Background: Patient portals have the potential to improve care for chronically ill patients by engaging them in their treatment. These platforms can work, for example, as a standalone self-management intervention or a tethered link to treatment providers in routine care. Many different types of portals are available for different patient groups, providing various features. Objective: This scoping review aims to summarize the current literature on patient portals for patients with diabetes mellitus and chronic heart disease regarding usage behavior and usability. Methods: We conducted this review according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement for scoping reviews. We performed database searches using PubMed, PsycInfo, and CINAHL, as well as additional searches in reviews and reference lists. We restricted our search to 2010. Qualitative and quantitative studies, and studies using both approaches that analyzed usage behavior or usability of patient portals were eligible. We mapped portal features according to broad thematic categories and summarized the results of the included studies separately according to outcome and research design. Results: After screening, we finally included 85 studies. Most studies were about patients with diabetes, included patients younger than 65 years, and were conducted in the United States. Portal features were categorized into educational/general information, reminder, monitoring, interactivity, personal health information, electronic/personal health record, and communication. Portals mostly provided educational, monitoring, and communication-related features. Studies reported on usage behavior including associated variables, usability dimensions, and suggestions for improvement. Various ways of reporting usage frequency were identified. A noticeable decline in portal usage over time was reported frequently. Age was most frequently studied in association with portal use, followed by gender, education, and eHealth literacy. Younger age and higher education were often associated with higher portal use. In two-thirds of studies reporting on portal usability, the portals were rated as user friendly and comprehensible, although measurement and reporting were heterogeneous. Portals were considered helpful for self-management through positive influences on motivation, health awareness, and behavioral changes. Helpful features for self-management were educational/general information and monitoring. Barriers to portal use were general (eg, aspects of design or general usability), related to specific situations during portal use (eg, login procedure), or not portal specific (eg, user skills and preferences). Frequent themes were aspects of design, usability, and technology. Suggestions for improvement were mainly related to technical issues and need for support. Conclusions: The current state of research emphasizes the importance of involving patients in the development and evaluation of patient portals. The consideration of various research designs in a scoping review is helpful for a deeper understanding of usage behavior and usability. Future research should focus on the role of disease burden, and usage behavior and usability among older patients.

Chronic coronary syndrome (CCS) is a potentially progressive clinical presentation of coronary artery disease (CAD). Clinical practice guidelines (CPGs) are available for prevention, diagnosis, and treatment. Embedded in the “ENLIGHT-KHK” healthcare project, a qualitative study was conducted to identify factors that influence guideline adherence from the perspective of general practitioners (GPs) and cardiologists (CA) in the ambulatory care sector in Germany. GPs and CAs were surveyed via telephone using an interview guide. The respondents were first asked about their individual approach to caring for patients with suspected CCS. Subsequently, the accordance of their approach with guideline recommendations was addressed. Finally, potential measures for assisting with guideline adherence were discussed. The semi-structured interviews were transcribed verbatim and analysed using a qualitative content analysis in accordance with Kuckartz and Rädiker. Factors influencing adherence to CPGs were categorised by assessing whether they (i) inhibited or facilitated guideline adherence, (ii) played a role in patients at risk of CCS or with suspected or known CCS, (iii) were mentioned in implicit or explicit thematic reference to CPGs, and (iv) were declared a practical problem. Based on interviews with ten GPs and five CAs, 35 potential influencing factors were identified. These emerged at four levels: patients, healthcare providers, CPGs, and the healthcare system. The most commonly cited barrier to guideline adherence among the respondents was structural aspects at the system level, including reachability of providers and services, waiting times, reimbursement through statutory health insurance (SHI) providers, and contract offers. There was a strong emphasis on interdependencies between factors acting at different levels. For instance, poor reachability of providers and services at the system level may result in inexpedience of guideline recommendations at the CPG level. Likewise, poor reachability of providers and services at the system level may be aggravated or alleviated by factors such as diagnostic preferences at the patient level or collaborations at the provider level. To assist with adherence to CPGs regarding CCS, promoting measures may be needed that account for interdependencies between barriers and facilitators at various healthcare levels. Respective measures should consider medically justified deviations from guideline recommendations in individual cases. German Clinical Trials Register: DRKS00015638; Universal Trial Number (UTN): U1111-1227-8055.

