Efficacy and safety of treatment with omalizumab for chronic spontaneous urticaria: A systematic review for the EAACI Biologicals Guidelines

This systematic review evaluates the efficacy and safety of omalizumab for chronic spontaneous urticaria (CSU). PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CSU-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Ten RCTs including 1620 subjects aged 12 to 75 years old treated with omalizumab for 16 to 40 weeks were evaluated. Omalizumab 150 mg does not result in clinically meaningful improvement (high certainty) of the urticaria activity score (UAS)7 (mean difference (MD) −5; 95%CI −7.75 to −2.25), and the itch severity score (ISS)7 (MD −2.15; 95% CI −3.2 to −1.1) does not increase (moderate certainty) quality of life (QoL) (Dermatology Life Quality Index (DLQI); MD −2.01; 95%CI −3.22 to −0.81) and decreases (moderate certainty) rescue medication use (MD −1.68; 95%CI −2.95 to −0.4). Omalizumab 300 mg results in clinically meaningful improvements (moderate certainty) of the UAS7 (MD −11.05; 95%CI −12.87 to −9.24), the ISS7 (MD −4.45; 95%CI −5.39 to −3.51), and QoL (high certainty) (DLQI; MD −4.03; 95% CI −5.56 to −2.5) and decreases (moderate certainty) rescue medication use (MD −2.04; 95%CI −3.19 to −0.88) and drug-related serious AEs (RR 0.77; 95%CI 0.20 to 2.91).     

Self-efficacy and health-related quality of life in chronic obstructive pulmonary disease: A meta-analysis

ObjectiveTo determine the association between self-efficacy and health-related quality of life (HRQoL) in people with Chronic Obstructive Pulmonary Disease (COPD) and the moderating effect of self-efficacy type (exercise task, exercise barrier, COPD symptom, general) and HRQoL type (generic, COPD specific).MethodsDatabases were searched systematically from inception to January 2019. Methodological quality was assessed, and a meta-analysis was conducted following PRISMA guidelines (PROSPERO protocol: CRD42018114846).ResultsAcross 31 coefficients, there was a positive relationship between self-efficacy and HRQoL (r = 0.38, 95 %CI [0.32, 0.45]). Exercise barrier self-efficacy had the strongest relationship to HRQoL (r = 0.42, 95 % CI [0.30, 0.52]), followed by COPD symptoms (r = 0.41, 95 % CI [0.33, 0.49]), exercise tasks (r = 0.40, 95 % CI [0.29, 0.50]), and general self-efficacy (r = 0.21, 95 % CI [0.14, 0.28]). Generic HRQoL had a similar relationship to self-efficacy (r = 0.38, 95 % CI [0.28, 0.47]) as COPD specific HRQoL (r = 0.38, 95 % CI [0.30, 0.46]).ConclusionThere is a moderate positive relationship between self-efficacy and HRQoL in COPD, with the relationship stronger for exercise and COPD symptoms than general self-efficacy.     

Unsupervised home-based resistance training for community-dwelling older adults: A systematic review and meta-analysis of randomized controlled trials

BackgroundWe aimed to summarize evidence on the safety, adherence and effectiveness of home-based resistance training (UHBRT) for improving health-related endpoints in community-dwelling older adults.MethodsRandomized controlled trials of UHBRT in older adults (≥60yrs) were included after a systematic search (PubMed, CINAHL, PsycInfo, SPORTDiscus, Web of Science, MEDLINE, Cochrane Central Register of Controlled Trials) until 02/19/2021. Adverse events and adherence rates were assessed as indicators of feasibility. Other endpoints included physical (muscle strength, muscle power, balance, physical performance) and mental-related measures (cognition, quality of life [QoL]) as well as other health-related variables (body composition, physical activity levels, falls).Results21 studies (N = 4,053) were included. No major adverse events were reported, with adherence averaging 67 % (range 47–97 %). UHBRT significantly improved lower-limb muscle strength (Hedges' g = 0.33; 95 % confidence interval [CI] = 0.11−0.57), muscle power measured through the sit-to-stand test (g = 0.44; 95 %CI = 0.06−0.84), and balance (assessed with the postural sway, g = 0.32; 95 %CI = 0.16−0.49). No benefits were found for other strength indices (handgrip strength), balance (single leg stance and functional reach test), physical performance (walking speed, TUG and SPPB), QoL, nor for the risk or rate of falls (all p > 0.05, g<0.61). No meta-analysis could be performed for the remaining endpoints.ConclusionsAlthough efforts are needed to increase adherence, preliminary evidence suggests that UHBRT can be safe and modestly effective for improving some measures of lower-limb muscle strength, balance, and muscle power in community-dwelling older adults. However, no benefits were found for other physical fitness measures, QoL or falls. More evidence is therefore needed to draw definite conclusions.     

