Factors that influence participation in physical activity for people with bipolar disorder: a synthesis of qualitative evidence.

Mental health problems contribute significantly to the overall disease burden worldwide and are major causes of disability, suicide, and ischaemic heart disease. People with bipolar disorder report lower levels of physical activity than the general population, and are at greater risk of chronic health conditions including cardiovascular disease and obesity. These contribute to poor health outcomes. Physical activity has the potential to improve quality of life and physical and mental well-being. To identify the factors that influence participation in physical activity for people diagnosed with bipolar disorder from the perspectives of service users, carers, service providers, and practitioners to help inform the design and implementation of interventions that promote physical activity. We searched MEDLINE, PsycINFO, and eight other databases to March 2021. We also contacted experts in the field, searched the grey literature, and carried out reference checking and citation searching to identify additional studies. There were no language restrictions. We included qualitative studies and mixed-methods studies with an identifiable qualitative component. We included studies that focused on the experiences and attitudes of service users, carers, service providers, and healthcare professionals towards physical activity for bipolar disorder. We extracted data using a data extraction form designed for this review. We assessed methodological limitations using a list of predefined questions. We used the "best fit" framework synthesis based on a revised version of the Health Belief Model to analyse and present the evidence. We assessed methodological limitations using the CASP Qualitative Checklist. We used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) guidance to assess our confidence in each finding. We examined each finding to identify factors to inform the practice of health and care professionals and the design and development of physical activity interventions for people with bipolar disorder. We included 12 studies involving a total of 592 participants (422 participants who contributed qualitative data to an online survey, 170 participants in qualitative research studies). Most studies explored the views and experiences of physical activity of people with experience of bipolar disorder. A number of studies also reported on personal experiences of physical activity components of lifestyle interventions. One study included views from family carers and clinicians. The majority of studies were from high-income countries, with only one study conducted in a middle-income country. Most participants were described as stable and had been living with a diagnosis of bipolar disorder for a number of years. We downgraded our confidence in several of the findings from high confidence to moderate or low confidence, as some findings were based on only small amounts of data, and the findings were based on studies from only a few countries, questioning the relevance of these findings to other settings. We also had very few perspectives of family members, other carers, or health professionals supporting people with bipolar disorder. The studies did not include any findings from service providers about their perspectives on supporting this aspect of care. There were a number of factors that limited people's ability to undertake physical activity. Shame and stigma about one's physical appearance and mental health diagnosis were discussed. Some people felt their sporting skills/competencies had been lost when they left school. Those who had been able to maintain exercise through the transition into adulthood appeared to be more likely to include physical activity in their regular routine. Physical health limits and comorbid health conditions limited activity. This included bipolar medication, being overweight, smoking, alcohol use, poor diet and sleep, and these barriers were linked to negative coping skills. Practical problems included affordability, accessibility, transport links, and the weather. Workplace or health schemes that offered discounts were viewed positively. The lack of opportunity for exercise within inpatient mental health settings was a problem. Facilitating factors included being psychologically stable and ready to adopt new lifestyle behaviours. There were positive benefits of being active outdoors and connecting with nature. Achieving balance, rhythm, and routine helped to support mood management. Fitting physical activity into a regular routine despite fluctuating mood or motivation appeared to be beneficial if practised at the right intensity and pace. Over- or under-exercising could be counterproductive and accelerate depressive or manic moods. Physical activity also helped to provide a structure to people's daily routines and could lead to other positive lifestyle benefits. Monitoring physical or other activities could be an effective way to identify potential triggers or early warning signs. Technology was helpful for some. People who had researched bipolar disorder and had developed a better understanding of the condition showed greater confidence in managing their care or providing care to others. Social support from friends/family or health professionals was an enabling factor, as was finding the right type of exercise, which for many people was walking. Other benefits included making social connections, weight loss, improved quality of life, and better mood regulation. Few people had been told of the benefits of physical activity. Better education and training of health professionals could support a more holistic approach to physical and mental well-being. Involving mental health professionals in the multidisciplinary delivery of physical activity interventions could be beneficial and improve care. Clear guidelines could help people to initiate and incorporate lifestyle changes. There is very little research focusing on factors that influence participation in physical activity in bipolar disorder. The studies we identified suggest that men and women with bipolar disorder face a range of obstacles and challenges to being active. The evidence also suggests that there are effective ways to promote managed physical activity. The research highlighted the important role that health and care settings, and professionals, can play in assessing individuals' physical health needs and how healthy lifestyles may be promoted. Based on these findings, we have provided a summary of key elements to consider for developing physical activity interventions for bipolar disorder.

McCartan CJ ，Yap J ，Best P ，Breedvelt J ，Breslin G ，Firth J ，Tully MA ，Webb P ，White C ，Gilbody S ，Churchill R ，Davidson G ... -  《Cochrane Database of Systematic Reviews》

Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.