Objective: For beneficial health outcomes sufficient and sustained physical activity levels are recommended but difficult to achieve. This systematic review evaluates the effectiveness of behavioural economics (BE)-informed interventions to increase individuals' physical activity level in the long-term. Methods: We conducted a systematic literature search using Medline (via PubMed), PsycInfo, and EconLit (both via EBSCOhost) including randomized controlled trials of at least 24 weeks duration that evaluated BE-informed interventions to promote physical activity in adults. Potential BE approaches were commitment devices, social incentives, motivational feedback, goal setting, gamification, and financial incentives. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for (cluster-) randomized trials. A random-effects meta-analysis was conducted to summarize the outcome measure daily step count. Results: Based on 13 studies with 4347 participants, the BE-informed interventions most often applied were commitment lotteries (n = 8) and social incentives (n = 7). Risk of bias assessment classified five studies as low, six as moderate, and two as high risk of bias. Significant results on study level towards BE-informed interventions were observed for commitment lotteries (n = 3) and gamification (n = 4). Including healthy and diseased individuals in the meta-analysis (n = 10), the increase in daily step count in experimental groups compared to control was statistically significant for the intervention period (standardized mean difference (SMD) = 0.13, 95%-CI: 0.00-0.25, I2 = 59%, p = 0.04) but not for the follow-up (SMD = 0.08, 95%-CI: -0.00-0.17, I2 = 17%, p = 0.06). Excluding high risk of bias studies (n = 2) resulted in statistically significant effects with reduced heterogeneity for both periods. Conclusion: Our review reveals a potential effect of BE-informed interventions to promote physical activity. The small effect underlines the importance to evaluate the behavioural channels which may explain the heterogeneity in individuals' responses to BE strategies.

BACKGROUNDAnaemia is common among cancer patients and they may require red blood cell transfusions. Erythropoiesis-stimulating agents (ESAs) and iron might help in reducing the need for red blood cell transfusions. However, it remains unclear whether the combination of both drugs is preferable compared to using one drug.OBJECTIVESTo systematically review the effect of intravenous iron, oral iron or no iron in combination with or without ESAs to prevent or alleviate anaemia in cancer patients and to generate treatment rankings using network meta-analyses (NMAs).SEARCH METHODSWe identified studies by searching bibliographic databases (CENTRAL, MEDLINE, Embase; until June 2021). We also searched various registries, conference proceedings and reference lists of identified trials.SELECTION CRITERIAWe included randomised controlled trials comparing intravenous, oral or no iron, with or without ESAs for the prevention or alleviation of anaemia resulting from chemotherapy, radiotherapy, combination therapy or the underlying malignancy in cancer patients.DATA COLLECTION AND ANALYSISTwo review authors independently extracted data and assessed risk of bias. Outcomes were on-study mortality, number of patients receiving red blood cell transfusions, number of red blood cell units, haematological response, overall mortality and adverse events. We conducted NMAs and generated treatment rankings. We assessed the certainty of the evidence using GRADE.MAIN RESULTSNinety-six trials (25,157 participants) fulfilled our inclusion criteria; 62 trials (24,603 participants) could be considered in the NMA (12 different treatment options). Here we present the comparisons of ESA with or without iron and iron alone versus no treatment. Further results and subgroup analyses are described in the full text. On-study mortality We estimated that 92 of 1000 participants without treatment for anaemia died up to 30 days after the active study period. Evidence from NMA (55 trials; 15,074 participants) suggests that treatment with ESA and intravenous iron (12 of 1000; risk ratio (RR) 0.13, 95% confidence interval (CI) 0.01 to 2.29; low certainty) or oral iron (34 of 1000; RR 0.37, 95% CI 0.01 to 27.38; low certainty) may decrease