Self-management support provided by trained asthma educators result in improved quality of life and asthma control compared to usual care: A systematic review and meta-analysis

ObjectivesWe sought to describe training activities on self-management support (SMS) for asthma educators and the effects of SMS provided by trained educators on asthma patient outcomes.MethodsWe conducted a systematic review of six medical databases and sought for trials assessing SMS provided for adults with asthma by trained educators. Two reviewers independently selected and extracted data on asthma educators’ training activities and patient outcomes. We performed meta-analyses for asthma-related quality of life (QoL) and asthma control.ResultsWe screened 3217 records and included 16 trials. Learning activities and assessments were reported in 8/16 and 4/16 trials, respectively. Compared to usual care, trained asthma educators provided SMS that resulted in clinically important improvements in QoL (pooled mean difference [MD] = 0.52; 95% confidence interval [95%CI]: 0.19 to 0.83) and asthma control (pooled MD= −0.68; 95%CI: −0.99 to −0.38).ConclusionAlthough asthma-specific SMS provided by trained educators had a beneficial effect over the current care, our results highlight the need to better describe training activities for asthma educators.Practice implicationsThis systematic review provides key elements of efficient training activities for asthma educators and reaffirms the importance of training educators to provide SMS in order to improve asthma patients’ QoL and asthma control.     

Transcranial direct current stimulation for balance rehabilitation in neurological disorders: A systematic review and meta-analysis

Postural instability is common in neurological diseases. Although transcranial direct current stimulation (tDCS) seems to be a promising complementary therapy, emerging evidence indicates mixed results and protocols’ characteristics. We conducted a systematic review and meta-analysis on PubMed, EMBASE, Scopus, and Web of Science to synthesize key findings of the effectiveness of single and multiple sessions of tDCS alone and combined with other interventions on balance in adults with neurological disorders. Thirty-seven studies were included in the systematic review and 33 in the meta-analysis. The reviewed studies did not personalize the stimulation protocol to individual needs/characteristics. A random-effects meta-analysis indicated that tDCS alone (SMD = −0.44; 95%CI = −0.69/−0.19; p < 0.001) and combined with another intervention (SMD = −0.31; 95%CI = −0.51/−0.11; p = 0.002) improved balance in adults with neurological disorders (small to moderate effect sizes). Balance improvements were evidenced regardless of the number of sessions and targeted area. In summary, tDCS is a promising therapy for balance rehabilitation in adults with neurological disorders. However, further clinical trials should identify factors that influence responsiveness to tDCS for a more tailored approach, which may optimize the clinical use of tDCS.     

Health-related quality of life measurement in women with polycystic ovary syndrome: a systematic review

The symptoms typically associated with polycystic ovary syndrome (PCOS) such as acne, hirsutism, irregular menses, amenorrhoea, obesity and subfertility are a major source of psychological morbidity and can negatively affect quality of life (QoL). We systematically searched the literature to identify the impact of symptoms and treatments for PCOS on health-related QoL (HRQoL) and to report on the types and psychometric properties of the instruments used. Papers were retrieved by systematically searching four electronic databases and hand searching relevant reference lists and bibliographies. Nineteen papers used a standardized questionnaire to measure health status; of these 12 (63.2%) used generic tools and 8 (42%) used the disease-specific PCOS questionnaire. Although a meta-analysis was not possible, it appears that weight concerns have a particular negative impact upon HRQoL, although the role of body mass index in affecting HRQoL scores is inconclusive from the available evidence. Acne is the area least reported upon in terms of its impact upon HRQoL. With the exception of three studies, most of the research has focused upon adult women with PCOS. Despite the benefits of HRQoL measures in research, few are being used to evaluate the outcomes of treatment for PCOS upon the subjective health status of women with the condition.     

