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Background/purpose: Three first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely available to treat advanced lung adenocarcinoma harboring EGFR mutation. However, studies comparing efficacy or effectiveness of these EGFR TKIs came out with inconclusive results. Methods: In this real-world data analysis with a nationwide retrospective cohort design, adult patients with newly diagnosed advanced lung adenocarcinoma with EGFR mutation between 2011 and 2016, who received a first-line EGFR TKI, were included. Overall survival (OS) and time to next treatment (TTNT) were compared between patients receiving different EGFR TKIs after overlap weighting. Results: We enrolled 10,431 patients, including 6,230, 2,359, and 1842 in gefitinib, erlotinib, and afatinib groups, respectively. The median (95% confidence interval [CI]) OS were 24.2 (22.9–26.2), 25.7 (24.0–27.9), and 29.1 (25.8–32.1) months for those receiving gefitinib, erlotinib, and afatinib, respectively (p = 0.001). The hazard ratios (95% CI) for the afatinib group were 0.85 (0.74–0.98) and 0.91 (0.79–1.05) comparing with the gefitinib and erlotinib groups, respectively. The median (95% CI) TTNT were 10.9 (10.4–11.2), 11.7 (11.3–12.1), 13.4 (12.5–14.3) months for those receiving gefitinib, erlotinib, and afatinib, respectively (p

Objective To examine patient experience, views, and opinions regarding the ineffectiveness of the current knee osteoarthritis (OA) treatments. Methods Nominal groups were conducted with consecutive clinic patients with knee OA, oversampling African Americans. Patients discussed and rank-ordered their concerns. Results Fourteen nominal groups with 48 knee OA patients were conducted with a mean age of 60.6 years (standard deviation, 9.8) and a knee OA duration of 7.8 years (sd, 5.4); 25% were men, and 54% were African American. The most frequently cited highly ranked concerns for the ineffectiveness of current knee OA treatments were as follows: (1) medication-related—(A) side effects (3 groups; 4% vote), (B) limited efficacy (5 groups; 11% vote), (C) medication not targeting underlying disease (7 groups; 16% vote), (D) lack of personalized medication use (3 groups; 4% vote), (E) temporary benefit (3 groups; 6% vote), and (F) fear of addiction/natural treatment preference (2 groups; 3% vote); (2) exercise/physical therapy-related—(G) exacerbation of joint pain (1 group; 3% vote), (H) difficulty in doing exercises (2 groups; 2% vote), (I) lack of motivation (8 groups; 12% vote), (J) technical challenges/lack of personalized exercise regimens (1 group; 1% vote), and (K) cost (2 groups; 3% vote); and (3) weight loss-related—(L) difficulty in achieving weight loss (4 groups; 6% vote) and (M) motivation (1 group; 1% vote). Conclusions A representative sample of participants with knee OA identified several barriers to the effectiveness of current knee OA treatments. This new knowledge provides insights for making the current treatment options potentially more usable and/or more effective.

Enhanced external counterpulsation (EECP) is believed to be a non-invasive treatment for coronary artery disease and angina. The aim of this study was to determine the safety and effectiveness of EECP in refractory angina patients through a systematic reviews and meta-analysis. We conducted a comprehensive search of the literature published on PubMed, Cochrane library, Scopus, ScienceDirect, Trip Database and Google Scholar databases using appropriate keywords and specific strategy with no time limit. Having selected and screened the studies based on the defined inclusion and exclusion criteria and evaluating their quality based on the Cochrane checklist. For the meta-analysis,the Mantel-Haenszel method or the generic Inverse Variance was used. Analyses were done with Review Manager 5.2 software. A number of 299 studies were initially reviewed and finally, seventeen studies were included in the meta-analysis based on the inclusion and exclusion criteria. Also, thirteen outcomes were analyzed and the results of meta-analysis in twelve outcomes including (Systolic Blood Pressure (7 studies), Diastolic Blood Pressure (7 studies), Pulse Pressure (4 studies), Mean Arterial Pressures (4 studies), Heart Rate (6 studies), Angina episodes (7 studies), Walking distance (2 studies),Canadian Cardiovascular Society classification (6 studies), Flow-Mediated Dilation (3 studies), Daily Nitrate Usage (4 studies), Exercise Treadmill Test-Time (2 studies), ST-segment depression (2 studies)demonstrated a significant clinical advantage in the EECP treatment effectiveness in patients with angina. No significant difference was observed regarding EECP usefulness (P = 0.18) in the outcome of brachial artery diameter (2 studies). Based on the meta-analysis, the results indicate the safety and effectiveness of EECP in patients with angina pectoris and indicate the usefulness of this treatment in these patients. In general, the authors believe that the general conclusion in this regard requires some studies with a large sample size and a control group assignment.

With increasing population aging and prevalence of type 2 diabetes (T2D) worldwide, prevention of diabetic complications remains a major unmet need. While cardiovascular outcomes of diabetes are improving over time, diabetic kidney disease (DKD) still leads to an exceedingly high rate of end-stage kidney disease (ESKD). A game-changing opportunity is offered by treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors. Randomized controlled trials (RCTs) have indisputably shown that SGLT2 inhibitors reduce the rate of DKD progression, the decline in estimated glomerular filtration rate (eGFR), and the development of ESKD. In parallel, SGLT2 inhibitors improve cardiovascular outcomes, especially the risk of hospitalization for heart failure. Real-world studies (RWSs) have largely confirmed the findings of RCTs in broader populations of subjects with T2D followed under routine care. In the present paper, we review RWSs exploring the renal effects of SGLT2 inhibitors and highlight the most critical challenges that can be encountered in designing and conducting such studies. Channelling bias (confounding by indication), time-lag bias, conditioning on the future, database heterogeneity, linearity of eGFR change over time, and duration of observation are critical issues that may undermine the robustness of RWS findings. We then elaborate on the new opportunities to overcome such limitations by describing the design and objectives of the DARWIN (DApagliflozin Real-World evIdeNce)-Renal study, a new RWS promoted by the Italian Diabetes Society. Fine-tuning of methods for comparative observational research will improve evidence derived from RWSs on the renal effects of SGLT2 inhibitors, aiding the evolving discussion regarding the place of SGLT2 inhibitors in T2D treatment algorithms in different stages of DKD.

Integrated strategies of community health promotion (ISCHP) are based on intersectoral collaborations using the Health in All Policies approach to address determinants of health. While effects on health determinants have been shown, evidence on the effectiveness of ISCHP on health outcomes is scarce. The aim of this study is to assess the long-term effects of ISCHP on diabetes mellitus mortality (DMM) in German communities. A nonrandomized evaluation based on secondary county-level official data (1998–2016) was performed. In April 2019, 149 communities in Germany with ISCHP out of 401 were identified. Communities with

ObjectivesThe History, ECG, Age, Risk Factors and Troponin (HEART) Score is a decision support tool applied by physicians in the emergency department developed to risk stratify low-risk patients presenting with chest pain. We assessed the potential value of this tool in prehospital setting, when applied by emergency medical services (EMS), and derived and validated a tool adapted to the prehospital setting in order to determine if it could assist with decisions regarding conveyance to a hospital.MethodsIn 2017, EMS personnel prospectively determined the HEART Score, including point-of-care (POC) troponin measurements, in patients presenting with chest pain, in the north of the Netherlands. The primary endpoint was a major adverse cardiac event (MACE), consisting of acute myocardial infarction or death, within 3 days. The components of the HEART Score were evaluated for their discriminatory value, cut-offs were calibrated for the prehospital setting and sex was substituted for cardiac risk factors to develop a prehospital HEART (preHEART) Score. This score was validated in an independent prospective cohort of 435 patients in 2018.ResultsAmong 1208 patients prospectively recruited in the first cohort, 123 patients (10.2%) developed a MACE. The HEART Score had a negative predictive value (NPV) of 98.4% (96.4–99.3), a positive predictive value (PPV) of 35.5% (31.8–39.3) and an area under the receiver operating characteristic curve (AUC) of 0.81 (0.78–0.85). The preHEART Score had an NPV of 99.3% (98.1–99.8), a PPV of 49.4% (42.0–56.9) and an AUC of 0.85 (0.82–0.88), outperforming the HEART Score or POC troponin measurements on their own. Similar results were found in a validation cohort.ConclusionsThe HEART Score can be used in the prehospital setting to assist with conveyance decisions and choice of hospitals; however, the preHEART Score outperforms both the HEART Score and single POC troponin measurements when applied by EMS personnel in the prehospital setting.

