Interventions for improving health literacy in migrants.

BACKGROUND: Health literacy (HL) is a determinant of health and important for autonomous decision-making. Migrants are at high risk for limited HL. Improving HL is important for equitable promotion of migrants' health. OBJECTIVES: To assess the effectiveness of interventions for improving HL in migrants. To assess whether female or male migrants respond differently to the identified interventions. SEARCH METHODS: We ran electronic searches to 2 February 2022 in CENTRAL, MEDLINE, Embase, PsycInfo and CINAHL. We also searched trial registries. We used a study filter for randomised controlled trials (RCTs) (RCT classifier). SELECTION CRITERIA: We included RCTs and cluster-RCTs addressing HL either as a concept or its components (access, understand, appraise, apply health information). DATA COLLECTION AND ANALYSIS: We used the methodological procedures recommended by Cochrane and followed the PRISMA-E guidelines. Outcome categories were: a) HL, b) quality of life (QoL), c) knowledge, d) health outcomes, e) health behaviour, f) self-efficacy, g) health service use and h) adverse events. We conducted meta-analysis where possible, and reported the remaining results as a narrative synthesis. MAIN RESULTS: We included 28 RCTs and six cluster-RCTs (8249 participants), all conducted in high-income countries. Participants were migrants with a wide range of conditions. All interventions were adapted to culture, language and literacy. We did not find evidence that HL interventions cause harm, but only two studies assessed adverse events (e.g. anxiety). Many studies reported results for short-term assessments (less than six weeks after total programme completion), reported here. For several comparisons, there were also findings at later time points, which are presented in the review text. Compared with no HL intervention (standard care/no intervention) or an unrelated HL intervention (similar intervention but different information topic) Self-management programmes (SMP) probably improve self-efficacy slightly (standardised mean difference (SMD) 0.28, 95% confidence interval (CI) 0.06 to 0.50; 2 studies, 333 participants; moderate certainty). SMP may improve HIV-related HL (understanding (mean difference (MD) 4.25, 95% CI 1.32 to 7.18); recognition of HIV terms (MD 3.32, 95% CI 1.28 to 5.36)) (1 study, 69 participants). SMP may slightly improve health behaviours (3 studies, 514 participants), but may have little or no effect on knowledge (2 studies, 321 participants) or subjective health status (MD 0.38, 95% CI -0.13 to 0.89; 1 study, 69 participants) (low certainty). We are uncertain of the effects of SMP on QoL, health service use or adverse events due to a lack of evidence. HL skills building courses (HLSBC) may improve knowledge (MD 10.87, 95% CI 5.69 to 16.06; 2 studies, 111 participants) and any generic HL (SMD 0.48, 95% CI 0.20 to 0.75; 2 studies, 229 participants), but may have little or no effect on depression literacy (MD 0.17, 95% CI -1.28 to 1.62) or any health behaviour (2 studies, 229 participants) (low certainty). We are uncertain if HLSBC improve QoL, health outcomes, health service use, self-efficacy or adverse