Description of the condition Malaria, an infectious disease transmitted by the bite of female mosquitoes from several Anopheles species, occurs in 87 countries with ongoing transmission (WHO 2020). The World Health Organization (WHO) estimated that, in 2019, approximately 229 million cases of malaria occurred worldwide, with 94% occurring in the WHO's African region (WHO 2020). Of these malaria cases, an estimated 409,000 deaths occurred globally, with 67% occurring in children under five years of age (WHO 2020). Malaria also negatively impacts the health of women during pregnancy, childbirth, and the postnatal period (WHO 2020). Sulfadoxine/pyrimethamine (SP), an antifolate antimalarial, has been widely used across sub-Saharan Africa as the first-line treatment for uncomplicated malaria since it was first introduced in Malawi in 1993 (Filler 2006). Due to increasing resistance to SP, in 2000 the WHO recommended that one of several artemisinin-based combination therapies (ACTs) be used instead of SP for the treatment of uncomplicated malaria caused by Plasmodium falciparum (Global Partnership to Roll Back Malaria 2001). However, despite these recommendations, SP continues to be advised for intermittent preventive treatment in pregnancy (IPTp) and intermittent preventive treatment in infants (IPTi), whether the person has malaria or not (WHO 2013). Description of the intervention Folate (vitamin B9) includes both naturally occurring folates and folic acid, the fully oxidized monoglutamic form of the vitamin, used in dietary supplements and fortified food. Folate deficiency (e.g. red blood cell (RBC) folate concentrations of less than 305 nanomoles per litre (nmol/L); serum or plasma concentrations of less than 7 nmol/L) is common in many parts of the world and often presents as megaloblastic anaemia, resulting from inadequate intake, increased requirements, reduced absorption, or abnormal metabolism of folate (Bailey 2015; WHO 2015a). Pregnant women have greater folate requirements; inadequate folate intake (evidenced by RBC folate concentrations of less than 400 nanograms per millilitre (ng/mL), or 906 nmol/L) prior to and during the first month of pregnancy increases the risk of neural tube defects, preterm delivery, low birthweight, and fetal growth restriction (Bourassa 2019). The WHO recommends that all women who are trying to conceive consume 400 micrograms (µg) of folic acid daily from the time they begin trying to conceive through to 12 weeks of gestation (WHO 2017). In 2015, the WHO added the dosage of 0.4 mg of folic acid to the essential drug list (WHO 2015c). Alongside daily oral iron (30 mg to 60 mg elemental iron), folic acid supplementation is recommended for pregnant women to prevent neural tube defects, maternal anaemia, puerperal sepsis, low birthweight, and preterm birth in settings where anaemia in pregnant women is a severe public health problem (i.e. where at least 40% of pregnant women have a blood haemoglobin (Hb) concentration of less than 110 g/L). How the intervention might work Potential interactions between folate status and malaria infection The malaria parasite requires folate for survival and growth; this has led to the hypothesis that folate status may influence malaria risk and severity. In rhesus monkeys, folate deficiency has been found to be protective against Plasmodium cynomolgi malaria infection, compared to folate-replete animals (Metz 2007). Alternatively, malaria may induce or exacerbate folate deficiency due to increased folate utilization from haemolysis and fever. Further, folate status measured via RBC folate is not an appropriate biomarker of folate status in malaria-infected individuals since RBC folate values in these individuals are indicative of both the person's stores and the parasite's folate synthesis. A study in Nigeria found that children with malaria infection had significantly higher RBC folate concentrations compared to children without malaria infection, but plasma folate levels were similar (Bradley-Moore 1985). Why it is important to do this review The malaria parasite needs folate for survival and growth in humans. For individuals, adequate folate levels are critical for health and well-being, and for the prevention of anaemia and neural tube defects. Many countries rely on folic acid supplementation to ensure adequate folate status in at-risk populations. Different formulations for folic acid supplements are available in many international settings, with dosages ranging from 400 µg to 5 mg. Evaluating folic acid dosage levels used in supplementation efforts may increase public health understanding of its potential impacts on malaria risk and severity and on treatment failures. Examining folic acid interactions with antifolate antimalarial medications and with malaria disease progression may help countries in malaria-endemic areas determine what are the most appropriate lower dose folic acid formulations for at-risk populations. The WHO has highlighted the limited evidence available and has indicated the need for further research on biomarkers of folate status, particularly interactions between RBC folate concentrations and tuberculosis, human immunodeficiency virus (HIV), and antifolate antimalarial drugs (WHO 2015b). An earlier Cochrane Review assessed the effects and safety of iron supplementation, with or without folic acid, in children living in hyperendemic or holoendemic malaria areas; it demonstrated that iron supplementation did not increase the risk of malaria, as indicated by fever and the presence of parasites in the blood (Neuberger 2016). Further, this review stated that folic acid may interfere with the efficacy of SP; however, the efficacy and safety of folic acid supplementation on these outcomes has not been established. This review will provide evidence on the effectiveness of daily folic acid supplementation in healthy and malaria-infected individuals living in malaria-endemic areas. Additionally, it will contribute to achieving both the WHO Global Technical Strategy for Malaria 2016-2030 (WHO 2015d), and United Nations Sustainable Development Goal 3 (to ensure healthy lives and to promote well-being for all of all ages) (United Nations 2021), and evaluating whether the potential effects of folic acid supplementation, at different doses (e.g. 0.4 mg, 1 mg, 5 mg daily), interferes with the effect of drugs used for prevention or treatment of malaria. To examine the effects of folic acid supplementation, at various doses, on malaria susceptibility (risk of infection) and severity among people living in areas with various degrees of malaria endemicity. We will examine the interaction between folic acid supplements and antifolate antimalarial drugs. Specifically, we will aim to answer the following. Among uninfected people living in malaria endemic areas, who are taking or not taking antifolate antimalarials for malaria prophylaxis, does taking a folic acid-containing supplement increase susceptibility to or severity of malaria infection? Among people with malaria infection who are being treated with antifolate antimalarials, does folic acid supplementation increase the risk of treatment failure? Criteria for considering studies for this review Types of studies Inclusion criteria Randomized controlled trials (RCTs) Quasi-RCTs with randomization at the individual or cluster level conducted in malaria-endemic areas (areas with ongoing, local malaria transmission, including areas approaching elimination, as listed in the World Malaria Report 2020) (WHO 2020) Exclusion criteria Ecological studies Observational studies In vivo/in vitro studies Economic studies Systematic literature reviews and meta-analyses (relevant systematic literature reviews and meta-analyses will be excluded but flagged for grey literature screening) Types of participants Inclusion criteria Individuals of any age or gender, living in a malaria endemic area, who are taking antifolate