Nine drug-resistant TB centres, some of them supported by Damien Foundation in Nepal where80% of multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB) patients are treated.To assess the uptake, effectiveness and safety of the 9-12-month shorter treatment regimen (STR) in MDR/RR-TB patients registered from January 2018 to December 2019.This was a cohort study involving secondary programme data.Of 631 patients, 301 (48.0%) started and continued STR. Key reasons for ineligibility to start/continue STR were baseline resistance or exposure to second-line drugs (62.0%), contact with extensively drug-resistant TB (XDR-TB) or pre-XDR-TB (7.0%) patients and unavailability of STR drugs (6.0%). Treatment success was 79.6%; unsuccessful outcomes were death (12.0%), lost to follow-up (5.3%), failure (2.7%) and not evaluated (0.7%). Unsuccessful outcomes were significantly associated with HIV positivity and patient age ⩾55 years, with adjusted relative risk of respectively 2.39 (95% CI 1.52-3.77) and 3.86 (95% CI 2.30-6.46). Post-treatment recurrence at 6 and 12 months was respectively 0.5% and 2.4%. Serious adverse events (SAEs) were seen in 15.3% patients - hepatotoxicity and ototoxicity were most common.STR had a modest uptake, high treatment success and low post-treatment recurrence. For proper detection and management of SAEs, improving pharmacovigilance might be considered. Availability of rapid diagnostic test for second-line drugs is crucial for correct patient management.Neuf centres de traitement de la TB pharmacorésistante, dont certains sont financés par Action Damien au Népal où80% des patients atteints de TB multirésistante/résistante à la rifampicine (MDR/RR-TB) sont traités.Évaluer l’utilisation, l’efficacité et l’innocuité d’un schéma thérapeutique plus court (STR) de 9-12 mois chez les patients atteints de MDR/RR-TB enregistrés de janvier 2018 à décembre 2019.Étude de cohorte comprenant des données programmatiques secondaires.Sur 631 patients, 301 (48,0%) ont démarré et poursuivi un STR. Les raisons principales d’inéligibilité à l’instauration/la poursuite d’un STR étaient une résistance initiale ou une exposition aux médicaments de deuxième intention (62,0%), un contact avec des patients atteints de TB ultrarésistante (XDR-TB) ou de pré-XDR-TB (7,0%) et la non-disponibilité des médicaments pour le STR (6,0%). Le taux de réussite thérapeutique était de 79,6%. Les résultats liés à la non-réussite thérapeutique étaient décès (12,0%), perte de vue (5,3%), échec thérapeutique (2,7%) et absence d’évaluation (0,7%). Les résultats liés à la non-réussite thérapeutique étaient significativement associés à l’infection par le VIH et aux patients âgés ⩾55 ans avec un risque relatif ajusté de 2,39 (IC 95% 1,52–3,77) et de 3,86 (IC 95% 2,30–6,46), respectivement. Le taux de récidive post-traitement à 6 et 12 mois était de 0,5% et 2,4%, respectivement. Des évènements indésirables graves (SAE) ont été observés chez 15,3% des patients, le plus souvent hépatotoxicité et ototoxicité.Le STR a été associé à une utilisation modérée, à une réussite thérapeutique élevée et à un faible taux de récidive post-traitement. Pour une détection et une prise en charge adéquates des SAE, l’amélioration de la pharmacovigilance peut être envisagée. La disponibilité de tests diagnostiques rapides pour les médicaments de deuxième intention est essentielle à une prise en charge adéquate des patients.

The incidence of bleeding is increased in high risk patients with critical conditions in Intensive Care Unit (ICU). Appropriate prophylaxis medicine is necessary to reduce the incidence of stress ulcer bleeding during hospitalization in ICU which further can minimize the cost of patient care in the ICU. Currently, lansoprazole and pantoprazole are used as a stress ulcers prophylaxis. Nevertheless, there has not been sufficient evidence proving their effectiveness. This study was aimed to compare the effectiveness and cost between iv lansoprazole and iv pantoprazole as a stress ulcer prophylaxis in ICU. In this retrospective observational study, the data were obtained from medical records of all patients admitted to ICU in a District Hospital in Yogyakarta from January 2014 until December 2016. Effectiveness of therapy were obtained from objective data in the medical record by looking at the incidence of major (clinically significant) and minor (overt gastrointestinal) bleeding. Chi-square analysis was performed to analyze the difference of bleeding incidence. The average cost was presented as Expected Monetary Value (EMV), which consisted of the cost of prophylaxis and treatment of bleeding. The difference in average cost was analyzed using independent t-test. A total of 119 patients were included in this study. There were 62 patients in the lansoprazole group and 47 patients in the pantoprazole group. Forty eight patients (77,4%) from lansoprazole group and 35 patients (61,4%) from pantoprazole group did not experience any GI bleeding. There was no statistical difference in the incidence of GI bleeding between the two groups (CI 95%, P-value = 0.057). The EMV of lansoprazole group was higher than pantoprazole group IDR 645.122,57 and IDR 511.629,39 respectively. In conclusion, there was no significant difference regarding the effectiveness between iv lansoprazole and iv pantoprazole as stress ulcer prophylaxis. Costs for the prophylaxis of stress ulcers is lower on the use of pantoprazole compared to lansoprazole.

Aim To assess the effect of different non‐pharmacological interventions on cancer‐related fatigue (CRF) in breast cancer (BC) patients and identify the most effective method for improving CRF. Design A systematic review and network meta‐analysis. Methods Literature will be searched in the ongoing trail in the Clinical Trials.gov, World Health Organization, the International Clinical Trials Registry Platform, Cochrane Library, PubMed, EMBASE, Web of Science and CINAHL, from the inception until December 31, 2020. Two independent researchers will rigorously screen the literature according to the inclusion and exclusion criteria and assess the risk of bias based on the Cochrane Collaboration's Tool of RCTs. Stata 13.0 and Aggregate Data Drug Information System will be used for data analysis. Results This protocol has been registered on the PROSPERO website (registration number is CRD42020222093). This study will provide the reliable evidence of the most effective non‐pharmacological intervention to improving CRF.

Aim We aimed to compare cardiovascular outcomes of patients with type 2 diabetes (T2D) who initiated GLP-1 receptor agonists (GLP-1RA) or basal insulin (BI) under routine care. Methods We accessed the administrative claims database of the Veneto Region (Italy) to identify new users of GLP-1RA or BI in 2014–2018. Propensity score matching (PSM) was implemented to obtain two cohorts of patients with superimposable characteristics. The primary endpoint was the 3-point major adverse cardiovascular events (3P-MACE). Secondary endpoints included 3P-MACE components, hospitalization for heart failure, revascularizations, and adverse events. Results From a background population of 5,242,201 citizens, 330,193 were identified as having diabetes. PSM produced two very well matched cohorts of 4063 patients each, who initiated GLP-1RA or BI after an average of 2.5 other diabetes drug classes. Patients were 63-year-old and only 15% had a baseline history of cardiovascular disease. During a median follow-up of 24 months in the intention-to-treat analysis, 3P-MACE occurred less frequently in the GLP-1RA cohort (HR versus BI 0.59; 95% CI 0.50–0.71; p Conclusions Patients with T2D who initiated a GLP-1RA experienced far better cardiovascular outcomes than did matched patients who initiated a BI in the same healthcare system. These finding supports prioritization of GLP-1RA as the first injectable regimen for the management of T2D.

Introduction: INTELLiVENT–Adaptive Support Ventilation (INTELLiVENT–ASV), an advanced closed–loop ventilation mode for use in intensive care unit (ICU) patients, is equipped with algorithms that automatically adjust settings on the basis of physiologic signals and patient’s activity. Here we describe its effectiveness, safety, and efficacy in various types of ICU patients. Areas covered: A systematic search conducted in MEDLINE, EMBASE, the Cochrane Central register of Controlled Trials (CENTRAL), and in Google Scholar identified 10 randomized clinical trials. Expert opinion: Studies suggest INTELLiVENT–ASV to be an effective automated mode with regard to the titrations of tidal volume, airway pressure, and oxygen. INTELLiVENT–ASV is as safe as conventional modes. However, thus far studies have not shown INTELLiVENT–ASV to be superior to conventional modes with regard to duration of ventilation and other patient–centered outcomes. Future studies are needed to test its efficacy.

Background While evidence-based psychotherapy (EBP) for posttraumatic stress disorder (PTSD) is a first-line treatment, its real-world effectiveness is unknown. We compared cognitive processing therapy (CPT) and prolonged exposure (PE) each to an individual psychotherapy comparator group, and CPT to PE in a large national healthcare system. Methods We utilized effectiveness and comparative effectiveness emulated trials using retrospective cohort data from electronic medical records. Participants were veterans with PTSD initiating mental healthcare (N = 265 566). The primary outcome was PTSD symptoms measured by the PTSD Checklist (PCL) at baseline and 24-week follow-up. Emulated trials were comprised of ‘person-trials,’ representing 112 discrete 24-week periods of care (10/07–6/17) for each patient. Treatment group comparisons were made with generalized linear models, utilizing propensity score matching and inverse probability weights to account for confounding, selection, and non-adherence bias. Results There were 636 CPT person-trials matched to 636 non-EBP person-trials. Completing ⩾8 CPT sessions was associated with a 6.4-point greater improvement on the PCL (95% CI 3.1–10.0). There were 272 PE person-trials matched to 272 non-EBP person-trials. Completing ⩾8 PE sessions was associated with a 9.7-point greater improvement on the PCL (95% CI 5.4–13.8). There were 232 PE person-trials matched to 232 CPT person-trials. Those completing ⩾8 PE sessions had slightly greater, but not statistically significant, improvement on the PCL (8.3-points; 95% CI 5.9–10.6) than those completing ⩾8 CPT sessions (7.0-points; 95% CI 5.5–8.5). Conclusions PTSD symptom improvement was similar and modest for both EBPs. Although EBPs are helpful, research to further improve PTSD care is critical.

Background In the densely populated slums of Kolkata, informal healthcare providers’ (IHP) diarrhea-related knowledge and rationality of practices should be improved to reduce risk of adverse outcome, expenditure, and antimicrobial resistance. Methods A multicomponent intervention was conducted among 140 representative IHPs in the slums of 8 wards in Kolkata to assess its impact on their diarrhea-related knowledge and practice. Six intervention modules in local languages were provided (1 per month) with baseline (N = 140) and postintervention (N = 124) evaluation. Results Mean overall (61.1 to 69.3; P Conclusions Multicomponent educational intervention resulted in sustainable improvement in diarrhea-related knowledge and practices among IHPs in slums of Kolkata. Policy implications should be advocated along with implementation and scale-up.

Objective To explore whether the deqi effect affects the effectiveness of manual acupuncture for treating knee osteoarthritis by a network meta-analysis (NMA). Methods Eight databases were searched for relevant published studies since inception through January 2021. Randomized control trials that compared manual acupuncture with deqi, manual acupuncture without deqi, and conventional treatment of western medicine were included. Languages were limited to English and Chinese. Two authors independently selected eligible studies, assessed methodological quality and the effects of deqi, and extracted outcome data. The mean difference (MD) and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated by Stata 15.0 to conduct an NMA based on a frequentist framework. Results Fourteen trials with a total of 1868 subjects were included. The direct and indirect comparisons were authentic, according to inconsistency tests. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pooled results indicated that there was no significant effect of deqi (SMD = −0.23, 95% CI [−0.81, 0.35]). The pooled results of visual analogue scale (VAS) were similar to those of WOMAC (MD = −0.53, 95% CI [−1.03, 0.02]). Conclusion As a summary of the currently available research, the NMA results indicated that deqi effect might not be the crucial factor for the effectiveness of manual acupuncture.