events, due to very low-certainty or a lack of evidence. Audio-/visual education without personal feedback (AVE) probably improves depression literacy (MD 8.62, 95% CI 7.51 to 9.73; 1 study, 202 participants) and health service use (MD -0.59, 95% CI -1.11 to -0.07; 1 study, 157 participants), but probably has little or no effect on health behaviour (risk ratio (RR) 1.07, 95% CI 0.91 to 1.25; 1 study, 135 participants) (moderate certainty). AVE may improve self-efficacy (MD 3.51, 95% CI 2.53 to 4.49; 1 study, 133 participants) and may slightly improve knowledge (MD 8.44, 95% CI -2.56 to 19.44; 2 studies, 293 participants) and intention to seek depression treatment (MD 1.8, 95% CI 0.43 to 3.17), with little or no effect on depression (SMD -0.15, 95% CI -0.40 to 0.10) (low certainty). No evidence was found for QoL and adverse events. Adapted medical instruction may improve understanding of health information (3 studies, 478 participants), with little or no effect on medication adherence (MD 0.5, 95% CI -0.1 to 1.1; 1 study, 200 participants) (low certainty). No evidence was found for QoL, health outcomes, knowledge, health service use, self-efficacy or adverse events. Compared with written information on the same topic SMP probably improves health numeracy slightly (MD 0.7, 95% CI 0.15 to 1.25) and probably improves print literacy (MD 9, 95% CI 2.9 to 15.1; 1 study, 209 participants) and self-efficacy (SMD 0.47, 95% CI 0.3 to 0.64; 4 studies, 552 participants) (moderate certainty). SMP may improve any disease-specific HL (SMD 0.67, 95% CI 0.27 to 1.07; 4 studies, 955 participants), knowledge (MD 11.45, 95% CI 4.75 to 18.15; 6 studies, 1101 participants) and some health behaviours (4 studies, 797 participants), with little or no effect on health information appraisal (MD 1.15, 95% CI -0.23 to 2.53; 1 study, 329 participants) (low certainty). We are uncertain whether SMP improves QoL, health outcomes, health service use or adverse events, due to a lack of evidence or low/very low-certainty evidence. AVE probably has little or no effect on diabetes HL (MD 2, 95% CI -0.15 to 4.15; 1 study, 240 participants), but probably improves information appraisal (MD -9.88, 95% CI -12.87 to -6.89) and application (RR 1.51, 95% CI 1.29 to 1.77) (1 study, 608 participants; moderate certainty). AVE may slightly improve knowledge (MD 8.35, 95% CI -0.32 to 17.02; low certainty). No short-term evidence was found for QoL, depression, health behaviour, self-efficacy, health service use or adverse events. AVE compared with another AVE We are uncertain whether narrative videos are superior to factual knowledge videos as the evidence is of very low certainty. Gender differences Female migrants' diabetes HL may improve slightly more than that of males, when receiving AVE (MD 5.00, 95% CI 0.62 to 9.38; 1 study, 118 participants), but we do not know whether female or male migrants benefit differently from other interventions due to very low-certainty or a lack of evidence. AUTHORS' CONCLUSIONS: Adequately powered studies measuring long-term effects (more than six months) of HL interventions in female and male migrants are needed, using well-validated tools and representing various healthcare systems.

