Population-Based Study of Pertussis Incidence and Risk Factors among Persons >50 Years of Age, Australia.

Despite vaccination programs, pertussis has been poorly controlled, especially among older adults in Australia. This longitudinal, retrospective, observational study aimed to estimate the incidence and risk factors of pertussis among persons ≥50 years of age in Australia in the primary care setting, including those with underlying chronic obstructive pulmonary disease (COPD) or asthma. We used the IQVIA general practitioner electronic medical record database to identify patients ≥50 years of age with a clinical diagnosis of pertussis during 2015-2019. Pertussis incidence rates ranged from 57.6 to 91.4 per 100,000 persons and were higher among women and highest in those 50-64 years of age. Patients with COPD or asthma had higher incidence rates and an increased risk for pertussis compared with the overall population ≥50 years of age. Our findings suggest that persons ≥50 years of age in Australia with COPD or asthma have a higher incidence of and risk for pertussis diagnosis.

Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients.

BACKGROUND: Kidney transplantation is the preferred management for patients with end-stage kidney disease (ESKD). However, it is often complicated by worsening or new-onset diabetes. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. This is an update of a review first published in 2017. OBJECTIVES: To evaluate the efficacy and safety of glucose-lowering agents for treating pre-existing and new onset diabetes in people who have undergone kidney transplantation. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 16 January 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs), quasi-RCTs and cross-over studies examining head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in patients who have received a kidney transplant and have diabetes were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Four authors independently assessed study eligibility and quality and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD) or standardised mean difference (SMD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI). MAIN RESULTS: Ten studies (21 records, 603 randomised participants) were included - three additional studies (five records) since our last review. Four studies compared more intensive versus less intensive insulin therapy; two studies compared dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo; one study compared DPP-4 inhibitors to insulin glargine; one study compared sodium glucose co-transporter 2 (SGLT2) inhibitors to placebo; and two studies compared glitazones and insulin to insulin therapy alone. The majority of studies had an unclear to a high risk of bias. There were no studies examining the effects of biguanides, glinides, GLP-1 agonists, or sulphonylureas. Compared to less intensive insulin therapy, it is unclear if more intensive insulin therapy has an effect on transplant or graft survival (4 studies, 301 participants: RR 1.12, 95% CI 0.32 to 3.94; I2 = 49%; very low certainty evidence), delayed graft function (2 studies, 153 participants: RR 0.63, 0.42 to 0.93; I2 = 0%; very low certainty evidence), HbA1c (1 study, 16 participants; very low certainty evidence), fasting blood glucose (1 study, 24 participants; very low certainty evidence), kidney function markers (1 study, 26 participants; very low certainty evidence), death (any cause) (3 studies, 208 participants" RR 0.68, 0.29 to 1.58; I2 = 0%; very low certainty evidence), hypoglycaemia (4 studies, 301 participants; very low certainty evidence) and medication discontinuation due to adverse effects (1 study, 60 participants; very low certainty evidence). Compared to placebo, it is unclear whether DPP-4 inhibitors have an effect on hypoglycaemia and medication discontinuation (2 studies, 51 participants; very low certainty evidence). However, DPP-4 inhibitors may reduce HbA1c and fasting blood glucose but not kidney function markers (1 study, 32 participants; low certainty evidence). Compared to insulin glargine, it is unclear if DPP-4 inhibitors have an effect on HbA1c, fasting blood glucose, hypoglycaemia or discontinuation due to adverse events (1 study, 45 participants; very low certainty evidence). Compared to placebo, SGLT2 inhibitors probably do not affect kidney graft survival (1 study, 44 participants; moderate certainty evidence), but may reduce HbA1c without affecting fasting blood glucose and eGFR long-term (1 study, 44 participants, low certainty evidence). SGLT2 inhibitors probably do not increase hypoglycaemia, and probably have little or no effect on medication discontinuation due to adverse events. However, all participants discontinuing SGLT2 inhibitors had urinary tract infections (1 study, 44 participants, moderate certainty evidence). Compared to insulin therapy alone, it is unclear if glitazones added to insulin have an effect on HbA1c or kidney function markers (1 study, 62 participants; very low certainty evidence). However, glitazones may make little or no difference to fasting blood glucose (2 studies, 120 participants; low certainty evidence), and medication discontinuation due to adverse events (1 study, 62 participants; low certainty evidence). No studies of DPP-4 inhibitors, or glitazones reported effects on transplant or graft survival, delayed graft function or death (any cause). AUTHORS' CONCLUSIONS: The efficacy and safety of glucose-lowering agents in the treatment of pre-existing and new-onset diabetes in kidney transplant recipients is questionable. Evidence from existing studies examining the effect of intensive insulin therapy, DPP-4 inhibitors, SGLT inhibitors and glitazones is mostly of low to very low certainty. Appropriately blinded, larger, and higher quality RCTs are needed to evaluate and compare the safety and efficacy of contemporary glucose-lowering agents in the kidney transplant population.