antimalarial medications (including but not limited to sulfadoxine/pyrimethamine (SP), pyrimethamine-dapsone, pyrimethamine, chloroquine and proguanil, cotrimoxazole) for the prevention or treatment of malaria (studies will be included if more than 70% of the participants live in malaria-endemic regions) Studies assessing participants with or without anaemia and with or without malaria parasitaemia at baseline will be included Exclusion criteria Individuals not taking antifolate antimalarial medications for prevention or treatment of malaria Individuals living in non-malaria endemic areas Types of interventions Inclusion criteria Folic acid supplementation Form: in tablet, capsule, dispersible tablet at any dose, during administration, or periodically Timing: during, before, or after (within a period of four to six weeks) administration of antifolate antimalarials Iron-folic acid supplementation Folic acid supplementation in combination with co-interventions that are identical between the intervention and control groups. Co-interventions include: anthelminthic treatment; multivitamin or multiple micronutrient supplementation; 5-methyltetrahydrofolate supplementation. Exclusion criteria Folate through folate-fortified water Folic acid administered through large-scale fortification of rice, wheat, or maize Comparators Placebo No treatment No folic acid/different doses of folic acid Iron Types of outcome measures Primary outcomes Uncomplicated malaria (defined as a history of fever with parasitological confirmation; acceptable parasitological confirmation will include rapid diagnostic tests (RDTs), malaria smears, or nucleic acid detection (i.e. polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), etc.)) (WHO 2010). This outcome is relevant for patients without malaria, given antifolate antimalarials for malaria prophylaxis. Severe malaria (defined as any case with cerebral malaria or acute P. falciparum malaria, with signs of severity or evidence of vital organ dysfunction, or both) (WHO 2010). This outcome is relevant for patients without malaria, given antifolate antimalarials for malaria prophylaxis. Parasite clearance (any Plasmodium species), defined as the time it takes for a patient who tests positive at enrolment and is treated to become smear-negative or PCR negative. This outcome is relevant for patients with malaria, treated with antifolate antimalarials. Treatment failure (defined as the inability to clear malaria parasitaemia or prevent recrudescence after administration of antimalarial medicine, regardless of whether clinical symptoms are resolved) (WHO 2019). This outcome is relevant for patients with malaria, treated with antifolate antimalarials. Secondary outcomes Duration of parasitaemia Parasite density Haemoglobin (Hb) concentrations (g/L) Anaemia: severe anaemia (defined as Hb less than 70 g/L in pregnant women and children aged six to 59 months; and Hb less than 80 g/L in other populations); moderate anaemia (defined as Hb less than 100 g/L in pregnant women and children aged six to 59 months; and less than 110 g/L in others) Death from any cause Among pregnant women: stillbirth (at less than 28 weeks gestation); low birthweight (less than 2500 g); active placental malaria (defined as Plasmodium detected in placental blood by smear or PCR, or by Plasmodium detected on impression smear or placental histology). Search methods for identification of studies A search will be conducted to identify completed and ongoing studies, without date or language restrictions. Electronic searches A search strategy will be designed to include the appropriate subject headings and text word terms related to each intervention of interest and study design of interest (see Appendix 1). Searches will be broken down by these two criteria (intervention of interest and study design of interest) to allow for ease of prioritization, if necessary. The study design filters recommended by the Scottish Intercollegiate Guidelines Network (SIGN), and those designed by Cochrane for identifying clinical trials for MEDLINE and Embase, will be used (SIGN 2020). There will be no date or language restrictions. Non-English articles identified for inclusion will be translated into English. If translations are not possible, advice will be requested from the Cochrane Infectious Diseases Group and the record will be stored in the "Awaiting assessment" section of the review until a translation is available. The following electronic databases will be searched for primary studies. Cochrane Central Register of Controlled Trials. Cumulative Index to Nursing and Allied Health Literature (CINAHL). Embase. MEDLINE. Scopus. Web of Science (both the Social Science Citation Index and the Science Citation Index). We will conduct manual searches of ClinicalTrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the United Nations Children's Fund (UNICEF) Evaluation and Research Database (ERD), in order to identify relevant ongoing or planned trials, abstracts, and full-text reports of evaluations, studies, and surveys related to programmes on folic acid supplementation in malaria-endemic areas. Additionally, manual searches of grey literature to identify RCTs that have not yet been published but are potentially eligible for inclusion will be conducted in the following sources. Global Index Medicus (GIM). African Index Medicus (AIM). Index Medicus for the Eastern Mediterranean Region (IMEMR). Latin American & Caribbean Health Sciences Literature (LILACS). Pan American Health Organization (PAHO). Western Pacific Region Index Medicus (WPRO). Index Medicus for the South-East Asian Region (IMSEAR). The Spanish Bibliographic Index in Health Sciences (IBECS) (ibecs.isciii.es/). Indian Journal of Medical Research (IJMR) (journals.lww.com/ijmr/pages/default.aspx). Native Health Database (nativehealthdatabase.net/). Scielo (www.scielo.br/). Searching other resources Handsearches of the five journals with the highest number of included studies in the last 12 months will be conducted to capture any relevant articles that may not have been indexed in the databases at the time of the search. We will contact the authors of included studies and will check reference lists of included papers for the identification of additional records. For assistance in identifying ongoing or unpublished studies, we will contact the Division of Nutrition, Physical Activity, and Obesity (DNPAO) and the Division of Parasitic Diseases and Malaria (DPDM) of the CDC, the United Nations World Food Programme (WFP), Nutrition International (NI), Global Alliance for Improved Nutrition (GAIN), and Hellen Keller International (HKI). Data collection and analysis Selection of studies Two review authors will independently screen the titles and abstracts of articles retrieved by each search to assess eligibility, as determined by the inclusion and exclusion criteria. Studies deemed eligible for inclusion by both review authors in the abstract screening phase will advance to the full-text screening phase, and full-text copies of all eligible papers will be retrieved. If full articles cannot be obtained, we will attempt to contact the authors to obtain further details of the studies. If such information is not obtained, we will classify the study as "awaiting assessment" until further information is published or made available to us. The same two review authors will independently assess the eligibility of full-text articles for inclusion in the systematic review. If any discrepancies occur between the studies selected by the two review authors, a third review author will provide arbitration. Each trial will be scrutinized to identify multiple publications from the same data set, and the justification for excluded trials will be documented. A PRISMA flow diagram of the study selection process will be presented to provide information on the number of records identified in the literature searches, the number of