The evolving role of social media in enhancing quality of life: a global perspective across 10 countries.

BACKGROUND: Excessive or inappropriate use of social media has been linked to disruptions in regular work, well-being, mental health, and overall reduction of quality of life. However, a limited number of studies documenting the impact of social media on health-related quality of life (HRQoL) are available globally. AIM: This study aimed to explore the perceived social media needs and their impact on the quality of life among the adult population of various selected countries. METHODOLOGY: A cross-sectional, quantitative design and analytical study utilized an online survey disseminated from November to December 2021. RESULTS: A total of 6689 respondents from ten countries participated in the study. The largest number of respondents was from Malaysia (23.9%), followed by Bangladesh (15.5%), Georgia (14.8%), and Turkey (12.2%). The prevalence of social media users was over 90% in Austria, Georgia, Myanmar, Nigeria, and the Philippines. The majority of social media users were from the 18-24 age group. Multiple regression analysis showed that higher education level was positively correlated with all four domains of WHOQoL. In addition, the psychological health domain of quality of life was positively associated in all countries. Predictors among Social Media Needs, Affective Needs (ß = -0.07), and Social Integrative Needs (ß = 0.09) were significantly associated with psychological health. CONCLUSION: The study illuminates the positive correlation between higher education levels and improved life quality among social media users, highlighting an opportunity for policymakers to craft education-focused initiatives that enhance well-being. The findings call for strategic interventions to safeguard the mental health of the global social media populace, particularly those at educational and health disadvantages.

Prevalence and Clinical Characteristics of Sleeping Paralysis: A Systematic Review and Meta-Analysis.

Sleep paralysis (SP) is a mixed state of consciousness and sleep, combining features of rapid eye movement (REM) sleep with those of wakefulness. The exact cause of SP is unknown, and its prevalence varies among the studies. We aim to identify SP's global prevalence, the affected population's characteristics, and the SP's clinical picture. We searched three databases (PubMed, Scopus, and Web of Science (WoS)) using a unique search strategy to identify eligible studies. All observational studies identifying the prevalence or frequency of sleeping paralysis were included. No exclusions are made based on country, race, or questionnaire. The analysis was performed using the latest version of R software (R Core Team, Vienna, Austria). The analysis included 76 studies from 25 countries with 167,133 participants. The global prevalence of SP was 30% (95% CI (22%, 39%)). There were similar frequencies of isolated SP and SP (33%, 95% CI (26%, 42%), I2 = 97%, P <0.01; 31%, 95% CI (21%, 43%), I2 = 100%, P = 0, respectively). A subgroup analysis showed that the majority of those who experienced SP were psychiatric patients (35%, 95% CI (20%, 55%), I2 = 96%, P <0.01). The prevalence among non-psychiatric patients was among students (34%, 95% CI (23%, 47%), I2 = 100%, P = 0). Auditory and visual hallucinations were reported in 24.25% of patients. Around 4% had only visual hallucinations. Meta-regression showed no association between the frequency of SP and sex. Publication bias was detected among the included studies through visual inspection of funnel plot asymmetry. Our findings revealed that 30% of the population suffered from SP, especially psychiatric patients and students. The majority of SP cases lacked associated hallucinations, while a noteworthy proportion experienced combined visual and auditory hallucinations.

The hypokalaemia that came from the cold.

While electrolyte disorders are common in nephrologists' clinical practice, hypothermia is a condition that nephrologists rarely encounter. Hypothermia can induce several pathophysiological effects on the human body, including hypokalaemia, which is reversible with rewarming. Despite growing evidence from animal research and human studies, the underlying mechanisms of hypothermia-induced hypokalaemia remain unclear. Boubes and colleagues recently presented a case series of hypokalaemia during hypothermia and rewarming, proposing a novel hypothesis for the underlying mechanisms. In this editorial, we review the current knowledge about hypothermia and associated electrolyte changes with insights into the effects of hypothermia on renal physiology.

A multinational cross-sectional study on the awareness and concerns of healthcare providers toward monkeypox and the promotion of the monkeypox vaccination.

