Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis.

BACKGROUND: Bisphosphonates and receptor activator of nuclear factor-kappa B ligand (RANKL)-inhibitors are amongst the bone-modifying agents used as supportive treatment in women with breast cancer who do not have bone metastases. These agents aim to reduce bone loss and the risk of fractures. Bisphosphonates have demonstrated survival benefits, particularly in postmenopausal women. OBJECTIVES: To assess and compare the effects of different bone-modifying agents as supportive treatment to reduce bone mineral density loss and osteoporotic fractures in women with breast cancer without bone metastases and generate a ranking of treatment options using network meta-analyses (NMAs). SEARCH METHODS: We identified studies by electronically searching CENTRAL, MEDLINE and Embase until January 2023. We searched various trial registries and screened abstracts of conference proceedings and reference lists of identified trials. SELECTION CRITERIA: We included randomised controlled trials comparing different bisphosphonates and RANKL-inihibitors with each other or against no further treatment or placebo for women with breast cancer without bone metastases. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias of included studies and certainty of evidence using GRADE. Outcomes were bone mineral density, quality of life, overall fractures, overall survival and adverse events. We conducted NMAs and generated treatment rankings. MAIN RESULTS: Forty-seven trials (35,163 participants) fulfilled our inclusion criteria; 34 trials (33,793 participants) could be considered in the NMA (8 different treatment options). Bone mineral density We estimated that the bone mineral density of participants with no treatment/placebo measured as total T-score was -1.34. Evidence from the NMA (9 trials; 1166 participants) suggests that treatment with ibandronate (T-score -0.77; MD 0.57, 95% CI -0.05 to 1.19) may slightly increase bone mineral density (low certainty) and treatment with zoledronic acid (T-score -0.45; MD 0.89, 95% CI 0.62 to 1.16) probably slightly increases bone mineral density compared to no treatment/placebo (moderate certainty). Risedronate (T-score -1.08; MD 0.26, 95% CI -0.32 to 0.84) may result in little to no difference compared to no treatment/placebo (low certainty). We are uncertain whether alendronate (T-score 2.36; MD 3.70, 95% CI -2.01 to 9.41) increases bone mineral density compared to no treatment/placebo (very low certainty). Quality of life No quantitative analyses could be performed for quality of life, as only three studies reported this outcome. All three studies showed only minimal differences between the respective interventions examined. Overall fracture rate We estimated that 70 of 1000 participants with no treatment/placebo had fractures. Evidence from the NMA (16 trials; 19,492 participants) indicates that treatment with clodronate or ibandronate (42 of 1000; RR 0.60, 95% CI 0.39 to 0.92; 40 of 1000; RR 0.57, 95% CI 0.38 to 0.86, respectively) decreases the number of fractures compared to no treatment/placebo (high certainty). Denosumab or zoledronic acid (51 of 1000; RR 0.73, 95% CI 0.52 to 1.01; 55 of 1000; RR 0.79, 95% CI 0.56 to 1.11, respectively) probably slightly decreases the number of fractures; and risedronate (39 of 1000; RR 0.56, 95% CI 0.15 to 2.16) probably decreases the number of fractures compared to no treatment/placebo (moderate certainty). Pamidronate (106 of 1000; RR 1.52, 95% CI 0.75 to 3.06) probably increases the number of fractures compared to no treatment/placebo (moderate certainty). Overall survival We estimated that 920 of 1000 participants with no treatment/placebo survived overall. Evidence from the NMA (17 trials; 30,991 participants) suggests that clodronate (924 of 1000; HR 0.95, 95% CI 0.77 to 1.17), denosumab (927 of 1000; HR 0.91, 95% CI 0.69 to 1.21), ibandronate (915 of 1000; HR 1.06, 95% CI 0.83 to 1.34) and zoledronic acid (925 of 1000; HR 0.93, 95% CI 0.76 to 1.14) may result in little to no difference regarding overall survival compared to no treatment/placebo (low certainty). Additionally, we are uncertain whether pamidronate (905 of 1000; HR 1.20, 95% CI 0.81 to 1.78) decreases overall survival compared to no treatment/placebo (very low certainty). Osteonecrosis of the jaw We estimated that 1 of 1000 participants with no treatment/placebo developed osteonecrosis of the jaw. Evidence from the NMA (12 trials; 23,527 participants) suggests that denosumab (25 of 1000; RR 24.70, 95% CI 9.56 to 63.83), ibandronate (6 of 1000; RR 5.77, 95% CI 2.04 to 16.35) and zoledronic acid (9 of 1000; RR 9.41, 95% CI 3.54 to 24.99) probably increases the occurrence of osteonecrosis of the jaw compared to no treatment/placebo (moderate certainty). Additionally, clodronate (3 of 1000; RR 2.65, 95% CI 0.83 to 8.50) may increase the occurrence of osteonecrosis of the jaw compared to no treatment/placebo (low certainty). Renal impairment We estimated that 14 of 1000 participants with no treatment/placebo developed renal impairment. Evidence from the NMA (12 trials; 22,469 participants) suggests that ibandronate (28 of 1000; RR 1.98, 95% CI 1.01 to 3.88) probably increases the occurrence of renal impairment compared to no treatment/placebo (moderate certainty). Zoledronic acid (21 of 1000; RR 1.49, 95% CI 0.87 to 2.58) probably increases the occurrence of renal impairment while clodronate (12 of 1000; RR 0.88, 95% CI 0.55 to 1.39) and denosumab (11 of 1000; RR 0.80, 95% CI 0.54 to 1.19) probably results in little to no difference regarding the occurrence of renal impairment compared to no treatment/placebo (moderate certainty). AUTHORS' CONCLUSIONS: When considering bone-modifying agents for managing bone loss in women with early or locally advanced breast cancer, one has to balance between efficacy and safety. Our findings suggest that bisphosphonates (excluding alendronate and pamidronate) or denosumab compared to no treatment or placebo likely results in increased bone mineral density and reduced fracture rates. Our survival analysis that included pre and postmenopausal women showed little to no difference regarding overall survival. These treatments may lead to more adverse events. Therefore, forming an overall judgement of the best ranked bone-modifying agent is challenging. More head-to-head comparisons, especially comparing denosumab with any bisphosphonate, are needed to address gaps and validate the findings of this review.