studies included and excluded, and the reasons for exclusion (Moher 2009). The list of excluded studies, along with their reasons for exclusion at the full-text screening phase, will also be created. Data extraction and management Two review authors will independently extract data for the final list of included studies using a standardized data specification form. Discrepancies observed between the data extracted by the two authors will be resolved by involving a third review author and reaching a consensus. Information will be extracted on study design components, baseline participant characteristics, intervention characteristics, and outcomes. For individually randomized trials, we will record the number of participants experiencing the event and the number analyzed in each treatment group or the effect estimate reported (e.g. risk ratio (RR)) for dichotomous outcome measures. For count data, we will record the number of events and the number of person-months of follow-up in each group. If the number of person-months is not reported, the product of the duration of follow-up and the number of children evaluated will be used to estimate this figure. We will calculate the rate ratio and standard error (SE) for each study. Zero events will be replaced by 0.5. We will extract both adjusted and unadjusted covariate incidence rate ratios if they are reported in the original studies. For continuous data, we will extract means (arithmetic or geometric) and a measure of variance (standard deviation (SD), SE, or confidence interval (CI)), percentage or mean change from baseline, and the numbers analyzed in each group. SDs will be computed from SEs or 95% CIs, assuming a normal distribution of the values. Haemoglobin values in g/dL will be calculated by multiplying haematocrit or packed cell volume values by 0.34, and studies reporting haemoglobin values in g/dL will be converted to g/L. In cluster-randomized trials, we will record the unit of randomization (e.g. household, compound, sector, or village), the number of clusters in the trial, and the average cluster size. The statistical methods used to analyze the trials will be documented, along with details describing whether these methods adjusted for clustering or other covariates. We plan to extract estimates of the intra-cluster correlation coefficient (ICC) for each outcome. Where results are adjusted for clustering, we will extract the treatment effect estimate and the SD or CI. If the results are not adjusted for clustering, we will extract the data reported. Assessment of risk of bias in included studies Two review authors (KSC, LFY) will independently assess the risk of bias for each included trial using the Cochrane 'Risk of bias 2' tool (RoB 2) for randomized studies (Sterne 2019). Judgements about the risk of bias of included studies will be made according to the recommendations outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021). Disagreements will be resolved by discussion, or by involving a third review author. The interest of our review will be to assess the effect of assignment to the interventions at baseline. We will evaluate each primary outcome using the RoB2 tool. The five domains of the Cochrane RoB2 tool include the following. Bias arising from the randomization process. Bias due to deviations from intended interventions. Bias due to missing outcome data. Bias in measurement of the outcome. Bias in selection of the reported result. Each domain of the RoB2 tool comprises the following. A series of 'signalling' questions. A judgement about the risk of bias for the domain, facilitated by an algorithm that maps responses to the signalling questions to a proposed judgement. Free-text boxes to justify responses to the signalling questions and 'Risk of bias' judgements. An option to predict (and explain) the likely direction of bias. Responses to signalling questions elicit information relevant to an assessment of the risk of bias. These response options are as follows. Yes (may indicate either low or high risk of bias, depending on the most natural way to ask the question). Probably yes. Probably no. No. No information (may indicate no evidence of that problem or an absence of information leading to concerns about there being a problem). Based on the answer to the signalling question, a 'Risk of bias' judgement is assigned to each domain. These judgements include one of the following. High risk of bias Low risk of bias Some concerns To generate the risk of bias judgement for each domain in the randomized studies, we will use the Excel template, available at www.riskofbias.info/welcome/rob-2-0-tool/current-version-of-rob-2. This file will be stored on a scientific data website, available to readers. Risk of bias in cluster randomized controlled trials For the cluster randomized trials, we will be using the RoB2 tool to analyze the five standard domains listed above along with Domain 1b (bias arising from the timing of identification or recruitment of participants) and its related signalling questions. To generate the risk of bias judgement for each domain in the cluster RCTs, we will use the Excel template available at https://sites.google.com/site/riskofbiastool/welcome/rob-2-0-tool/rob-2-for-cluster-randomized-trials. This file will be stored on a scientific data website, available to readers. Risk of bias in cross-over randomized controlled trials For cross-over randomized trials, we will be using the RoB2 tool to analyze the five standard domains listed above along with Domain 2 (bias due to deviations from intended interventions), and Domain 3 (bias due to missing outcome data), and their respective signalling questions. To generate the risk of bias judgement for each domain in the cross-over RCTs, we will use the Excel template, available at https://sites.google.com/site/riskofbiastool/welcome/rob-2-0-tool/rob-2-for-crossover-trials, for each risk of bias judgement of cross-over randomized studies. This file will be stored on a scientific data website, available to readers. Overall risk of bias The overall 'Risk of bias' judgement for each specific trial being assessed will be based on each domain-level judgement. The overall judgements include the following. Low risk of bias (the trial is judged to be at low risk of bias for all domains). Some concerns (the trial is judged to raise some concerns in at least one domain but is not judged to be at high risk of bias for any domain). High risk of bias (the trial is judged to be at high risk of bias in at least one domain, or is judged to have some concerns for multiple domains in a way that substantially lowers confidence in the result). The 'risk of bias' assessments will inform our GRADE evaluations of the certainty of evidence for our primary outcomes presented in the 'Summary of findings' tables and will also be used to inform the sensitivity analyses; (see Sensitivity analysis). If there is insufficient information in study reports to enable an assessment of the risk of bias, studies will be classified as "awaiting assessment" until further information is published or made available to us. Measures of treatment effect Dichotomous data For dichotomous data, we will present proportions and, for two-group comparisons, results as average RR or odds ratio (OR) with 95% CIs. Ordered categorical data Continuous data We will report results for continuous outcomes as the mean difference (MD) with 95% CIs, if outcomes are measured in the same way between trials. Where some studies have reported endpoint data and others have reported change-from-baseline data (with errors), we will combine these in the meta-analysis, if the outcomes were reported using the same scale. We will use the standardized mean difference (SMD), with 95% CIs, to combine trials that measured the same outcome but used different methods. If we do not find three or more studies for a pooled analysis, we will summarize the results in a narrative