or increase and ESA alone (103 of 1000; RR 1.12, 95% CI 0.92 to 1.35; moderate certainty) probably slightly increases on-study mortality. Additionally, treatment with intravenous iron alone (271 of 1000; RR 2.95, 95% CI 0.71 to 12.34; low certainty) may increase and oral iron alone (24 of 1000; RR 0.26, 95% CI 0.00 to 19.73; low certainty) may increase or decrease on-study mortality. Haematological response We estimated that 90 of 1000 participants without treatment for anaemia had a haematological response. Evidence from NMA (31 trials; 6985 participants) suggests that treatment with ESA and intravenous iron (604 of 1000; RR 6.71, 95% CI 4.93 to 9.14; moderate certainty), ESA and oral iron (527 of 1000; RR 5.85, 95% CI 4.06 to 8.42; moderate certainty), and ESA alone (467 of 1000; RR 5.19, 95% CI 4.02 to 6.71; moderate certainty) probably increases haematological response. Additionally, treatment with oral iron alone may increase haematological response (153 of 1000; RR 1.70, 95% CI 0.69 to 4.20; low certainty). Red blood cell transfusions We estimated that 360 of 1000 participants without treatment for anaemia needed at least one transfusion. Evidence from NMA (69 trials; 18,684 participants) suggests that treatment with ESA and intravenous iron (158 of 1000; RR 0.44, 95% CI 0.31 to 0.63; moderate certainty), ESA and oral iron (144 of 1000; RR 0.40, 95% CI 0.24 to 0.66; moderate certainty) and ESA alone (212 of 1000; RR 0.59, 95% CI 0.51 to 0.69; moderate certainty) probably decreases the need for transfusions. Additionally, treatment with intravenous iron alone (268 of 1000; RR 0.74, 95% CI 0.43 to 1.28; low certainty) and with oral iron alone (333 of 1000; RR 0.92, 95% CI 0.54 to 1.57; low certainty) may decrease or increase the need for transfusions. Overall mortality We estimated that 347 of 1000 participants without treatment for anaemia died overall. Low-certainty evidence from NMA (71 trials; 21,576 participants) suggests that treatment with ESA and intravenous iron (507 of 1000; RR 1.46, 95% CI 0.87 to 2.43) or oral iron (482 of 1000; RR 1.39, 95% CI 0.60 to 3.22) and intravenous iron alone (521 of 1000; RR 1.50, 95% CI 0.63 to 3.56) or oral iron alone (534 of 1000; RR 1.54, 95% CI 0.66 to 3.56) may decrease or increase overall mortality. Treatment with ESA alone may lead to little or no difference in overall mortality (357 of 1000; RR 1.03, 95% CI 0.97 to 1.10; low certainty). Thromboembolic events We estimated that 36 of 1000 participants without treatment for anaemia developed thromboembolic events. Evidence from NMA (50 trials; 15,408 participants) suggests that treatment with ESA and intravenous iron (66 of 1000; RR 1.82, 95% CI 0.98 to 3.41; moderate certainty) probably slightly increases and with ESA alone (66 of 1000; RR 1.82, 95% CI 1.34 to 2.47; high certainty) slightly increases the number of thromboembolic events. None of the trials reported results on the other comparisons. Thrombocytopenia or haemorrhage We estimated that 76 of 1000 participants without treatment for anaemia developed thrombocytopenia/haemorrhage. Evidence from NMA (13 trials, 2744 participants) suggests that treatment with ESA alone probably leads to little or no difference in thrombocytopenia/haemorrhage (76 of 1000; RR 1.00, 95% CI 0.67 to 1.48; moderate certainty). None of the trials reported results on other comparisons. Hypertension We estimated that 10 of 1000 participants without treatment for anaemia developed hypertension. Evidence from NMA (24 trials; 8383 participants) suggests that treatment with ESA alone probably increases the number of hypertensions (29 of 1000; RR 2.93, 95% CI 1.19 to 7.25; moderate certainty). None of the trials reported results on the other comparisons.AUTHORS' CONCLUSIONSWhen considering ESAs with iron as prevention for anaemia, one has to balance between efficacy and safety. Results suggest that treatment with ESA and iron probably decreases number of blood transfusions, but may increase mortality and the number of thromboembolic events. For most outcomes the different comparisons within the network were not fully connected, so ranking of all treatments together was not possible. More head-to-head comparisons including all evaluated treatment combinations are needed to fill the gaps and prove results of this review.