First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis.

BACKGROUND: Since the approval of tyrosine kinase inhibitors, angiogenesis inhibitors and immune checkpoint inhibitors, the treatment landscape for advanced renal cell carcinoma (RCC) has changed fundamentally. Today, combined therapies from different drug categories have a firm place in a complex first-line therapy. Due to the large number of drugs available, it is necessary to identify the most effective therapies, whilst considering their side effects and impact on quality of life (QoL). OBJECTIVES: To evaluate and compare the benefits and harms of first-line therapies for adults with advanced RCC, and to produce a clinically relevant ranking of therapies. Secondary objectives were to maintain the currency of the evidence by conducting continuous update searches, using a living systematic review approach, and to incorporate data from clinical study reports (CSRs). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, conference proceedings and relevant trial registries up until 9 February 2022. We searched several data platforms to identify CSRs. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating at least one targeted therapy or immunotherapy for first-line treatment of adults with advanced RCC. We excluded trials evaluating only interleukin-2 versus interferon-alpha as well as trials with an adjuvant treatment setting. We also excluded trials with adults who received prior systemic anticancer therapy if more than 10% of participants were previously treated, or if data for untreated participants were not separately extractable. DATA COLLECTION AND ANALYSIS: All necessary review steps (i.e. screening and study selection, data extraction, risk of bias and certainty assessments) were conducted independently by at least two review authors. Our outcomes were overall survival (OS), QoL, serious adverse events (SAEs), progression-free survival (PFS), adverse events (AEs), the number of participants who discontinued study treatment due to an AE, and the time to initiation of first subsequent therapy. Where possible, analyses were conducted for the different risk groups (favourable, intermediate, poor) according to the International Metastatic Renal-Cell Carcinoma Database Consortium Score (IMDC) or the Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Our main comparator was sunitinib (SUN). A hazard ratio (HR) or risk ratio (RR) lower than 1.0 is in favour of the experimental arm. MAIN RESULTS: We included 36 RCTs and 15,177 participants (11,061 males and 4116 females). Risk of bias was predominantly judged as being 'high' or 'some concerns' across most trials and outcomes. This was mainly due to a lack of information about the randomisation process, the blinding of outcome assessors, and methods for outcome measurements and analyses. Additionally, study protocols and statistical analysis plans were rarely available. Here we present the results for our primary outcomes OS, QoL, and SAEs, and for all risk groups combined for contemporary treatments: pembrolizumab + axitinib (PEM+AXI), avelumab + axitinib (AVE+AXI), nivolumab + cabozantinib (NIV+CAB), lenvatinib + pembrolizumab (LEN+PEM), nivolumab + ipilimumab (NIV+IPI), CAB, and pazopanib (PAZ). Results per risk group and results for our secondary outcomes are reported in the summary of findings tables and in the full text of this review. The evidence on other treatments and comparisons can also be found in the full text. Overall survival (OS) Across risk groups, PEM+AXI (HR 0.73, 95% confidence interval (CI) 0.50 to 1.07, moderate certainty) and NIV+IPI (HR 0.69, 95% CI 0.69 to 1.00, moderate certainty) probably improve OS, compared to SUN, respectively. LEN+PEM may improve OS (HR 0.66, 95% CI 0.42 to 1.03, low certainty), compared to SUN. There is probably little or no difference in OS between PAZ and SUN (HR 0.91, 95% CI 0.64 to 1.32, moderate certainty), and we are uncertain whether CAB improves OS when compared to SUN (HR 0.84, 95% CI 0.43 to 1.64, very low certainty). The median survival is 28 months when treated with SUN. Survival may improve to 43 months with LEN+PEM, and probably improves to: 41 months with NIV+IPI, 39 months with PEM+AXI, and 31 months with PAZ. We are uncertain whether survival improves to 34 months with CAB. Comparison data were not available for AVE+AXI and NIV+CAB. Quality of life (QoL) One RCT measured QoL using FACIT-F (score range 0 to 52; higher scores mean better QoL) and reported that the mean