Background: The aim of this study was to explore potential healthcare workers' (HCWs) concerns about the monkeypox virus in order to create practical solutions to manage this disease. Methods: Online cross-sectional research was conducted in 11 Arabic countries (Egypt, Saudi Arabia, Yemen, Syria, Libya, Algeria, Tunisia, Iraq, Palestine, Jordan, and Sudan) from 2 August 2022 to 28 December 2022. Results: Approximately 82% of respondents felt the need to acquire further information. The acceptability of the vaccine against monkeypox has been indicated by more than half of the participants (54.5%). Furthermore, we state that 45% of the participants are knowledgeable about the monkeypox virus, and 53.1% of the participants have never been affected with COVID-19 before are more worried about COVID-19 than about monkeypox. Participants diagnosed with COVID-19 were 0.63 times less likely to worry about monkeypox than those who were not diagnosed with COVID-19. A greater willingness to get the monkeypox vaccination was seen among the age group 21-30 years (42.4%) compared to the other age groups. Conclusion: Most healthcare professionals have a moderate knowledge of the monkeypox virus. Furthermore, they demonstrated a low willingness to get the vaccination against the monkeypox virus.

Syrians' awareness of cardiovascular disease risk factors and warning indicators: a descriptive cross-sectional study.

The awareness of cardiovascular diseases (CVDs) contributes to the complications and fatality rates from these diseases among individuals; however, no previous study in Syria was conducted on this topic; thus, this study aims to assess Syrians' awareness of CVDs warning symptoms and risk factors. This online cross-sectional study was performed in Syria between the 1st and 25th of August 2022. The inclusion criteria for the sample were citizens of Syria over 18 who currently reside in Syria. The questionnaire included open- and closed-ended questions to assess the awareness of CVDs. A total of 1201 participants enrolled in the study with a response rate of 97.2%; more than half of the participants (61.4%) were aged 18-24. The most recognizable risk factors and warning signs when asking close-ended and open-ended questions were smoking (95.2%, 37.1%) and chest pain (87.8%, 24.8%), respectively. Overall knowledge scores for risk factors and warning signs were (61.5%). Regarding knowledge score of CVDs risk factors and warning signs, participants aged 45-54 scored higher than other age groups, and respondents with a university education level had a higher score than other educational levels (15.7 ± 0.3), (14.5 ± 0.1), respectively. Participants aged 45-54 have a higher probability of good knowledge of CVDs risk factors and warning signs than participants aged 18-24 (OR = 4.8, P value < 0.001), while participants living in the countryside were less likely to have good knowledge of CVDs risk factors and warning signs than city residents (OR = 0.6, P value < 0.05). According to our results, there is inadequate knowledge of the risk factors and warning signs of CVDs. Consequently, there is a greater need to raise CVD awareness and learning initiatives on the disease's risk factors and symptoms.

Glucagon-like peptide-1 receptor-agonists treatment for cardio-metabolic parameters in schizophrenia patients: a systematic review and meta-analysis.

Aims: We performed this meta-analysis to evaluate the efficacy and safety of glucagon-like peptide-1 receptor-agonists (GLP-1RA) treatment on cardio-metabolic parameters among antipsychotic-treated patients with schizophrenia. Methods: We searched the Web of Science, Cochrane Central Register of Controlled Trials, PubMed, PsycINFO, and Scopus for relevant Randomized Clinical trials (RCTs) from inception until 1 August 2022. Documents were screened for qualified articles, and all concerned outcomes were pooled as risk ratios (RR) or mean difference (MD) in the meta-analysis models using Review Manager (RevMan version 5.4). Results: Pooling data from 7 RCTs (398 patients) showed that GLP-1 RA was superior to placebo with regard to body weight [MD = - 4.68, 95% CI (-4.90,-4.46), P < 0.00001], waist circumference [MD = - 3.66, 95% CI (-3.89,-3.44), P < 0.00001], body mass index (BMI) [MD = - 1.09, 95% CI (-1.25,-0.93), P < 0.00001], systolic blood pressure (SBP) [MD = - 3.07, 95% CI (-3.61,-2.53), P < 0.00001], and diastolic blood pressure (DBP) [MD = - 2.02, 95% CI (-2.42,-1.62), P < 0.00001]. The total effect did not favor either of the two groups with respect to insulin and respiratory adverse events {[MD = - 0.06, 95% CI (-0.36, 0.24), p = 0.70], [RR = 0.66, 95% CI (0.31, 1.40), p = 0.28]; respectively}. Conclusion: Our analysis revealed that GLP-1 RA treatment is safe and effective on cardio-metabolic parameters over control in antipsychotic-treated patients with schizophrenia. Nevertheless, the present evidence is not sufficient to confirm the safety and efficacy of GLP-1RA treatment on insulin and respiratory adverse events. Therefore, further studies are recommended. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022333040.

