Culture-based prescribing to improve mental health: a scoping review protocol

Objective: The objective of this review is to investigate what is known about culture-based prescribing to improve mental health and well-being. Introduction: Culture-based prescribing, where a person is referred by a clinical professional to an arts or cultural activity aimed at improving mental health and well-being, is increasingly used as a community-based source of support. Although culture-based prescribing seems promising, the field is heterogeneous with respect to definition, underlying hypotheses, and cultural activity, and this hampers its further development and implementation. Inclusion criteria: We will consider publications that report on or explore culture-based prescribing to improve mental health and well-being for adults suffering from symptoms related to mental health conditions who are seeking care from any clinical professional. Methods: We will search 8 electronic literature databases for published or unpublished reports on culture-based prescribing, without time limits. We will also search for gray literature and screen reference lists of relevant reviews. No language restrictions will be applied during the screening process, but for data extraction, we will only extract studies in languages our team has proficiency in. The screening and data extraction will be performed by 2 reviewers, independently. Data analysis will be descriptive, with results tabulated separately for each subquestion. The results will be complemented with a narrative summary

Epidemiology of Chronic Pain in Denmark and Sweden

Introduction. Estimates on the epidemiology of chronic pain vary widely throughout Europe. It is unclear whether this variation reflects true differences between populations or methodological factors. Information on the epidemiology of chronic pain can support decision makers in allocating adequate health care resources. Methods. In order to obtain epidemiological data on chronic pain in Denmark and Sweden, we conducted a literature review of epidemiological data primarily on chronic noncancer pain, prioritising studies of highest quality, recency, and validity by conducting a systematic search for relevant studies. Following quality assessment, data were summarised and assigned to the research questions. Results. The prevalence of moderate to severe noncancer pain was estimated at 16% in Denmark and 18% in Sweden. Chronic pain impacts negatively on perceived health status, quality of life and is associated with increased cost. Despite using pain medications, a large proportion of chronic pain sufferers have inadequate pain control. There was a lack of high-quality and low-bias studies with clear inclusion criteria. Conclusions. In both Denmark and Sweden, chronic pain is a common health problem which is potentially undertreated and warrants attention of health care workers, policy makers and researchers. Future research should utilise clear reporting guidelines to assist decision and policy makers, in this important area

PCSK9 inhibitors and ezetimibe with or without statin therapy for cardiovascular risk reduction: a systematic review and network meta-analysis.

OBJECTIVE To compare the impact of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on cardiovascular outcomes in adults taking maximally tolerated statin therapy or who are statin intolerant. DESIGN Network meta-analysis. DATA SOURCES Medline, EMBASE, and Cochrane Library up to 31 December 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Randomised controlled trials of ezetimibe and PCSK9 inhibitors with ≥500 patients and follow-up of ≥6 months. MAIN OUTCOME MEASURES We performed frequentist fixed-effects network meta-analysis and GRADE (grading of recommendations, assessment, development, and evaluation) to assess certainty of evidence. Results included relative risks (RR) and absolute risks per 1000 patients treated for five years for non-fatal myocardial infarction (MI), non-fatal stroke, all-cause mortality, and cardiovascular mortality. We estimated absolute risk differences assuming constant RR (estimated from network meta-analysis) across different baseline therapies and cardiovascular risk thresholds; the PREDICT risk calculator estimated cardiovascular risk in primary and secondary prevention. Patients were categorised at low to very high cardiovascular risk. A guideline panel and systematic review authors established the minimal important differences (MID) of 12 per 1000 for MI and 10 per 1000 for stroke. RESULTS We identified 14 trials assessing ezetimibe and PCSK9 inhibitors among 83 660 adults using statins. Adding ezetimibe to statins reduced MI (RR 0.87 (95% confidence interval 0.80 to 0.94)) and stroke (RR 0.82 (0.71 to 0.96)) but not all-cause mortality (RR 0.99 (0.92 to 1.06)) or cardiovascular mortality (RR 0.97 (0.87 to 1.09)). Similarly, adding PCSK9 inhibitor to statins reduced MI (0.81 (0.76 to 0.87)) and stroke (0.74 (0.64 to 0.85)) but not all-cause (0.95 (0.87 to 1.03)) or cardiovascular mortality (0.95 (0.87 to 1.03)). Among adults with very high cardiovascular risk, adding PCSK9 inhibitor was likely to reduce MI (16 per 1000) and stroke (21 per 1000) (moderate to high certainty); whereas adding ezetimibe was likely to reduce stroke (14 per 1000), but the reduction of MI (11 per 1000) (moderate certainty) did not reach MID. Adding ezetimibe to PCSK9 inhibitor and statin may reduce stroke (11 per 1000), but the reduction of MI (9 per 1000) (low certainty) did not reach MID. Adding PCSK9 inhibitors to statins and ezetimibe may reduce MI (14 per 1000) and stroke (17 per 1000) (low certainty). Among adults with high cardiovascular risk, adding PCSK9 inhibitor probably reduced MI (12 per 1000) and stroke (16 per 1000) (moderate certainty); adding ezetimibe probably reduced stroke (11 per 1000), but the reduction in MI did not achieve MID (8 per 1000) (moderate certainty). Adding ezetimibe to PCSK9 inhibitor and statins did not reduce outcomes beyond MID, while adding PCSK9 inhibitor to ezetimibe and statins may reduce stroke (13 per 1000). These effects were consistent in statin-intolerant patients. Among moderate and low cardiovascular risk groups, adding PCSK9 inhibitor or ezetimibe to statins yielded little or no benefit for MI and stroke. CONCLUSIONS Ezetimibe or PCSK9 inhibitors may reduce non-fatal MI and stroke in adults at very high or high cardiovascular risk who are receiving maximally tolerated statin therapy or are statin-intolerant, but not in those with moderate and low cardiovascular risk