Background The Communities That Care (CTC) prevention planning and implementation system trains communities throughout a five-phase cycle to (1) build capacity for prevention, (2) adopt science-based prevention, (3) assess the prevention needs of adolescents living in the community, (4) select, and (5) implement evidence-based programs according to their needs. After CTC proved to be effective and cost-effective in the U.S., it is being used by an increasing number of communities in Germany. The aim of this study is to evaluate the effectiveness and cost-effectiveness of CTC in Germany. Methods Communities in CTC-phases 1 to 3 (n = 21) and individually-matched comparison communities (n = 21) were recruited for a non-randomised trial. To assess long-term outcomes, (1) a cohort of 5th Grade students will be surveyed biennially concerning behaviours (antisocial behaviour and substance use) and well-being as well as risk and protective factors. Additionally, (2) biennial cross-sectional surveys will be conducted in 6th, 8th, 10th, and 11th Grade in each community. To assess short-term outcomes, a cohort of ten key informants per community will be surveyed biennially concerning adoption of science-based prevention, collaboration, community support and community norms. (4) In a cross-sectional design, all ongoing prevention programs and activities in the communities will be assessed biennially and data will be collected about costs, implementation and other characteristics of the programs and activities. (5) To monitor the CTC implementation, the members of the local CTC-boards will be surveyed annually (cross-sectional design) about team functioning and coalition capacity. Data analysis will include general and generalised mixed models to assess the average treatment effect of CTC. Mediation analyses will be performed to test the logical model, e.g., adoption of science-based prevention as a mediator for the effectiveness of the CTC approach. Discussion This is the first controlled study to evaluate the effectiveness of a comprehensive community prevention approach in Germany. Evaluating the effectiveness of CTC in Germany is an important prerequisite for further diffusion of the CTC approach. Trial registration This study was registered with German Clinical Trial Register: DRKS00022819 on Aug 18, 2021.

The prevalence of metabolic syndrome among individuals with severe mental illness is considerably higher than in the general population, contributing to the 15–20-year shorter life expectancy of this client population. The aim of this pilot study was to evaluate the effectiveness of a novel, complex psychosocial program to reduce metabolic syndrome. Members of both the intervention (n = 78) and control (n = 31) group were psychiatric outpatients with severe/persistent mental illness struggling with one or more symptoms of metabolic syndrome. Beyond the default elements of similar programs such as diet and exercise, the intervention covered medication use, sleep hygiene, stress management, as well as addressing spiritual needs, mindfulness, addictions, and self-care. Assessment of metabolic indicators were completed at baseline, at the end of the 11-week intervention, and 6 months post-intervention. The trajectory of change over time was significantly more favorable in the treatment than in the control group in terms of waist circumference (p = 0.013, η2 = 0.093) and a positive trend emerged in relation to blood glucose level (p = 0.082, η2 = 0.057). However, no statistically reliable difference was observed between the intervention and the control group regarding the other outcome variables (body mass index, systolic and diastolic blood pressure, serum triglyceride level, serum HDL cholesterol level, overall metabolic syndrome severity). These findings suggest that to produce more robust benefits, psychosocial interventions targeting the metabolic health of individuals with complex mental health needs should be either longer in duration if resources permit or narrower in focus (diet and exercise mainly) if resources are scarce. Supplementary Information The online version contains supplementary material available at 10.1007/s12144-021-02269-3.

Objective To assess the protective effect of exclusive breastfeeding and the effectiveness of maternal vaccination in reducing pertussis-like illness. Method This was a case-control study conducted in sentinel hospitals for pertussis in Recife between July 2016 and July 2018. Cases included children aged under six months with symptoms compatible with pertussis (pertussis-like illness). Controls included children aged under six months, living in the metropolitan region of Recife with no diagnosis of pertussis-like illness and matched by the same hospital and birth date. Results Seventy-three cases and 194 controls were included. The diagnosis of pertussis-like illness was predominantly clinical (97,2%). Amongst the main symptoms, paroxysmal cough was observed in 95.89% of cases and vomiting in 53.4%. There were 29 hospitalized cases and no deaths. Out of the 73 cases, 47 were born to mothers vaccinated against pertussis during pregnancy, and the mothers of 144 of the 194 controls had been vaccinated. The protective effect of breastfeeding was of 74% (95% CI;38%, 89%). Children younger than six months, who were exclusively breastfed and with mothers vaccinated against pertussis during pregnancy were 5 times less likely to develop pertussis-like illness, corresponding to a protection of 79% (95% CI;31%, 94%). The effectiveness of maternal vaccination against pertussis-like illness in children under six months was low (27%) and not statistically significant (CI 95%; −34% a 60%). Conclusions Exclusive breastfeeding protects children under six months from pertussis-like illness and may be enhanced when associated with maternal vaccination. These strategies should be encouraged because they also protect against pertussis-like illnesses.

Background and objective Some studies observed a benefit of PD patients after treatment with safinamide in some non-motor symptoms. Our aim was to analyze the effectiveness of safinamide on sleep and daytime sleepiness in Parkinson’s disease (PD) patients. Material and methods SAFINONMOTOR is a prospective open-label single-arm study conducted in 5 centers from Spain. In this analysis, a secondary objective of the study, the score in the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) at V1 (baseline) and V4 (6 months ± 1 month) were compared. Results Fifty patients were included between May/2019 and February/2020 (age 68.5 ± 9.12 years; 58% women; 6.4 ± 5.1 years from diagnosis). At 6 months, 44 patients completed the follow-up (88%). The PSQI total score was reduced by 19.8% (from 10.43 ± 4.02 at V1 to 8.36 ± 4.41 at V4; p = 0.001). By domains, improvement was observed in subjective sleep quality (PSQI-C1; − 23.9%; p = 0.009), sleep latency (PSQI-C2; − 25%; p = 0.025), sleep duration (PSQI-C3; − 40%; p = 0.001), and habitual sleep efficiency (PSQI-C4; − 25.9%; p = 0.023). A significant reduction (− 24.7%) in the ESS total score from V1 to V4 was observed as well (from 9.20 ± 5.64 to 6.93 ± 5.11; p = 0.012). Specifically, the improvement in daytime sleepiness was observed in sitting and reading (p = 0.024) and sitting inactive in a public space (p = 0.027). A total of 21 adverse events in 11 patients (22%) were reported, 5 of which were severe (not related to safinamide). Conclusion Safinamide was well-tolerated and improved sleep and daytime sleepiness in PD patients at 6 months. Supplementary Information The online version contains supplementary material available at 10.1007/s10072-021-05607-2.

Background/aim The purpose of this study was to compare efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) and gemcitabine-cisplatin as first-line therapy in patients with pancreatic cancer. Materials and methods Pancreaticobiliary cancer patients who had Eastern Cooperative Oncology Group performance status score of 0 or 1 (on a scale of 0 to 5, with higher scores indicating greater severity of illness) were evaluated to receive folfirinox or gemcitabine plus cisplatin. The primary endpoints were progression-free and overall survival time. Safety analysis was also evaluated as secondary measures. Results There were 32 patients in the folfirinox group and 36 patients in the gemcitabine-cisplatin group. The median overall survival was 18.1 months (7.5–28.7) in the folfirinox group as compared with 9.7 months (6.5–13) in the gemcitabine-cisplatin group (p = 0.009). Median progression-free survival was 16.2 months (9–23.4) in the folfirinox group and 6.9 months (6.1–7.6) in the gemcitabine-cisplatin group (p = 0.001). Conclusion Folfirinox is an option for the first-line treatment of patients with pancreatic cancer and good performance status.

We performed a systematic review and meta-analysis for the effectiveness of Favipiravir on the fatality and the requirement of mechanical ventilation for the treatment of moderate to severe COVID-19 patients. We searched available literature and reported it by using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Until June 1, 2021, we searched PubMed, bioRxiv, medRxiv, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar by using the keywords “Favipiravir” and terms synonymous with COVID-19. Studies for Favipiravir treatment compared to standard of care among moderate and severe COVID-19 patients were included. Risk of bias assessment was performed using Revised Cochrane risk of bias tool for randomized trials (RoB 2) and ROBINS-I assessment tool for non-randomized studies. We defined the outcome measures as fatality and requirement for mechanical ventilation. A total of 2702 studies were identified and 12 clinical trials with 1636 patients were analyzed. Nine out of 12 studies were randomized controlled trials. Among the randomized studies, one study has low risk of bias, six studies have moderate risk of bias, and 2 studies have high risk of bias. Observational studies were identified as having moderate risk of bias and non-randomized study was found to have serious risk of bias. Our meta-analysis did not reveal any significant difference between the intervention and the comparator on fatality rate (OR 1.11, 95% CI 0.64–1.94) and mechanical ventilation requirement (OR 0.50, 95% CI 0.13–1.95). There is no significant difference in fatality rate and mechanical ventilation requirement between Favipiravir treatment and the standard of care in moderate and severe COVID-19 patients.

Objective Mexico has the second largest prevalence of obesity among adults worldwide, a condition especially affecting the low-income population. There is a pressing need to improve therapeutic options for weight loss. Phentermine is an old and low-cost agent given as an adjuvant therapy for obesity for a 12-week period, at an initial dose of 15 mg or 30 mg. However, there are no precise guidelines on the suitability of both the starting dose and the continuation of treatment for 6 months. The aim of this study was to evaluate the 3- and 6-month efficacy and safety of phentermine in obese Mexican patients to elucidate the aforementioned. Materials and methods In this prospective, multi-center, open-label study, 932 obese adults received 15 mg or 30 mg phentermine once daily for 6 months. Results 30 mg phentermine was more effective than 15 mg phentermine in improving anthropometric variables in the 3-month follow-up, but not after completing the 6-month treatment period. Nearly 40% of 3-month non-responders reached a body weight reduction of at least 5% at 6 months. Conversely, ~ 65% and 25% of 3-month responders maintained or improved, respectively, their body weight reduction with long-term phentermine. Potential tolerance as weight regain was ~ 10% from 3 to 6 months. None of the doses increased cardiovascular risk, although mild-to-moderate adverse events were more frequent with 30 mg phentermine. Conclusion 30 mg phentermine was more effective than 15 mg phentermine after 3 months, but not at 6 months of treatment. An important number of subjects could benefit following the therapy from 3 to 6 months.