Monkeypox Post-COVID-19: Knowledge, Worrying, and Vaccine Adoption in the Arabic General Population.

BACKGROUND: The outbreak of monkeypox was declared a global public health emergency by the World Health Organization on 23 July 2022. There have been 60,000 cases reported worldwide, most of which are in places where monkeypox has never been seen due to the travel of people who have the virus. This research aims to evaluate the general Arabic population in regard to the monkeypox disease, fears, and vaccine adoption after the WHO proclaimed a monkeypox epidemic and to compare these attitudes to those of the COVID-19 pandemic. METHODS: This cross-sectional study was performed in some Arabic countries (Syria, Egypt, Qatar, Yemen, Jordan, Sudan, Algeria, and Iraq) between 18 August and 7 September 2022. The inclusion criteria were the general public residing in Arabic nations and being older than 18. This questionnaire has 32 questions separated into three sections: sociodemographic variables, prior COVID-19 exposure, and COVID-19 vaccination history. The second portion assesses the knowledge and anxieties about monkeypox, while the third section includes the generalized anxiety disorder (GAD7) scale. Logistic regression analyses were performed to compute the adjusted odds ratios (aOR) and their confidence intervals (95%CI) using STATA (version 17.0). RESULTS: A total of 3665 respondents from 17 Arabic countries were involved in this study. Almost two-thirds (n = 2427, 66.2%) of the participants expressed more worry about COVID-19 than monkeypox diseases. Regarding the major cause for concern about monkeypox, 39.5% of participants attributed their anxiety to the fear that they or a member of their family may contract the illness, while 38.4% were concerned about monkeypox becoming another worldwide pandemic. According to the GAD 7 score, 71.7% of the respondents showed very low anxiety toward monkeypox and 43.8% of the participants scored poor levels of knowledge about monkeypox disease. Participants with previous COVID-19 infection showed a 1.206 times greater acceptance to receive the monkeypox vaccine than those with no previous infection. A 3.097 times higher concern for monkeypox than COVID-19 was shown by the participants who perceived monkeypox as dangerous and virulent than those who did not. Participants who have a chronic disease (aOR: 1.32; 95%CI: 1.09-1.60); participants worried about monkeypox (aOR: 1.21; 95%CI: 1.04-1.40), and perceived monkeypox as a dangerous and virulent disease (aOR: 2.25; 95%CI: 1.92-2.65); and excellent knowledge level (aOR: 2.28; 95%CI: 1.79-2.90) have emerged as significant predictors. CONCLUSIONS: Our study reported that three-fourths of the participants were more concerned about COVID-19 than monkeypox disease. In addition, most of the participants have inadequate levels of knowledge regarding monkeypox disease. Hence, immediate action should be taken to address this problem. Consequently, learning about monkeypox and spreading information about its prevention is crucial.

Mental health, risk perception, and coping strategies among healthcare workers in Egypt during the COVID-19 pandemic.

