 24 months may be higher with fexinidazole compared with NECT. Nine of the 264 people who took fexinidazole died, compared with two of the 130 people who took NECT. Fexinidazole probably increases the number of people who relapse during two years. Fourteen people in the fexinidazole group relapsed, and none in the NECT group. Adverse events were very common in both groups over the two years, and there is not likely to be much difference between the two drugs (247/264 in the fexinidazole group and 121/130 in the NECT group). We do not know about the effect of fexinidazole on serious adverse events, as the evidence is very uncertain. There were 31/264 serious adverse events in the fexinidazole group and 13/130 in the NECT group at 24 months. How up to date is this review? The evidence is current to 14 May 2021.

PurposeChronic primary pain conditions are characterized by significant functional disability, emotional distress, and diagnostic uncertainty. Health-related guilt associated with coping and living with chronic pain is poorly understood. There had been no attempts to synthesize findings on health-related guilt across studies. Therefore, the aim of this study was to conduct a systemic review of evidence, to enable an understanding of the role of health-related guilt in chronic primary pain, and to provide directions for future research.MethodA search strategy was developed based on our eligibility criteria. Four databases (PsycINFO, Scopus, PubMed, and Web of Science) were searched for relevant papers from inception to 8 July 2020. Data from 12 qualitative and six quantitative studies were synthesized narratively.ResultsThe review of qualitative studies resulted in three themes, relating to the management of pain, diagnostic uncertainty/legitimizing pain, and how participants’ actions or inactions affect others. These findings were integrated with evidence from quantitative studies, which showed that higher levels of guilt were associated with more pain and pain interference, functional impairment, and poorer psychological and social functioning.ConclusionsThe findings demonstrate that health-related guilt is an important psychological factor associated with more pain and poorer function in people with chronic primary pain conditions. Future research should examine health-related guilt as a potential mediating/moderating factor leading to more distress and suffering in this population and as a potential target for interventions.

Aim: To assess the effectiveness of supported employment interventions for improving competitive employment in populations of people with conditions other than only severe mental illness. Background: Supported employment interventions have been extensively tested in severe mental illness populations. These approaches may be beneficial outside of these populations. Methods: We searched PubMed, Embase, CINAHL, PsycInfo, Web of Science, Scopus, JSTOR, PEDro, OTSeeker, and NIOSHTIC for trials including unemployed people with any condition and including severe mental illness if combined with other co-morbidities or other specific circumstances (e.g., homelessness). We excluded trials where inclusion was based on severe mental illness alone. Two reviewers independently assessed risk of bias (RoB v2.0) and four reviewers extracted data. We assessed rates of competitive employment as compared to traditional vocational rehabilitation or waiting list/services as usual. Findings: Ten randomised controlled trials (913 participants) were included. Supported employment was more effective than control interventions for improving competitive employment in seven trials: in people with affective disorders [risk ratio (RR) 10.61 (1.49, 75.38)]; mental disorders and justice involvement [RR 4.44 (1.36,14.46)]; veterans with posttraumatic stress disorder (PTSD) [RR 2.73 (1.64, 4.54)]; formerly incarcerated veterans [RR 2.17 (1.09, 4.33)]; people receiving methadone treatment [RR 11.5 (1.62, 81.8)]; veterans with spinal cord injury at 12 months [RR 2.46 (1.16, 5.22)] and at 24 months [RR 2.81 (1.98, 7.37)]; and young people not in employment, education, or training [RR 5.90 (1.91–18.19)]. Three trials did not show significant benefits from supported employment: populations of workers with musculoskeletal injuries [RR 1.38 (1.00, 1.89)]; substance abuse [RR 1.85 (0.65, 5.41)]; and formerly homeless people with mental illness [RR 1.55 (0.76, 3.15)]. Supported employment interventions may be beneficial to people from more diverse populations than those with severe mental illness alone. Defining competitive employment and increasing (and standardising) measurement of non-vocational outcomes may help to improve research in this area.