form. Unit of analysis issues Cluster-randomized trials We plan to combine results from both cluster-randomized and individually randomized studies, providing there is little heterogeneity between the studies. If the authors of cluster-randomized trials conducted their analyses at a different level from that of allocation, and they have not appropriately accounted for the cluster design in their analyses, we will calculate the trials' effective sample sizes to account for the effect of clustering in data. When one or more cluster-RCT reports RRs adjusted for clustering, we will compute cluster-adjusted SEs for the other trials. When none of the cluster-RCTs provide cluster-adjusted RRs, we will adjust the sample size for clustering. We will divide, by the estimated design effects (DE), the number of events and number evaluated for dichotomous outcomes and the number evaluated for continuous outcomes, where DE = 1 + ((average cluster size 1) * ICC). The derivation of the estimated ICCs and DEs will be reported. We will utilize the intra-cluster correlation coefficient (ICC), derived from the trial (if available), or from another source (e.g., using the ICCs derived from other, similar trials) and then calculate the design effect with the formula provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021). If this approach is used, we will report it and undertake sensitivity analysis to investigate the effect of variations in ICC. Studies with more than two treatment groups If we identify studies with more than two intervention groups (multi-arm studies), where possible we will combine groups to create a single pair-wise comparison or use the methods set out in the Cochrane Handbook to avoid double counting study participants (Higgins 2021). For the subgroup analyses, when the control group was shared by two or more study arms, we will divide the control group (events and total population) over the number of relevant subgroups to avoid double counting the participants. Trials with several study arms can be included more than once for different comparisons. Cross-over trials From cross-over trials, we will consider the first period of measurement only and will analyze the results together with parallel-group studies. Multiple outcome events In several outcomes, a participant might experience more than one outcome event during the trial period. For all outcomes, we will extract the number of participants with at least one event. Dealing with missing data We will contact the trial authors if the available data are unclear, missing, or reported in a format that is different from the format needed. We aim to perform a 'per protocol' or 'as observed' analysis; otherwise, we will perform a complete case analysis. This means that for treatment failure, we will base the analyses on the participants who received treatment and the number of participants for which there was an inability to clear malarial parasitaemia or prevent recrudescence after administration of an antimalarial medicine reported in the studies. Assessment of heterogeneity Heterogeneity in the results of the trials will be assessed by visually examining the forest plot to detect non-overlapping CIs, using the Chi2 test of heterogeneity (where a P value of less than 0.1 indicates statistical significance) and the I2 statistic of inconsistency (with a value of greater than 50% denoting moderate levels of heterogeneity). When statistical heterogeneity is present, we will investigate the reasons for it, using subgroup analysis. Assessment of reporting biases We will construct a funnel plot to assess the effect of small studies for the main outcome (when including more than 10 trials). Data synthesis The primary analysis will include all eligible studies that provide data regardless of the overall risk of bias as assessed by the RoB2 tool. Analyses will be conducted using Review Manager 5.4 (Review Manager 2020). Cluster-RCTs will be included in the main analysis after adjustment for clustering (see the previous section on cluster-RCTs). The meta-analysis will be performed using the Mantel-Haenszel random-effects model or the generic inverse variance method (when adjustment for clustering is performed by adjusting SEs), as appropriate. Subgroup analysis and investigation of heterogeneity The overall risk of bias will not be used as the basis in conducting our subgroup analyses. However, where data are available, we plan to conduct the following subgroup analyses, independent of heterogeneity. Dose of folic acid supplementation: higher doses (4 mg or more, daily) versus lower doses (less than 4 mg, daily). Moderate-severe anaemia at baseline (mean haemoglobin of participants in a trial at baseline below 100 g/L for pregnant women and children aged six to 59 months, and below 110 g/L for other populations) versus normal at baseline (mean haemoglobin above 100 g/L for pregnant women and children aged six to 59 months, and above 110 g/L for other populations). Antimalarial drug resistance to parasite: known resistance versus no resistance versus unknown/mixed/unreported parasite resistance. Folate status at baseline: Deficient (e.g. RBC folate concentration of less than 305 nmol/L, or serum folate concentration of less than 7nmol/L) and Insufficient (e.g. RBC folate concentration from 305 to less than 906 nmol/L, or serum folate concentration from 7 to less than 25 nmol/L) versus Sufficient (e.g. RBC folate concentration above 906 nmol/L, or serum folate concentration above 25 nmol/L). Presence of anaemia at baseline: yes versus no. Mandatory fortification status: yes, versus no (voluntary or none). We will only use the primary outcomes in any subgroup analyses, and we will limit subgroup analyses to those outcomes for which three or more trials contributed data. Comparisons between subgroups will be performed using Review Manager 5.4 (Review Manager 2020). Sensitivity analysis We will perform a sensitivity analysis, using the risk of bias as a variable to explore the robustness of the findings in our primary outcomes. We will verify the behaviour of our estimators by adding and removing studies with a high risk of bias overall from the analysis. That is, studies with a low risk of bias versus studies with a high risk of bias. Summary of findings and assessment of the certainty of the evidence For the assessment across studies, we will use the GRADE approach, as outlined in (Schünemann 2021). We will use the five GRADE considerations (study limitations based on RoB2 judgements, consistency of effect, imprecision, indirectness, and publication bias) to assess the certainty of the body of evidence as it relates to the studies which contribute data to the meta-analyses for the primary outcomes. The GRADEpro Guideline Development Tool (GRADEpro) will be used to import data from Review Manager 5.4 (Review Manager 2020) to create 'Summary of Findings' tables. The primary outcomes for the main comparison will be listed with estimates of relative effects, along with the number of participants and studies contributing data for those outcomes. These tables will provide outcome-specific information concerning the overall certainty of evidence from studies included in the comparison, the magnitude of the effect of the interventions examined, and the sum of available data on the outcomes we considered. We will include only primary outcomes in the summary of findings tables. For each individual outcome, two review authors (KSC, LFY) will independently assess the certainty of the evidence using the GRADE approach (Balshem 2011). For assessments of the overall certainty of evidence for each outcome that includes pooled data from included trials, we will downgrade the evidence from 'high certainty' by one level for serious (or by two for very serious) study limitations (risk of bias, indirectness of evidence, serious inconsistency, imprecision of effect estimates, or potential publication bias).