Lower FIB-4 threshold in patients with diabetes improves diagnostic accuracy of the test in a Hispanic population.

Background: Non-invasive tests (NITs) can be used to estimate the severity of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) but their diagnostic accuracy is variable. Hispanic patients are at increased risk of NAFLD and diabetes. We evaluate the diagnostic performance of the fibrosis index based on 4 factors (FIB-4) in a population of Hispanic patients who underwent vibration-controlled transient elastography (VCTE). Methods: A total of 1,524 patients underwent VCTE at University of California, Los Angeles from July 18, 2019 to June 7, 2022. Ultimately 110 patients were identified as Hispanic, with confirmed NAFLD. Sensitivity, specificity, positive predictive value and negative predictive value of FIB-4 threshold ≥1.3 were calculated. Logistic regression models were used to determine updated thresholds for patients with and without diabetes based on Youden's index. Results: Of the 110 patients, the majority (65%) were female. Prevalence of diabetes was higher in the group with clinically significant fibrosis (76% vs. 36%, P<0.001). Using a FIB-4 threshold ≥1.3 to predict clinically significant fibrosis (F2-F4 on VCTE), area under the receiver operating characteristic (AUROC) was 0.74. By incorporating diabetes status, AUROC was 0.81 when employing a FIB-4 threshold of ≥1.0 in patients with diabetes and ≥1.5 in patients without diabetes. Conclusions: Using a FIB-4 threshold of ≥1.0 in patients with diabetes and ≥1.5 in patients without diabetes improves the diagnostic performance of the test. The new FIB-4 including diabetes status will lead to improved screening in patients who are at risk of clinically significant fibrosis.

Physical exercise for people with Parkinson's disease: a systematic review and network meta-analysis.