Background: Hemodialysis (HD) and peritoneal dialysis (PD) are deemed medically equivalent for therapy of end-stage renal disease (ESRD) and reimbursed by the German statutory health insurance (SHI). However, although the home dialysis modality PD is associated with higher patient autonomy than HD, for unknown reasons, PD uptake is low in Germany. Hence, we compared HD with PD regarding health economic outcomes, particularly costs, as potentially relevant factors for the predominance of HD. Methods: Claims data from two German health insurance funds were analysed in a retrospective cohort study regarding the prevalence of HD and PD in 2013–2016. Propensity score matching created comparable HD and PD groups (n = 436 each). Direct annual health care costs were compared. A sensitivity analysis included a comparison of different matching techniques and consideration of transportation costs. Additionally, hospitalisation and survival were investigated using Poisson regression and Kaplan-Meier curves. Results: Total direct annual average costs were higher for HD (€47,501) than for PD (€46,235), but not significantly (p = 0.557). The additional consideration of transportation costs revealed an annual cost advantage of €7000 for PD. HD and PD differed non-significantly in terms of hospitalisation and survival rates (p = 0.610/p = 0.207). Conclusions: PD has a slight non-significant cost advantage over HD, especially when considering transportation costs.

The present commentary discusses how social media big data could be used in mental health research to assess the impact of major global crises such as the COVID-19 pandemic. We first provide a brief overview of the COVID-19 situation and the challenges associated with the assessment of its global impact on mental health using conventional methods. We then propose social media big data as a possible unconventional data source, provide illustrative examples of previous studies, and discuss the advantages and challenges associated with their use for mental health research. We conclude that social media big data represent a valuable resource for mental health research, however, several methodological limitations and ethical concerns need to be addressed to ensure safe use.

Background Clinical studies indicate that strength-balance training for active fall prevention can prevent fractures in older people. The present modelling study evaluates the cost-effectiveness of fall prevention exercise (FPE) provided to independently living older people compared to no intervention in Germany. Method We designed a Markov model to evaluate the cost-effectiveness of a group-based FPE-program provided to independently living people ≥75 years from the perspective of the German statutory health insurance (SHI). Input data was obtained from public databases, clinical trials and official statistics. The incremental cost-effectiveness ratio (ICER) was presented as costs per avoided hip fracture. Additionally, we performed deterministic and probabilistic sensitivity analyses and, estimated monetary consequences for the SHI in a budget impact analysis (BIA). Results For women, the costs per hip fracture avoided amounted to €52,864 (men: €169,805). Results of deterministic and probabilistic sensitivity analyses confirmed the robustness of the results. According to the BIA, for the reimbursement of FPE additional costs of €3.0 million (women) and €7.8 million (men) are expected for the SHI. Conclusions Group-based FPE appears to be no cost-effective option to prevent fall-related hip fractures in independently living elderly. To allow a more comprehensive statement on the cost effectiveness of FPE fracture types other than hip should be increasingly evaluated in clinical trials.

Background About 70% to 80% of adults with cancer experience chemotherapy -induced nausea and vomiting (CI NV). CINV remains one of the most distressing symptoms associated with cancer therapy and is associated with decreased adherence to chemotherapy. Combining 5hydroxytryptamine-3 (5 -HT,) receptor antagonists with corticosteroids or additionally with neurokinin-1 (NK,) receptor antagonists is effective in preventing CINV among adults receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Various treatment options are available, but direct head -to -head comparisons do not allow comparison of all treatments versus another. Objectives " In adults with solid cancer or haematological malignancy receiving HEC - To compare the effects of antiemetic treatment combinations including NK, receptor antagonists, 5 -HT, receptor antagonists, and corticosteroids on prevention of acute phase (Day 1), delayed phase (Days 2 to 5), and overall (Days 1 to 5) chemotherapy -induced nausea and vomiting in network meta -analysis (NMA) To generate a clinically meaningful