post-score was 9.00 points higher (9.86 lower to 27.86 higher, very low certainty) with PAZ than with SUN. Comparison data were not available for PEM+AXI, AVE+AXI, NIV+CAB, LEN+PEM, NIV+IPI, and CAB. Serious adverse events (SAEs) Across risk groups, PEM+AXI probably increases slightly the risk for SAEs (RR 1.29, 95% CI 0.90 to 1.85, moderate certainty) compared to SUN. LEN+PEM (RR 1.52, 95% CI 1.06 to 2.19, moderate certainty) and NIV+IPI (RR 1.40, 95% CI 1.00 to 1.97, moderate certainty) probably increase the risk for SAEs, compared to SUN, respectively. There is probably little or no difference in the risk for SAEs between PAZ and SUN (RR 0.99, 95% CI 0.75 to 1.31, moderate certainty). We are uncertain whether CAB reduces or increases the risk for SAEs (RR 0.92, 95% CI 0.60 to 1.43, very low certainty) when compared to SUN. People have a mean risk of 40% for experiencing SAEs when treated with SUN. The risk increases probably to: 61% with LEN+PEM, 57% with NIV+IPI, and 52% with PEM+AXI. It probably remains at 40% with PAZ. We are uncertain whether the risk reduces to 37% with CAB. Comparison data were not available for AVE+AXI and NIV+CAB. AUTHORS' CONCLUSIONS: Findings concerning the main treatments of interest comes from direct evidence of one trial only, thus results should be interpreted with caution. More trials are needed where these interventions and combinations are compared head-to-head, rather than just to SUN. Moreover, assessing the effect of immunotherapies and targeted therapies on different subgroups is essential and studies should focus on assessing and reporting relevant subgroup data. The evidence in this review mostly applies to advanced clear cell RCC.

"The system has to be health literate, too" - perspectives among healthcare professionals on health literacy in transcultural treatment settings.

BACKGROUND: Effective communication is a central aspect of organizational health literacy. Healthcare professionals are expected to ensure an effective and satisfactory flow of information and to support their patients in accessing, understanding, appraising, and applying health information. This qualitative study aimed to examine the health literacy-related challenges, needs, and applied solutions of healthcare professionals when engaging with persons with a migrant background. Based on the integrated model of health literacy (Sørensen et al., BMC Public Health 12:80, 2012), we focused on environmental, personal, and situational factors that shape health literacy in transcultural treatment settings. METHODS: We conducted five focus group discussions with healthcare professionals (N = 31) who are in regular contact with persons with a migrant background. Discussions were transcribed verbatim and analyzed using qualitative content analysis by applying a deductive-inductive categorization procedure. Deductive categories were derived from the integrated model of health literacy. RESULTS: Challenges included a mismatch in the provision and use of health services. Participants regarded easily accessible services and outreach counselling as helpful solutions. Further challenges were the migrant patients' distrust in healthcare professionals and the German healthcare system, the participants' uncertainty in dealing with patients' expectations and needs, and the patients' non-compliance with appointments. Environmental factors included systemic lack of time and economic pressure. Both were reported as impeding the flow of information in all treatment settings. Participants with a migrant background themselves (n = 16) regarded this personal factor as an opportunity that increased patients' trust in them. They also reported challenges such as high levels of responsibility felt when ad hoc interpreting for colleagues. CONCLUSIONS: Known issues observed in the delivery of healthcare for the majority population (i.e., systemic lack of time, economic pressure) appear to be intensified in the context of migration. An increasingly diverse patient clientele indicates a growing need for culture-sensitive, health-literate healthcare organizations. A corresponding diversity of the health workforce is desirable and should be strengthened by national finance and educational programs. Healthcare professionals who interpret for colleagues should be given the necessary time. Further studies are needed to develop appropriate interventions for improving health literacy at individual and organizational levels. Funding for interpreting services should be expanded.

