This article examines anticipatory economic stress—or the stress of future economic crises or events that may negatively impact material well‐being—for LGBTQ adults. Using qualitative interview data ...from 76 LGBTQ adults, three main sources of anticipatory economic stress emerged: the family, the workplace, and health care. Following an intersectionality framework, these anticipatory economic stressors are experienced differently across gender and racial lines, heightening anticipatory economic stress for LGBTQ people of color and transgender respondents. This article has significant implications for understanding the role of future economic stress in the present and provides important insight into what specific forms of anticipatory economic stress that shape the lives of LGBTQ individuals.
Autoimmune and allergic diseases occur when an individual mounts an inappropriate immune response to a self-antigen or an innocuous environmental antigen. This triggers a pathogenic T-cell response ...resulting in damage to specific tissues and organs. In type 1 diabetes (T1D), this manifests as destruction of the insulin-secreting β cells, resulting in a life-long dependency on recombinant insulin. Modulation of the pathogenic T-cell response with antigen-specific peptide immunotherapy offers the potential to restore the immune homeostasis and prevent further tissue destruction. Recent clinical advances with peptide therapy approaches in both T1D and other diseases are beginning to show encouraging results. New technologies targeting the peptides to specific cell types are also moving from pre-clinical development to the clinic. While many challenges remain in clinical development, not least selection of the optimal dose and dosing frequency, this is clearly becoming a very active field of drug development.
To provide the level and trends of prevalence, incidence and disability adjusted life years (DALYs) for rheumatoid arthritis (RA) in 195 countries from 1990 to 2017 by age, sex, Socio-demographic ...Index (SDI; a composite of sociodemographic factors) and Healthcare Access and Quality (an indicator of health system performance) Index.
Data from the Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2017 were used. GBD 2017 modelled the burden of RA for 195 countries from 1990 to 2017, through a systematic analysis of mortality and morbidity data to estimate prevalence, incidence and DALYs. All estimates were presented as counts and age-standardised rates per 100 000 population, with uncertainty intervals (UIs).
Globally, the age-standardised point prevalence and annual incidence rates of RA were 246.6 (95% UI 222.4 to 270.8) and 14.9 (95% UI 13.3 to 16.4) in 2017, which increased by 7.4% (95% UI 5.3 to 9.4) and 8.2% (95% UI 5.9 to 10.5) from 1990, respectively. However, the age-standardised rate of RA DALYs per 100 000 population was 43.3 (95% UI 33.0 to 54.5) in 2017, which was a 3.6% (95% UI -9.7 to 0.3) decrease from the 1990 rate. The age-standardised prevalence and DALY rates increased with age and were higher in females; the rates peaked at 70-74 and 75-79 age groups for females and males, respectively. A non-linear association was found between age-standardised DALY rate and SDI. The global age-standardised DALY rate decreased from 1990 to 2012 but then increased and reached higher than expected levels in the following 5 years to 2017. The UK had the highest age-standardised prevalence rate (471.8 (95% UI 428.9 to 514.9)) and age-standardised incidence rate (27.5 (95% UI 24.7 to 30.0)) in 2017. Canada, Paraguay and Guatemala showed the largest increases in age-standardised prevalence rates (54.7% (95% UI 49.2 to 59.7), 41.8% (95% UI 35.0 to 48.6) and 37.0% (95% UI 30.9 to 43.9), respectively) and age-standardised incidence rates (48.2% (95% UI 41.5 to 55.1), 43.6% (95% UI 36.6 to 50.7) and 36.8% (95% UI 30.4 to 44.3), respectively) between 1990 and 2017.
RA is a major global public health challenge. The age-standardised prevalence and incidence rates are increasing, especially in countries such as Canada, Paraguay and Guatemala. Early identification and treatment of RA is vital especially among females, in order to reduce the ongoing burden of this condition. The quality of health data needs to be improved for better monitoring of disease burden.
The European Association of Urology Non-neurogenic Male Lower Urinary Tract Symptoms Panel has comprehensively reviewed the available literature of male incontinence. This review provides the latest ...information on the diagnosis and management of stress and urge urinary incontinence in males.