BACKGROUND: Physical exercise is effective in managing Parkinson's disease (PD), but the relative benefit of different exercise types remains unclear. OBJECTIVES: To compare the effects of different types of physical exercise in adults with PD on the severity of motor signs, quality of life (QoL), and the occurrence of adverse events, and to generate a clinically meaningful treatment ranking using network meta-analyses (NMAs). SEARCH METHODS: An experienced information specialist performed a systematic search for relevant articles in CENTRAL, MEDLINE, Embase, and five other databases to 17 May 2021. We also searched trial registries, conference proceedings, and reference lists of identified studies up to this date. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing one type of physical exercise for adults with PD to another type of exercise, a control group, or both. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. A third author was involved in case of disagreements. We categorized the interventions and analyzed their effects on the severity of motor signs, QoL, freezing of gait, and functional mobility and balance up to six weeks after the intervention using NMAs. Two review authors independently assessed the risk of bias using the risk of bias 2 (RoB 2) tool and rated the confidence in the evidence using the CINeMA approach for results on the severity of motor signs and QoL. We consulted a third review author to resolve any disagreements. Due to heterogeneous reporting of adverse events, we summarized safety data narratively and rated our confidence in the evidence using the GRADE approach. MAIN RESULTS: We included 154 RCTs with a total of 7837 participants with mostly mild to moderate disease and no major cognitive impairment. The number of participants per study was small (mean 51, range from 10 to 474). The NMAs on the severity of motor signs and QoL included data from 60 (2721 participants), and 48 (3029 participants) trials, respectively. Eighty-five studies (5192 participants) provided safety data. Here, we present the main results. We observed evidence of beneficial effects for most types of physical exercise included in our review compared to a passive control group. The effects on the severity of motor signs and QoL are expressed as scores on the motor scale of the Unified Parkinson's Disease Rating Scale (UPDRS-M) and the Parkinson's Disease Questionnaire 39 (PDQ-39), respectively. For both scales, higher scores denote higher symptom burden. Therefore, negative estimates reflect improvement (minimum clinically important difference: -2.5 for UPDRS-M and -4.72 for PDQ-39). Severity of motor signs The evidence from the NMA (60 studies; 2721 participants) suggests that dance and gait/balance/functional training probably have a moderate beneficial effect on the severity of motor signs (dance: mean difference (MD) -10.18, 95% confidence interval (CI) -14.87 to -5.36; gait/balance/functional training: MD -7.50, 95% CI -11.39 to -3.48; moderate confidence), and multi-domain training probably has a small beneficial effect on the severity of motor signs (MD -5.90, 95% CI -9.11 to -2.68; moderate confidence). The evidence also suggests that endurance, aqua-based, strength/resistance, and mind-body training might have a small beneficial effect on the severity of motor signs (endurance training: MD -5.76, 95% CI -9.78 to -1.74; aqua-based training: MD -5.09, 95% CI -10.45 to 0.40; strength/resistance training: MD -4.96, 95% CI -9.51 to -0.40; mind-body training: MD -3.62, 95% CI -7.24 to 0.00; low confidence). The evidence is very uncertain about the effects of "Lee Silverman Voice training BIG" (LSVT BIG) and flexibility training on the severity of motor signs (LSVT BIG: MD -6.70, 95% CI -16.48 to 3.08; flexibility training: MD 4.20, 95% CI -1.61 to 9.92; very low confidence). Quality of life The evidence from the NMA (48 studies; 3029 participants) suggests that aqua-based training probably has a large beneficial effect on QoL (MD -15.15, 95% CI -23.43 to -6.87; moderate confidence). The evidence also suggests that mind-body, gait/balance/functional, and multi-domain training and dance might have a small beneficial effect on QoL (mind-body training: MD -7.22, 95% CI -13.57 to -0.70; gait/balance/functional training: MD -6.17, 95% CI -10.75 to -1.59; multi-domain training: MD -5.29, 95% CI -9.51 to -1.06; dance: MD -3.88, 95% CI -10.92 to 3.00; low confidence). The evidence is very uncertain about the effects of gaming, strength/resistance, endurance, and flexibility training on QoL (gaming: MD -8.99, 95% CI -23.43 to 5.46; strength/resistance training: MD -6.70, 95% CI -12.86 to -0.35; endurance training: MD -6.52, 95% CI -13.74 to 0.88; flexibility training: MD 1.94, 95% CI -10.40 to 14.27; very low confidence). Adverse events Only 85 studies (5192 participants) provided some kind of safety data, mostly only for the intervention groups. No adverse events (AEs) occurred in 40 studies and no serious AEs occurred in four studies. AEs occurred in 28 studies. The most frequently reported events were falls (18 studies) and pain (10 studies). The evidence is very uncertain about the effect of physical exercise on the risk of adverse events (very low confidence). Across outcomes, we observed little evidence of differences between exercise types. AUTHORS' CONCLUSIONS: We found evidence of beneficial effects on the severity of motor signs and QoL for most types of physical exercise for people with PD included in this review, but little evidence of differences between these interventions. Thus, our review highlights the importance of physical exercise regarding our primary outcomes severity of motor signs and QoL, while the exact exercise type might be secondary. Notably, this conclusion is consistent with the possibility that specific motor symptoms may be treated most effectively by PD-specific programs. Although the evidence is very uncertain about the effect of exercise on the risk of adverse events, the interventions included in our review were described as relatively safe. Larger, well-conducted studies are needed to increase confidence in the evidence. Additional studies recruiting people with advanced disease severity and cognitive impairment might help extend the generalizability of our findings to a broader range of people with PD.