Prevalence and factors related to COVID-19 vaccine hesitancy and unwillingness in Canada: A systematic review and meta-analysis

This systematic review and meta-analysis examined the prevalence and factors associated with vaccine hesitancy and vaccine unwillingness in Canada. Eleven databases were searched in March 2022. The pooled prevalence of coronavirus disease 2019 (COVID-19) vaccine hesitancy and unwillingness was estimated. Subgroup analyses and meta-regressions were performed. Out of 667 studies screened, 86 full-text articles were reviewed, and 30 were included in the systematic review. Twenty-four articles were included in the meta-analysis; 12 for the pooled prevalence of vaccine hesitancy (42.3% [95% CI, 33.7%–51.0%]) and 12 for vaccine unwillingness (20.1% [95% CI, 15.2%−24.9%]). Vaccine hesitancy was higher in females (18.3% [95% CI, 12.4%−24.2%]) than males (13.9% [95% CI, 9.0%−18.8%]), and in rural (16.3% [95% CI, 12.9%−19.7%]) versus urban areas (14.1% [95%CI, 9.9%−18.3%]). Vaccine unwillingness was higher in females (19.9% [95% CI, 11.0%−24.8%]) compared with males (13.6% [95% CI, 8.0%−19.2%]), non-White individuals (21.7% [95% CI, 16.2%−27.3%]) than White individuals (14.8% [95% CI, 11.0%−18.5%]), and secondary or less (24.2% [95% CI, 18.8%−29.6%]) versus postsecondary education (15.9% [95% CI, 11.6%−20.2%]). Factors related to racial disparities, gender, education level, and age are discussed.     

The different role of PD-L1 in head and neck squamous cell carcinomas: A meta-analysis

Programmed cell death-ligands 1 (PD-L1) is a promising immune target for tumor immunotherapy. We conducted this meta-analysis to investigate association between PD-L1 expression and clinicopathological characteristics of head and neck squamous cell carcinomas (HNSCC). Electronic databases were searched for eligible studies. Hazard ratio (HR) with 95 % confidence interval (CI) were extracted to assess the relationship between PD-L1 expression and overall survival (OS) and disease-free survival (DFS) of patients. Odds ratio (OR) with 95 %CI were applied to assess the association between PD-L1 expression and clinicopathological features. A total of 1729 patients were identified for this meta-analysis. PD-L1 expression was higher in female patients in HNSCC (OR = 0.58, 95 %CI:0.44–0.76). In oral squamous cell carcinoma (OSCC), female(OR = 0.56, 95 %CI: 0.41–0.77)and lower grade(OR = 0.48, 95 %CI: 0.24-0.93)were associated with the higher PD-L1 level. There was no significant association between OS and PD-L1 in OSCC patients (HR = 0.89, 95 %CI: 0.37–2.14). In oropharyngeal squamous cell carcinoma (OPSCC), PD-L1 was overexpressed in younger patients (OR = 0.43, 95 %CI: 0.21−0.86), higher tumor grade (OR = 2.46, 95 %CI: 1.38–4.37)and positive HPV status (OR = 2.09, 95 %CI:1.42-3.07). No significant correlation was detected between PD-L1 expression and OS in OPSCC patients (HR = 0.78, 95 %CI: 0.57–1.06). However, the higher PD-L1 expression in tumor cells indicated a better DFS of OPSCC (HR = 0.34, 95 %CI: 0.18-0.67). This meta-analysis demonstrated that PD-L1 overexpression in HNSCC associated with female patients. However, no significant difference was observed in OS or DFS, except the DFS in OPSCC.     

Benefits and harms of exercise therapy in people with multimorbidity: A systematic review and meta-analysis of randomised controlled trials

