Evolving Role of Viltolarsen for Treatment of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is one of the most prevalent X-linked inherited neuromuscular disorders, with an estimated incidence between 1 in 3500 and 5000 live male births. The median life expectancy at birth is around 30 years due to a rapid and severe disease progression. Currently, there is no cure for DMD, and the standard of care is mainly palliative therapy and glucocorticoids to mitigate symptoms and improve quality of life. Recent advances in phosphorodiamidate morpholino antisense oligonucleotide (PMO) technology has proven optimistic in providing a disease-modifying therapy rather than a palliative treatment option through correcting the primary genetic defect of DMD by exon skipping. However, as a result of the high variance in mutations of the dystrophin gene causing DMD, it has been challenging to tailor an effective therapy in most patients. Viltolarsen is effective in 8% of patients and accurately skips exon 53, reestablishing the reading frame and producing a functional form of dystrophin and milder disease phenotype. Results of recently concluded preclinical and clinical trials show significantly increased dystrophin protein expression, no severe adverse effects, and stabilization of motor function. In summary, viltolarsen has provided hope for those working toward giving patients a safe and viable treatment option for managing DMD. This review summarizes an overview of the presentation, pathophysiology, genetics, and current treatment guidelines of DMD, pharmacological profile of viltolarsen, and a summary of the safety and efficacy with additional insights using recent clinical trial data.

Improving the standardisation, timeliness and efficiency of the occupational therapy admission process in an older adult inpatient service.

Occupational therapists (OTs) are at the forefront of providing recovery-oriented care for older people through timely assessments of patient's engagement in daily living activities among many other interventions. This aids a timely, safe and successful discharge from hospital.This project built on the foundations of previous work while considering the context and requirements of two older adult wards, the rates of admission and staff retention. The specific aim agreed was for 90% of patients admitted to the older adults' inpatient units to be assessed by the occupational therapy (OTY) team within days of admission by December 2022.The OTs worked in collaboration to initiate two tests of change with a total of five PDSA cycles.Our tests of change resulted in an increase of patients engaging in OTY initial assessments within seven days of admission from 47.65% (May to November 2021) to 78% (December 2021 to December 2022).Our team embarked on a quality improvement project to improve standardisation, efficiency and timeliness of the OTY process in an older adult inpatient service by using a pragmatic measure and tests of change evidenced in a previous study. This evidenced the generalisability of the findings of this study. While we were able to improve the timeliness of OTY initial assessments, we concluded that the overall impact on outcomes such as timely discharge was also dependent on other clinical and social factors.

Vitamin A-Mediated Birth Defects: A Narrative Review.

Vitamin A deficiency (VAD) or excess in expectant mothers can result in fetal abnormalities such as night blindness, bone anomalies, or epithelial cell problems. In contrast, excessive vitamin A in pregnancy can precipitate fetal central nervous system deformities. During pregnancy, a pregnant woman should monitor her vitamin A intake ensuring she gets the recommended dosage, but also ensuring she doesn't exceed the recommended dosage, because either one can result in teratogenicity in the fetus. The widespread and unregulated use of multivitamins and supplements makes consuming doses greater than the recommended quantity more common in developed countries. While vitamin A excess is more common in developed countries, deficiency is most prevalent in developing countries. With proper maintenance, regulation, and education about VAD and excess, a pregnant mother can diminish potential harm to her fetus and potential teratogenic risks.

Hypocalciuria as a Predictor of Reduced Intestinal Calcium Absorption.

Impaired intestinal calcium absorption contributes to osteoporosis, but its measurement is limited to research settings. We hypothesized that 24-hour urine calcium (24HUC) values could diagnose low fractional calcium absorption (FCA). We performed a post hoc analysis of clinical trial data to determine whether 24HUC predicted low FCA compared with the gold standard dual calcium isotope method. Two hundred thirty postmenopausal women <75 years old without osteoporosis underwent 445 FCA measurements using calcium isotopes (8 mg of oral 44Ca, 3 mg of intravenous 42Ca) and a 24-hour inpatient urine collection at 0 and 12 months. We determined subjects' total calcium intake via review of food diaries and supplements. Net calcium absorption (NCA) was total calcium intake × FCA. NCA and 24HUC values demonstrated a positive correlation (r = 0.34; 95% confidence interval, 0.25 to 0.42; P < 0.001). We calculated sensitivity, specificity, positive (PPV) and negative predictive value (NPV) for the ability of 24HUC thresholds to predict calcium malabsorption. When low calcium absorption was defined as <120 mg/d, a 24HUC value <150 mg demonstrated 65% sensitivity, 67% specificity, 31% PPV, and 89% NPV. When calcium malabsorption was defined as <100 mg/d, a 24HUC value <150 mg demonstrated 72% sensitivity, 65% specificity, 22% PPV, and 94% NPV. A 24HUC value <150 mg demonstrated a high NPV for calcium malabsorption. We suggest that 24HUC levels can exclude calcium malabsorption in postmenopausal women.

Muscle Cramps Do Not Improve With Correction of Vitamin D Insufficiency.

BACKGROUND: Minimal treatment options exist for idiopathic muscle cramps. OBJECTIVE: We evaluated whether correction of vitamin D insufficiency relieved muscle cramps in postmenopausal women. METHODS: We conducted a post hoc analysis of a randomized, double-blind, placebo-controlled trial at a single academic medical center in the Midwest to evaluate the benefits of treating vitamin D insufficiency. Two hundred thirty postmenopausal women participated. Eligible women were ≤75 years old, 5 years past menopause or oophorectomy, or ≥60 years if they had previously undergone hysterectomy without oophorectomy. Women had vitamin D insufficiency at baseline (25-hydroxyvitamin D 14-27 ng/mL). We excluded subjects with a glomerular filtration rate <45 mL/minute. INTERVENTIONS FOR CLINICAL TRIALS: Participants completed food diaries, laboratory studies, and functional tests including the Timed Up and Go test, Physical Activity Scale for the Elderly, Health Assessment Questionnaire (a measure of disability), and pain scores. Subjects recorded muscle cramp frequency and severity using a standardized form at 6 visits over 1 year. RESULTS: During the trial, over half of participants (n=121, 53%) reported muscle cramps. Despite unequivocal vitamin D repletion, vitamin D had no effect on muscle cramps. Pain levels, disability, and dietary potassium predicted presence of cramps. Serum albumin and physical activity were inversely associated with, and disability was positively associated with, severity of muscle cramps. CONCLUSIONS: Further studies are needed to evaluate the link between pain, disability, dietary potassium intake, and muscle cramps.