BACKGROUND: Coronavirus disease-19 emerged in December 2019. Healthcare workers were exposed to this highly infectious virus during the pandemic and suffered several social and psychological consequences, such as anxiety, psychological distress, and burnout. OBJECTIVES: To assess the psychological distress, anxiety, depression, coping strategies, risk perception, and attitude toward interprofessional teamwork among Egyptian healthcare workers during the COVID-19 pandemic. METHODS: We conducted a cross-sectional online survey which consisted of five sections. The primary outcomes were anxiety (GAD-7), depression (PHQ-9), risk perception towards COVID-19, interprofessional teamwork attitude, and coping strategies during the Coronavirus disease-19 pandemic. The web-based questionnaire was distributed to Egyptian healthcare workers from the 20th of April 2020 to the 20th of May 2020. A snowball sampling method was used. Regression analysis was conducted to test the relationship between the socioeconomic characteristics and the previously mentioned outcomes. RESULTS: A total of 403 participants responded to the online questionnaire. The majority were females (70.5%) and within the age group of 26-40 years (77.7%), with 2-5 years of work experience (43.2%). Most participants were pharmacists (33%) and physicians (22.1%). Eighty-two participants (21%) reported moderate to severe anxiety, and 79 participants reported (19.4%) moderate to severe depressive symptoms. In the univariate model, the marital status was associated with depression (OR 0.47, 95% CI 0.28-0.78), anxiety (OR 0.52, 95% CI 0.32-0.85), and an attitude toward interprofessional teamwork (ß = -1.96 95% CI -2.72 to -1.2). Providing direct care to the patients was associated with lower anxiety symptoms (AOR 0.256, 95% CI 0.094-0.697). More severe anxiety and depressive symptoms were associated with difficulties in everyday life and the professional work environment (AOR 4.246 and 3.3, P = 0.003 and 0.01, respectively). Availability of mental health facilities at the workplace was associated with a lower risk perception towards COVID-19 (ß = -0.79, 95% CI -1.24 to -0.34) and a more positive attitude towards teamwork (ß = 2.77 95% CI 1.38-4.15). CONCLUSIONS: According to our results, the COVID-19 pandemic was associated with mild anxiety and depression among healthcare workers in Egypt, especially pharmacists and physicians. We recommend more research targeting the mental health of healthcare workers in Egypt. If proven cost-effective and needed, wide-scale mental health screening and public health campaigns can facilitate effective prevention and treatment strategies. In addition, the availability of mental health facilities at the workplace could alleviate some of the risk perception associated with health emergencies and improve interprofessional teamwork.

Possible Mechanisms of the Neuroprotective Actions of Date Palm Fruits Aqueous Extracts against Valproic Acid-Induced Autism in Rats.

The current study aimed to determine how palm date aqueous fruit extracts (AFE) affected the autistic-like behaviors brought on by valproic acid (VPA) injection, as well as any potential contributions from Sirt-1, oxidative stress, apoptosis, and autophagy. The pregnant Sprague Dawley females were treated with VPA at 12.5th gestation day and pregnant females and their offspring were treated with AFE orally at doses of 4 mg/Kg by gastric gavage for 45 days after birth. The elevated plus-T maze, water maze, and rotarod tests were used to examine autism-like behaviors. At the end of the study, the expression of Nrf2, heme oxygenase (HO-1), Sirt-1, caspase-3 (a marker of apoptosis), LC3 (a marker of autophagy), and NFκB (inflammatory cytokines) were evaluated along with the oxidative stress in brain tissues and the histological changes in the cerebellum and hippocampus. The neurobehavioral assessments significantly declined due to VPA, which also significantly increased oxidative stress in the brain tissues and significantly decreased Nrf2 and HO-1 expression. Additionally, VPA administration caused significant increase in the expression of caspase-3 in the cerebellar cortex, not in the hippocampus; LC3 and NFκB in the hippocampus, not in the cerebellar cortex; and significant reduction in the expression of Sirt-1 in the hippocampus, not in the cerebellum. On the other hand, AFE treatment significantly improved the neurobehavioral changes as well as it improved significantly the oxidative stress and the expression of LC3, NFκB, NrF2, HO-1, and Sirt-1 in the cerebellum and hippocampus. Conclusions: AFE administration might improve the autistic-like symptoms induced by VPA in rats via attenuation of the oxidative stress, upregulation of Nrf2 and HO-1, Sirt-1 and LC3 expression with downregulation of caspase-3, and NFκB expression in the cerebellum and hippocampus.

In Vivo Mechanism of Action of Sodium Caprate for Improving the Intestinal Absorption of a GLP1/GIP Coagonist Peptide.