treatment ranking according to treatment safety and efficacy In adults with solid cancer or haematological malignancy receiving MEC - To compare whether antiemetic treatment combinations including NK, receptor antagonists, 5 -HT, receptor antagonists, and corticosteroids are superior for prevention of acute phase (Day 1), delayed phase (Days 2 to 5), and overall (Days 1 to 5) chemotherapyinduced nausea and vomitingtotreatment combinations including 5 -HT, receptor antagonists and corticosteroids solely, in network meta analysis - To generate a clinically meaningful treatment ranking according to treatment safety and efficacy Search methods We searched CENTRAL, MEDLIN E, Embase, conference proceedings, and study registries from 1988 to February 2021 for randomised controlled trials (RCTs). Selection criteria We included RCTs including adults with any cancer receiving HEC or MEC (according to the latest definition) and comparing combination therapies of NK, and 5 -HT, inhibitors and corticosteroids for prevention of CINV. Data collection and analysis We used standard methodological procedures expected by Cochrane. We expressed treatment effects as risk ratios (RRs). Prioritised outcomes were complete control of vomiting du ring delayed and overall phases, complete control of nausea during the overall phase, quality of life, serious adverse events (SAEs), and on -study mortality. We assessed GRADE and developed 12 'Summary of findings' tables. We report results of most crucial outcomes in the abstract, that is, complete control of vomiting during the overall phase and SAEs. For a comprehensive illustration of results, we randomly chose aprepitant plus granisetron as exemplary reference treatment for HEC, and granisetron as exemplary reference treatment for MEC. Main results Highly emetogenic chemotherapy (*EC) We included 73 studies reporting on 25,275 participants and comparing 14 treatment combinations with NK, and 5 -HT, inhibitors. All treatment combinations included corticosteroids. Complete control of vomiting during the overall phase We estimated that 704 of 1000 participants achieve complete control of vomiting in the overall treatment phase (one to five days) when treated with aprepitant + granisetron. Evidence from NMA (39 RCTs, 21,642 participants; 12 treatment combinations with NK, and 5 -HT, inhibitors) suggests that the following drug com binations are more efficacious than a prepitant + granisetron for completely controlling vomiting during the overall treatment phase (one to five days): fosnetupitant+ palonosetron (810 of 1000; RR 1.15, 95 A) confidence interval (CI) 0.97 to 1.37; moderate certainty), aprepitant + palonosetron (753 of 1000; RR 1.07, 95% CI 1.98 to 1.18; low -certainty), aprepitant + ramosetron (753 of 1000; RR 1.07, 95% CI 0.95 to 1.21; low certainty), and fosaprepitant + palonosetron (746 of 1000; RR 1.06, 95% CI 0.96 to 1.19; low certainty). Netupitant + palonosetron (704 of 1000; RR 1.00, 95% CI 0.93 to 1.08; high -certainty) and fosaprepitant + granisetron (697 of 1000; RR 0.99, 95% CI 0.93 to 1.06; high -certainty) have little to no impact on complete control of vomiting during the overall treatment phase (one to five days) when compared to aprepitant + granisetron, respectively. Evidence further suggeststhat the following drug combinations are less efficacious than aprepitant + granisetron in completely controlling vomiting during the overall treatment phase (one to five days) (ordered by decreasing efficacy): aprepitant + ondansetron (676 of 1000; RR 0.96, 95% CI 0.88 to 1.05; low certainty), fosaprepitant + ondansetron (662 of 1000; RR 0.94, 95% CI 0.85 to 1.04; low certainty), casopitant + ondansetron (634 of 1000; RR 0.90, 95% CI 0.79 to 1.03; low certainty), rolapitant + granisetron (627 of 1000; RR 0.89, 95% CI 0.78 to 1.01; moderate certainty), and rolapitant + ondansetron (598 of 1000; RR 0.85, 95% CI 0.65 to 1.12; low certainty). We could not include two treatment combinations (eziopitant + granisetron, aprepitant + tropisetron) in NMA for this outcome because of missing direct comparisons. Serious adverse events We estimated that 35 of 1000 participants experience any SAEs when treated with aprepitant + granisetron. Evidence from N MA (23 RCTs, 16,065 participants; 11 treatment combinations) suggests that fewer participants may experience SAEs when treated with the following drug combinations than with aprepitant+ granisetron: fosaprepitant+ ondansetron (8 of 1000; RR 0.23, 95% CI 0.05 to 1.07; low certainty), casopitant + ondansetron (8 of 1000; RR 0.24, 95% CI 0.04 to 1.39; low certainty), netupitant+ palonosetron (9 of 1000; RR 0.27, 95% CI 0.05 to 1.58; low certainty), fosaprepitant + granisetron (13 of 1000; RR 0.37, 95% a 0.09 to 1.50; low certainty), and rolapitant + granisetron (20 of 