BACKGROUND: The global pandemic coronavirus disease 2019 (COVID-19) has become a major public health problem and presents an unprecedented challenge. However, no specific drugs were currently proven. This study aimed to evaluate the comparative efficacy and safety of pharmacological interventions in patients with COVID-19. METHODS: Medline, Embase, the Cochrane Library, and clinicaltrials.gov were searched for randomized controlled trials (RCTs) in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/SARS-CoV. Random-effects network meta-analysis within the Bayesian framework was performed, followed by the Grading of Recommendations Assessment, Development, and Evaluation system assessing the quality of evidence. The primary outcome of interest includes mortality, cure, viral negative conversion, and overall adverse events (OAEs). Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size. RESULTS: Sixty-six RCTs with 19,095 patients were included, involving standard of care (SOC), eight different antiviral agents, six different antibiotics, high and low dose chloroquine (CQ_HD, CQ_LD), traditional Chinese medicine (TCM), corticosteroids (COR), and other treatments. Compared with SOC, a significant reduction of mortality was observed for TCM (OR = 0.34, 95% CI: 0.20-0.56, moderate quality) and COR (OR = 0.84, 95% CI: 0.75-0.96, low quality) with improved cure rate (OR = 2.16, 95% CI: 1.60-2.91, low quality for TCM; OR = 1.17, 95% CI: 1.05-1.30, low quality for COR). However, an increased risk of mortality was found for CQ_HD vs. SOC (OR = 3.20, 95% CI: 1.18-8.73, low quality). TCM was associated with decreased risk of OAE (OR = 0.52, 95% CI: 0.38-0.70, very low quality) but CQ_HD (OR = 2.51, 95% CI: 1.20-5.24) and interferons (IFN) (OR = 2.69, 95% CI: 1.02-7.08) vs. SOC with very low quality were associated with an increased risk. CONCLUSIONS: COR and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care. CQ_HD might increase the risk of mortality. CQ, IFN, and other antiviral agents could increase the risk of OAEs. The current evidence is generally uncertain with low-quality and further high-quality trials are needed.

Background & aims: Treatment of hepatitis C virus (HCV) by elbasvir/grazoprevir (EBR/GZR) was found to be efficacious and well tolerated in clinical trials. This study aimed to evaluate the effectiveness and tolerability of EBR/GZR in the treatment of HCV genotype 1-infected Taiwanese patients. Methods: Chronic hepatitis C patients infected with GT1b or 1a without resistance-associated substitution, and treated with 12-week EBR/GZR were enrolled from 10 hospitals in Taiwan between August 2017 and December 2018. All clinical and virologic data were collected at each participating center. Primary efficacy endpoint was sustained virologic response at week 12 (SVR12) after end of the EBR/GZR therapy, assessed in the per-protocol population, which excluded patients with important deviations from the protocol. Analysis was also performed based on the modified full analysis set, which included all allocated patients receiving at least 4-week medication. Virologic failure was recorded as breakthrough, nonresponse, or relapse. Safety was assessed through collection of adverse events, physical examination, vital signs, and standard laboratory evaluations. Results: Per protocol SVR12 rates were 99.5% (1169/1175) for all HCV genotype 1 patients. Among patients with stage 4 or 5 chronic kidney diseases, 100% (107/107) achieved SVR12. In univariate analyses, variables associated with SVR12 were treatment termination (P

Endrias Markos Woldesemayat School of Public Health, College of Medicine and Health Sciences, Hawassa University, Hawassa, EthiopiaCorrespondence: Endrias Markos Woldesemayat Email endromark@yahoo.comIntroduction: In Ethiopia, no studies assessing the cost-effectiveness of follow-up of smear-negative chronic coughers in detecting smear-positive tuberculosis (TB) (PTB+) cases have been reported.Objective: This article describes the cost-effectiveness of community-based follow-up of smear-negative chronic coughers in detecting PTB+ cases.Methods: Two alternative strategies of TB case finding, namely community-based follow-up of smear-negative chronic coughers and passive TB case finding, were compared. Participants were selected randomly in the active TB case finding approach, while purposively in the passive TB case finding strategy. In November 2012 and January 2015, costs related to TB diagnosis were collected using structured questionnaires from sample of 60 patients in each strategy. Data on health system cost and direct and indirect costs incurred by patients and their caretakers were collected in Ethiopian Birr and converted into USD for analysis. Exchange rate for the data collection period of chronic coughers was 1 USD = 18.16 ETB and for passive case finding period was 1 USD = 20.24 ETB. Cost-effectiveness was calculated in terms of cost per PTB+ cases detected.Results: The overall cost of TB case finding was lower under active case finding approach than under passive TB case finding approach (USD 27.4 vs. 27.6). Active case finding approach was cost-effective by 43.4% and it is highly cost-effective when the duration of follow-up is reduced to 7 months or less.Conclusion: Active case finding approach is a cost-effective approach of TB case finding. The cost benefit obtained could be even higher when the follow-up duration is minimized.Keywords: cost, effectiveness, chronic coughers, smear-positive TB

Introduction Fire acupuncture is commonly used for the treatment of psoriasis vulgaris, but the efficacy and safety of fire acupuncture for psoriasis vulgaris remain unclear. Methods This systematic review and meta-analysis will be conducted and reported strictly according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five databases including China National Knowledge Infrastructure (CNKI), Wanfang, VIP, Chinese biomedical literature, and Pubmed will be retrieved for potentially eligible studies from their inception to Jan. 2021. All randomized clinical trials comparing fire acupuncture versus no fire acupuncture in the treatment of psoriasis vulgaris will be retrieved and assessed for inclusion. RevMan5.3 software provided by Cochrane collaboration will be used for the analysis. Randomized Clinical Trials Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. The primary endpoint is the total effective rate, the secondary outcomes are the Psoriasis Area Severity Index (PASI) score, the recurrence rate and the adverse reactions. Results This study will systematically evaluate the efficacy and safety of fire acupuncture for psoriasis vulgaris. The results will be published in a peer-reviewed journal. Conclusion This systematic review will evaluate the effects of fire acupuncture in patients with psoriasis vulgaris, thus providing evidence to the clinical application of this therapy.

background：In recent years, platelet-rich plasma has been used in burn wound repair, plastic surgery, bone and tendon ligament injury repair and other treatment at home and abroad. Clinical studies indicate that platelet-rich plasma has a good curative effect on repairing burn wounds. The residual wounds formed after large area severe burns are difficult to cure and have recurrent attacks. Because the action mechanism of platelet-rich plasma is unclear, its clinical efficacy of platelet-rich plasma in repairing severe burn wounds is controversial. And there is no relevant systematic evaluation of platelet-rich plasma in repairing severe burn wounds now. Objective：Meta analysis was used to evaluate the efficacy and safety of platelet-rich plasma in repairing severe burn wounds. Methods：Randomized controlled clinical trial of using platelet-rich plasma to repair severe burn wounds were retrieved by computer WanFang ，China National Knowledge Infrastructure （CNKI），China Science and Technology Journal Database（VIP），China Biology Medicine disc, Embase, PubMed, Web of Science and Cochrane Library from the establishment of the database to September 2020. Two researchers independently extract data and assess the quality of the included literature, and Meta analysis of the included literature is carried out by using RevMan5.3 software. Results：In this study, the efficacy and safety of platelet-rich plasma in repairing severe burn wounds are evaluated from the aspects of wound healing rate, wound healing time, scar index, visual simulation score (VAS), the number of layers of dressing, the number of times of changing gauze, frequency of dressing change, the positive rate of wound bacterial culture and the incidence of inflammatory reaction. Conclusions：Platelet-rich plasma has a good curative effect on the repair of severe burn wounds. This study provides reliable evidence for the clinical use of platelet-rich plasma in the clinical repair of severe burn wounds.

Introduction Golimumab is a human monoclonal antibody that inhibits tumor necrosis factor-α (TNF-α). Inhibition of TNF-α by golimumab inhibits the inflammatory response, thereby modulating the immune response in immune-mediated inflammatory diseases. Although the efficacy of golimumab has been demonstrated in randomized controlled trials (RCTs), various patient populations, such as those at high risk of infection, including those with latent tuberculosis and various comorbidities, or on co-administered medications, were excluded from the RCTs. Therefore, safety cannot be sufficiently evaluated by RCTs in the patient group with heterogenous characteristics. The aim of this study was to assess the safety and effectiveness of golimumab in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondyloarthritis (AS) in a real-world setting in Korea. Methods We conducted an open-label, prospective, non-interventional study as post-marketing surveillance. Safety was evaluated by collecting and recording adverse events, and effectiveness was evaluated by assessing disease activity using DAS28-CRP, DAS28-ESR, ACR20, and ASAS20 outcome measures. Multiple logistic regression was performed to identify factors associated with the incidence of adverse events, and changes in disease activity scores from baseline were analyzed using the Wilcoxon signed-rank test. Results A total 673 patients were enrolled, of whom 621 were included in the safety analysis. During the study, 97 adverse drug reactions (ADRs) were reported in 62 patients (10.0%). The most frequently reported ADRs were related to infection, including nasopharyngitis (0.8%), upper respiratory tract infection (0.6%), and herpes zoster (0.5%). The mean (± standard deviation) changes from baseline in global disease activity at weeks 12 and 24 were − 3.37 ± 2.529 and − 3.68 ± 2.404, respectively, with statistical significance. In those patients with RA, 72.5 and 47.0% of individuals had a good response based on DAS28-CRP and DAS28-ESR outcomes at week 24. At week 24, 71.4% of patients with PsA had an ACR20 response and 72.9% of patients with AS had an ASAS20 response. Conclusion In the real-world setting, golimumab was safe and effective in Korean patients with RA, PsA, and AS. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-021-00352-6.