Micronutrient intake and status in Central and Eastern Europe compared with other European countries, results from the EURRECA network

Objective: To compare micronutrient intakes and status in Central and Eastern Europe (CEE) with those in other European countries and with reference values. Design: Review of the micronutrient intake/status data from open access and grey literature sources from CEE. Setting: Micronutrients studied were folate, iodine, Fe, vitamin B-12 and Zn (for intake and status) and Ca, Cu, Se, vitamin C and vitamin D (for intake). Intake data were based on validated dietary assessment methods; mean intakes were compared with average nutrient requirements set by the Nordic countries or the US Institute of Medicine. Nutritional status was assessed using the status biomarkers and cut-off levels recommended primarily by the WHO. Subjects: For all population groups in CEE, the mean intake and mean/median status levels were compared between countries and regions: CEE, Scandinavia, Western Europe and Mediterranean. Results: Mean micronutrient intakes of adults in the CEE region were in the same range as those from other European regions, with exception of Ca (lower in CEE). CEE children and adolescents had poorer iodine status, and intakes of Ca, folate and vitamin D were below the reference values. Conclusions: CEE countries are lacking comparable studies on micronutrient intake/status across all age ranges, especially in children. Available evidence showed no differences in micronutrient intake/status in CEE populations in comparison with other European regions, except for Ca intake in adults and iodine and Fe status in children. The identified knowledge gaps urge further research on micronutrient intake/status of CEE populations to make a basis for evidence-based nutrition policy

PCSK9 inhibitors and ezetimibe for the reduction of cardiovascular events: a clinical practice guideline with risk-stratified recommendations.