Urinary incontinence (UI) is a common condition in elderly men causing a severe worsening of quality of life, and a significant cost for both patients and health systems.
To report a practical, evidence-based, guideline on definitions, pathophysiology, diagnostic workup, and treatment options for men with different forms of UI.
A comprehensive literature search, limited to studies representing high levels of evidence and published in the English language, was performed. Databases searched included Medline, EMBASE, and the Cochrane Libraries. A level of evidence and a grade of recommendation were assigned.
UI can be classified into stress urinary incontinence (SUI), urge urinary incontinence (UUI), and mixed urinary incontinence. A detailed description of the pathophysiology and diagnostic workup has been reported. Simple clinical interventions, behavioural and physical modifications, and pharmacological treatments comprise the initial management for all kinds of UI. Surgery for SUI includes bulking agents, male sling, and compression devices. Surgery for UUI includes bladder wall injection of botulinum toxin A, sacral nerve stimulation, and cystoplasty/urinary diversion.
This 2022 European Association of Urology guideline summary provides updated information on definition, pathophysiology, diagnosis, and treatment of male UI.
Male urinary incontinence comprises a broad subject area, much of which has been covered for the first time in the literature in a single manuscript. The European Association of Urology Non-neurogenic Male Lower Urinary Tract Symptoms Guideline Panel has released this new guidance, with the aim to provide updated information for urologists to be able to follow diagnostic and therapeutic indications for optimising patient care.
Excess mortality and residual disability are common after hip fracture.
Twelve months of high-intensity weight-lifting exercise and targeted multidisciplinary interventions will result in lower ...mortality, nursing home admissions, and disability compared with usual care after hip fracture.
Randomized, controlled, parallel-group superiority study.
Outpatient clinic
Patients (n = 124) admitted to public hospital for surgical repair of hip fracture between 2003 and 2007.
Twelve months of geriatrician-supervised high-intensity weight-lifting exercise and targeted treatment of balance, osteoporosis, nutrition, vitamin D/calcium, depression, cognition, vision, home safety, polypharmacy, hip protectors, self-efficacy, and social support.
Functional independence: mortality, nursing home admissions, basic and instrumental activities of daily living (ADLs/IADLs), and assistive device utilization.
Risk of death was reduced by 81% (age-adjusted OR 95% CI = 0.19 0.04-0.91; P < .04) in the HIPFIT group (n = 4) compared with usual care controls (n = 8). Nursing home admissions were reduced by 84% (age-adjusted OR 95% CI = 0.16 0.04-0.64; P < .01) in the experimental group (n = 5) compared with controls (n = 12). Basic ADLs declined less (P < .0001) and assistive device use was significantly lower at 12 months (P = .02) in the intervention group compared with controls. The targeted improvements in upper body strength, nutrition, depressive symptoms, vision, balance, cognition, self-efficacy, and habitual activity level were all related to ADL improvements (P < .0001-.02), and improvements in basic ADLs, vision, and walking endurance were associated with reduced nursing home use (P < .0001-.05).
The HIPFIT intervention reduced mortality, nursing home admissions, and ADL dependency compared with usual care.
Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure disorder in which pure red blood cell aplasia is associated with physical malformations and a predisposition to cancer. Twentyfive ...percent of patients with DBA have mutations in a gene encoding ribosomal protein S19 (RPS19). Our previous proof-of-concept studies demonstrated that DBA phenotype could be successfully treated using lentiviral vectors in Rps19-deficient DBA mice. In our present study, we developed a clinically applicable single gene, self-inactivating lentiviral vector, containing the human RPS19 cDNA driven by the human elongation factor 1a short promoter, which can be used for clinical gene therapy development for RPS19-deficient DBA. We examined the efficacy and safety of the vector in a Rps19-deficient DBA mouse model and in human primary RPS19-deficient CD34+ cord blood cells. We observed that transduced Rps19-deficient bone marrow cells could reconstitute mice long-term and rescue the bone marrow failure and severe anemia observed in Rps19-deficient mice, with a low risk of mutagenesis and a highly polyclonal insertion site pattern. More importantly, the vector can also rescue impaired erythroid differentiation in human primary RPS19-deficient CD34+ cord blood hematopoietic stem cells. Collectively, our results demonstrate the efficacy and safety of using a clinically applicable lentiviral vector for the successful treatment of Rps19-deficient DBA in a mouse model and in human primary CD34+ cord blood cells. These findings show that this vector can be used to develop clinical gene therapy for RPS19-deficient DBA patients.