Young Adult Depression, Antidepressant Prescriptions, and Therapy Intensification in People With Incident Depression in the United States.

Objective: To evaluate the temporal trend in young adult depression, prescription patterns of first- and second-line antidepressants, and factors influencing therapy intensification for depression stratified by sex.Methods: A retrospective cohort of people aged ≥ 18 years with incident depression between 2006 and 2017 was extracted from the Centricity Electronic Medical Records.Results: Among 2,201,086 people with depression (82% on antidepressants), the mean age was 47 years, 29% were male, 40% had cardiometabolic multimorbidity, and 32% were diagnosed at age < 40 years (young adult depression). Prevalence of young adult depression increased significantly from 26% to 36% with a higher proportion in females compared to males (34% vs 26%) between 2006 and 2017. Selective serotonin reuptake inhibitors (SSRIs) were the most prescribed first-line antidepressant (56%), with a prescribing rate increase from 47 per 1,000 person-years to 81 per 1,000 person-years. Among first-line antidepressant recipients, 23% had treatment intensification after a median of 17 months. Compared to those aged 60-70 years, younger males and females had a similar significantly higher treatment intensification risk (range of hazard ratio [HR], 1.09-1.46). Cardiometabolic multimorbidity was associated with a 2% (HR CI, 1.01-1.05) and 7% (HR CI, 1.05-1.09) higher treatment intensification risk in males and females, respectively, while anxiety increased the treatment intensification risk by 63% (HR CI, 1.57-1.68) in males and 57% (HR CI, 1.52-1.62) in females. Non-Whites and SSRI initiators had lower risks of treatment intensification (all HR CI < 1).Conclusions: More than one-third of US adults with depression are aged < 40 years with an increasing trend among females. The temporal antidepressant prescribing rates were similar between sex, while significant ethnic disparity in therapy intensification was observed between sex.

Antidepressant prescriptions and therapy intensification in men and women newly diagnosed with depression in the UK.

BACKGROUND: Evidence on therapeutic interventions and factors driving treatment intensification (TI) in people with incident depression in UK are scarce. AIMS: To explore antidepressant prescribing patterns and factors influencing TI. DESIGN: and setting: Retrospective cohort study of adults with incident depression diagnosed between 2006 and 2017 using UK primary care database. METHODS: Patterns of antidepressant prescriptions, and factors influencing TI were evaluated by sex. RESULTS: In 931,302 people with depression (90% initiating antidepressants), mean age was 39 years, 41% were male, 14% had cardiometabolic multimorbidity (CMM), and 54% were diagnosed at < 40 years. Being the most prescribed first-line antidepressant (62%), SSRI prescribing rate increased from 66 per 1000 person-years to 170 per 1000 person-years; 24% (2% dose escalation, 4% adding, 18% switching) of first-line antidepressant initiators intensified with 13 months median time to TI. Compared to 60-70 years, younger adults had significantly higher TI risk (range of hazards ratio, HR: 1.08-1.42). CMM and anxiety were associated with 15-24% and 39-49% significantly higher TI risks respectively. First-line antidepressant and deprivation status influenced TI differently by gender. CONCLUSIONS: Men and women with depression in UK have different antidepressant prescription patterns in real-world. Age at diagnosis, deprivation status and cardiometabolic multimorbidity are the major sociodemographic and non-psychiatric risk factors for therapeutic changes.