ObjectivesTo investigate the benefits and harms of exercise therapy on physical and psychosocial health in people with multimorbidity.DesignSystematic review of randomised controlled trials (RCTs). Data sources MEDLINE, EMBASE, CENTRAL and CINAHL from 1990 to April 20th, 2020 and Cochrane reviews on the effect of exercise therapy for each of the aforementioned conditions, reference lists of the included studies, the WHO registry and citation tracking on included studies in Web of Science.Eligibility criteria for study selectionRCTs investigating the benefit of exercise therapy in people with multimorbidity, defined as two or more of the following conditions: osteoarthritis (of the knee or hip), hypertension, type 2 diabetes, depression, heart failure, ischemic heart disease, and chronic obstructive pulmonary disease on at least one of the following outcomes: Health-related quality of life (HRQoL), physical function, depression or anxiety.Summary and quality of the evidenceMeta-analyses using a random-effects model to assess the benefit of exercise therapy and the risk of non-serious and serious adverse events according to the Food and Drug Administration definition. Meta-regression analyses to investigate the impact of pre-specified mediators of effect estimates. Cochrane ‘Risk of Bias Tool’ 2.0 and the GRADE assessment to evaluate the overall quality of evidence.ResultsTwenty-three RCTs with 3363 people, testing an exercise therapy intervention (mean duration 13.0 weeks, SD 4.0) showed that exercise therapy improved HRQoL (standardised mean difference (SMD) 0.37, 95 % CI 0.14 to 0.61) and objectively measured physical function (SMD 0.33, 95 % CI 0.17 to 0.49), and reduced depression symptoms (SMD -0.80, 95 % CI -1.21 to -0.40) and anxiety symptoms (SMD -0.49, 95 % CI -0.99 to 0.01). Exercise therapy was not associated with an increased risk of non-serious adverse events (risk ratio 0.96, 95 % CI 0.53–1.76). By contrast, exercise therapy was associated with a reduced risk of serious adverse events (risk ratio 0.62, 95 % CI 0.49 to 0.78). Meta-regression showed that increasing age was associated with lower effect sizes for HRQoL and greater baseline depression severity was associated with greater reduction of depression symptoms. The overall quality of evidence for all the outcomes was downgraded to low, mainly due to risk of bias, inconsistency and indirectness.ConclusionsExercise therapy appears to be safe and to have a beneficial effect on physical and psychosocial health in people with multimorbidity. Although the evidence supporting this was of low quality, it highlights the potential of exercise therapy in the management and care of this population.     

The mental health of women with polycystic ovary syndrome: a systematic review and meta-analysis

Polycystic ovary syndrome (PCOS) has been proposed to be associated with several mental health problems, including anxiety, depression, diminished sexual satisfaction, and lowered health-related quality of life, etc. A systematic review and meta-analysis of published literature was conducted comparing the mental health of women with and without PCOS. Ten English and Chinese databases were searched up to 12/31/2018. Random-effects models were introduced, and subgroup analysis, sensitivity test, and meta-regression were carried out to determine the source for heterogeneity among studies. Forty-six studies, including 30,989 participants (9265 women with PCOS and 25,638 controls), were qualified for review according to the inclusion criteria. Twenty-eight studies reported depression symptoms, 22 studies were on anxiety, 16 studies showed quality of life (QoL) status, 12 studies were about sexual dysfunction, five on emotional distress, four on binge eating, and four on somatization. Women with PCOS reported significantly higher depression (SMD = 0.64; 95% CI 0.50–0.78), anxiety (SMD = 0.63; 95% CI 0.50–0.77), lower QoL (SMD = − 0.55; 95% CI −0.69 to −0.40), and not significant sexual dysfunction (SMD = − 0.24; 95% CI − 0.49 to 0.01). Studies from different countries, adopting various diagnosis criteria, using diverse instruments, as well as in different years, have reported heterogenetic results. Women with PCOS in China reported a larger effect size of depression and anxiety than patients from other countries. The results of this study have indicated that women with PCOS suffer from depression, anxiety, and experience a lower quality of life, whereas their sexual function is not distinct from that of healthy women. Psychological health care interventions for women with PCOS were addressed.

     

Is living alone a risk factor of frailty? A systematic review and meta-analysis

ObjectivesTo examine the association of living alone with frailty in cross-sectional and longitudinal studies by a systematic review and meta-analysis.DesignSystematic review and meta-analysis.Setting and participantsCommunity-dwelling older adults with a mean age of >60 years.MethodsA systematic search of the literature was conducted according to the PRISMA guidelines. We searched PubMed in February 2019 without language restriction for cohort studies that examined the associations between living alone and frailty. The reference lists of the relevant articles and the included articles were reviewed for additional studies. We calculated pooled odds ratios (OR) of the presence and incidence of frailty for living alone from cross-sectional and longitudinal studies.ResultsAmong the 203 studies identified, data of 44 cross-sectional studies (46 cohorts) and 6 longitudinal studies were included in this review. The meta-analysis showed that older adults living alone were more likely to be frail than those who were not (46 cohorts: pooled OR = 1.28, 95 % confidence interval (CI) = 1.13–1.45, p < 0.001). Gender-stratified analysis showed that only men living alone were at an increased risk of being frail (20 cohorts: pooled OR = 1.71, 95 %CI = 1.49–1.96), while women were not (22 cohorts: pooled OR = 1.00, 95 %CI = 0.83–1.20). No significant association was observed in a meta-analysis of longitudinal studies (6 cohorts: pooled OR = 0.88, 95 %CI = 0.76–1.03).Conclusions/ImplicationsThe present systematic review and meta-analysis showed a significant cross-sectional association between living alone and frailty, especially in men. However, living alone did not predict incident frailty. More studies controlling for important confounders, such as social networks, are needed to further enhance our understanding of how living alone is associated with frailty among older adults.     