CLINICAL QUESTION In adults with low density lipoprotein (LDL) cholesterol levels >1.8 mmol/L (>70 mg/dL) who are already taking the maximum dose of statins or are intolerant to statins, should another lipid-lowering drug be added, either a proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor or ezetimibe, to reduce the risk of major cardiovascular events? If so, which drug is preferred? Having decided to use one, should we add the other lipid-lowering drug? CURRENT PRACTICE Most guidelines emphasise LDL cholesterol targets in their recommendations for prescribing PCSK9 inhibitors and/or ezetimibe in adults at high risk of experiencing a major adverse cardiovascular event. However, to achieve these goals in very high risk patients with statins alone is almost impossible, so physicians are increasingly considering other lipid-lowering drugs solely for achieving LDL cholesterol treatment goals rather than for achieving important absolute cardiovascular risk reduction. Most guidelines do not systematically assess the cardiovascular benefits of adding PCSK9 inhibitors and/or ezetimibe for all risk groups across primary and secondary prevention, nor do they report, in accordance with explicit judgments of assumed patients' values and preferences, absolute benefits and harms and potential treatment burdens. RECOMMENDATIONS The guideline panel provided mostly weak recommendations, which means we rely on shared decision making when applying these recommendations. For adults already using statins, the panel suggests adding a second lipid-lowering drug in people at very high and high cardiovascular risk but recommends against adding it in people at low cardiovascular risk. For adults who are intolerant to statins, the panel recommends using a lipid-lowering drug in people at very high and high cardiovascular risk but against adding it in those at low cardiovascular risk. When choosing to add another lipid-lowering drug, the panel suggests ezetimibe in preference to PCSK9 inhibitors. The panel suggests further adding a PCSK9 inhibitor to ezetimibe for adults already taking statins at very high risk and those at very high and high risk who are intolerant to statins. HOW THIS GUIDELINE WAS CREATED An international panel including patients, clinicians, and methodologists produced these recommendations following standards for trustworthy guidelines and using the GRADE approach. The panel identified four risk groups of patients (low, moderate, high, and very high cardiovascular risk) and primarily applied an individual patient perspective in moving from evidence to recommendations, though societal issues were a secondary consideration. The panel considered the balance of benefits and harms and burdens of starting a PCSK9 inhibitor and/or ezetimibe, making assumptions of adults' average values and preferences. Interactive evidence summaries and decision aids accompany multi-layered recommendations, developed in an online authoring and publication platform (www.magicapp.org) that also allows re-use and adaptation. THE EVIDENCE A linked systematic review and network meta-analysis (14 trials including 83 660 participants) of benefits found that PCSK9 inhibitors or ezetimibe probably reduce myocardial infarctions and stroke in patients with very high and high cardiovascular risk, with no impact on mortality (moderate to high certainty evidence), but not in those with moderate and low cardiovascular risk. PCSK9 inhibitors may have similar effects to ezetimibe on reducing non-fatal myocardial infarction or stroke (low certainty evidence). These relative benefits were consistent, but their absolute magnitude varied based on cardiovascular risk in individual patients (for example, for 1000 people treated with PCSK9 inhibitors in addition to statins over five years, benefits ranged from 2 fewer strokes in the lowest risk to 21 fewer in the highest risk). Two systematic reviews on harms found no important adverse events for these drugs (moderate to high certainty evidence). PCSK9 inhibitors require injections that sometimes result in injection site reactions (best estimate 15 more per 1000 in a 5 year timeframe), representing a burden and harm that may matter to patients. The MATCH-IT decision support tool allows you to interact with the evidence and your patients across the alternative options: https://magicevidence.org/match-it/220504dist-lipid-lowering-drugs/. UNDERSTANDING THE RECOMMENDATIONS The stratification into four cardiovascular risk groups means that, to use the recommendations, physicians need to identify their patient's risk first. We therefore suggest, specific to various geographical regions, using some reliable risk calculators that estimate patients' cardiovascular risk based on a mix of known risk factors. The largely weak recommendations concerning the addition of ezetimibe or PCSK9 inhibitors reflect what the panel considered to be a close balance between small reductions in stroke and myocardial infarctions weighed against the burdens and limited harms.Because of the anticipated large variability of patients' values and preferences, well informed choices warrant shared decision making. Interactive evidence summaries and decision aids linked to the recommendations can facilitate such shared decisions. The strong recommendations against adding another drug in people at low cardiovascular risk reflect what the panel considered to be a burden without important benefits. The strong recommendation for adding either ezetimibe or PCSK9 inhibitors in people at high and very high cardiovascular risk reflect a clear benefit.The panel recognised the key uncertainty in the evidence concerning patient values and preferences, namely that what most people consider important reductions in cardiovascular risks, weighed against burdens and harms, remains unclear. Finally, availability and costs will influence decisions when healthcare systems, clinicians, or people consider adding ezetimibe or PCSK9 inhibitors

Genetic Evidence Supporting the Association of Protease and Protease Inhibitor Genes with Inflammatory Bowel Disease: A Systematic Review

As part of the European research consortium IBDase, we addressed the role of proteases and protease inhibitors (P/PIs) in inflammatory bowel disease (IBD), characterized by chronic mucosal inflammation of the gastrointestinal tract, which affects 2.2 million people in Europe and 1.4 million people in North America. We systematically reviewed all published genetic studies on populations of European ancestry (67 studies on Crohn's disease [CD] and 37 studies on ulcerative colitis [UC]) to identify critical genomic regions associated with IBD. We developed a computer algorithm to map the 807 P/PI genes with exact genomic locations listed in the MEROPS database of peptidases onto these critical regions and to rank P/PI genes according to the accumulated evidence for their association with CD and UC. 82 P/PI genes (75 coding for proteases and 7 coding for protease inhibitors) were retained for CD based on the accumulated evidence. The cylindromatosis/turban tumor syndrome gene (CYLD) on chromosome 16 ranked highest, followed by acylaminoacyl-peptidase (APEH), dystroglycan (DAG1), macrophage-stimulating protein (MST1) and ubiquitin-specific peptidase 4 (USP4), all located on chromosome 3. For UC, 18 P/PI genes were retained (14 proteases and 4protease inhibitors), with a considerably lower amount of accumulated evidence. The ranking of P/PI genes as established in this systematic review is currently used to guide validation studies of candidate P/PI genes, and their functional characterization in interdisciplinary mechanistic studies in vitro and in vivo as part of IBDase. The approach used here overcomes some of the problems encountered when subjectively selecting genes for further evaluation and could be applied to any complex disease and gene family