1000; RR 0.57, 95% CI 0.19 to 1.70; low certainty). Evidence is very uncertain about the effects of a prepitant + ondansetron (8 of 1000; RR 0.22, 95% Cl 0.04 to 1.14; very low certainty), aprepitant + ramosetron (11 of 1000; RR 0.31, 95% CI 0.05 to 1.90; very low certainty), fosaprepitant + palonosetron (12 of 1000; RR 0.35, 95% CI 0.04 to 2.95; very low certainty), fosnetu pitant + palonosetron (13 of 1000; RR 0.36, 95% CI 0.06 to 2.16; very low certainty), and aprepitant+ paionosetron (17 of 1000; RR 0.48, 95% CI 0.05 to 4.78; very low certainty) on the risk of SAEs when compared to aprepitant + gran isetron, respectively. We could not include three treatment combinations (eziopitant + granisetron, aprepitant + tropisetron, rolapitant + ondansetron) in NMA for this outcome because of missing direct comparisons. Moderately emetogenic chemotherapy (MEC) We included 38 studies reporting on 12,038 participants and comparing 15 treatment combinations with NK, and 5-HT, inhibitors, or 5H T, inhibitors solely. Ali treatment combinations included corticosteroids. Complete control of vomiting during the overall phase We estimated that 555 of 1000 participants achieve complete control of vomiting in the overall treatment phase (one to five days) when treated with granisetron. Evidence from NMA (22 RCTs, 7800 participants; 11 treatment combinations) suggests that the following drug combinations are more efficacious than granisetron in completely controlling vomiting during the overall treatment phase (one to five days): aprepitant + paionosetron (716 of 1000; RR 1.29, 950/0 CI 1.00 to 1.66; low certainty), netupitant+ pa[onosetron (694 of 1000; RR 1.25, 95% CI 0.92 to 1.70; low certainty), and rola pitant + granisetron (660 of 1000; RR 1.19, 95% CI 1.06 to 1.33; high certainty). Palonosetron (588 of 1000; RR 1.06, 95% CI 0.85 to 1.32; low certainty) and aprepitant + granisetron (577 of 1000; RR 1.06, 95% CI 0.85 to 1.32; low certainty) may or may not increase complete response in the overall treatment phase (one to five days) when compared to gra nisetron, respectively. Azasetron (560 of 1000; RR 1.01, 95% CI 0.76 to 1.34; low certainty) may result in little to no difference in complete response in the overall treatment phase (one to five days) when compared to gran isetron. Evidence further suggests that the following drug combinations are less efficacious than gra nisetron in completely controlling vomiting during the overall treatment phase (one to five days) (ordered by decreasing efficacy): fosaprepitant + ondansetron (500 of 100; RR 0.90, 95% CI 0.66 to 1.22; low certainty), aprepitant + ondansetron (477 of 1000; RR 0.86, 95% CI 0.64 to 1.17; low certainty), casopitant + ondansetron (461 of 1000; RR 0.83, 95% CI 0.62 to 1.12; [ow certainty), and ondansetron (433 of 1000; RR 0.78, 95% CI 0.59 to 1.04; [ow certainty). We could not include five treatment combinations (fosaprepitant + granisetron, azasetron, dolasetron, ramosetron, tropisetron in NMA for this outcome because of missing direct comparisons. Serious adverse events We estimated that 153 of 1000 participants experience any SAEs when treated with gra nisetron. Evidence from pair-wise comparison (1 RCT, 1344 participants) suggests that more participants may experience SAEs when treated with rola pita nt + granisetron (176 of 1000; RR 1.15, 95% CI 0.88 to 1.50; low certainty). NMA was not feasible for this outcome because of missing direct comparisons. Certainty of evidence Our main reason for downgrading was serious or very serious imprecision (e.g. due to wide 95% Cls crossing or including unity, few events leading to wide 95% Cls, or small information size). Additional reasons fordowngrading some comparisons or vvhole networks were serious study [imitations due to high risk of bias or moderate inconsistency within networks. Authors' conclusions This field of supportive cancer care is very well researched. However, new drugs or drug combinations are continuously emerging and need to be systematica Ely researched and assessed. For people receiving HEC, synthesised evidence does not suggest one su perior treatment for prevention and control of chemotherapyinduced nausea and vomiting. For people receiving MEC, synthesised evidence does not suggest superiority for treatments including both NK, and 5 -HT, inhibitors when compared to treatments including 5-HT, inhibitors only. Rather, the results of our NMA suggest that the choice of 5 -HT, inhibitor may have an impact on treatment efficacy in preventing CINV. When interpreting the results of this systematic review, it is important for the reader to understand that NMAs are no substitute for direct head -to -head comparisons, and that results of our NMA do not necessariEy rule out differences that could be c[inica Ely re[evant for some individuals.