Crider K ，Williams J ，Qi YP ，Gutman J ，Yeung L ，Mai C ，Finkelstain J ，Mehta S ，Pons-Duran C ，Menéndez C ，Moraleda C ，Rogers L ，Daniels K ，Green P ... -  《Cochrane Database of Systematic Reviews》

Healthcare workers' perceptions and experiences of communicating with people over 50 years of age about vaccination: a qualitative evidence synthesis.

Infectious diseases are a major cause of illness and death among older adults. Vaccines can prevent infectious diseases, including against seasonal influenza, pneumococcal diseases, herpes zoster and COVID-19. However, the uptake of vaccination among older adults varies across settings and groups. Communication with healthcare workers can play an important role in older people's decisions to vaccinate. To support an informed decision about vaccination, healthcare workers should be able to identify the older person's knowledge gaps, needs and concerns. They should also be able to share and discuss information about the person's disease risk and disease severity; the vaccine's effectiveness and safety; and practical information about how the person can access vaccines. Therefore, healthcare workers need good communication skills and to actively keep up-to-date with the latest evidence. An understanding of their perceptions and experiences of this communication can help us train and support healthcare workers and design good communication strategies. To explore healthcare workers' perceptions and experiences of communicating with older adults about vaccination. We searched MEDLINE, CINAHL and Scopus on 21 March 2020. We also searched Epistemonikos for related reviews, searched grey literature sources, and carried out reference checking and citation searching to identify additional studies. We searched for studies in any language. We included qualitative studies and mixed-methods studies with an identifiable qualitative component. We included studies that explored the perceptions and experiences of healthcare workers and other health system staff towards communication with adults over the age of 50 years or their informal caregivers about vaccination. We extracted data using a data extraction form designed for this review. We assessed methodological limitations using a list of predefined criteria. We extracted and assessed data regarding study authors' motivations for carrying out their study. We used a thematic synthesis approach to analyse and synthesise the evidence. We used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in each finding. We examined each review finding to identify factors that may influence intervention implementation and we developed implications for practice. We included 11 studies in our review. Most studies explored healthcare workers' views and experiences about vaccination of older adults more broadly but also mentioned communication issues specifically. All studies were from high-income countries. The studies focused on doctors, nurses, pharmacists and others working in hospitals, clinics, pharmacies and nursing homes. These healthcare workers discussed different types of vaccines, including influenza, pneumococcal and herpes zoster vaccines. The review was carried out before COVID-19 vaccines were available. We downgraded our confidence in several of the findings from high confidence to moderate, low or very low confidence. One reason for this was that some findings were based on only small amounts of data. Another reason was that the findings were based on studies from only a few countries, making us unsure about the relevance of these findings to other settings. Healthcare workers reported that older adults asked about vaccination to different extents, ranging from not asking about vaccines at all, to great demand for information (high confidence finding). When the topic of vaccination was discussed, healthcare workers described a lack of information, and presence of misinformation, fears and concerns about vaccines among older adults (moderate confidence). The ways in which healthcare workers discussed vaccines with older adults appeared to be linked to what they saw as the aim of vaccination communication. Healthcare workers differed among themselves in their perceptions of this aim and about their own roles and the roles of older adults in vaccine decisions. Some healthcare workers thought it was important to provide information but emphasised the right and responsibility of older adults to decide for themselves. Others used information to persuade and convince older adults to vaccinate in order to increase 'compliance' and 'improve' vaccination rates, and in some cases to gain financial benefits. Other healthcare workers tailored their approach to what they believed the older adult needed or wanted (moderate confidence). Healthcare workers believed that older adults' decisions could be influenced by several factors, including the nature of the healthcare worker-patient relationship, the healthcare worker's status, and the extent to which healthcare workers led by example (low confidence). Our review also identified factors that are likely to influence how communication between healthcare workers and older adults take place. These included issues tied to healthcare workers' views and experiences regarding the diseases in question and the vaccines; as well as their views and experiences of the organisational and practical implementation of vaccine services. There is little research focusing specifically on healthcare workers' perceptions and experiences of communication with older adults about vaccination. The studies we identified suggest that healthcare workers differed among themselves in their perceptions about the aim of this communication and about the role of older adults in vaccine decisions. Based on these findings and the other findings in our review, we have developed a set of questions or prompts that may help health system planners or programme managers when planning or implementing strategies for vaccination communication between healthcare workers and older adults.

Glenton C ，Carlsen B ，Lewin S ，Wennekes MD ，Winje BA ，Eilers R ，VITAL consortium ... -  《Cochrane Database of Systematic Reviews》

Promoting and supporting self-management for adults living in the community with physical chronic illness: A systematic review of the effectiveness and meaningfulness of the patient-practitioner encounter.