Sodium caprate (C10) has been widely evaluated as an intestinal permeation enhancer for the oral delivery of macromolecules. However, the effect of C10 on the intestinal absorption of peptides with different physicochemical properties and its permeation-enhancing effect in vivo remains to be understood. Here, we evaluated the effects of C10 on intestinal absorption in rats with a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GIP-GLP1) dual agonist peptide (LY) and semaglutide with different enzymatic stabilities and self-association behaviors as well as the oral exposure of the LY peptide in minipigs. Furthermore, we investigated the mechanism of action (MoA) of C10 for improving the intestinal absorption of the LY peptide in vivo via live imaging of the rat intestinal epithelium and tissue distribution of the LY peptide in minipigs. The LY peptide showed higher proteolytic stability in pancreatin and was a monomer in solution compared to that in semaglutide. C10 increased in vitro permeability in the minipig intestinal organoid monolayer to a greater extent for the LY peptide than for semaglutide. In the rat jejunal closed-loop model, C10 increased the absorption of LY peptide better than that of semaglutide, which might be attributed to higher in vitro proteolytic stability and permeability of the LY peptide. Using confocal live imaging, we observed that C10 enabled the rapid oral absorption of a model macromolecule (FD4) in the rat intestine. In the duodenum tissues of minipigs, C10 was found to qualitatively reduce the tight junction protein level and allow peptide uptake to the intestinal cells. C10 decreased the transition temperature of the artificial lipid membrane, indicating an increase in membrane fluidity, which is consistent with the above in vivo imaging results. These data indicated that the LY's favorable physicochemical properties combined with the effects of C10 on the intestinal mucosa resulted in an ∼2% relative bioavailability in minipigs.

A Meta-Analysis and Cohort Study of Histopathologic and Clinical Outcomes in ANCA-Negative versus -Positive Vasculitis.

BACKGROUND: ANCA-negative pauci-immune glomerulonephritis (PIGN) represents a rare and often under-studied subgroup of the vasculitides. This study aims to investigate differences in the clinical phenotype, renal histological features, and clinical outcomes of patients with PIGN, with and without serum ANCA positivity. METHODS: A cohort of biopsy-proven PIGN with and without detectable circulating ANCA was constructed from a single center between 2006 and 2016. Primary outcomes compared clinical presentation and histopathological features according to ANCA status, with multivariate Cox regression to compare mortality and ESKD. A systematic review and meta-analysis of the published literature was undertaken. RESULTS: In our cohort of 146 patients, 22% (n=32) had ANCA-negative disease, with a comparatively younger mean age at diagnosis; 51.4 versus 65.6 years (P<0.001). In total, 14 studies, inclusive of our cohort, were eligible for meta-analysis, totaling 301 patients who were ANCA negative. Those with ANCA-negative disease tended to have fewer extrarenal symptoms and a higher frequency of renal-limited disease, but both failed to reach statistical significance (P=0.92 and P=0.07). The risk of ESKD was significantly higher in seronegative disease (RR, 2.28; 95% confidence interval, 1.42 to 3.65; P<0.001), reflecting our experience, with a fivefold increased risk of ESKD in ANCA-negative disease (P<0.001). No significant difference in the chronicity of histopathological findings was seen and the meta-analysis showed no difference in morality (RR, 1.22; 95% confidence interval, 0.63 to 2.38; P=0.55). CONCLUSION: Our findings demonstrate that ANCA-negative PIGN presents in younger patients, with fewer extrarenal manifestations and higher ESKD risk, despite a lack of difference in histopathology. This study provides the impetus for further research into the pathogenesis, treatment response, and duration of immunotherapy in ANCA-negative disease. We suggest that the absence of positive ANCA serology should not discourage treatment and for clinical trials to include patients who are ANCA negative.

Identification of a Multi-Component Formulation for Intestinal Delivery of a GLP-1/Glucagon Co-agonist Peptide.