Cost effectiveness of hepatitis C direct acting agents.

INTRODUCTION: Introduction of direct acting antivirals (DAA) has transformed treatment of chronic hepatitis C (HCV) and made the elimination of HCV an achievable goal set forward by World Health Organization by 2030. Multiple barriers need to be overcome for successful eradication of HCV. Availability of pan-genotypic HCV regimens has decreased the need for genotype testing but maintained high efficacy associated with DAAs. AREAS COVERED: In this review, we will assess the cost-effectiveness of DAA treatment in patients with chronic HCV disease, with emphasis on general, cirrhosis, and vulnerable populations. EXPERT OPINION: Multiple barriers exist limiting eradication of HCV, including cost to treatment, access, simplified testing, and implementing policy to foster treatment for all groups of HCV patients. Clinically, DAAs have drastically changed the landscape of HCV, but focused targeting of vulnerable groups is needed. Public policy will continue to play a strong role in eliminating HCV. While we will focus on the cost-effectiveness of DAA, several other factors regarding HCV require on going attention, such as increasing public awareness and decreasing social stigma associated with HCV, offering universal screening followed by linkage to treatment and improving preventive interventions to decrease spread of HCV.

Risk Factors Contributing to Reinfection by SARS-CoV-2: A Systematic Review.

This article aims to systematize the evidence regarding risk factors associated with COVID-19 reinfection. We conducted a systematic review of all the scientific publications available until August 2022. To ensure the inclusion of the most recent and relevant information, we searched the PubMed and Scopus databases. Thirty studies were reviewed, with a significant proportion being analytical observational case-control and cohort studies. Upon qualitative analysis of the available evidence, it appears that the probability of reinfection is higher for individuals who are not fully immunized when exposed to a new variant, females, those with pre-existing chronic diseases, individuals aged over 60, and those who have previously experienced severe symptoms of the disease or are immunocompromised. In conclusion, further analytical observational case-control studies are necessary to gain a better understanding of the risk factors associated with SARS-CoV-2 (COVID-19) reinfection.

Physical exercise for people with Parkinson's disease: a systematic review and network meta-analysis.