Interim PET-results for prognosis in adults with Hodgkin lymphoma: a systematic review and meta-analysis of prognostic factor studies.

BACKGROUND: Hodgkin lymphoma (HL) is one of the most common haematological malignancies in young adults and, with cure rates of 90%, has become curable for the majority of individuals. Positron emission tomography (PET) is an imaging tool used to monitor a tumour's metabolic activity, stage and progression. Interim PET during chemotherapy has been posited as a prognostic factor in individuals with HL to distinguish between those with a poor prognosis and those with a better prognosis. This distinction is important to inform decision-making on the clinical pathway of individuals with HL. OBJECTIVES: To determine whether in previously untreated adults with HL receiving first-line therapy, interim PET scan results can distinguish between those with a poor prognosis and those with a better prognosis, and thereby predict survival outcomes in each group. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL and conference proceedings up until April 2019. We also searched one trial registry (ClinicalTrials.gov). SELECTION CRITERIA: We included retrospective and prospective studies evaluating interim PET scans in a minimum of 10 individuals with HL (all stages) undergoing first-line therapy. Interim PET was defined as conducted during therapy (after one, two, three or four treatment cycles). The minimum follow-up period was at least 12 months. We excluded studies if the trial design allowed treatment modification based on the interim PET scan results. DATA COLLECTION AND ANALYSIS: We developed a data extraction form according to the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). Two teams of two review authors independently screened the studies, extracted data on overall survival (OS), progression-free survival (PFS) and PET-associated adverse events (AEs), assessed risk of bias (per outcome) according to the Quality in Prognosis Studies (QUIPS) tool, and assessed the certainty of the evidence (GRADE). We contacted investigators to obtain missing information and data. MAIN RESULTS: Our literature search yielded 11,277 results. In total, we included 23 studies (99 references) with 7335 newly-diagnosed individuals with classic HL (all stages). Participants in 16 studies underwent (interim) PET combined with computed tomography (PET-CT), compared to PET only in the remaining seven studies. The standard chemotherapy regimen included ABVD (16) studies, compared to BEACOPP or other regimens (seven studies). Most studies (N = 21) conducted interim PET scans after two cycles (PET2) of chemotherapy, although PET1, PET3 and PET4 were also reported in some studies. In the meta-analyses, we used PET2 data if available as we wanted to ensure homogeneity between studies. In most studies interim PET scan results were evaluated according to the Deauville 5-point scale (N = 12). Eight studies were not included in meta-analyses due to missing information and/or data; results were reported narratively. For the remaining studies, we pooled the unadjusted hazard ratio (HR). The timing of the outcome measurement was after two or three years (the median follow-up time ranged from 22 to 65 months) in the pooled studies. Eight studies explored the independent prognostic ability of interim PET by adjusting for other established prognostic factors (e.g. disease stage, B symptoms). We did not pool the results because the multivariable analyses adjusted for a different set of factors in each study. Overall survival Twelve (out of 23) studies reported OS. Six of these were assessed as low risk of bias in all of the first four domains of QUIPS (study participation, study attrition, prognostic factor measurement and outcome measurement). The other six studies were assessed as unclear, moderate or high risk of bias in at least one of these four domains. Four studies were assessed as low risk, and eight studies as high risk of bias for the domain other prognostic factors (covariates). Nine studies were assessed as low risk, and three studies as high risk of bias for the domain 'statistical analysis and reporting'. We pooled nine studies with 1802 participants. Participants with HL who have a negative interim PET scan result probably have a large advantage in OS compared to those with a positive interim PET scan result (unadjusted HR 5.09, 95% confidence interval (CI) 2.64 to 9.81, I² = 44%, moderate-certainty evidence). In absolute values, this means that 900 out of 1000 participants with a negative interim PET scan result will probably survive longer than three years compared to 585 (95% CI 356 to 757) out of 1000 participants with a positive result. Adjusted results from two studies also indicate an independent prognostic value of interim PET scan results (moderate-certainty evidence). Progression-free survival Twenty-one studies reported PFS. Eleven out of 21 were assessed as low risk of bias in the first four domains. The remaining were assessed as unclear, moderate or high risk of bias in at least one of the four domains. Eleven studies were assessed as low risk, and ten studies as high risk of bias for the domain other prognostic factors (covariates). Eight studies were assessed as high risk, thirteen as low risk of bias for statistical analysis and reporting. We pooled 14 studies with 2079 participants. Participants who have a negative interim PET scan result may have an advantage in PFS compared to those with a positive interim PET scan result, but the evidence is very uncertain (unadjusted HR 4.90, 95% CI 3.47 to 6.90, I² = 45%, very low-certainty evidence). This means that 850 out of 1000 participants with a negative interim PET scan result may be progression-free longer than three years compared to 451 (95% CI 326 to 569) out of 1000 participants with a positive result. Adjusted results (not pooled) from eight studies also indicate that there may be an independent prognostic value of interim PET scan results (low-certainty evidence). PET-associated adverse events No study measured PET-associated AEs. AUTHORS' CONCLUSIONS: This review provides moderate-certainty evidence that interim PET scan results predict OS, and very low-certainty evidence that interim PET scan results predict progression-free survival in treated individuals with HL. This evidence is primarily based on unadjusted data. More studies are needed to test the adjusted prognostic ability of interim PET against established prognostic factors.