Background Multiple myeloma is a bone marrow-based hematological malignancy accounting for approximately two per cent of cancers. First-line treatment for transplant-ineligible individuals consists of multiple drug combinations of bortezomib (V), tenalidomide (R), or thalidomide (T). However, access to these medicines is restricted in many countries worldwide. Objectives To assess and compare the effectiveness and safety of multiple drug combinations of V. R, and T for adults with newly diagnosed transplant-ineligible multiple myeloma and to inform an application for the inclusion of these medicines into the World Health Organization's (WHO) list of essential medicines. Search methods We searched CENTRAL and MEDLI NE, conference proceedings and study registries on 14 February 2019 for randomised controlled trials (RCTs) comparing multiple drug combinations of V, R and 7 for adults with newly diagnosed transplant-ineligible multiple myeloma. Selection criteria We included RCTs comparing combination therapies of V, R, and T, plus melphatan and prednisone (MP) or dexamethasone (D) for first-line treatment of adults with transplant-ineligible multiple myeloma. We excluded trials including adults with relapsed or refractory disease, trials comparing drug therapies to other types of therapy and trials including second-generation novel agents. Data collection and analysis Two review authors independently extracted data and assessed risk of bias of included trials. As effect measures we used hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and risk ratios (RRs) for adverse events. An HR or RR < 1 indicates an advantage for the intervention compared to the main comparator MR Where available, we extracted quality of life (QoL) data (scores of standardised questionnaires). Results quoted are from network meta-analysis (N MA) unless stated. Main results We included 25 studies (148 references) comprising 11,403 participants and 21 treatment regimens. Treatments were differentiated be tween restricted treatment duration (treatment with a pre-specified amount of cycles) and continuous therapy (treatment administered until disease progression, the person becomes intolerant to the drug, or treatment given for a prolonged period). Continuous therapies are indicated with a "c". Risk of bias was generally high across studies due to the open-label study design. Overall survival (OS) Evidence suggests that treatment with RD (HR 0.63 (95% confidence interval (Cl) 0.40 to 0.99), median OS 55.2 months (35.2 to 87.0)); IMP (HR 0.75 (95% C10.58 to 0.97), median OS' 46.4 months (35,9 to 60.0)); and VRDc (HR 0.49 (95% Cl 0.26 to 0.92), median OS 71.0 months (37.8 to 133.8)) probably increases survival compared to median reported OS of 34.8 months with MP (moderate certainty). Treatment with VMP may result in a large increase in OS, compared to MP (HR 0.70 (95%CI 0.45 to 1.07), median OS 49.7 months (32.5 to 77.3)), low certainty). Progression-free survival (PFS) Treatment withRD (HR 0.65 (95% 00.44 to 0.96), median PFS: 24.9 months (16.9 to 36.8)); TMP (HR 0.63 (95% Cl 0.50 to 0.78), median PFS:25,7 months (20.8 to 32.4)); VMP (HR 0.56 (95% Cl 0.35 to 0.90), median PFS: 28.9 months (18.0 to 46.3)); and VRDc (HR 0.34(95% Cl 0.20 to 0.58), median PFS: 47.6 months (27.9 to 81.0)) may result in a large increase in PFS (low certainty) compared to MP (median reported PFS: 16.2 months). Adverse events The risk of polyneuropathies may be lower with RD compared to treatment with MP (RR 0,57 (95% Cl 0.16 to 1.99), risk for RD: 0.5% (0. 