ABSTRACT
The gills of most teleost fishes lack plasma-accessible carbonic anhydrase (paCA) that could participate in CO2 excretion. We tested the prevailing hypothesis that paCA would interfere with ...red blood cell (RBC) intracellular pH regulation by β-adrenergic sodium-proton exchangers (β-NHE) that protect pH-sensitive haemoglobin–oxygen (Hb–O2) binding during an acidosis. In an open system that mimics the gills, β-NHE activity increased Hb–O2 saturation during a respiratory acidosis in the presence or absence of paCA, whereas the effect was abolished by NHE inhibition. However, in a closed system that mimics the tissue capillaries, paCA disrupted the protective effects of β-NHE activity on Hb–O2 binding. The gills are an open system, where CO2 generated by paCA can diffuse out and is not available to acidifying the RBCs. Therefore, branchial paCA in teleosts may not interfere with RBC pH regulation by β-NHEs, and other explanations for the evolutionary loss of the enzyme must be considered.
Background: Pancreatitis can be challenging from a diagnostic and management point of view in both canine and feline patients.
Aim of the article: This article considers the differences in anatomy ...and pathophysiology between dogs and cats and discusses a practical approach to these cases in the clinic. It also highlights when it's appropriate to manage these cases the same way, as well as the critical times when clinicians should remember that cats aren't just small dogs.
To estimate the global burden of low back pain (LBP).
LBP was defined as pain in the area on the posterior aspect of the body from the lower margin of the twelfth ribs to the lower glutaeal folds ...with or without pain referred into one or both lower limbs that lasts for at least one day. Systematic reviews were performed of the prevalence, incidence, remission, duration, and mortality risk of LBP. Four levels of severity were identified for LBP with and without leg pain, each with their own disability weights. The disability weights were applied to prevalence values to derive the overall disability of LBP expressed as years lived with disability (YLDs). As there is no mortality from LBP, YLDs are the same as disability-adjusted life years (DALYs).
Out of all 291 conditions studied in the Global Burden of Disease 2010 Study, LBP ranked highest in terms of disability (YLDs), and sixth in terms of overall burden (DALYs). The global point prevalence of LBP was 9.4% (95% CI 9.0 to 9.8). DALYs increased from 58.2 million (M) (95% CI 39.9M to 78.1M) in 1990 to 83.0M (95% CI 56.6M to 111.9M) in 2010. Prevalence and burden increased with age.
LBP causes more global disability than any other condition. With the ageing population, there is an urgent need for further research to better understand LBP across different settings.
To estimate the global burden of rheumatoid arthritis (RA), as part of the Global Burden of Disease 2010 study of 291 conditions and how the burden of RA compares with other conditions.
The optimum ...case definition of RA for the study was the American College of Rheumatology 1987 criteria. A series of systematic reviews were conducted to gather age-sex-specific epidemiological data for RA prevalence, incidence and mortality. Cause-specific mortality data were also included. Data were entered into DisMod-MR, a tool to pool available data, making use of study-level covariates to adjust for country, region and super-region random effects to estimate prevalence for every country and over time. The epidemiological data, in addition to disability weights, were used to calculate years of life lived with disability (YLDs). YLDs were added to the years of life lost due to premature mortality to estimate the overall burden (disability-adjusted life years (DALYs)) for RA for the years 1990, 2005 and 2010.
The global prevalence of RA was 0.24% (95% CI 0.23% to 0.25%), with no discernible change from 1990 to 2010. DALYs increased from 3.3 million (M) (95% CI 2.6 M to 4.1 M) in 1990 to 4.8 M (95% CI 3.7 M to 6.1 M) in 2010. This increase was due to a growth in population and increase in aging. Globally, of the 291 conditions studied, RA was ranked as the 42nd highest contributor to global disability, just below malaria and just above iodine deficiency (measured in YLDs).
RA continues to cause modest global disability, with severe consequences in the individuals affected.
PDF