Prognostic models for newly-diagnosed chronic lymphocytic leukaemia in adults: a systematic review and meta-analysis.

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is the most common cancer of the lymphatic system in Western countries. Several clinical and biological factors for CLL have been identified. However, it remains unclear which of the available prognostic models combining those factors can be used in clinical practice to predict long-term outcome in people newly-diagnosed with CLL. OBJECTIVES: To identify, describe and appraise all prognostic models developed to predict overall survival (OS), progression-free survival (PFS) or treatment-free survival (TFS) in newly-diagnosed (previously untreated) adults with CLL, and meta-analyse their predictive performances. SEARCH METHODS: We searched MEDLINE (from January 1950 to June 2019 via Ovid), Embase (from 1974 to June 2019) and registries of ongoing trials (to 5 March 2020) for development and validation studies of prognostic models for untreated adults with CLL. In addition, we screened the reference lists and citation indices of included studies. SELECTION CRITERIA: We included all prognostic models developed for CLL which predict OS, PFS, or TFS, provided they combined prognostic factors known before treatment initiation, and any studies that tested the performance of these models in individuals other than the ones included in model development (i.e. 'external model validation studies'). We included studies of adults with confirmed B-cell CLL who had not received treatment prior to the start of the study. We did not restrict the search based on study design. DATA COLLECTION AND ANALYSIS: We developed a data extraction form to collect information based on the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). Independent pairs of review authors screened references, extracted data and assessed risk of bias according to the Prediction model Risk Of Bias ASsessment Tool (PROBAST). For models that were externally validated at least three times, we aimed to perform a quantitative meta-analysis of their predictive performance, notably their calibration (proportion of people predicted to experience the outcome who do so) and discrimination (ability to differentiate between people with and without the event) using a random-effects model. When a model categorised individuals into risk categories, we pooled outcome frequencies per risk group (low, intermediate, high and very high). We did not apply GRADE as guidance is not yet available for reviews of prognostic models. MAIN RESULTS: From 52 eligible studies, we identified 12 externally validated models: six were developed for OS, one for PFS and five for TFS. In general, reporting of the studies was poor, especially predictive performance measures for calibration and discrimination; but also basic information, such as eligibility criteria and the recruitment period of participants was often missing. We rated almost all studies at high or unclear risk of bias according to PROBAST. Overall, the applicability of the models and their validation studies was low or unclear; the most common reasons were inappropriate handling of missing data and serious reporting deficiencies concerning eligibility criteria, recruitment period, observation time and prediction performance measures. We report the results for three models predicting OS, which had available data from more than three external validation studies: CLL International Prognostic Index (CLL-IPI) This score includes five prognostic factors: age, clinical stage, IgHV mutational status, B2-microglobulin and TP53 status. Calibration: for the low-, intermediate- and high-risk groups, the pooled five-year survival per risk group from validation studies corresponded to the frequencies observed in the model development study. In the very high-risk group, predicted survival from CLL-IPI was lower than observed from external validation studies. Discrimination: the pooled c-statistic of seven external validation studies (3307 participants, 917 events) was 0.72 (95% confidence interval (CI) 0.67 to 0.77). The 95% prediction interval (PI) of this model for the c-statistic, which describes the expected interval for the model's discriminative ability in a new external validation study, ranged from 0.59 to 0.83. Barcelona-Brno score Aimed at simplifying the CLL-IPI, this score includes three prognostic factors: IgHV mutational status, del(17p) and del(11q). Calibration: for the low- and intermediate-risk group, the pooled survival per risk group corresponded to the frequencies observed in the model development study, although the score seems to overestimate survival for the high-risk group. Discrimination: the pooled c-statistic of four external validation studies (1755 participants, 416 events) was 0.64 (95% CI 0.60 to 0.67); 95% PI 0.59 to 0.68. MDACC 2007 index score The authors presented two versions of this model including six prognostic factors to predict OS: age, B2-microglobulin, absolute lymphocyte count, gender, clinical stage and number of nodal groups. Only one validation study was available for the more comprehensive version of the model, a formula with a nomogram, while seven studies (5127 participants, 994 events) validated the simplified version of the model, the index score. Calibration: for the low- and intermediate-risk groups, the pooled survival per risk group corresponded to the frequencies observed in the model development study, although the score seems to overestimate survival for the high-risk group. Discrimination: the pooled c-statistic of the seven external validation studies for the index score was 0.65 (95% CI 0.60 to 0.70); 95% PI 0.51 to 0.77. AUTHORS' CONCLUSIONS: Despite the large number of published studies of prognostic models for OS, PFS or TFS for newly-diagnosed, untreated adults with CLL, only a minority of these (N = 12) have been externally validated for their respective primary outcome. Three models have undergone sufficient external validation to enable meta-analysis of the model's ability to predict survival outcomes. Lack of reporting prevented us from summarising calibration as recommended. Of the three models, the CLL-IPI shows the best discrimination, despite overestimation. However, performance of the models may change for individuals with CLL who receive improved treatment options, as the models included in this review were tested mostly on retrospective cohorts receiving a traditional treatment regimen. In conclusion, this review shows a clear need to improve the conducting and reporting of both prognostic model development and external validation studies. For prognostic models to be used as tools in clinical practice, the development of the models (and their subsequent validation studies) should adapt to include the latest therapy options to accurately predict performance. Adaptations should be timely.

Interim PET-results for prognosis in adults with Hodgkin lymphoma: a systematic review and meta-analysis of prognostic factor studies.