Hospital revisits after paediatric tonsillectomy: a cohort study.

BACKGROUND: Tonsillectomy, with or without adenoidectomy, is the leading reason for paediatric unplanned hospital readmission, some of which are potentially avoidable. Reducing unplanned hospital revisits would improve patient safety and decrease use of healthcare resources. This study aimed to describe the incidence, timing and risk factors for any surgery-related hospital revisits (both emergency presentation and readmission) following paediatric tonsillectomy and adenotonsillectomy in a large state-wide cohort. METHODS: We conducted a population-based cohort study using linked administrative datasets capturing all paediatric tonsillectomy and adenotonsillectomy surgeries performed between 2010 and 2015 in the state of Victoria, Australia. The primary outcome was presentation to the emergency department or hospital readmission within 30-day post-surgery. RESULTS: Between 2010 and 2015, 46,583 patients underwent 47,054 surgeries. There was a total of 4758 emergency department presentations (10.11% total surgeries) and 2750 readmissions (5.84% total surgeries). Haemorrhage was the most common reason for both revisit types, associated with 33.02% of ED presentations (3.34% total surgeries) and 67.93% of readmissions (3.97% total surgeries). Day 5 post-surgery was the median revisit time for both ED presentations (IQR 3-7) and readmission (IQR 3-8). Predictors of revisit included older age, public and metropolitan hospitals and peri-operative complications during surgery. CONCLUSIONS: Haemorrhage was the most common reason for both emergency department presentation and hospital readmission. The higher risk of revisits associated with older children, surgeries performed in public and metropolitan hospitals, and in patients experiencing peri-operative complications, suggest the need for improved education of postoperative care for caregivers, and avoidance of inappropriate early discharge.

Smell and Taste Dysfunction in Patients With COVID-19: A Systematic Review and Meta-analysis.

OBJECTIVE: To estimate the prevalence of olfactory and gustatory dysfunctions (OGDs) among patients infected with novel coronavirus disease 2019 (COVID-19). METHODS: A systematic review was conducted by searching MEDLINE, EMBASE, and the preprint server MedRxiv from their inception until May 11, 2020, using the terms anosmia or hyposmia or dysosmia or olfactory dysfunction or olfaction disorder or smell dysfunction or ageusia or hypogeusia or dysgeusia or taste dysfunction or gustatory dysfunction or neurological and COVID-19 or 2019 novel coronavirus or 2019-nCoV or SARS-CoV-2. The references of included studies were also manually screened. Only studies involving patients with diagnostic-confirmed COVID-19 infection were included. Random-effects meta-analysis was performed. RESULTS: Twenty-four studies with data from 8438 patients with test-confirmed COVID-19 infection from 13 countries were included. The pooled proportions of patients presenting with olfactory dysfunction and gustatory dysfunction were 41.0% (95% CI, 28.5% to 53.9%) and 38.2% (95% CI, 24.0% to 53.6%), respectively. Increasing mean age correlated with lower prevalence of olfactory (coefficient = -0.076; P=.02) and gustatory (coefficient = -0.073; P=.03) dysfunctions. There was a higher prevalence of olfactory dysfunctions with the use of objective measurements compared with self-reports (coefficient = 2.33; P=.01). No significant moderation of the prevalence of OGDs by sex was observed. CONCLUSION: There is a high prevalence of OGDs among patients infected with COVID-19. Routine screening for these conditions could contribute to improved case detection in the ongoing COVID-19 pandemic. However, to better inform population screening measures, further studies are needed to establish causality.

Angiotensin converting enzyme genotypes and mortality from COVID-19: An ecological study.