There has been a reported rise in the number of people with chronic illness (also referred to as long-term disease) in the Western world. One hundred million people in the United States have at least one chronic condition and in the United Kingdom (UK) as many as 17.5 million adults may be living with chronic disease. New models of care have been developed which recognise the complexities of managing care where there is overlap between the wider community, the health care system and provider organisations, for example, the Chronic Care Model and the Expert Patient Programme. These new models herald a shift away from the idea of chronically ill patients as passive recipients of care towards active engagement, in partnership with health professionals, in managing their own care.Partnership, ideally, involves collaborative care and self-management education. This may support self-care alongside medical, preventative and health maintenance interventions. In this context the nature of the patient-practitioner consultation in promoting self-care takes on a new importance. The overall objective of the review was to determine the best available evidence regarding the promotion and support of self-care management for adults living in the community with chronic illness during the patient-practitioner encounter. Specifically the review sought to determine: What is the effectiveness of the patient-practitioner encounter in promoting and supporting self-care management of people with chronic illness? What are the individual and organisational factors which help or hinder recognition, promotion and support of chronic disease self-care management strategies? What are the similarities and differences between how 'effectiveness' is defined in this context by patients and different practitioners? The review focussed on self-caring adults aged nineteen years and older living in the community, with a physical chronic illness, and not currently being treated as an in-patient. For example, people with diabetes, asthma, arthritis, coronary disease, lung disease, heart failure, epilepsy, kidney disease and inflammatory bowel disease. Since patients meet various professionals in a variety of community settings regarding their care, a practitioner in this review included doctors (physicians and General Practitioners), nurses, nurse specialists, dieticians, podiatrists and community health workers.A variety of outcomes measures was used to evaluate effective self-care management. These included physiological measurements such as: HbA1c, blood pressure, body weight, lipids; lifestyle measurements, for example physical activity; and self-care determinants such as knowledge, attitude; and self-care behaviours regarding, for example, diet and physical exercise, and medication. The outcome measures used to explore the meaningfulness of the patient-practitioner encounter, concerned patients', physicians' and nurses' views and perceptions of self-care management and support.The review considered all types of quantitative and qualitative evidence regarding the patient-practitioner encounter where self-care in chronic illness was the focus. The quantitative studies reviewed included systematic reviews, randomised controlled trials (RCTs), quasi-experimental studies, and survey studies.Qualitative studies reviewed included interview designs, vignette technique, qualitative evaluation, grounded theory, and exploratory descriptive design. The search sought to find both published and unpublished studies between 1990 and 2005. The year 1990 was deemed appropriate since it precedes the development of the Chronic Care Model in which self-management support for people living with chronic illness is heralded as an important part of care-management. An initial search of CINAHL and MEDLINE databases was undertaken to identify appropriate search terms regarding self-care and chronic illness. A search strategy was then developed using all identified MeSH headings and key words and the following databases were searched: - Ovid CINAHL; Ovid MEDLINE (R); Ovid EMBASE; Ovid EBM Reviews (CDSR, ACP Journal Club, DARE, CCTR); ASSIA; SIGLE; Digital Dissertations; and British Library's Zetoc Services. Thirty-two papers were considered applicable to the review topic from the title and abstract. Two reviewers used the appropriate critical appraisal instruments designed by the Joanna Briggs Institute (JBI) to assess methodological quality of papers retrieved for review, and agreed on the papers for inclusion. A total of 18 papers reporting 16 studies were included in the review (3 papers reported from the same study): 12 quantitative studies, 5 qualitative studies and 1 study using mixed methods. These papers were heterogeneous in nature, diverse in subject matter and considered a wide range of physiological, psychological, sociological and behavioural self-care outcome measures. Data were extracted by the two independent reviewers using a variety of data extraction instruments developed by JBI. The heterogeneous nature of the quantitative studies prevented meta-analysis and so these studies are presented in narrative summary. Meta-synthesis of the qualitative data was performed for the six qualitative pieces following the process of meta-synthesis set out in the JBI-QARI software package. The process of meta-synthesis embodied in this programme involves the aggregation or synthesis of findings. Seven syntheses were produced from fifty findings. For effective patient-centeredness to be established patients should be able to discuss their own ideas about self-care actions, including lifestyle management in an unhurried fashion and with a practitioner who has the time and who is willing to listen. Patient-centred interventions aimed at providers such as patient-centred training and patient-centred materials were shown to have a positive effect on the patient-centeredness of an encounter, but their effect on self-care outcomes was not clear. Interventions directed at enhancing patient participation in the encounter were shown to effect diabetes self-care and self-behaviour.Nurses were shown to have an effective role in educating patients and facilitating adherence to treatment. Patients found nurses approachable and some studies showed that when given the choice, patients were more likely to contact a nurse (than a doctor) regarding their care.Professional interventions such as education, and organisational interventions such as management of regular review and follow up, were shown to improve process outcomes in the management of a patient-practitioner encounter. When patient-orientated interventions were added to professional and organisational interventions, in which patient education and / or the role of the nurse was enhanced, patient health outcomes were improved.The different patient-orientated interventions reviewed highlighted some of the elements that can effectively support self-care management during a patient-practitioner encounter. These are information giving, including the use of a guidebook, the use of care plans, the structure of treatment using checklists, and education and support for staff in 'collaboratives'.Comprehensive, well-paced, user-friendly information is effective in supporting and promoting self-care management in a variety of ways. It informs and reassures patients and their families. It can be used during a doctor/patient consultation to assist communication between doctors and patients, and may help patients feel more involved in their care.For information to effect self-care management, it is important that it is given at diagnosis and from then onwards so that the implications of good self-care management in relation to long term health outcomes are established.Care plans and self-management plans can be useful in facilitating patients' discussion of self-care actions and lifestyle management.Organisational factors affect opportunities for professionals to support patient self-care management. These include time, resources, the existing configuration and expectations of a consultation, the opportunity for open access to appointments, the ability to see the same doctor and early referral to other professional groups.Correlational design studies indicated that individual psychological factors, such as attachment style and autonomy support given to a patient during a patient-practitioner encounter, have a relationship to self-care behaviours and outcomes.Correlational design studies indicated that both general communication and diabetic specific communication used during a patient-practitioner encounter have a positive effect on patient self-care management and outcomes for patients with diabetes.Consultations about self-care for patients with chronic illness tend to be medically focussed and do not always include discussion of patients' views of the routines and self-care actions. This can lead to tension and unresolved issues between the patient and professional.Studies in the context of diabetes self-management reveal that professionals can effectively support patients in a number of ways. These include assisting the orientation of patients towards skills and competencies needed for self-care; sharing knowledge and information; endorsing the patient's view that he or she is the most reliable and accurate source of information about his or her physiological function; trusting the patients' interpretations of their physiological function, and modifying advice in response to patients in accordance with their bodily cues and experiences. The nature of the patient-practitioner encounter is multifaceted involving patient, professional and organisational factors. Patient-orientated interventions are the most effective in effecting positive self-care behavioural and health outcomes. Patient participation in the patient-practitioner encounter is a key factor in influencing self-care outcomes. Patients' self-care management involves social as well as medical management. Professionals need to recognise and value patients' views and experiences in order to support their self-care management. Patients need information at diagnosis and from then onwards to enable good self-care management. It is important to enable patient participation during the patient-practitioner encounter.For patients' self-care needs to be addressed opportunities for patients to talk about their diet, routines and lifestyle management need to be incorporated into the encounter. Extra time in consultations may be required. Care plans can help to facilitate this discussion.To support patients with their self-care management, both sharing of medical and nursing knowledge, and recognition of the value of patient's knowledge and experiences are vital.Nurses relate well to patients who want to discuss self-care management.Professional interventions and organisational interventions can improve the management of a patient-practitioner encounter. Patient-orientated interventions in addition to good management of the encounter can improve health care outcomes. Patient focussed interventions have a positive effect on patient self-care outcomes. Further research regarding patients' self-care and health outcomes and behaviours is needed to establish which patient focussed interventions in particular are effective.Qualitative research has proved to be important in understanding the different ways that professionals and patients approach self-care management during an encounter. More qualitative research would assist an understanding of the processes that inspire effective partnership between patients and professionals to support the establishment of self-care management of chronic illness.