1 to 1.8), mean reported risk for MP: 0.9% (10 of 1074 patients affected), low certainty). However, the Cis are also compatible with no difference or an increase in neuropathies. Treatment with TMP (RR 4.44 (95% C11.77 to 11.11), risk: 4.0% (1.6 to 10.0)) and VMP (RR 88.22 (95% C15.36 to 1451.11), risk: 79.4% (4.8 to 1306.0)) probably results in a large increase in polyneuropathies compared to MP (moderate certainty). No study reported the amount of participants with grade z: 3 polyneuropathies for treatment with VRDc. VMP probably increases the proportion of participants with serious adverse events (SAEs) compared to MP (RR 1.28 (95% C11.06 to 1.54), risk for VMP: 46.2% (38.3 to 55.6), mean risk for MP: 36.1% (177 of 490 patients affected), moderate certainty). RD, TMP, and VRDc were not connected to MP in the network and the risk of SAEs could not be compared. Treatment with RD (RR 4.18 (95% Cl 2.13 to 8.20), NMA-risk: 38.5% (19.6 to 75.4)); and TMP (RR 4.10 (95% Cl 2.40 to 7.01), risk: 37.7% (22.1 to 64.5)) results in a large increase of withdrawals from the trial due to adverse events (high certainty) compared to MP (mean reported risk: 9.2% (77 of 837 patients withdrew)). The risk is probably slightly increased with VMP (RR 1.06 (95% Cl 0.63 to 1.81), risk: 9.75% (5.8 to 16.7), moderate certainty), while it is much increased with VRDc (RR 8.92 (95%CI 3,82 to 20.84), risk: 82.1% (35.1 to 191.7), high certainty) compared to MR Quality of life QoL was reported in four studies for seven different treatment regimens (MP, MPc, RD, RMP, RMPc, TMP, TMPc) and was measured with four different tools. Assessment and reporting differed between studies and could not be meta-analysed. However, all studies reported an improvement of QoL after initiation of anti-myeloma treatment for all assessed treatment regimens: Authors' conclusions Based on our four pre-selected comparisons of interest, continuous treatment with VRD had the largest survival benefit compared with MP, while RD and TMP also probably considerably increase survival. However, treatment combinations of V, R, and T also substantially increase the incidence of AEs, and lead to a higher risk of treatment discontinuation. Their effectiveness and safety profiles may best be analysed in further randomised head-to-head trials. Further trials should focus on consistent reporting of safety outcomes and should use a standardised instrument to evaluate QoL to ensure comparability of treatment-combinations.

BACKGROUND:Cost-of-illness (CoI) studies are important instruments for estimating the socioeconomic burden of specified diseases. CoI studies provide important information about the cost structure of a disease, the resulting research need, approaches to improve aspects of care and, monetary consequences from different perspectives. This information can be useful for healthcare research and health policy. Due to heterogeneity of available Cost-of-Illness studies, the working group 'Health Economics' of the German Network for Healthcare Research (DNVF) in accordance with the German Society for Health Economics (DGGÖ) developed an instrument for the planning, conduct and assessment of CoI studies. METHODS:The checklist was developed based on a systematic literature search of published national and international checklists as well as guidelines and recommendations for development and assessment of CoI studies and health economic evaluations. Structure and subject matter of the generic checklist was designed, approved and, finally, examined in a pretest by the working group. RESULTS:Based on the results of the literature search (n=2 454), 58 articles were used for the identification of relevant criteria for the checklist. With respect to the results of the pretest, 6 dimensions were included in the checklist: (i) general aspects, (ii) identification of resources, (iii) description and quantification of resource consumption, (iv) valuation of resources (v) analysis and presentation of results and (vi) discussion and conclusion. In total, the 6 dimensions were operationalized through 37 items. CONCLUSION:This checklist is an initial approach to improve transparency and understanding of CoI studies in terms of the extent, structure and development of the socioeconomic burden of diseases. The checklist supports the comparability of different studies and facilitates study conception.