This systematic review and meta-analysis aimed to determine the effectiveness of brentuximab vedotin (BV) in relapsed/refractory classical Hodgkin lymphoma (R/R cHL) in the clinical practice setting using most recent results. A total of 32 observational studies reporting on treatment patterns, overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and adverse events were found. After four cycles, a random-effect model yielded pooled ORR and CR rates of 62.6% (95% confidence interval (CI): 56.0-68.9; I-2 = 9.7%) and 32.9% (95% CI, 20.8-46.3, I-2 = 64.8%), respectively. Regarding survival, 1-year, 2-year, and 5-year PFS ranged from 52.1% to 63.2%, 45.2% to 56.2%, and 31.9% to 33.0%, respectively. OS rates were 68.2-82.7%, 58.0-81.9%, and 58.0-62.0%, respectively. Most common adverse events were hematological toxicities (neutropenia: 13.3-23%, anemia: 8.8-39.0%, and thrombocytopenia: 4-4.6%), and grade >= 3 peripheral neuropathy (3.3-7.3%). This study supports the effectiveness and safety of BV in R/R cHL patients in the real-world setting.

Introduction: Chronic low back pain (CLBP) is a leading cause of disability, yet there is limited high-quality evidence to identify the most suitable pharmacological therapy. The purpose of this Japanese nationwide, multicenter, prospective study was to compare the effectiveness of four representative drug therapies―acetaminophen, celecoxib, loxoprofen, and a tramadol and acetaminophen (T+A) combination drug―to establish evidence for a drug of choice for CLBP. Methods: Patients with CLBP (N=471) received one of the four treatments and were evaluated, prospectively and comprehensively, once every month for six months using a visual analog scale (VAS) for LBP, the Japanese Orthopedic Association (JOA) score, the JOA Back Pain Evaluation Questionnaire (JOABPEQ), the Roland-Morris Disability Questionnaire (RDQ), the EuroQol five-dimensions three-levels (EQ-5D-3L), and the Short Form-8 item health survey (SF-8). We conducted multivariable linear regression analyses of the four drugs at 1 and 6 months after drug allocation. Differences with P

Background Transesophageal echocardiography (TEE) is a useful tool in preoperative evaluation of patients undergoing transvenous lead extraction (TLE). Hypothesis Echocardiographic phenomena may determine the difficulty and safety of the procedure. Methods Data from 936 transesophageal examinations (TEE) performed at a high volume center in patients awaiting TLE from 2015 to 2019 were assessed. Results TEE revealed a total of 1156 phenomena associated with the implanted leads in 697 (64.85%) patients, including: asymptomatic masses on endocardial leads (AMEL) (58.65%), vegetations (12,73%), fibrous tissue binding the lead to the vein or heart wall (33.76%), lead‐to‐lead binding sites (18.38%), excess lead loops (19.34%), intramural penetration of the lead tip (16.13%) and lead‐dependent tricuspid dysfunction (LDTD) (6.41%). Risk factors for technical difficulties during TLE in multivariate analysis were: fibrous tissue binding the lead to atrial wall (OR = 1.738; p

Introduction Dolutegravir (DTG), a novel HIV-integrase strand transfer inhibitor (INSTI), is usually used with multiple antiretrovirals (ARVs) for treatment of HIV. DTG is now approved as Tivicay tablets in over 120 countries and Triumeq combination tablets (DTG/abacavir [ABC]/lamivudine [3TC]) in over 90 countries. In Japan, these formulations have been marketed since 2014 and 2015. The post-marketing prospective surveillance has been conducted as part of the HIV-Related Drug (HRD) cooperative survey aimed to collect actual drug use information in all of these DTG-treated patients in accordance with conditions for initial approvals. Methods The survey has been conducted to evaluate long-term safety and effectiveness of DTG since 2014, for approximately 6 years. The safety was evaluated by incidence of adverse drug reactions (ADRs) and change in body weight. The effectiveness was evaluated by plasma HIV RNA copies/mL and peripheral CD4+ cell counts. Results Of 2292 patients in 30 Japanese sites, 565 (24.65%) reported ADRs. The most common ADR was blood creatinine increased (4.28%). Incidence of ADRs was statistically significantly higher in patients with severe symptoms (Centers for Disease Control and Prevention [CDC] categories B and C) than those with category A, and in patients with comorbidities than those without comorbidities. Whereas incidence of ADRs was statistically significantly lower in antiretroviral therapy (ART)-experienced patients than that in ART-naïve patients. Incidence of ADRs related to suicide or self-injurious behavior was statistically significantly higher in patients with comorbidities of psychiatric disorders than those without comorbidities. The body weight tended to increase over time and those changes and percentage changes from baseline were greater in ART-naïve patients compared with ART-experienced patients. HIV RNA copies/mL and CD4+ cell counts showed favorable shifts from baseline in both ART-naïve and ART-experienced patients. Conclusion The results of the survey identified no new safety and effectiveness risks in Japanese patients with HIV/AIDS treated with DTG. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01842-3.

Objective Inappropriate prescribing of drugs is associated with unnecessary harms for patients and healthcare costs. Interventions to reduce these prescriptions are widely studied, yet the effectiveness of different types of interventions remains unclear. Therefore, we provide an overview regarding the effectiveness of intervention types that aim to reduce inappropriate drug prescriptions, unrestricted by target drugs, population or setting. Methods For this overview, systematic reviews (SRs) were used as the source for original studies. EMBASE and MEDLINE were searched from inception to August 2018. All SRs aiming to evaluate the effectiveness of interventions to reduce inappropriate prescribing of drugs were eligible for inclusion. The SRs and their original studies were screened for eligibility. Interventions of the original studies were categorized by type of intervention. The percentage of interventions showing a significant reduction of inappropriate prescribing were reported per intervention category. Key findings Thirty-two SRs were included, which provided 319 unique interventions. Overall, 61.4% of these interventions showed a significant reduction in inappropriate prescribing of drugs. Strategies that were most frequently effective in reducing inappropriate prescribing were multifaceted interventions (73.2%), followed by interventions containing additional diagnostic tests (antibiotics) (70.4%), computer interventions (69.2%), audit and feedback (66.7%), patient-mediated interventions (62.5%) and multidisciplinary (team) approach (57.1%). The least frequently effective intervention was an education for healthcare professionals (50.0%). Conclusion The majority of the interventions were effective in reducing inappropriate prescribing of drugs. Multifaceted interventions most frequently showed a significant reduction of inappropriate prescribing. Education for healthcare professionals is the most frequently included intervention in this overview, yet this category is least frequently effective.

Background High-dose intravenous immunoglobulin (IVIG) is the mainstay of treatment for Kawasaki disease (KD). Usually, 2 g/kg of IVIG is administered over 10–24 h, depending on the institution or physician, but the association between infusion speed and effectiveness has not been reported. In this study, we evaluated the differences in efficacy and safety between two different IVIG administration speeds. Methods This was a multicenter, unblinded, randomized controlled study. Patients newly diagnosed with KD were randomized into two groups: one who received IVIG over 12 h (12H group, double speed), and one that received IVIG over 24 h (24H group, reference speed). The endpoints included the duration of fever, incidence of coronary artery abnormalities (CAAs) and of adverse events. Laboratory data were evaluated before and after IVIG administration. Results A total of 39 patients were enrolled. There was no difference between groups in fever duration after the initiation of IVIG (21 h vs. 21.5 h, p = 0.325), and no patient experienced CAAs. Two adverse events were observed in the 12H group (elevation of aspartate aminotransferase and vomiting), however no severe adverse events requiring treatments or extension of hospital stay were observed in either group. After initial IVIG administration, the change ratio of inflammatory markers, such as white blood cell counts, neutrophils, C-reactive protein, and albumin, did not show significant differences between the two groups. On the other hand, a greater increase of serum immunoglobulin G from its baseline level was observed in the 24H group compared to the 12H group (3037 ± 648 mg/dl vs. 2414 ± 248 mg/dl, p Conclusion The efficacy and safety of IVIG administered over 12 h (double speed) were similar to those administered over 24 h (reference speed). Trial registration University Hospital Medical Information Network (UMIN000014665). Registered 27 July 2014 – Prospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000017058

Ilaria Bertoldi,1 Roberto Caporali2 1Medical Department, Pfizer Italy, Rome, Italy; 2Department of Clinical Sciences and Community Health, University of Milan and ASST Pini-CTO Hospital, Milan, ItalyCorrespondence: Roberto CaporaliDepartment of Clinical Sciences and Community Health, University of Milan and ASST Pini-CTO Hospital, Milan, ItalyEmail roberto.caporali@unimi.itAbstract: Tofacitinib is an oral Janus kinase (JAK) inhibitor indicated for the treatment of rheumatoid arthritis (RA). The efficacy and safety/tolerability of tofacitinib have been extensively evaluated as monotherapy and combination therapy in multiple, randomised, multicentre studies in patients with RA. Tofacitinib as monotherapy (as first- and second-line treatment) or as combination with methotrexate (MTX) or other csDMARDs as second- and third-line treatment is effective and generally well tolerated in patients with RA. This article focuses on recent real-world evidence investigating the effectiveness, treatment persistence and safety/tolerability of tofacitinib in patients with RA. With this purpose, a literature review was conducted from April 2018 up to October 2020 for the effectiveness, persistence and safety of tofacitinib for the treatment of RA, primarily focusing on real-world studies. These retrospective and prospective and observational studies demonstrate the effectiveness of tofacitinib, thus supporting pivotal data from the clinical trial programme. Treatment persistence was generally comparable to that of biologic disease-modifying anti-rheumatic drugs. Safety findings in these observational studies were consistent with the known safety profile of the approved dose of 5 mg twice daily.Keywords: rheumatoid arthritis, real-world, effectiveness, persistence

Gaza Strip is exposed to the danger of the novel coronavirus pandemic ‘nCOVID‐19’ spread, which exacerbates the crises severity on this besieged area since 2007. This study aims to identify the preventive actions during the action effectiveness implemented by the Central Emergency Committee and the Ministry of Health to reduce the coronavirus spread in Gaza Strip. The researchers have followed the descriptive and the analytical methodology of the purposive sample responses data from the preventive medicine workers, the security team, and the members of the Central Emergency Committee.The most important results of the study showed that targeted peoples have been reexamined several times to ensure that they are recovered from the disease with an average of 81.0%. The reliability and accuracy of the detection tests of the coronavirus disease were of an average of 79.33%. In addition, the results demonstrate the existence of a strong correlation between the preventive action taken by the Central Emergency Committee and the effectiveness of the procedures to prevent the coronavirus pandemic. Also, the study shows a statistical significance effect at the level of significance (α ≤ 0.05) regarding the prevention procedures from the coronavirus pandemic and the effectiveness of the procedures.