Rees S ，Williams A 《-》

Survivor, family and professional experiences of psychosocial interventions for sexual abuse and violence: a qualitative evidence synthesis.

It is well-established that experiencing sexual abuse and violence can have a range of detrimental impacts; a wide variety of interventions exist to support survivors in the aftermath. Understanding the experiences and perspectives of survivors receiving such interventions, along with those of their family members, and the professionals who deliver them is important for informing decision making as to what to offer survivors, for developing new interventions, and enhancing their acceptability. This review sought to: 1. identify, appraise and synthesise qualitative studies exploring the experiences of child and adult survivors of sexual abuse and violence, and their caregivers, regarding psychosocial interventions aimed at supporting survivors and preventing negative health outcomes in terms of benefits, risks/harms and barriers; 2. identify, appraise and synthesise qualitative studies exploring the experiences of professionals who deliver psychosocial interventions for sexual abuse and violence in terms of perceived benefits, risks/harms and barriers for survivors and their families/caregivers; 3. develop a conceptual understanding of how different factors influence uptake, dropout or completion, and outcomes from psychosocial interventions for sexual abuse and violence; 4. develop a conceptual understanding of how features and types of interventions responded to the needs of different user/survivor groups (e.g. age groups; types of abuse exposure; migrant populations) and contexts (healthcare/therapeutic settings; low- and middle-income countries (LMICs)); 5. explore how the findings of this review can enhance our understanding of the findings from the linked and related reviews assessing the effectiveness of interventions aimed at supporting survivors and preventing negative health outcomes. In August 2021 we searched MEDLINE, Embase, PsycINFO and nine other databases. We also searched for unpublished reports and qualitative reports of quantitative studies in a linked systematic review, together with reference checking, citation searches and contacting authors and other researchers to identify relevant studies. We included qualitative and mixed-methods studies (with an identifiable qualitative component) that were linked to a psychosocial intervention aimed at supporting survivors of sexual abuse and violence. Eligible studies focused on at least one of three participant groups: survivors of any age, gender, sexuality, ethnicity or [dis]ability who had received a psychosocial intervention; their carers, family members or partners; and professionals delivering such interventions. We placed no restrictions in respect of settings, locations, intervention delivery formats or durations. Six review authors independently assessed the titles, abstracts and full texts identified. We extracted data using a form designed for this synthesis, then used this information and an appraisal of data richness and quality in order to stratify the studies using a maximum variation approach. We assessed the methodological limitations using the Critical Skills Appraisal Programme (CASP) tool. We coded directly onto the sampled papers using NVivo and synthesised data using a thematic synthesis methodology and used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in each finding. We used a narrative synthesis and matrix model to integrate our qualitative evidence synthesis (QES) findings with those of intervention review findings. We identified 97 eligible studies and sampled 37 of them for our analysis. Most sampled studies were from high-income countries, with four from middle-income and two from low-income countries. In 27 sampled studies, the participants were survivors, in three they were intervention facilitators. Two included all three of our stakeholder groups, and five included two of our groups. The studies explored a wide range of psychosocial interventions, with only one type of intervention explored in more than one study. The review indicates that features associated with the context in which interventions were delivered had an impact on how individuals accessed and experienced interventions. This included organisational features, such as staff turnover, that could influence survivors' engagement with interventions; the setting or location in which interventions were delivered; and the characteristics associated with who delivered the interventions. Studies that assess the effectiveness of interventions typically assess their impact on mental health; however, as well as finding benefits to mental health, our QES found that study participants felt interventions also had positive impacts on their physical health, mood, understanding of trauma, interpersonal relationships and enabled them to re-engage with a wide range of areas in their lives. Participants explained that features of interventions and their contexts that best enabled them to benefit from interventions were also often things that could be a barrier to benefiting from interventions. For example, the relationship with the therapist, when open and warm was a benefit, but if such a relationship could not be achieved, it was a barrier. Survivors' levels of readiness and preparedness to both start and end interventions could have positive (if they were ready) or negative (if they were not) impacts. Study participants identified the potential risks and harms associated with completing interventions but felt that it was important to face and process trauma. Some elements of interventions were specific to the intervention type (e.g. faith-based interventions), or related to an experience of an intervention that held particular relevance to subgroups of survivors (e.g. minority groups); these issues could impact how individuals experienced delivering or receiving interventions. We had high or moderate confidence in all but one of our review findings. Further research in low- and middle-income settings, with male survivors of sexual abuse and violence and those from minority groups could strengthen the evidence for low and moderate confidence findings. We found that few interventions had published quantitative and qualitative evaluations. Since this QES has highlighted important aspects that could enable interventions to be more suitable for survivors, using a range of methodologies would provide valuable information that could enhance intervention uptake, completion and effectiveness. This study has shown that although survivors often found interventions difficult, they also appreciated that they needed to work through trauma, which they said resulted in a wide range of benefits. Therefore, listening to survivors and providing appropriate interventions, at the right time for them, can make a significant difference to their health and well-being.

Brown SJ ，Carter GJ ，Halliwell G ，Brown K ，Caswell R ，Howarth E ，Feder G ，O'Doherty L ... -  《Cochrane Database of Systematic Reviews》