PURPOSE: Oral delivery of therapeutic peptides has been challenging due to multiple physiological factors and physicochemical properties of peptides. We report a systematic approach to identify formulation compositions combining a permeation enhancer and a peptidase inhibitor that minimize proteolytic degradation and increase absorption of a peptide across the small intestine. METHODS: An acylated glucagon-like peptide-1/glucagon co-agonist peptide (4.5 kDa) was selected as a model peptide. Proteolytic stability of the peptide was investigated in rat and pig SIF. Effective PEs and multiple component formulations were identified in rats. Relative bioavailability of the peptide was determined in minipigs via intraduodenal administration (ID) of enteric capsules. RESULTS: The peptide degraded rapidly in the rat and pig SIF. Citric acid, SBTI, and SBTCI inhibited the enzymatic degradation. The peptide self-associated into trimers in solution, however, addition of PEs monomerized the peptide. C10 was the most effective PE among tested PEs (DPC, LC, rhamnolipid, C12-maltosides, and SNAC) to improve intestinal absorption of the peptide in the rat IJ-closed loop model. A combination of C10 and SBTI or SBTCI increased the peptide exposure 5-tenfold compared to the exposure with the PE alone in the rat IJ-cannulated model, and achieved 1.06 ± 0.76% bioavailability in minipigs relative to subcutaneous via ID administration using enteric capsules. CONCLUSION: We identified SBTI and C10 as an effective peptidase inhibitor and PE for intestinal absorption of the peptide. The combination of SBTI and C10 addressed the peptide physiochemical properties and provides a formulation strategy to achieve intestinal delivery of this peptide.

Characterization and impact of peptide physicochemical properties on oral and subcutaneous delivery.

Peptides, an emerging modality within the biopharmaceutical industry, are often delivered subcutaneously with evolving prospects on oral delivery. Barrier biology within the subcutis or gastrointestinal tract is a significant challenge in limiting absorption or otherwise disrupting peptide disposition. Aspects of peptide pharmacokinetic performance and ADME can be mitigated with careful molecular design that tailors for properties such as effective size, hydrophobicity, net charge, proteolytic stability, and albumin binding. In this review, we endeavor to highlight effective techniques in qualifying physicochemical properties of peptides and discuss advancements of in vitro models of subcutaneous and oral delivery. Additionally, we will delineate empirical findings around the relationship of these physicochemical properties and in vivo (animal or human) impact. We conclude that robust peptide characterization methods and in vitro techniques with demonstrated correlations to in vivo data are key routines to incorporate in the drug discovery and development to improve the probability of technical and commercial success of peptide therapeutics.

Progress and limitations of oral peptide delivery as a potentially transformative therapy.

INTRODUCTION: Numerous formulation technologies have been developed to overcome challenges of oral peptide delivery. Understanding the advantages and limitations of each technology is important for the development of new delivery systems to enable oral delivery of peptides designed for parenteral administration. AREAS COVERED: This review summarizes key learnings from the use of permeation enhancers (PEs) for oral peptide delivery associated with solid dosage form optimization to maximize the PE effect. Furthermore, we will highlight the most recent emerging delivery strategies to improve oral peptide bioavailability such as nanoparticles, self-emulsifying drug delivery systems, gut shuttles, and ingestible devices. In addition, advantages and limitations of these technologies will be compared with the permeation enhancer technology. EXPERT OPINION: Despite the success of permeation enhancer technology in the FDA-approved oral peptide products, oral peptide delivery is still facing the immense challenge of low-to-single digit oral bioavailability. Optimization of drug product attributes such as dissolution kinetics is critical to improve permeation enhancer efficacy. The next frontiers to substantially increase oral bioavailability and transform injectable peptides to oral deliverables may be ingestible devices and ligand-mediated transport (gut shuttles). However, clinical studies are necessary to inform the safety and efficacy of these emerging technologies.

Recent advances in proteolytic stability for peptide, protein, and antibody drug discovery.

Introduction: To discover and develop a peptide, protein, or antibody into a drug requires overcoming multiple challenges to obtain desired properties. Proteolytic stability is one of the challenges and deserves a focused investigation.Areas covered: This review concentrates on improving proteolytic stability by engineering the amino acids around the cleavage sites of a liable peptide, protein, or antibody. Peptidases are discussed on three levels including all peptidases in databases, mixtures based on organ and tissue types, and individual peptidases. The technique to identify cleavage sites is spotlighted on mass spectrometry-based approaches such as MALDI-TOF and LC-MS. For sequence engineering, the replacements that have been commonly applied with a higher chance of success are highlighted at the beginning, while the rarely used and more complicated replacements are discussed later. Although a one-size-fits-all approach does not exist to apply to different projects, this review provides a 3-step strategy for effectively and efficiently conducting the proteolytic stability experiments to achieve the eventual goal of improving the stability by engineering the molecule itself.Expert opinion: Improving the proteolytic stability is a spiraling up process sequenced by testing and engineering. There are many ways to engineer amino acids, but the choice must consider the cost and properties affected by the changes of the amino acids.