BACKGROUND: Hodgkin lymphoma (HL) is one of the most common haematological malignancies in young adults and, with cure rates of 90%, has become curable for the majority of individuals. Positron emission tomography (PET) is an imaging tool used to monitor a tumour's metabolic activity, stage and progression. Interim PET during chemotherapy has been posited as a prognostic factor in individuals with HL to distinguish between those with a poor prognosis and those with a better prognosis. This distinction is important to inform decision-making on the clinical pathway of individuals with HL. OBJECTIVES: To determine whether in previously untreated adults with HL receiving first-line therapy, interim PET scan results can distinguish between those with a poor prognosis and those with a better prognosis, and thereby predict survival outcomes in each group. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL and conference proceedings up until April 2019. We also searched one trial registry (ClinicalTrials.gov). SELECTION CRITERIA: We included retrospective and prospective studies evaluating interim PET scans in a minimum of 10 individuals with HL (all stages) undergoing first-line therapy. Interim PET was defined as conducted during therapy (after one, two, three or four treatment cycles). The minimum follow-up period was at least 12 months. We excluded studies if the trial design allowed treatment modification based on the interim PET scan results. DATA COLLECTION AND ANALYSIS: We developed a data extraction form according to the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). Two teams of two review authors independently screened the studies, extracted data on overall survival (OS), progression-free survival (PFS) and PET-associated adverse events (AEs), assessed risk of bias (per outcome) according to the Quality in Prognosis Studies (QUIPS) tool, and assessed the certainty of the evidence (GRADE). We contacted investigators to obtain missing information and data. MAIN RESULTS: Our literature search yielded 11,277 results. In total, we included 23 studies (99 references) with 7335 newly-diagnosed individuals with classic HL (all stages).Participants in 16 studies underwent (interim) PET combined with computed tomography (PET-CT), compared to PET only in the remaining seven studies. The standard chemotherapy regimen included ABVD (16) studies, compared to BEACOPP or other regimens (seven studies). Most studies (N = 21) conducted interim PET scans after two cycles (PET2) of chemotherapy, although PET1, PET3 and PET4 were also reported in some studies. In the meta-analyses, we used PET2 data if available as we wanted to ensure homogeneity between studies. In most studies interim PET scan results were evaluated according to the Deauville 5-point scale (N = 12).Eight studies were not included in meta-analyses due to missing information and/or data; results were reported narratively. For the remaining studies, we pooled the unadjusted hazard ratio (HR). The timing of the outcome measurement was after two or three years (the median follow-up time ranged from 22 to 65 months) in the pooled studies.Eight studies explored the independent prognostic ability of interim PET by adjusting for other established prognostic factors (e.g. disease stage, B symptoms). We did not pool the results because the multivariable analyses adjusted for a different set of factors in each study.Overall survivalTwelve (out of 23) studies reported OS. Six of these were assessed as low risk of bias in all of the first four domains of QUIPS (study participation, study attrition, prognostic factor measurement and outcome measurement). The other six studies were assessed as unclear, moderate or high risk of bias in at least one of these four domains. Nine studies were assessed as high risk, and three studies as moderate risk of bias for the domain study confounding. Eight studies were assessed as low risk, and four studies as high risk of bias for the domain statistical analysis and reporting.We pooled nine studies with 1802 participants. Participants with HL who have a negative interim PET scan result probably have a large advantage in OS compared to those with a positive interim PET scan result (unadjusted HR 5.09, 95% confidence interval (CI) 2.64 to 9.81, I² = 44%, moderate-certainty evidence). In absolute values, this means that 900 out of 1000 participants with a negative interim PET scan result will probably survive longer than three years compared to 585 (95% CI 356 to 757) out of 1000 participants with a positive result.Adjusted results from two studies also indicate an independent prognostic value of interim PET scan results (moderate-certainty evidence).Progression-free survival Twenty-one studies reported PFS. Eleven out of 21 were assessed as low risk of bias in the first four domains. The remaining were assessed as unclear, moderate or high risk of bias in at least one of the four domains. Eleven studies were assessed as high risk, nine studies as moderate risk and one study as low risk of bias for study confounding. Eight studies were assessed as high risk, three as moderate risk and nine as low risk of bias for statistical analysis and reporting.We pooled 14 studies with 2079 participants. Participants who have a negative interim PET scan result may have an advantage in PFS compared to those with a positive interim PET scan result, but the evidence is very uncertain (unadjusted HR 4.90, 95% CI 3.47 to 6.90, I² = 45%, very low-certainty evidence). This means that 850 out of 1000 participants with a negative interim PET scan result may be progression-free longer than three years compared to 451 (95% CI 326 to 569) out of 1000 participants with a positive result.Adjusted results (not pooled) from eight studies also indicate that there may be an independent prognostic value of interim PET scan results (low-certainty evidence).PET-associated adverse eventsNo study measured PET-associated AEs. AUTHORS' CONCLUSIONS: This review provides moderate-certainty evidence that interim PET scan results predict OS, and very low-certainty evidence that interim PET scan results predict progression-free survival in treated individuals with HL. This evidence is primarily based on unadjusted data. More studies are needed to test the adjusted prognostic ability of interim PET against established prognostic factors.

Gender differences of health literacy in persons with a migration background: a systematic review and meta-analysis.