Associations between loneliness and physical frailty in community-dwelling older adults: A systematic review and meta-analysis

ObjectivesOlder adults may be at increased risk of loneliness. Frailty is also common in older adults, however, associations between loneliness and frailty have been understudied. This systematic review and meta-analysis aimed to explore evidence on how loneliness and frailty are correlated.MethodsA systematic search of the literature was conducted using 4 electronic databases in February 2022 for any studies published in 2000 or later that provided cross-sectional or longitudinal associations between loneliness and physical frailty in community-dwelling older adults. A meta-analysis was attempted to combine data when possible.ResultsFrom 1386 studies identified by the initial search, 16 studies were included for this review. Standardized mean difference (SMD) meta-analysis based on mean loneliness score across 3 frailty groups provided by 6 cross-sectional studies showed that worse frailty status was significantly associated with a higher degree of loneliness (SMD between frail and robust, frail and prefrail, and prefrail and robust were 0.77 (95% confidence interval (CI)= 0.57–0.96), 0.37 (95%CI=0.25–0.50), and 0.30 (95%CI=0.20–0.40), respectively.) Meta-analyses combining cross-sectional data from 6 studies revealed that frailty was significantly associated with a higher risk of loneliness compared with robustness (3 studies: pooled OR=3.51, 95%CI=2.70–4.56 for frailty, pooled OR=1.88, 95%CI=1.57–2.25 for prefrailty) and compared with non-frailty (4 studies: pooled OR=2.05, 95%CI=1.76–2.39). A meta-analysis involving two longitudinal studies showed that baseline loneliness was associated with a significantly higher risk of worsening frailty (2 studies: pooled OR=1.41, 95%CI=1.16–1.72).ConclusionsThis systematic review and meta-analysis was the first, to our knowledge, to quantitatively demonstrate significant cross-sectional and longitudinal associations between loneliness and frailty in community-dwelling older adults.     

Efficacy and safety of treatment with biologicals (benralizumab,dupilumab and omalizumab) for severe allergic asthma: A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma

Allergic asthma is a frequent asthma phenotype. Both IgE and type 2 cytokines are increased, with some degree of overlap with other phenotypes. Systematic reviews assessed the efficacy and safety of benralizumab, dupilumab and omalizumab (alphabetical order) vs standard of care for patients with uncontrolled severe allergic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. All three biologicals reduced with high certainty the annualized asthma exacerbation rate: benralizumab incidence rate ratios (IRR) 0.63 (95% CI 0.50 − 0.81); dupilumab IRR 0.58 (95%CI 0.47 − 0.73); and omalizumab IRR 0.56 (95%CI 0.42 − 0.73). Benralizumab and dupilumab improved asthma control with high certainty and omalizumab with moderate certainty; however, none reached the minimal important difference (MID). Both benralizumab and omalizumab improved QoL with high certainty, but only omalizumab reached the MID. Omalizumab enabled ICS dose reduction with high certainty. Benralizumab and omalizumab showed an increase in drug-related adverse events (AEs) with low to moderate certainty. All three biologicals had moderate certainty for an ICER/QALY value above the willingness to pay threshold. There was high certainty that in children 6-12 years old omalizumab decreased the annualized exacerbation rate [IRR 0.57 (95%CI 0.45-0.72)], improved QoL [relative risk 1.43 (95%CI 1.12 −1.83)], reduced ICS [mean difference (MD) −0.45 (95% CI −0.58 to −0.32)] and rescue medication use [ MD −0.41 (95%CI −0.66 to −0.15)].     