Objective:To identify predictors of prognosis and trial outcomes in prospective studies of people with chronic headache.Methods:This was a systematic review of published literature in peer-reviewed journals. We included (1) randomized controlled trials (RCTs) of interventions for chronic headache that reported subgroup analyses and (2) prospective cohort studies, published in English, since 1980. Participants included adults with chronic headache (including chronic headache, chronic migraine, and chronic tension-type headache with or without medication overuse headache). We searched key databases using free text and MeSH terms. Two reviewers independently extracted data and assessed the methodologic quality of studies and overall quality of evidence identified using appropriate published checklists.Results:We identified 16,556 titles, removed 663 duplicates, and reviewed 199 articles, of which 27 were included in the review—17 prospective cohorts and 10 RCTs with subgroup analyses reported. There was moderate-quality evidence indicating that depression, anxiety, poor sleep and stress, medication overuse, and poor self-efficacy for managing headaches are potential prognostic factors for poor prognosis and unfavorable outcomes from preventive treatment in chronic headache. There was inconclusive evidence about treatment expectations, age, age at onset, body mass index, employment, and several headache features.Conclusions:This review identified several potential predictors of poor prognosis and worse outcome postinterventions in people with chronic headache. The majority of these are modifiable. The findings also highlight the need for more longitudinal high-quality research of prognostic factors in chronic headache.

Background There is a lack of research available that examines the diverse population of frequent users of Urgent and Emergency Healthcare services throughout England. The motivations and decision-making processes which frequent users take into consideration when selecting episodic treatment from: Out of Hours GPs; NHS111; Ambulance Services and Emergency Departments are not full examined. Most research explores this population by focusing on the patient’s demographics or preliminary diagnosis, rather than their unmet needs that has instigated the urgent and emergency contact. Subjective terminology and arbitrary thresholds are employed across these services to identify these individuals, with little standardisation or clinical justification to the reasons why they have been selected. Through understanding the unmet needs of this heterogenous population, improved individualised patient centred support and management options should be achieved. Aims The aim was to analyse the underlying reasons why frequent users of Urgent and Emergency Healthcare Services in England, select and request episodic instances of care, rather than the consistent approach provided within primary care. Methods A systematic mapping exercise was undertaken to create a comprehensive understanding of how these services are currently working with regard to frequent users. The search produced 5094 articles which were screened against the inclusion criteria, leaving 156 articles to be analysed. Data was extracted and a thematic synthesis was used to analyse this diverse population. From this analysis, a taxonomy of sub-groups of frequent users was formed and their underlying needs identified. Thirty-two clinical semi-structured interviews throughout these services were undertaken, to gain critical feedback on the robustness and viability of the taxonomy. A purposeful sampling method ensured that clinical practitioners that had substantial experience in supporting and managing these complex and vulnerable individuals participated within the research. The qualitative data received from clinicians with knowledge and skills of working with this population prompted adjustments to the original taxonomy. Results The taxonomy sub-divided the main heterogeneous group into 5 main groups: Elderly and Frail; Mental Health; Substance Misuse; Chronic Conditions; and Homeless and Vulnerably Housed. Within each sub-group, unmet needs were identified and further categorised. A hidden population of patients that were accessing urgent and emergency healthcare services due to unresolved pain emerged. This population was categorised into: persistent or chronic pain; acute episodes of severe pain (crisis) and addiction, opioid-induced hyperalgesia or tolerance factors. The reasons attributed to the patients’ frequent contacts were due to the breakdown of their relationship with their GP, polypharmacy issues, access to primary care treatments, perceptions and judgements from clinicians and lack of adequate clinical training around pain management both in primary and acute settings. These high intensity users of urgent and emergency healthcare services are often the most vulnerable and complex members of our society. Conclusion Repeated episodic instances of care, which are often given in urgent and emergency healthcare settings relating to pain management are not proactively allowing individuals to manage their long-term outcomes. Understanding the patients’ unmet needs and what has instigated their frequent contacts to services, could enable clinicians to signpost into other specialised services which will improve the patients’ quality of care. Furthermore, Improved pain management training in both the primary and acute services relating to high intensity users could diminish the negative experiences faced by these individuals and frustrations felt within day to day practice.

ObjectiveTo systematically review the qualitative literature of the lived experience of people with a chronic headache disorder.BackgroundChronic headaches affect 3%–4% of the population. The most common chronic headache disorders are chronic migraine, chronic tension-type headache and medication overuse headache. We present a systematic review and meta-ethnographic synthesis of the lived experience of people with chronic headache.MethodsWe searched seven electronic databases, hand-searched nine journals and used a modified Critical Appraisal Skills Programme checklist to appraise study quality. Following thematic analysis we synthesised the data using a meta-ethnographic approach.ResultsWe identified 3586 unique citations; full texts were examined for 86 studies and 4 were included in the review. Included studies differed in their foci: exploring, patient-centred outcomes, chronic headache as a socially invisible disease, psychological processes mediating impaired quality of life, and the process of medication overuse. Initial thematic analysis and subsequent synthesis gave three overarching themes: ‘headache as a driver of behaviour’ (directly and indirectly), ‘the spectre of headache’ and ‘strained relationships’.ConclusionThis meta-synthesis of published qualitative evidence demonstrates that chronic headaches have a profound effect on people’s lives, showing similarities with other pain conditions. There were insufficient data to explore the similarities and differences between different chronic headache disorders.