BACKGROUND: Physical exercise is effective in managing Parkinson's disease (PD), but the relative benefit of different exercise types remains unclear. OBJECTIVES: To compare the effects of different types of physical exercise in adults with PD on the severity of motor signs, quality of life (QoL), and the occurrence of adverse events, and to generate a clinically meaningful treatment ranking using network meta-analyses (NMAs). SEARCH METHODS: An experienced information specialist performed a systematic search for relevant articles in CENTRAL, MEDLINE, Embase, and five other databases to 17 May 2021. We also searched trial registries, conference proceedings, and reference lists of identified studies up to this date. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing one type of physical exercise for adults with PD to another type of exercise, a control group, or both. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. A third author was involved in case of disagreements.  We categorized the interventions and analyzed their effects on the severity of motor signs, QoL, freezing of gait, and functional mobility and balance up to six weeks after the intervention using NMAs. Two review authors independently assessed the risk of bias using the risk of bias 2 (RoB 2) tool and rated the confidence in the evidence using the CINeMA approach for results on the severity of motor signs and QoL. We consulted a third review author to resolve any disagreements. Due to heterogeneous reporting of adverse events, we summarized safety data narratively and rated our confidence in the evidence using the GRADE approach. MAIN RESULTS: We included 156 RCTs with a total of 7939 participants with mostly mild to moderate disease and no major cognitive impairment. The number of participants per study was small (mean 51, range from 10 to 474). The NMAs on the severity of motor signs and QoL included data from 71 (3196 participants), and 55 (3283 participants) trials, respectively. Eighty-five studies (5192 participants) provided safety data. Here, we present the main results. We observed evidence of beneficial effects for most types of physical exercise included in our review compared to a passive control group. The effects on the severity of motor signs and QoL are expressed as scores on the motor scale of the Unified Parkinson Disease Rating Scale (UPDRS-M) and the Parkinson's Disease Questionnaire 39 (PDQ-39), respectively. For both scales, higher scores denote higher symptom burden. Therefore, negative estimates reflect improvement (minimum clinically important difference: -2.5 for UPDRS-M and -4.72 for PDQ-39). Severity of motor signs The evidence from the NMA (71 studies; 3196 participants) suggests that dance has a moderate beneficial effect on the severity of motor signs (mean difference (MD) -10.32, 95% confidence interval (CI) -15.54 to -4.96; high confidence), and aqua-based, gait/balance/functional, and multi-domain training might have a moderate beneficial effect on the severity of motor signs (aqua-based: MD -7.77, 95% CI -13.27 to -2.28; gait/balance/functional: MD -7.37, 95% CI -11.39 to -3.35; multi-domain: MD -6.97, 95% CI -10.32 to -3.62; low confidence). The evidence also suggests that mind-body training and endurance training might have a small beneficial effect on the severity of motor signs (mind-body: MD -6.57, 95% CI -10.18 to -2.81; endurance: MD -6.43, 95% CI -10.72 to -2.28; low confidence). Flexibility training might have a trivial or no effect on the severity of motor signs (MD 2.01, 95% CI -4.82 to 8.98; low confidence). The evidence is very uncertain about the effects of strength/resistance training and "Lee Silverman Voice training BIG" (LSVT BIG) on the severity of motor signs (strength/resistance: MD -6.97, 95% CI -11.93 to -2.01; LSVT BIG: MD -5.49, 95% CI -14.74 to 3.62; very low confidence). Quality of life The evidence from the NMA (55 studies; 3283 participants) suggests that aqua-based training probably has a large beneficial effect on QoL (MD -14.98, 95% CI -23.26 to -6.52; moderate confidence). The evidence also suggests that endurance training might have a moderate beneficial effect, and that gait/balance/functional and multi-domain training might have a small beneficial effect on QoL (endurance: MD -9.16, 95% CI -15.68 to -2.82; gait/balance/functional: MD -5.64, 95% CI -10.04 to -1.23; multi-domain: MD -5.29, 95% CI -9.34 to -1.06; low confidence). The evidence is very uncertain about the effects of mind-body training, gaming, strength/resistance training, dance, LSVT BIG, and flexibility training on QoL (mind-body: MD -8.81, 95% CI -14.62 to -3.00; gaming: MD -7.05, 95% CI -18.50 to 4.41; strength/resistance: MD -6.34, 95% CI -12.33 to -0.35; dance: MD -4.05, 95% CI -11.28 to 3.00; LSVT BIG: MD 2.29, 95% CI -16.03 to 20.44; flexibility: MD 1.23, 95% CI -11.45 to 13.92; very low confidence). Adverse events Only 85 studies (5192 participants) provided some kind of safety data, mostly only for the intervention groups. No adverse events (AEs) occurred in 40 studies and no serious AEs occurred in four studies. AEs occurred in 28 studies. The most frequently reported events were falls (18 studies) and pain (10 studies). The evidence is very uncertain about the effect of physical exercise on the risk of adverse events (very low confidence). Across outcomes, we observed little evidence of differences between exercise types. AUTHORS' CONCLUSIONS: We found evidence of beneficial effects on the severity of motor signs and QoL for most types of physical exercise for people with PD included in this review, but little evidence of differences between these interventions. Thus, our review highlights the importance of physical exercise regarding our primary outcomes severity of motor signs and QoL, while the exact exercise type might be secondary. Notably, this conclusion is consistent with the possibility that specific motor symptoms may be treated most effectively by PD-specific programs. Although the evidence is very uncertain about the effect of exercise on the risk of adverse events, the interventions included in our review were described as relatively safe. Larger, well-conducted studies are needed to increase confidence in the evidence. Additional studies recruiting people with advanced disease severity and cognitive impairment might help extend the generalizability of our findings to a broader range of people with PD.

Effects of Resistance Training on Motor- and Non-Motor Symptoms in Patients with Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Previous reviews indicated positive effects of resistance training (RT) on motor outcomes in Parkinson's disease (PD). However, inconsistencies between the included studies exist, and non-motor outcomes have only scarcely been considered in a review on RT in PD. OBJECTIVE: To analyze the RT effects on motor- and non-motor outcomes in PD patients compared to passive and physically active control groups (i.e., other structured physical interventions). METHODS: We searched CENTRAL, MEDLINE, EMBASE, and CINAHL for randomized controlled trials of RT in PD. After identifying 18 studies, a meta-analysis was conducted for the outcomes muscle strength, motor impairment, freezing of gait (FoG), mobility and balance, quality of life (QoL), depression, cognition, and adverse events. Meta-analyses with random models were calculated using mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CI). RESULTS: When comparing RT with passive control groups, the meta-analyses showed significant large effects on muscle strength (SMD = -0.84, 95% CI -1.29--0.39, p = 0.0003), motor impairment (SMD = -0.81, 95% CI -1.34--0.27, p = 0.003), mobility and balance (MD = -1.81, 95% CI -3.13--0.49, p = 0.007), and small significant effects on QoL (SMD = -0.48, 95% CI -0.86--0.10, p = 0.01). RT compared with physically active control groups reached no significant results for any outcome. CONCLUSIONS: RT improves muscle strength, motor impairment, mobility and balance, QoL, and depression in PD patients. However, it is not superior to other physically active interventions. Therefore, exercise is important for PD patients but according to this analysis, its type is of secondary interest.

Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer of the lymphatic system. About 30% to 40% of people with DLBCL experience relapse and 10% are refractory to first-line treatment usually consisting of R-CHOP chemotherapy. Of those eligible for second-line treatment, commonly consisting of salvage chemotherapy followed by autologous stem-cell transplantation (ASCT), around 50% experience relapse. With a median overall survival of less than six to 12 months, the prognosis of individuals who relapse or are refractory (r/r) to advanced lines of treatment or of those who are ineligible for ASCT, is very poor. With the introduction of chimeric antigen receptor (CAR) T-cell therapy, a novel treatment option for these people is available. OBJECTIVES: To assess the benefits and harms of chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory (r/r) DLBCL. SEARCH METHODS: An experienced information specialist performed a systematic database search for relevant articles on CENTRAL, MEDLINE and Embase until September 11th, 2020. We also searched trial registries and reference lists of identified studies up to this date. All search results were screened by two authors independently and a third author was involved in case of discrepancies. SELECTION CRITERIA: We included prospectively planned trials evaluating CAR T-cell therapy for people with r/r DLBCL. We had planned to include randomised controlled trials (RCTs) and we flexibly adapted eligibility criteria to the most reliable study designs available. We excluded studies involving fewer than 10 participants with r/r DLBCL and studies with a proportion of participants with r/r DLBCL below 70%, unless data were reported separately for this subgroup. DATA COLLECTION AND ANALYSIS: Two review authors extracted data and performed risk of bias ratings independently. A third author was involved in case of disagreements. As our search did not yield any completed RCTs, prospective controlled non-randomised studies of interventions (NRSIs) or prospective observational studies with a control group, we did not meta-analyse data and reported all results narratively. We adopted the GRADE approach to assess the certainty of the evidence for prioritised outcomes. MAIN RESULTS: We identified 13 eligible uncontrolled studies evaluating a single or multiple arms of CAR T-cell therapies. We also identified 38 ongoing studies, including three RCTs. Ten studies are awaiting classification due to completion with no retrievable results data or insufficient data to justify inclusion. The mean number of participants enrolled, treated with CAR T-cell therapy and evaluated in the included studies were 79 (range 12 to 344; data unavailable for two studies), 61 (range 12 to 294; data unavailable for one study) and 52 (range 11 to 256), respectively. Most studies included people with r/r DLBCL among people with other haematological B-cell malignancies. Participants had received at least a median of three prior treatment lines (data unavailable for four studies), 5% to 50% had undergone ASCT (data unavailable for five studies) and, except for two studies, 3% to 18% had undergone allogenic stem-cell transplantation (data unavailable for eight studies). The overall risk of bias was high for all studies, in particular, due to incomplete follow-up and the absence of blinding. None of the included studies had a control group so that no adequate comparative effect measures could be calculated. The duration of follow-up varied substantially between studies, in particular, for harms. Our certainty in the evidence is very low for all outcomes. Overall survival was reported by eight studies (567 participants). Four studies reported survival rates at 12 months which ranged between 48% and 59%, and one study reported an overall survival rate of 50.5% at 24 months. The evidence is very uncertain about the effect of CAR T-cell therapy on overall survival. Two studies including 294 participants at baseline and 59 participants at the longest follow-up (12 months or 18 months) described improvements of quality of life measured with the EuroQol 5-Dimension 5-Level visual analogue scale (EQ-5D-5L VAS) or Function Assessment of Cancer Therapy-Lymphoma (FACT-Lym). The evidence is very uncertain about the effect of CAR T-cell therapy on quality of life. None of the studies reported treatment-related mortality. Five studies (550 participants) reported the occurrence of adverse events among participants, ranging between 99% and 100% for any grade adverse events and 68% to 98% for adverse events grade ≥ 3. In three studies (253 participants), 56% to 68% of participants experienced serious adverse events, while in one study (28 participants), no serious adverse events occurred. CAR T-cell therapy may increase the risk of adverse events and serious adverse events but the evidence is very uncertain about the exact risk. The occurrence of cytokine release syndrome (CRS) was reported in 11 studies (675 participants) under use of various grading criteria. Five studies reported between 42% and 100% of participants experiencing CRS according to criteria described in Lee 2014. CAR T-cell therapy may increase the risk of CRS but the evidence is very uncertain about the exact risk. Nine studies (575 participants) reported results on progression-free survival, disease-free survival or relapse-free survival. Twelve-month progression-free survival rates were reported by four studies and ranged between 44% and 75%. In one study, relapse-free survival remained at a rate of 64% at both 12 and 18 months. The evidence is very uncertain about the effect of CAR T-cell therapy on progression-free survival. Thirteen studies (620 participants) provided data on complete response rates. At six months, three studies reported complete response rates between 40% and 45%. The evidence is very uncertain about the effect of CAR T-cell therapy on complete response rates. AUTHORS' CONCLUSIONS: The available evidence on the benefits and harms of CAR T-cell therapy for people with r/r DLBCL is limited, mainly because of the absence of comparative clinical trials. The results we present should be regarded in light of this limitation and conclusions should be drawn very carefully. Due to the uncertainty in the current evidence, a large number of ongoing investigations and a risk of substantial and potentially life-threatening complications requiring supplementary treatment, it is critical to continue evaluating the evidence on this new therapy.