Do randomized clinical trials with inadequate blinding report enhanced placebo effects for intervention groups and nocebo effects for placebo groups? A protocol for a meta-epidemiological study of PDE-5 inhibitors

Abstract Background Patients’ expectations of treatment effects may contribute to positive (placebo) and negative (nocebo) outcomes. The effect of patient expectations may be pronounced in subjectively assessed conditions, such as male erectile dysfunction. The aim of this project is to examine the magnitude of expectancy in trials of phosphodiesterase-5 inhibitors. We hypothesize that randomized controlled trials with inadequate blinding will report enhanced placebo effects for intervention groups and nocebo effects for placebo groups, compared with adequately blinded studies. Methods/design We will quantify the magnitude of expectancy by comparing the effect estimates of trials with inadequate and adequate blinding. Blinding will be assessed using four domains from the Cochrane ‘risk-of-bias’ tool: allocation concealment; blinding of patient; caregiver; and outcome assessor. Our secondary aim is to identify factors that can modify expectations, such as prior experience with the intervention and drug side effects. We will perform an electronic search using a combination of controlled vocabulary and free text words in the following databases: MEDLINE, EMBASE, CENTRAL, and a clinical trials register. We will include randomized controlled trials, with either parallel or crossover design, that compare one phosphodiesterase-5 inhibitor with a placebo. The study’s primary aim should be to investigate the efficacy of phosphodiesterase-5 inhibitors for treating male erectile dysfunction. Screening will take place at two levels: abstracts and titles, followed by full text reports. Two reviewers will independently extract data on the primary outcome and assess risk of bias. We will meta-analyze treatment effects, if appropriate, to assess the magnitude of enhanced placebo effects and nocebo effects in intervention and placebo groups, respectively. We will explore possible mediators of placebo and nocebo effects with subgroup and meta-regression analyses. Discussion Treatments may confer significant costs and risk of adverse effects; it is important, therefore, to determine whether the effects of treatments are larger than expectancy alone. If treatment expectations can be used in a non-deceptive way to produce clinically advantageous outcomes, then it may be possible to incorporate such mechanisms into evidence-based healthcare decision-making.</p

The uniqueness of the human dentition as forensic evidence: a systematic review on the technological methodology

The uniqueness of human dentition is routinely approached as identification evidence in forensic odontology. Specifically in bitemark and human identification cases, positive identifications are obtained under the hypothesis that two individuals do not have the same dental features. The present study compiles methodological information from articles on the uniqueness of human dentition to support investigations into the mentioned hypothesis. In April 2014, three electronic library databases (SciELO®, MEDLINE®/PubMed®, and LILACS®) were systematically searched. In parallel, reference lists of relevant studies were also screened. From the obtained articles (n = 1235), 13 full-text articles were considered eligible. They were examined according to the studied parameters: the sample size, the number of examined teeth, the registration technique for data collection, the methods for data analysis, and the study outcomes. Six combinations of studied data were detected: (1) dental shape, size, angulation, and position (n = 1); (2) dental shape, size, and angulation (n = 4); (3) dental shape and size (n = 5); (4) dental angulation and position (n = 2); (5) dental shape and angulation (n = 1); and (6) dental shape (n = 1). The sample size ranged between 10 and 1099 human dentitions. Ten articles examined the six anterior teeth, while three articles examined more teeth. Four articles exclusively addressed three-dimensional (3D) data registration, while six articles used two-dimensional (2D) imaging. In three articles, both imaging registrations were combined. Most articles (n = 9) explored the data using landmark placement. The other articles (n = 4) comprised digital comparison of superimposed dental contours. Although there were large methodological variations within the investigated articles, the uniqueness of human dentition remains unproved.status: publishe

Systematic screening and assessment of psychosocial well-being and care needs of people with cancer