Effects of the COVID-19 pandemic on sleep quality in children and adolescents: A systematic review and meta-analysis

We synthesise the literature on the potential influence of the COVID-19 pandemic on sleep quality in children and adolescents. The search identified studies that examined the relationship between sleep quality and disorders during the COVID-19 pandemic. It began in May 2021 and has had two updates with the last in January 2022. The databases used were LILACS, PubMed, and EMBASE. Random effects models were performed to explore heterogeneity between studies. Data were presented as continuous variables (mean value and standard deviation) to perform a meta-analysis. Twenty-nine studies from 16 countries were identified: Nine had children and eight had adolescents. The overall quality of the studies ranged from high (27.6%) to medium (65.5%) and low (6.9%). Eight studies were eligible for meta-analysis. There was an increase in sleep duration during the pandemic when compared with the previous period 0.33 (95%CI −0.07; 0.60) (p < 0.001) and late bedtime 0.78 (95%CI −0.33; 1.22) (p < 0.001). A trend toward reduced sleep efficiency was also detected 0.54 (95%CI −0.75; −0.33) p = 0.20. Parents’ reports of increased use of screen media/electronic devices were associated with worse sleep quality. The results suggest an influence of the pandemic on sleep characteristics such as increased sleep duration, late bedtimes, and poor sleep quality. These alterations were related to changes in family routines during this period.     

Efficacy and safety of treatment with biologicals for severe chronic rhinosinusitis with nasal polyps: A systematic review for the EAACI guidelines

This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared with the standard of care. PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CRSwNP-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. RCTs evaluated (dupilumab-2, omalizumab-4, mepolizumab-2, and reslizumab-1) included 1236 adults, with follow-up of 20–64 weeks. Dupilumab reduces the need for surgery (NFS) or oral corticosteroid (OCS) use (RR 0.28; 95% CI 0.20–0.39, moderate certainty) and improves with high certainty smell evaluated with UPSIT score (mean difference (MD) +10.54; 95% CI +9.24 to +11.84) and quality of life (QoL) evaluated with SNOT-22 (MD −19.14; 95% CI −22.80 to −15.47), with fewer treatment-related adverse events (TAEs) (RR 0.95; 95% CI 0.89–1.02, moderate certainty). Omalizumab reduces NFS (RR 0.85; 95% CI 0.78–0.92, high certainty), decreases OCS use (RR 0.38; 95% CI 0.10–1.38, moderate certainty), and improves high certainty smell (MD +3.84; 95% CI +3.64 to +4.04) and QoL (MD −15.65; 95% CI −16.16 to −15.13), with increased TAE (RR 1.73; 95% CI 0.60–5.03, moderate certainty). There is low certainty for mepolizumab reducing NFS (RR 0.78; 95% CI 0.64–0.94) and improving QoL (MD −13.3; 95% CI −23.93 to −2.67) and smell (MD +0.7; 95% CI −0.48 to +1.88), with increased TAEs (RR 1.64; 95% CI 0.41–6.50). The evidence for reslizumab is very uncertain.     

The effectiveness of tocilizumab and its comparison with tumor necrosis factor alpha inhibitors for Takayasu Arteritis: A systematic review and meta-analysis

Takayasu arteritis (TAK) refractory to conventional disease-modifying anti-rheumatic drugs (DMARDs) is commonly treated with biologic DMARDs such as tocilizumab or tumor necrosis factor-alpha inhibitors (TNFi). The 2021 American College of Rheumatology (ACR) recommendations preferred TNFi to tocilizumab. Therefore, we conducted a systematic review with meta-analysis to assess the evidence base for tocilizumab in TAK by updating a previous systematic review on DMARDs in TAK through searches on MEDLINE, Pubmed Central, Scopus, major international Rheumatology conference abstracts, and clinical trial databases from January 2021 to November 2022. Thirty-five studies involving 1082 TAK [one randomized controlled trial (RCT), eleven controlled and twenty-one uncontrolled studies, most of moderate to high quality] had evaluated tocilizumab in TAK. The RCT of tocilizumab versus placebo failed to meet its primary end-point of superiority of tocilizumab on an intention-to-treat analysis (hazard ratio 0.41, 95%CI 0.15–1.10) but successfully met the secondary end-point of superiority on per-protocol analysis (hazard ratio 0.34, 95%CI 0.11–1.00). A meta-analysis of six studies identified similar rates of clinical remission [risk ratio (RR) tocilizumab vs TNFi 1.03, 95%CI 0.91–1.17)], angiographic stabilization (RR 1.00, 95%CI 0.72–1.40) or adverse events (RR 0.84, 95%CI 0.54–1.31) with tocilizumab or TNFi. A meta-analysis of three studies identified superior clinical response (RR 1.55, 95%CI 1.15–2.10) and adverse effect profile (RR 0.45, 95%CI 0.25–0.80) with tocilizumab than cyclophosphamide. Pooled data from uncontrolled studies identified clinical response in 85%(95%CI 79–91%) and angiographic stabilization in 82% (95%CI 68–94%). Our study suggests similar evidence for treating TAK with tocilizumab or TNFi, contrary to the ACR 2021 recommendations.     