Caso de publicación duplicada sobre complicaciones posquirúrgicas en pacientes operados por hernias inguinales / Case of duplicate publication about post-surgical in patients with complications of inguinal hernias

Recientemente leímos con interés el artículo publicado por Saliou y otros, titulado Factores asociados a las complicaciones de la cirugía electiva de las hernias inguinales1 (artículo I) en el cual describen las características asociadas a las complicaciones posquirúrgicas, de pacientes atendidos por hernias inguinales, en el Servicio de Cirugía General del Hospital Provincial Docente Saturnino Lora, de una ciudad de Cuba. Sin embargo, este trabajo publicado en la Revista Cubana de Medicina Militar presenta resultados similares a otro publicado previamente en la Revista Cubana de Cirugía, realizado por los mismos autores, cuyo título es "Complicaciones posquirúrgicas de las hernias inguinales"2 (artículo II). Al analizar el contenido de ambos artículos, siguiendo las directrices del Comité Internacional de Directores de Revistas Biomédicas (ICMJE),3 el artículo I sería una publicación duplicada, porque no muestra una clara diferencia entre ambos trabajos, ni cita adecuadamente al artículo II. Además, existe una superposición notoria de los resultados que fueron presentados en ambos trabajos. Esto genera problemas, porque se podría contabilizar inadvertidamente a ambos resultados, lo cual crea un escenario epidemiológico sesgado para posteriores investigaciones. Para que un trabajo sea considerado como una publicación secundaria autorizada, el artículo I debería cumplir las siguientes características: i) la publicación secundaria debería estar dirigido a diferentes lectores, ii) la publicación secundaria debería informar que se basa en un trabajo publicado anteriormente mediante una nota o cita y iii) el título de la publicación secundaria también debería señalar de que se trata de una versión secundaria.3 Esto no se evidencia en el artículo I, a pesar de que el artículo II ya estaba publicado (fecha de aprobación: octubre del 2019 vs fecha de publicación: abril - junio del 2019, respectivamente). En el caso de tratarse de manuscritos basados en la misma base de datos, que también contempla el ICMJE,3 el método analítico y las conclusiones deberían ser marcadamente diferentes, sin embargo, esto no queda claro entre ambos manuscritos. Si bien el artículo I efectúa una asociación entre las complicaciones posquirúrgicas, y algunas características de los pacientes operados por hernias inguinales, y el artículo II solo describe las características de las complicaciones posquirúrgicas de estos pacientes, se observa una aparente omisión intencional de datos en el artículo II, para poder dar estas ligeras diferencias entre ambos artículos. En este artículo no se presentan datos iniciales tales como edad, sexo y antecedentes clínicos necesarios para una mejor comprensión de los resultados. Todas estas características de los pacientes, solo aparecen para el análisis del...(AU)

A multi-site review of policies affecting opportunities for children with developmental disabilities to become bilingual.

This review of special education and language-in-education policies at six sites in four countries (Canada, United States, United Kingdom, and Netherlands) aimed to determine the opportunities for bilingualism provided at school for children with developmental disabilities (DD). While research has demonstrated that children with DD are capable of learning more than one language (see Kay Raining Bird, Genesee, & Verhoeven, this issue), it was not clear whether recent policies reflect these findings. The review, conducted using the same protocol across sites, showed that special education policies rarely addressed second language learning explicitly. However, at all sites, the policies favoured inclusion and educational planning based on individual needs, and thus implied that students with DD would have opportunities for second language learning. The language-in-education policies occasionally specified the support individuals with special needs would receive. At some sites, policies and educational options provided little support for minority languages, a factor that could contribute to subtractive bilingualism. At others, we found stronger support for minority languages and optional majority languages: conditions that could be more conducive to additive bilingualism.