Treatment Outcomes of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis in Patients Over Age 75 Years: A Meta-Analysis.

BACKGROUND: The benefits of treating anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) in advancing age remains unclear with most published studies defining elderly as ≥65 years. This study aims to determine outcomes of induction immunosuppression in patients aged ≥75 years. METHODS: A cohort of patients aged ≥75 years with a diagnosis of AAV between 2006 and 2018 was constructed from 2 centres. Follow-up was to 2 years or death. Analysis included multivariable Cox regression to compare mortality and end-stage renal disease (ESRD) based on receipt of induction immunosuppression therapy with either cyclophosphamide or rituximab. A systematic review of outcome studies was subsequently undertaken amongst this patient group through Pubmed, Cochrane and Embase databases from inception until October 16, 2019. RESULTS: Sixty-seven patients were identified. Mean age was 79 ± 2.9 years and 82% (n = 55) received induction immunosuppression. Following systematic review, 4 studies were eligible for inclusion, yielding a combined total of 290 patients inclusive of our cohort. The aggregated 1-year mortality irrespective of treatment was 31% (95% CI 25-36%). Within our cohort, induction immunosuppression therapy was associated with a significantly lower 2-year mortality risk (hazard ratio [HR] 0.29 [95% CI 0.09-0.93]). The pooled HR by meta-analysis confirmed this with a significant risk reduction for death (HR 0.31 [95% CI 0.16-0.57], I2 = 0%). Treated patients had a lower pooled rate of ESRD, but was not statistically significant (HR 0.71 [95% CI 0.15-3.35]). CONCLUSION: This meta-analysis suggests that patients ≥75 years with AAV do benefit from induction immunosuppression with a significant survival benefit. Age alone should not be a limiting factor when considering treatment.

Propensity score matched mortality comparisons of peritoneal and in-centre haemodialysis: systematic review and meta-analysis.

BACKGROUND: Accurate comparisons of haemodialysis (HD) and peritoneal dialysis (PD) survival based on observational studies are difficult due to substantial residual confounding that arises from imbalances between treatments. Propensity score matching (PSM) comparisons confer additional advantages over conventional methods of adjustment by further reducing selection bias between treatments. We conducted a systematic review of studies that compared mortality between in-centre HD with PD using a PSM-based approach. METHODS: A sensitive search strategy identified all citations in the PubMed, Cochrane and EMBASE databases from inception through November 2018. Pooled PD versus HD mortality hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated through random-effects meta-analysis. A subsequent meta-regression explored factors to account for between-study variation. RESULTS: The systematic review yielded 214 citations with 17 cohort studies and 113 578 PSM incident dialysis patients. Cohort periods spanned the period 1993-2014. The pooled HR for PD versus HD was 1.06 (95% CI 0.99-1.14). There was considerable variation by country, however, mortality risks for PD versus HD remained virtually unchanged when stratified by geographical region with HRs of 1.04 (95% CI 0.94-1.15), 1.14 (95% CI 0.99-1.32) and 0.98 (0.87-1.10) for European, Asian and American cohorts, respectively. Subgroup meta-analyses revealed similar risks for patients with diabetes [HR 1.09 (95% CI 0.98-1.21)] and without diabetes [HR 0.99 (95% CI 0.90-1.09)]. Heterogeneity was substantial (I2 = 87%) and was largely accounted for by differences in cohort period, study type and country of origin. Together these factors explained a substantial degree of between-studies variance (R2 = 90.6%). CONCLUSIONS: This meta-analysis suggests that PD and in-centre HD carry equivalent survival benefits. Reported differences in survival between treatments largely reflect a combination of factors that are unrelated to clinical efficacy.