Background Cannabidiol (CBD) is a primary component in the cannabis plant; however, in recent years, interest in CBD treatments has outpaced scientific research and regulatory advancement resulting in a confusing landscape of misinformation and unsubstantiated health claims. Within the limited results from randomized controlled trials, and lack of trust in product quality and known clinical guidelines and dosages, real-world evidence (RWE) from countries with robust regulatory frameworks may fill a critical need for patients and healthcare professionals. Despite growing evidence and interest, no real-world data (RWD) studies have yet investigated patients’ reports of CBD impact on symptom control in the common expression of pain, anxiety, depression, and poor wellbeing. The objective of this study is to assess the impact of CBD-rich treatment on symptom burden, as measured with a specific symptom assessment scale (ESAS-r). Methods This retrospective observational study examined pain, anxiety, depression symptoms, and wellbeing in 279 participants over 18 years old, prescribed with CBD-rich treatment at a network of clinics dedicated to medical cannabis in Quebec, Canada. Data were collected at baseline, 3 (FUP1), and 6 (FUP2) month after treatment initiation. Groups were formed based on symptom severity (mild vs moderate/severe) and based on changes to treatment plan at FUP1 (CBD vs THC:CBD). Two-way mixed ANOVAs were used to assess ESAS-r scores differences between groups and between visits. Results All average ESAS-r scores decreased between baseline and FUP1 (all ps < 0.003). The addition of delta-9-tetrahydrocannabinol (THC) during the first follow-up had no effect on symptom changes. Patients with moderate/severe symptoms experienced important improvement at FUP1 (all ps < 0.001), whereas scores on pain, anxiety, and wellbeing of those with mild symptoms actually increased. Differences in ESAS-r scores between FUP1 and FUP2 were not statistically different. Conclusion This retrospective observational study suggests CBD-rich treatment has a beneficial impact on pain, anxiety, and depression symptoms as well as overall wellbeing only for patients with moderate to severe symptoms; however, no observed effect on mild symptoms. The results of this study contribute to address the myths and misinformation about CBD treatment and demand further investigation.

Background The reestablishment of continuity after Hartmann operation is considered a major surgical procedure with high morbidity and mortality. The optimal interval time between the Hartman procedure and reversal is controversial. Our study aimed to evaluate the effectiveness of laparoscopic Hartmann reversal and to determine the optimal timing of operation. Methods All patients who underwent laparoscopic Hartmann reversal from 2008 to 2019 (11 years) at the University Medical Center (UMC) in Ho Chi Minh City were recruited and divided into 2 groups according to the interval time (≤ 4 or>4months). The short-term operative outcomes of these groups were compared. Results There were 66 patients who underwent laparoscopic Hartmann reversal (mean age: 63.2 years old); ~ 77% of them had colorectal cancer, and 17% had complicated diverticular disease. Themortality rate, anastomotic leakage rate, and overall complication rate were 0%, 1.5%, and 13.2%, respectively. Early operation was performed in 36 patients, and late reversal in 28 patients. There was no difference in mortality, anastomotic leakage, operative complications, and hospital stay between the two groups. Conclusion Laparoscopic Hartmann reversal was effective with acceptable morbidity and mortality at the UMC. There was no observed impact of the interval time between the Hartmann procedure and laparoscopic Hartmann reversal on the short-term operative outcomes. Resumo Introdução O reestabelecimento da continuidade após a cirurgia de Hartmann é considerado um procedimento cirúrgico de grande porte com altas morbidade e mortalidade. O tempo ideal de intervalo entre a cirurgia de Hartmann e a reversão é controverso. Nosso estudo teve como objetivo avaliar a eficácia da reversão da cirurgia de Hartmann e determinar o momento ideal para a cirurgia. Métodos Todos os pacientes submetidos à reversão laparoscópica da cirurgia de Hartmann entre 2008 e 2019 (11 anos) no Centro Médico Universitário (UMC, na sigla em inglês) na cidade de Ho Chi Minh foram recrutados e divididos em 2 grupos de acordo como tempo de intervalo (≤ 4 ou>4meses). Os resultados pós-operatórios de curto prazo destes grupos foram comparados. Resultados Um total de 66 pacientes foram submetidos à reversão laparoscópica da cirurgia de Hartmann (mediana de idade: 63.2 anos); ~ 77 deles tinha câncer colorretal, e 17% tinham doença diverticular complicada. As taxas de mortalidade, de vazamento, e de complicações em geral foram de 0%, 1,5%, e 13,2%, respectivamente. Cirurgia precoce foi realizada em 36 pacientes, e reversão tardia foi realizada em 28 pacientes. Não houve diferença em mortalidade, vazamento anastomótico, complicações operatórias e duração da internação entre os dois grupos. Conclusão A reversão laparoscópica da cirurgia de Hartmann foi eficaz, com morbidade e mortalidade aceitáveis no UMC. Não foi observado qualquer impacto no tempo de intervalo entre a cirurgia de Hartmann e a reversão laparoscópica nos resultados pós-operatórios de curto prazo.

Background Globally, liver cancer is the most frequent fatal malignancy. The aim of the present study was to explore the effectiveness of ultrasound (US)-guided percutaneous transhepatic puncture in patients with low-level alpha-fetoprotein (AFP) liver cancer. Methods A total of 300 patients with primary liver cancer (PLC) (with AFP level ≤200 ng/mL and who underwent fine-needle aspiration) who were admitted to Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2016 to December 2020 were selected to participate in the present study. Data, such as the expression of AFP and the biological characteristics of cells related to follow-up information, were retrospectively analyzed. Results Patients with AFP content 20 mm. Implantation and metastasis accounted for 5% of complications, and gastrointestinal bleeding accounted for 7%. Among the adverse reactions, nausea and vomiting accounted for 15%, diarrhea accounted for 10%, and bone marrow suppression accounted for 8%. Conclusions US-guided percutaneous transhepatic puncture has high sensitivity, high specificity, and is relatively safe, with a low complication rate in patients with low-level AFP liver cancer, and has certain clinical diagnostic value.

Background Long-term community mental health treatment for non-psychotic disorder patients with severe mental illness (SMI) who are perceived as difficult by clinicians, is poorly developed and lacks a structured, goal-centred approach. This study compares (cost-)effectiveness of Interpersonal Community Psychiatric Treatment (ICPT) with Care As Usual (CAU) on quality of life and clinician perceived difficulty in the care for non-psychotic disorder SMI-patients. A multi-centre cluster-randomized clinical tria was conducted in which Community Mental Health Nurses (Clinicians) in three large community mental health services in the Netherlands were randomly allocated to providing either ICPT or CAU to included patients. A total of 56 clinicians were randomized, who treated a total of 93 patients (59 in ICPT-group and 34 in CAU-group). Methods Primary outcome measure is patient-perceived quality of life as measured by the Manchester Short Assessment of Quality of Life (MANSA). Secondary outcome measures include clinician-perceived difficulty, general mental health, treatment outcomes, illness management and recovery, therapeutic relationship, care needs and social network. Patients were assessed at baseline, during treatment (6 months), after treatment (12 months) and at 6 months follow-up (18 months). Linear mixed-effects models for repeated measurements were used to compare mean changes in primary and secondary outcomes between intervention and control group of patients over time on an intention to treat basis. Potential efficiency was investigated from a societal perspective. Economic evaluation was based on general principles of a cost-effectiveness analysis. Outcome measures for health economic evaluation, were costs, and Quality Adjusted Life Years (QALYs). Results Half of the intended number of patients were recruited. There was no statistically significant treatment effect found in the MANSA (0.17, 95%-CI [− 0.058,0.431], p = 0.191). Treatment effects showed significant improvement in the Different Doctor-Patient Relationship Questionnaire-scores and a significant increase in the Illness Management and Recovery–scale Client-version scores). No effects of ICPT on societal and medical costs nor QALYs were found. Conclusions This is the first RCT to investigate the (cost)-effectiveness of ICPT. Compared with CAU, ICPT did not improve quality of life, but significantly reduced clinician-perceived difficulty, and increased subjective illness management and recovery. No effects on costs or QALY’s were found. Trial registration NTR 3988, registered 13 May 2013.

Postprandial hyperglycemia is an independent risk factor for cardiovascular disease (CVD). Bolus insulins aim to mimic the physiological action of endogenous insulin secreted in response to food intake to control peaks of postprandial glycemia (PPG). Ultrafast insulin aspart is insulin with a high rate of absorption into the bloodstream that is designed to mimic the physiological prandial release of insulin more accurately than currently available short-acting or ultra-short-acting insulin preparations. The high bioavailability of ultrafast insulin aspart was achieved through the addition of two excipients — nicotinamide and L-arginine. At the same time, L-arginine ensures the stability of the drug, and nicotinamide is responsible for the accelerated absorption of insulin after subcutaneous administration. The results of clinical studies showed that subcutaneous injection of ultra-fast-acting insulin aspart provided an earlier onset of action and a greater effect of lowering blood glucose levels compared with ultra-short-acting aspart. The use of ultrafast insulin aspart both with subcutaneous injections and with CSII provided better control of PPG compared to the analogue of ultra-short-acting aspart. Moreover, the use of ultra-fast-acting insulin aspart 20 minutes after the start of a meal was not inferior to the ultra-short-acting aspart administered before meals in terms of HbA1c control. This emphasizes the possibility of using ultra-fast insulin aspart both before and after meals, without impairing glycemic control.