Access to Opportunities for Bilingualism for Individuals with Developmental Disabilities: Key Informant Interviews.

The purpose of this article is to describe the results of a thematic analysis of 79 semi-structured interviews collected at six research sites in four countries in relation to the inclusion and exclusion of students with developmental disabilities (DD) in and from special education and bilingual opportunities. The participants were individuals with expertise either in special needs and/or language education to support bilingualism (e.g., second language (L2) instruction), who served as key informants about service delivery and/or policy in these areas. Six themes emerged as salient during the analysis: we include all kids, special needs drives it, time/scheduling conflicts, IEP/IPP/statement drives it, it's up to the parents, and service availability. The results suggested that access to language programs and services is limited for children with DD, even though participants at all sites reported adherence to a philosophy of inclusion. A priority on special education services over language services was identified, as well as barriers to providing children with DD access to programs and services to support bilingual development. Some of these barriers included time and scheduling conflicts and limited service availability. Additionally, the role of parents in decision making was affirmed, although, in contrast to special education services, decision-making about participation or exemption from language programs was typically left up to the parents. Overall, the results suggest a need for greater attention to providing supports for both first (L1) and L2 language development for bilingual children with DD and greater access to available language programs.

Professional practices and opinions about services available to bilingual children with developmental disabilities: An international study.

This study aimed to gather information from school- and clinic-based professionals about their practices and opinions pertaining to the provision of bilingual supports to students with developmental disabilities. Using an online survey, data were collected in six socio-culturally and linguistically diverse locations across four countries: the United States, Canada, the United Kingdom, and the Netherlands. In total, 361 surveys were included in the analysis from respondents who were primarily teachers and speech-language pathologists working in schools, daycares/preschools, or community-based clinics. The overall picture that emerged from the data reflected a disconnection between practice and opinion. In general, respondents believed that children with both mild and severe disabilities are capable of learning a second language, although their opinions were more neutral for the latter group. However, children with both mild and severe disabilities who spoke only a minority language at home had less access to services for second language learners than did their typically developing peers, although respondents agreed that such services should be more available. Regardless of clinical group, children who lived in homes where a minority language was spoken were often exposed to, assessed in, and treated in the majority language only; again, respondents generally disagreed with these practices. Finally, second language classes were less available to children in the two disability groups compared to typically developing bilingual children, with general agreement that the opportunity to acquire a second language should be more available, especially to those with mild disabilities. Although the results indicate that there is a considerable gap between current practices and professional opinions, professionals appear to be more supportive of bilingual educational opportunities for these populations than was suggested by previous research.

Encuesta sobre grado de satisfacción y evaluación de calidad de atención por familiares de enfermos de UCI / Survey on the degree of satisfaction and evaluation of the quality of attention by family of ICU patients

El soporte familiar puede disminuir la ansiedad, favorecer la recuperación y la integración del paciente en nuestras unidades. La familia como grupo social de la UCI también tiene necesidades de apoyo psíquico y emocional. Hemos estudiado el grado de satisfacción y la evaluación de calidad que hacen los familiares de enfermos (FE) de nuestro servicio. Metodología: Aplicamos una encuesta anónima a los FE con un cuestionario estructurado que pide respuestas definidas ("bueno", "malo") y que no permite términos medios, sobre diversos aspectos ambientales y del proceso de atención en nuestra unidad. También se solicitó la opinión acerca de la técnica y humana del equipo de salud. los resultados se recogieron en una base de datos informática y se aplicó prueba de Chi2. Resultados: De los 12 aspectos analizados los que recibieron una mejor evaluación fueron la calidad técnica-humana del equipo de salud y el respeto a las creencias personales y religiosas (100 por ciento aprobación), el régimen de una visita por día recibió la menor apreciación favorable (65,2 por ciento) y la única valoración negativa fue la información telefónica (47,3 por ciento). La evaluación subjetiva de la calidad técnica y humana de la atención de los funcionarios se muestra en el gráfico. Conclusión: Existe un fuerte predominio de apreciación favorable. Resultó con menor calificación positiva la existencia de una sola visita diaria y fue evaluada negativamente la información telefónica entregada. La opinión sobre calidad de la atención brindada por funcionarios tuvo una tendencia más propicia para los profesionales.