BACKGROUND: Angiotensin converting enzyme (ACE) genotypes are known to be associated with development of acute respiratory distress syndrome (ARDS) and resultant mortality. In the present study, we examined the association between distribution frequency of ACE genotypes and COVID-19 mortality. METHODS: We undertook an ecological study to examine the association between ACE genotypes and COVID-19 mortality across 25 countries to represent different geographical regions of the world. The population frequencies of ACE genotypes were drawn from previously published reports and data on COVID-19-related mortality were extracted from 'Worldometer'. Multivariable analyses were also undertaken adjusting for age (median age), sex (percentage of females) and the number of COVID-19 tests undertaken. Associations between genotypes deletion/deletion (DD) and insertion/insertion (II) prevalence and COVID-19-related mortality (per million people per day since the first diagnosed case) were evaluated. RESULTS: The frequency of II genotype is highest in east Asian countries and lower among the European and African countries. An inverse geographical distribution frequency was noted for DD genotype. Increasing II genotype frequency was significantly associated with decreased COVID-19 mortality rates (adjusted incident rate ratio [IRR] 0.3, 95% confidence interval [CI]: 0.002-0.7, p = 0.03). However, no association was found between DD genotype frequency and COVID-19 mortality rates (adjusted IRR 4.3, 95% CI: 0.5-41.2, p = 0.2). CONCLUSIONS: Distribution frequency of ACE insertion/insertion (II) genotype may have a significant influence on COVID-19 mortality. This information has potential utility for resource planning at a systemic level, as well as for clinical management.

Global Incidence of Frailty and Prefrailty Among Community-Dwelling Older Adults: A Systematic Review and Meta-analysis.

Importance: Frailty is a common geriatric syndrome of significant public health importance, yet there is limited understanding of the risk of frailty development at a population level. Objective: To estimate the global incidence of frailty and prefrailty among community-dwelling adults 60 years or older. Data Sources: MEDLINE, Embase, PsycINFO, Web of Science, CINAHL Plus, and AMED (Allied and Complementary Medicine Database) were searched from inception to January 2019 without language restrictions using combinations of the keywords frailty, older adults, and incidence. The reference lists of eligible studies were hand searched. Study Selection: In the systematic review, 2 authors undertook the search, article screening, and study selection. Cohort studies that reported or had sufficient data to compute incidence of frailty or prefrailty among community-dwelling adults 60 years or older at baseline were eligible. Data Extraction and Synthesis: The methodological quality of included studies was assessed using The Joanna Briggs Institute's Critical Appraisal Checklist for Prevalence and Incidence Studies. Meta-analysis was conducted using a random-effects (DerSimonian and Laird) model. Main Outcomes and Measures: Incidence of frailty (defined as new cases of frailty among robust or prefrail individuals) and incidence of prefrailty (defined as new cases of prefrailty among robust individuals), both over a specified duration. Results: Of 15 176 retrieved references, 46 observational studies involving 120 805 nonfrail (robust or prefrail) participants from 28 countries were included in this systematic review. Among the nonfrail individuals who survived a median follow-up of 3.0 (range, 1.0-11.7) years, 13.6% (13 678 of 100 313) became frail, with the pooled incidence rate being 43.4 (95% CI, 37.3-50.4; I2 = 98.5%) cases per 1000 person-years. The incidence of frailty was significantly higher in prefrail individuals than robust individuals (pooled incidence rates, 62.7 [95% CI, 49.2-79.8; I2 = 97.8%] vs 12.0 [95% CI, 8.2-17.5; I2 = 94.9%] cases per 1000 person-years, respectively; P for difference < .001). Among robust individuals in 21 studies who survived a median follow-up of 2.5 (range, 1.0-10.0) years, 30.9% (9974 of 32 268) became prefrail, with the pooled incidence rate being 150.6 (95% CI, 123.3-184.1; I2 = 98.9%) cases per 1000 person-years. The frailty and prefrailty incidence rates were significantly higher in women than men (frailty: 44.8 [95% CI, 36.7-61.3; I2 = 97.9%] vs 24.3 [95% CI, 19.6-30.1; I2 = 8.94%] cases per 1000 person-years; prefrailty: 173.2 [95% CI, 87.9-341.2; I2 = 99.1%] vs 129.0 [95% CI, 73.8-225.0; I2 = 98.5%] cases per 1000 person-years). The incidence rates varied by diagnostic criteria and country income level. The frailty and prefrailty incidence rates were significantly reduced when accounting for the risk of death. Conclusions and Relevance: Results of this study suggest that community-dwelling older adults are prone to developing frailty. Increased awareness of the factors that confer high risk of frailty in this population subgroup is vital to inform the design of interventions to prevent frailty and to minimize its consequences.