Background: The real-world effectiveness of natalizumab in people with relapsing multiple sclerosis (PwRMS) in Argentina and Chile has not been reported. Objective: To evaluate the effectiveness of natalizumab treatment in PwRMS in Argentina and Chile, in clinical practice. Methods: We conducted a multicenter retrospective and observational study. We reviewed the medical records of PwRMS who had been treated with natalizumab for at least one year, without any interruption in MS treatment that lasted more than 12 weeks. We analyzed changes in annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) score and magnetic resonance imaging (MRI). Results: We enrolled 117 PwRMS treated with natalizumab. Natalizumab treatment was associated with a significant reduction in ARR from baseline after one year and two years of treatment (from 1.97 to 0.06 and 0.09 respectively; p

The German Prevention Act underlines the need for an evidence-based approach to prevention and health promotion. It is unclear which steps and processes are necessary for the evolving system of prevention and health promotion in Germany to meet this requirement. This overview article aims to define and operationalize evidence-based interventions in prevention and health promotion and describes the necessary organizational support and capacity building to foster evidence-based action in practice.Based on the international scientific literature and the Federal Centre for Health Education's Memorandum on Evidence-based Prevention and Health Promotion, the term evidence-based intervention is defined and operationalized, and implementation requirements in terms of organizational processes and capacity building are described and discussed.To foster implementation of evidence-based action in practice, decision makers in policy and practice should draw on a shared understanding of the concept of evidence-based interventions and of the need for evaluations that assure generating evidence while implementing interventions. Moreover, organizational support is necessary, such as emphasizing the value of evidence-based action within organizations, ensuring access to existing evidence databases with a transparent and relevant presentation of evidence, advancing competencies of the workforce in searching for and interpreting evidence syntheses, as well as promoting a systematic cooperation between practitioners and researchers.Implementing the above-described elements for more evidence-based action is an important step towards strengthening the evolving system of prevention and health promotion as a fifth pillar of the German health system.Für die Umsetzung des Präventionsgesetzes in einem sich entwickelnden System Prävention und Gesundheitsförderung (PGF) ist die Anforderung der Evidenzbasierung formuliert. Vor diesem Hintergrund stellt sich die Frage, welche Schritte, Prozesse und Vorgehensweisen in diesem System benötigt werden, um der Anforderung zunehmend gerecht zu werden. Dieser Übersichtsartikel diskutiert für Deutschland, wie evidenzbasierte Maßnahmen in der Praxis operationalisiert werden können und welche organisationalen Rahmenbedingungen und Kapazitäten für ein evidenzbasiertes Handeln von AkteurInnen notwendig sind.Aufbauend auf internationalen wissenschaftlichen Erkenntnissen und dem Memorandum Evidenzbasierte Prävention und Gesundheitsförderung der Bundeszentrale für gesundheitliche Aufklärung (BZgA) wird zunächst das Verständnis von evidenzbasierten Maßnahmen erläutert und im Weiteren werden Elemente zur Umsetzung von mehr Evidenzbasierung skizziert.Neben der transparenten und einheitlichen Darstellung in Datenbanken und Empfehlungen ist es notwendig, bei EntscheidungsträgerInnen in Praxis und Politik ein gemeinsames Verständnis von evidenzbasierten Interventionen und von Anforderungen für eine Evaluation, die Evidenzbasierung sichert, zu schaffen. Darüber hinaus kann evidenzbasiertes Handeln von EntscheidungsträgerInnen gefördert werden durch Wertschätzung gegenüber Evidenzbasierung in ihren Organisationen, durch Gewährleistung eines regelhaften Zugangs zu Evidenzdatenbanken, durch verbesserte Kompetenzen in Bezug auf Interpretation von Evidenz und durch eine systematische Zusammenarbeit mit der Wissenschaft.Mehr Evidenzbasierung ist eine Voraussetzung für die nachhaltige Verankerung von PGF als fünfte Säule des Gesundheitssystems.

The database "Insights for healthy settings" was developed by the GKV-Bündnis für Gesundheit, a joint initiative of all health insurance funds for developing and implementing setting-based health promotion and prevention measures. It aims to support health insurance funds and other practice partners in planning and implementing evidence-based health promotion and prevention measures in different settings. The database complements existing intervention databases by providing insights based on findings from systematic reviews. This article aims to present the database, describe possible applications, and discuss options for further development.The database contains findings on the effectiveness and strategies for implementation of setting-based health promotion and prevention measures. In addition to structured summaries of systematic reviews, it includes summaries of scoping reviews and rapid reviews. Different search options (e.g., free text search, subject headings, and search filters) can be used to find database entries (currently n = 13). Quality-assured database entries are created by means of a standardized form and based on the four-eyes principle. To allow for easy access, key findings are presented briefly, and technical terms are clarified. Experts from health insurance funds are continuously involved in the development process of the database.As part of the database's further development, new reviews of the GKV-Bündnis für Gesundheit as well as from other sources will be added. Additionally, quality assessments of included reviews will be depicted and supporting activities developed to further encourage translation of scientific knowledge into practice.Die Datenbank „Wissen für gesunde Lebenswelten“ wurde durch das GKV-Bündnis für Gesundheit, eine gemeinsame Initiative der gesetzlichen Krankenversicherung (GKV) zur Weiterentwicklung und Umsetzung von Gesundheitsförderung und Prävention in Lebenswelten, entwickelt. Sie soll Krankenkassen und weitere Fachkräfte und Beteiligte in der Praxis bei der Planung und Umsetzung evidenzbasierter Maßnahmen der Gesundheitsförderung und Prävention in Lebenswelten unterstützen. In Ergänzung zu bestehenden Interventionsdatenbanken stellt sie Erkenntnisse aus systematischen Übersichtsarbeiten zur Verfügung. Ziel dieses Beitrags ist es, die Datenbank vorzustellen, Nutzungsmöglichkeiten zu beschreiben sowie Weiterentwicklungsmöglichkeiten zu diskutieren.Die Datenbank beinhaltet Erkenntnisse zu Wirksamkeit und Umsetzungsstrategien lebensweltbezogener Maßnahmen der Gesundheitsförderung und Prävention. Sie enthält strukturierte Zusammenfassungen von 3 Arten Übersichtsarbeiten: systematische Reviews, Scoping-Reviews und Rapid-Reviews. Die Datenbankeinträge (aktuell n = 13) können mit verschiedenen Suchfunktionen (u. a. Freitextsuche, Schlagwortsuche und Suchfilter) recherchiert werden. Die Erstellung der Datenbankeinträge erfolgt qualitätsgesichert mittels eines standardisierten Formulars und im Vieraugenprinzip. Zentrale Informationen sind kurz dargestellt und Fachbegriffe erläutert, um einen niedrigschwelligen Zugang zu ermöglichen. Expertinnen und Experten der gesetzlichen Krankenkassen werden fortlaufend in den Entwicklungsprozess der Datenbank eingebunden.Im Rahmen der Weiterentwicklung ist geplant, die Datenbank um Erkenntnisse aus neuen Übersichtsarbeiten des GKV-Bündnisses für Gesundheit sowie aus weiteren Quellen zu ergänzen. Zudem werden zukünftig Qualitätsbewertungen der eingeschlossenen Übersichtsarbeiten dargestellt und begleitende Maßnahmen zur Förderung des Wissenschafts-Praxis-Transfers entwickelt.

Budesonide MMX is a low bioavailability corticosteroid oral once-daily formulation, which has a controlled rate of release throughout the colon, thanks to the multimatrix (MMX) formulation. It has been available for a decade in the USA and Europe for the induction of remission in patients with active, mild to moderate ulcerative colitis, particularly for those not responsive to mesalamine. The efficacy of budesonide MMX in this setting has been assessed by registrative randomized controlled trials showing a higher rate of clinical and endoscopic remission at 8 weeks compared with placebo, mostly in patients with proctosigmoiditis and left-side colitis. Since it is available in our therapeutic armamentarium, a few studies have confirmed the effectiveness of budesonide MMX also in real-life, highlighting the high rate of clinical response and remission and the high safety profile. In the present review, we summarise clinical trials and real-life results of budesonide MMX, assessing its use and predictors of response and non-response in real-life.

Objective: To assess the effectiveness, feasibility and acceptability of botulinum toxin in healing chronic anal fissures in our population. Study Design: Prospective observational study. Place and Duration of Study: Combined Military Hospital, Multan, from Jan 2019 till Dec 2019. Methodology: Eighty patients were enrolled in the study out of which 72 completed the study. 33 IU of botulinum toxin A was injected in the intersphincteric groove in the perianal region. Outcome measures for effectiveness included pain score and fissure healing rates at 2, 6, 16 and 24 weeks after the injection. Healing rate was calculated as percentage and pre and post injection pain scores were compared by using paired sample t-test. Patient acceptability was assessed based on the proportion of patients who accepted the treatment. The average treatment cost was also calculated. Results: A total number of 250 patients were found to be eligible for the study. A purposive sampling technique was used. Eighty patients took part in the study with an acceptability rate of 32%. Seventy two patients completed the study with a completion rate of 90%. Amongst 72 patients, 47 (65.3%) were female and 25 (34.7%) were male. The complete healing rate after 3 months of botulinum toxin injection was 49 (68.1%). There was a significant reduction in pain scores at 2, 6, 16, and 24 weeks of study (p

Background Acupuncture for post-stroke depression (PSD) has been evolving, but uncertainty remains. To assess the existing evidence from randomized clinical trials (RCTs) of acupuncture for PSD, we sought to draw conclusions by synthesizing RCTs. Methods An exhaustive literature search was conducted in seven electronic databases from their inception dates to April 19, 2020, to identify systematic reviews (SRs) and meta-analyses (MAs) on this topic. The primary RCTs included in the SRs/MAs were identified. We also conducted a supplementary search for RCTs published from January 1, 2015, to May 12, 2020. Two reviewers extracted data separately and pooled data using RevMan 5.3 software. The quality of evidence was critically appraised with the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system. Results A total of 17 RCTs involving 1402 patients were included. Meta-analysis showed that participants who received a combination of acupuncture and conventional treatments exhibited significantly lower scores on the HAM-D17, HAM-D24 and HAM-D (MD, − 5.08 [95% CI, − 6.48 to − 3.67], I2 = 0%), (MD, − 9.72 [95% CI, − 14.54 to − 4.91], I2 = 65%) and (MD, − 2.72 [95% CI, − 3.61 to − 1.82], respectively) than those who received conventional treatment. However, there was no significant difference in acupuncture versus antidepressants in terms of the 17-item, 24-item and HAM-D scales (MD, − 0.43 [95% CI, − 1.61 to 0.75], I2 = 51%), (MD, − 3.09 [95% CI, − 10.81 to 4.63], I2 = 90%) and (MD, − 1.55 [95% CI, − 4.36 to 1.26], I2 = 95%, respectively). For adverse events, acupuncture was associated with fewer adverse events than antidepressants (RR, 0.16 [95% CI, 0.07 to 0.39], I2 = 35%), but there was no significant difference in the occurrence of adverse events between the combination of acupuncture and conventional treatments versus conventional treatments (RR, 0.63 [95% CI, 0.21 to 1.83], I2 = 38%). The quality of evidence was low to very low due to the substantial heterogeneity among the included studies. Conclusions The current review indicates that acupuncture has greater effect on PSD and better safety profile than antidepressants, but high-quality evidence evaluating acupuncture for PSD is still needed.