Variations and morphometric features of the vermiform appendix: A systematic review and meta-analysis of 114,080 subjects with clinical implications

Determining the true and indisputable data regarding the vermiform appendix (VA) morphology is of a great clinical interest. The aim of this study was to provide the best evidence-based anatomical overview of the variations in location and size of VA using a systematic and meta-analytical approach. A systematic review with meta-analysis was performed of studies reporting variants of the location and morphometric data regarding the VA. The MEDLINE/PubMed, ScienceDirect, EMBASE, BIOSIS, SciELO, and Web of Science databases were thoroughly searched throughout June 2018. The reported locations of the body of the VA were re-classified into a new, standardized classification system divided into nine categories. The AQUA tool was used to assess the quality of included studies. The research was conducted following PRISMA guidelines and registered at PROPSERO database. Our meta-analysis included 242 studies (n = 114,080). Overall, the VA was most commonly found in the retrocecal location (32.1%, 95%CI: 29.2–35.1), followed by the pelvic (28.5%, 95%CI: 26.7–30.4) and ileal (14.5%, 95%CI: 11.8–17.7) locations. Subjects without known appendiceal pathologies had significantly smaller VA outer diameters (5.84 mm, 95%CI: 5.68–5.99) than patients diagnosed with acute appendicitis (10.64 mm, 95%CI: 10.14–11.15). The overall pooled mean length of the VA was 80.29 mm (95%CI: 76.68–83.89). Significant differences were found in size of the VA between imaging modalities. The results obtained from this evidence-based anatomy study will improve the clinical understanding of the VA anatomy, which in turn will have major implications for clinical practice. Clin. Anat. 32:85–98, 2019. © 2019 Wiley Periodicals, Inc.     

Evidence on multimorbidity from definition to intervention: An overview of systematic reviews

The increasing challenge of multiple chronic diseases (multimorbidity) requires more evidence-based knowledge and effective practice. In order to better understand the existing evidence on multimorbidity, we performed a systematic review of systematic reviews on multimorbidity with pre-established search strategies and exclusion criteria by searching multiple databases and grey literature. Of 8006 articles found, 53 systematic reviews (including meta-analysis and qualitative research synthesis performed in some reviews) that stated multimorbidity as the main focus were included, with 79% published during 2013–2016. Existing evidence on definition, measurement, prevalence, risk factors, health outcomes, clinical practice and medication (polypharmacy), and intervention and management were identified and synthesised. There were three major definitions from three perspectives. Seven studies on prevalence reported a range from 3.5% to 100%. As six studies showed, depression, hypertension, diabetes, arthritis, asthma, and osteoarthritis were prone to be comorbid with other conditions. Four groups of risk factors and eight multimorbidity associated outcomes were explored by five and six studies, respectively. Nine studies evaluated interventions, which could be categorized into either organizational or patient-oriented, the effects of these interventions were varied. Self-management process, priority setting and decision making in multimorbidity were synthesised by evidence from 4 qualitative systematic reviews. We were unable to draw solid conclusions from this overview due to the heterogeneity in methodology and inconsistent findings among included reviews. As suggested by all included studies, there is a need for prospective research, especially longitudinal cohort studies and randomized control trials, to provide more definitive evidence on multimorbidity.     

ARIA‐suggested drugs for allergic rhinitis: what impact on quality of life? A GA2LEN Review

Allergic diseases constitute a global health problem, as they have an increasing economic and social impact and, especially, they can deeply interfere with the patients' daily life, being a cause of physical and emotional discomfort. This is why the health-related quality-of-life (HRQoL) has become increasingly important in health care research; in fact, the assessment of the impact the disease and its treatment have on patients, provides a more comprehensive approach in outcome evaluation. Numerous validated questionnaires are available and many studies have been performed evaluating HRQoL in people affected by allergic rhinitis (AR), thus testifying a great interest in this topic. The aims of the present review are: to examine the scientific literature of the last 3 years dealing with the impact of AR treatments suggested by allergic rhinitis and its impact on asthma guidelines on patients' QoL, and to identify the unexplored or not-fully-investigated areas concerning this issue.