OBJECTIVE: To investigate gender differences of health literacy in individuals with a migration background. DESIGN: Systematic review and meta-analysis. OVID/MEDLINE, PsycINFO and CINAHL were searched in March 2018 and July 2020. SETTING: Studies had to provide health literacy data for adult women and men with a migration background, collected with a standardised instrument, or report results that demonstrated the collection of such data. Health literacy data were extracted from eligible studies or requested from the respective authors. Using a random-effects model, a meta-analysis was conducted to assess standardised mean differences (SMDs) of health literacy in men and women. Two researchers independently assessed risk of bias for each included study using the Appraisal Tool for Cross-Sectional Studies. RESULTS: Twenty-four studies were included in this systematic review. Thereof, 22 studies (8012 female and 5380 male participants) were included in the meta-analyses. In six studies, gender-specific health literacy scores were reported. The authors of additional 15 studies provided their data upon request and for one further study data were available online. Women achieved higher health literacy scores than men: SMD=0.08, 95% CI 0.002 to 0.159, p=0.04, I2=65%. Another 27 studies reported data on female participants only and could not be included due to a lack of comparable studies with male participants only. Authors of 56 other eligible studies were asked for data, but without success. CONCLUSION: Men with a migration background-while being much less frequently examined-may have lower health literacy than women. As heterogeneity between studies was high and the difference became statistically insignificant when excluding studies with a high risk of bias, this result must be interpreted with caution. There is a paucity of research on the social and relational aspects of gender in relation to health literacy among people with a migration background, especially for men. PROSPERO REGISTRATION NUMBER: CRD42018085555.

[The "gender" variable in the research process: Requirements contained in the application guidelines of funding institutions in the health sector]. / Die Variable "Geschlecht" im Forschungsprozess: Anforderungen in den Antragsrichtlinien von Förderinstitutionen im Gesundheitswesen.

BACKGROUND: When addressing the variable "gender" in health research designs, a distinction is made between biological ("sex") and sociocultural or psychosocial aspects ("gender"). In health research, it is important to avoid systematic errors that may result when gender aspects are inappropriately or not sufficiently addressed (so-called gender bias). A gender bias occurs, for instance, when the presence of gender differences is assumed without empirical evidence or when research data that was generated from samples of male participants is automatically applied to women. Funding institutions can create incentives for researchers to integrate gender-sensitive analyses into their research projects and to consider the potential influence of the "gender" variable. The aim of this study was to explore which explicit requirements concerning gender aspects applicants to German funding institutions in the various health sectors need to meet in their research designs. METHODS: From March to June 2019, we researched funding institutions in the health sector at the German federal level. We examined the funding guidelines of each identified institution in light of their requirements for applicants to take gender aspects into consideration in their research. We explored this in a two-step procedure (online document search and e-mail contact). RESULTS: We examined 18 institutions. Information on the requirements for applicants to address gender aspects in their research projects was identified for four institutions: the German Federal Ministry of Education and Research, the German Federal Ministry of Health, the German Research Foundation, and the Volkswagen Stiftung. In particular, the consideration of gender aspects for planned research projects was used as an evaluation criterion in the institutions' application guidelines available online. If considered relevant for a planned research project, the consideration of gender aspects affects project planning, implementation and evaluation of results. Eight institutions had no such requirements. For the remaining six institutions, we were not able to find any such information, neither by document research nor through e-mail contact. DISCUSSION AND CONCLUSION: Only a few funding institutions in the health sector have so far included requirements regarding the consideration of the "gender" variable in health research in their application guidelines. Furthermore, the funding institutions' requirements are somewhat heterogeneous and need standardization. Funding institutions in the health sector could identify research needs and set new research priorities in order to expand the empirical evidence on gender aspects in the various health sectors and to increase the social benefit of the scientific results obtained. In this way, applicants can be sensitized and encouraged to consider gender aspects in their research projects and, if necessary, to conduct them in a gender-differentiated manner.

Gender-Specific Aspects of Health Literacy: Perceptions of Interactions with Migrants among Health Care Providers in Germany.

Health literacy can be described as a complex process shaped by individual resources and preferences and by the nature and quality of health-related information people encounter. The main objective of this study was to explore the views of health care professionals on how gender as a personal determinant of health literacy affected their interactions with migrant patients. The interrelated challenges, needs and applied solutions were analyzed from a health literacy perspective. Five focus group discussions with health care professionals working with migrants (n = 31) were conducted in Cologne, Germany, audio recorded, transcribed and analyzed by qualitative content analysis. Gender-specific aspects, such as the gender of health care providers as a factor, were portrayed above all in relation to patients from Turkey and Arab countries regarding access to and understanding of health-related information. These statements exclusively represent the possibly biased or assumptions-based perspectives of health care professionals on their migrant patients and were made against the background of a systemic lack of time and the challenge of overcoming language barriers. Especially in this context, reducing time pressure and improving communication in the treatment setting may be to the benefit of all actors within healthcare.