Introduction. The complexity of the interaction between type 2 diabetes mellitus (T2DM), comorbidities, and emerging complications requires a clinical approach that manages risk while maintaining indicated therapeutic goals. The objective of the study was to analyse the frequency and effectiveness of mono- and combined glucose-lowering therapy in T2DM patients with obesity and chronic pancreatitis (CP). Material and methods. The retrospective study analysed 579 medical records of T2DM patients, who were divided in the following groups: group 1- patients with normal body weight and without CP (n=67); group 2 – patients with normal body weight and with CP (n=32); group 3- overweight patients without CP (n=126); group 4 – overweight patients with CP (n=33); group 5 – obese patients without CP (n=262); group 6 – obese patients with CP (n=59). When evaluating the effectiveness of the received therapy, the target value of HbA1c less than 7% was considered. Results. Most of the patients with T2DM+CP and T2DM with normal body weight received combined therapy. The presence of CP significantly influences the choice of treatment for T2DM, particularly, 81.5% of patients with T2DM and CP were prescribed combined therapy. There was no significant difference between serum glucose and HbA1c levels in patients with only T2DM and comorbid T2DM+CP+overweight/obesity regarding monotherapy vs combined glucose-lowering therapy. However, glucose and HbA1c levels in patients with only T2DM on monotherapy were significantly lower, respectively, by 41.72% and 25.64% vs patients with comorbid CP and overweight/obesity, who were also prescribed monotherapy. Conclusion. The presence of CP significantly influences the choice of treatment for T2DM, while overweight/obesity is not a criterion for choosing mono- or combined glucose-lowering therapy. The use of metformin as monotherapy and the use of combined therapy in most of patients with only T2DM and comorbid T2DM do not achieve the target levels of glucose and HbA1c.

Objectives: To compare the characteristics of patients undergoing treatment with continuous intestinal infusion of levodopa–carbidopa (CIILC) for advanced Parkinson's disease and the data on the effectiveness and safety of CIILC in the different autonomous communities (AC) of Spain. Methods: A retrospective, longitudinal, observational study was carried out into 177 patients from 11 CAs who underwent CIILC between January 2006 and December 2011. We analysed data on patients’ clinical and demographic characteristics, variables related to effectiveness (changes in off time/on time with or without disabling dyskinesia; changes in Hoehn and Yahr scale and Unified Parkinson's Disease Rating Scale scores; non-motor symptoms; and Clinical Global Impression scale scores) and safety (adverse events), and the rate of CIILC discontinuation. Results: Significant differences were observed between CAs for several baseline variables: duration of disease progression prior to CIILC onset, off time (34.9%–59.7%) and on time (2.6%–48.0%; with or without disabling dyskinesia), Hoehn and Yahr score during on time, Unified Parkinson's Disease Rating Scale-III score during both on and off time, presence of =4 motor symptoms, and CIILC dose. Significant differences were observed during follow-up (>24 months in 9 of the 11 CAs studied) for the percentage of off time and on time without disabling dyskinesia, adverse events frequency, and Clinical Global Impression scores. The rate of CIILC discontinuation was between 20% and 40% in 9 CAs (78% and 80% in remaining 2 CAs). Conclusions: This study reveals a marked variability between CAs in terms of patient selection and CIILC safety and effectiveness. These results may have been influenced by patients’ baseline characteristics, the availability of multidisciplinary teams, and clinical experience. Resumen: Objetivos: Comparar las características de los pacientes con enfermedad de Parkinson avanzada en tratamiento con infusión intestinal continua de levodopa-carbidopa (IICLC) y los datos de efectividad y seguridad de IICLC entre diferentes comunidades autónomas (CC. AA.). Métodos: Estudio longitudinal observacional y retrospectivo. Se incluyeron 177 pacientes de 11 CC. AA. que iniciaron tratamiento con IICLC entre enero de 2006 y diciembre de 2011. Se compararon las características clínicas y demográficas, las variables de efectividad (cambios en el tiempo OFF, ON con y sin discinesias discapacitantes, cambios en la escala de Hoehn y Yahr y puntuación de la Unified Parkinson's Disease Rating Scale, síntomas no motores e Impresión Clínica Global) y seguridad (acontecimientos adversos), y la tasa de suspensión de IICLC. Resultados: Se hallaron diferencias significativas entre las CC. AA. en diversas variables basales: duración de la enfermedad hasta el inicio de IICLC, tiempo OFF (34,9-59,7%) y ON (con o sin discinesias; 2,6-48,0%), Hoehn y Yahr en ON, Unified Parkinson's Disease Rating Scale-III en ON y OFF, presencia de = 4 síntomas motores y dosis de IICLC. En el seguimiento (> 24 meses en 9 de 11 CC. AA.) hubo diferencias significativas en el porcentaje de tiempo OFF, tiempo ON sin discinesias discapacitantes, frecuencia de acontecimientos adversos e Impresión Clínica Global. La tasa de suspensión fue de entre 20-40% en todas las CC. AA., excepto en 2 (78 y 80%). Conclusiones: Este estudio muestra una amplia variabilidad en la selección de los pacientes y en la efectividad y seguridad de IICLC entre las diferentes CC. AA. Podrían influir las características basales de los pacientes, la disponibilidad de un equipo multidisciplinar y la experiencia clínica.

Objective To evaluate whether it is safe and effective for orthopaedic medical staff to provide support to the work against COVID‐19. Methods One hundred and twenty‐two orthopaedic medical staff from the orthopaedic center of Zhongnan Hospital of Wuhan University were included in this retrospective investigation. A total of 43 surgeons and 69 nurses provided medical support in the treatment of COVID‐19 patients from 1 January 2020 to 8 April 2020 in four different hospitals in Wuhan. We collected data on the age, gender, and body temperature of orthopaedic medical staff, as well as the results for their chest CT scans, SARS‐CoV‐2 RNA, SARS‐CoV‐2 IgM and SARS‐CoV‐2 IgG tests, and training and examinations on COVID‐19 knowledge. We also collected data on the time span of work, the number of infected staff during the support period, the number of COVID‐19 patients the surgeons treated and the cure rate, the performance of the surgeons as assessed by the specialists and patients, and the number of infected staff during the pandemic. Results Among the 49 surgeons and 73 nurses, 43 surgeons and 69 nurses provided support against COVID‐19. A total of 12 surgeons and 11 nurses provided support in the fields of respiration, intensive care, and emergency. A total of 34 surgeons and 58 nurses worked in the designated wards restructured for COVID‐19 in the orthopaedic building. The average time span of work for the surgeons and nurses was 14.78 ± 3.64 days and 24.77 ± 7.58 days, respectively. No staff were infected during the support period. Over 1000 patients were received in the fever clinic by orthopaedic surgeons. The overall number of the treated hospitalized patients was 622. Among these patients, 226 cases were mild, 318 were mild to moderate, and 58 were severe or critical. The cure rate was 96.01%, 99.37%, and 52.00% respectively. The performance of the surgeons was scored 87.02 ± 3.17 and 90.69 ± 3.58 by the specialists and the patients, respectively. During the whole pandemic, 3 surgeons and 3 nurses who did not participate in the support work were infected in the early stages. The morbidity of all the orthopaedic staff was 4.92% during the whole pandemic, while no one was infected during the support work. Conclusion Our investigation indicated that although they worked outside their specialty, it was safe and effective for the orthopaedic staff to provide medical support in the work against COVID‐19 with adequate precautions and proper training., A total of 112 orthopaedic medical staff provided support in COVID‐19 work, and none were infected with COVID‐19. Six hundred and twenty‐two patients with mild to critical disease were treated with cure rates comparable to those in the published literature. Thus, it is safe and effective for medical staff from other specialties to provide support in the work against COVID‐19.

Background Eptinezumab, an anti-calcitonin gene-related peptide monoclonal antibody recently approved in the United States for preventive treatment of migraine in adults, was found to be well tolerated in double-blind, placebo-controlled studies in patients with episodic and chronic migraine. The objective of the PREVAIL study was to evaluate the long-term safety, immunogenicity, and impact on patient-reported outcomes of repeat doses of eptinezumab in patients with chronic migraine. Methods PREVAIL was an open-label, phase 3 trial comprising a 48-week treatment phase followed by a second 48-week treatment phase. Adults with chronic migraine received eptinezumab 300 mg by 30-min intravenous administration every 12 weeks for up to 8 doses. Patients were followed for 20 weeks after the final infusion (end-of-study visit at week 104). Results Overall, 128 adults (mean age, 41.5 years) with chronic migraine were included. During the 2 years, the most frequently reported treatment-emergent adverse events were nasopharyngitis (14.1%), upper respiratory tract infection (7.8%), sinusitis (7.8%), influenza (6.3%), bronchitis (5.5%), and migraine (5.5%). The rate of study-drug discontinuation due to adverse events was 6.3%, which included 3 patients with infusion-related hypersensitivity. The incidence of anti-eptinezumab antibodies peaked at week 24 and declined despite continued dosing, to nondetectable levels at week 104. Improvements in patient-reported outcomes were observed at first assessment (week 4) and generally sustained through week 104. Conclusion In adults with chronic migraine, eptinezumab 300 mg demonstrated a favorable safety profile, limited long-term immunogenicity, early and sustained reductions in migraine-related burden, and improvements in health-related quality of life over 2 years. Trial registration ClinicalTrials.gov (Identifier: NCT02985398).