ObjectivesTo assess the effect of non-pharmacological self-management interventions against usual care, and to explore different components and delivery methods within those interventionsParticipantsPeople living with migraine and/or tension-type headacheInterventionsNon-pharmacological educational or psychological self-management interventions; excluding biofeedback and physical therapy.We assessed the overall effectiveness against usual care on headache frequency, pain intensity, mood, headache-related disability, quality of life and medication consumption in meta-analysis.We also provide preliminary evidence on the effectiveness of intervention components and delivery methods.ResultsWe found a small overall effect for the superiority of self-management interventions over usual care, with a standardised mean difference (SMD) of −0.36 (−0.45 to −0.26) for pain intensity; −0.32 (−0.42 to −0.22) for headache-related disability, 0.32 (0.20 to 0.45) for quality of life and a moderate effect on mood (SMD=0.53 (−0.66 to −0.40)). We did not find an effect on headache frequency (SMD=−0.07 (−0.22 to 0.08)).Assessment of components and characteristics suggests a larger effect on pain intensity in interventions that included explicit educational components (−0.51 (−0.68 to −0.34) vs −0.28 (−0.40 to −0.16)); mindfulness components (−0.50 (−0.82 to −0.18) vs 0.34 (−0.44 to −0.24)) and in interventions delivered in groups vs one-to-one delivery (0.56 (−0.72 to −0.40) vs −0.39 (−0.52 to −0.27)) and larger effects on mood in interventions including a cognitive–behavioural therapy (CBT) component with an SMD of −0.72 (−0.93 to −0.51) compared with those without CBT −0.41 (−0.58 to −0.24).ConclusionOverall we found that self-management interventions for migraine and tension-type headache are more effective than usual care in reducing pain intensity, mood and headache-related disability, but have no effect on headache frequency. Preliminary findings also suggest that including CBT, mindfulness and educational components in interventions, and delivery in groups may increase effectiveness.Trial registration numberPROSPERO 2016:CRD42016041291

Study Design\ud A systematic review of randomised controlled trials (RCTs) \ud Objective\ud To determine the effects of active rehabilitation on functional outcome following lumbar spinal stenosis surgery when compared with 'usual postoperative care'.\ud Summary of background data\ud Surgery rates for lumbar spinal stenosis have risen, yet outcomes remain suboptimal. Post-operative rehabilitation has been suggested as a tool to improve post-operative function but, to date, there is limited evidence to support its use.\ud Methods\ud CENTRAL (The Cochrane Library), the Cochrane Back Review Group Trials Register, MEDLINE, EMBASE, CINAHL and PEDro electronic databases were searched. Randomised controlled trials (RCTs) comparing the effectiveness of active rehabilitation with usual care in adults with lumbar spinal stenosis who had undergone primary spinal decompression surgery were included. Two authors independently selected studies, assessed the risk of bias, and extracted the data in line with the recommendations of the Cochrane Back Review Group. Study results were pooled in a meta-analysis when appropriate using functional status as the primary outcome, with secondary outcomes including measures of leg pain, low back pain, and global improvement/general health. The GRADE approach was used to assess the quality of the evidence.\ud Results\ud Our searches yielded 1,726 articles, of which three studies (N = 373 participants) were suitable for inclusion in meta-analysis. All included studies were deemed to have low risk of bias; no study had unacceptably high dropout rates. There was moderate evidence suggesting that active rehabilitation was more effective than usual care in improving both short- and long-term functional status following surgery. Similar findings were noted for secondary outcomes, including short-term improvement in low back pain and long-term improvement in both low back pain and leg pain. \ud Conclusions\ud We obtained moderate-quality evidence indicating that postoperative active rehabilitation after decompression surgery for lumbar spinal stenosis is more effective than usual care. Further work is required particularly with respect to the cost effectiveness of such interventions.