BACKGROUND: Receiving a diagnosis of cancer and the subsequent related treatments can have a significant impact on an individual's physical and psychosocial well-being. To ensure that cancer care addresses all aspects of well-being, systematic screening for distress and supportive care needs is recommended. Appropriate screening could help support the integration of psychosocial approaches in daily routines in order to achieve holistic cancer care and ensure that the specific care needs of people with cancer are met and that the organisation of such care is optimised. OBJECTIVES: To examine the effectiveness and safety of screening of psychosocial well-being and care needs of people with cancer. To explore the intervention characteristics that contribute to the effectiveness of these screening interventions. SEARCH METHODS: We searched five electronic databases in January 2018: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, and CINAHL. We also searched five trial registers and screened the contents of relevant journals, citations, and references to find published and unpublished trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and non-randomised controlled trials (NRCTs) that studied the effect of screening interventions addressing the psychosocial well-being and care needs of people with cancer compared to usual care. These screening interventions could involve self-reporting of people with a patient-reported outcome measures (PROMs) or a semi-structured interview with a screening interventionist, and comprise a solitary screening intervention or screening with guided actions. We excluded studies that evaluated screening integrated as an element in more complex interventions (e.g. therapy, coaching, full care pathways, or care programmes). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data and assessed methodological quality for each included study using the Cochrane tool for RCTs and the Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tool for NRCTs. Due to the high level of heterogeneity in the included studies, only three were included in meta-analysis. Results of the remaining 23 studies were analysed narratively. MAIN RESULTS: We included 26 studies (18 RCTs and 8 NRCTs) with sample sizes of 41 to 1012 participants, involving a total of 7654 adults with cancer. Two studies included only men or women; all other studies included both sexes. For most studies people with breast, lung, head and neck, colorectal, prostate cancer, or several of these diagnoses were included; some studies included people with a broader range of cancer diagnosis. Ten studies focused on a solitary screening intervention, while the remaining 16 studies evaluated a screening intervention combined with guided actions. A broad range of intervention instruments was used, and were described by study authors as a screening of health-related quality of life (HRQoL), distress screening, needs assessment, or assessment of biopsychosocial symptoms or overall well-being. In 13 studies, the screening was a self-reported questionnaire, while in the remaining 13 studies an interventionist conducted the screening by interview or paper-pencil assessment. The interventional screenings in the studies were applied 1 to 12 times, without follow-up or from 4 weeks to 18 months after the first interventional screening. We assessed risk of bias as high for eight RCTs, low for five RCTs, and unclear for the five remaining RCTs. There were further concerns about the NRCTs (1 = critical risk study; 6 = serious risk studies; 1 = risk unclear).Due to considerable heterogeneity in several intervention and study characteristics, we have reported the results narratively for the majority of the evidence.In the narrative synthesis of all included studies, we found very low-certainty evidence for the effect of screening on HRQoL (20 studies). Of these studies, eight found beneficial effects of screening for several subdomains of HRQoL, and 10 found no effects of screening. One study found adverse effects, and the last study did not report quantitative results. We found very low-certainty evidence for the effect of screening on distress (16 studies). Of these studies, two found beneficial effects of screening, and 14 found no effects of screening. We judged the overall certainty of the evidence for the effect of screening on HRQoL to be very low. We found very low-certainty evidence for the effect of screening on care needs (seven studies). Of these studies, three found beneficial effects of screening for several subdomains of care needs, and two found no effects of screening. One study found adverse effects, and the last study did not report quantitative results. We judged the overall level of evidence for the effect of screening on HRQoL to be very low. None of the studies specifically evaluated or reported adverse effects of screening. However, three studies reported unfavourable effects of screening, including lower QoL, more unmet needs, and lower satisfaction.Three studies could be included in a meta-analysis. The meta-analysis revealed no beneficial effect of the screening intervention on people with cancer HRQoL (mean difference (MD) 1.65, 95% confidence interval (CI) -4.83 to 8.12, 2 RCTs, 6 months follow-up); distress (MD 0.0, 95% CI -0.36 to 0.36, 1 RCT, 3 months follow-up); or care needs (MD 2.32, 95% CI -7.49 to 12.14, 2 RCTs, 3 months follow-up). However, these studies all evaluated one specific screening intervention (CONNECT) in people with colorectal cancer.In the studies where some effects could be identified, no recurring relationships were found between intervention characteristics and the effectiveness of screening interventions. AUTHORS' CONCLUSIONS: We found low-certainty evidence that does not support the effectiveness of screening of psychosocial well-being and care needs in people with cancer. Studies were heterogeneous in population, intervention, and outcome assessment.The results of this review suggest a need for more uniformity in outcomes and reporting; for the use of intervention description guidelines; for further improvement of methodological certainty in studies and for combining subjective patient-reported outcomes with objective outcomes.status: publishe

Occupational therapy in multiple sclerosis

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. Main objective To assess the benefits and harms of occupational therapy interventions for improving daily functioning, participation, and quality of life in people with multiple sclerosis. Secondary objectives To assess whether the effects of occupational therapy interventions differ according to the format of intervention delivery (individually versus group) and to the location of service delivery (outpatient, inpatient, or home-based therapy)