Circadian Rhythms in Patients with ST-Elevation Myocardial Infarction

BACKGROUND: Circadian rhythms with regard to time of symptom onset for patients with acute myocardial infarction have been observed, although their relationship to outcomes has been debated. We evaluated these rhythms in patients with ST-elevation myocardial infarction as a function of the 24-hour circadian cycle. METHODS AND RESULTS: The relationship between onset of symptoms during the 24-hour circadian cycle and prehospital delays from symptom onset to hospital arrival, timeliness of reperfusion, and in-hospital death was assessed in 2143 patients with ST-elevation myocardial infarction presenting from 2004-2008 at 1 of 3 tertiary-care healthcare ST-elevation myocardial infarction systems. There was a significant association between time of onset and the circadian cycle, with the greatest percentage (39%) of patients experiencing onset between 8 AM and 3 PM (P\u3c0.001). Time of onset was associated with prehospital delay and timeliness of reperfusion. Patients with onset from 12 AM to 5:59 AM had median prehospital delays of 121 minutes versus 70 minutes from 12 PM to 5:59 PM (P\u3c0.001). Patients with onset time from 12 AM to 5:59 AM had median door-to-balloon times of 75 minutes versus 60 minutes from 6 AM to 11:59 AM (P\u3c0.001). Using multivariable modeling to control for baseline patient characteristics, prehospital delay, and timeliness of reperfusion, there was no significant association between time of symptom onset with in-hospital death. CONCLUSIONS: Patients with ST-elevation myocardial infarction exhibit significant circadian patterns in symptom onset, prehospital delay, and timeliness of reperfusion. Patients who develop symptoms from 12 AM to 5:59 AM present with longer prehospital delays and have longer door-to-balloon times. After multivariable adjustment, there was no significant association between circadian patterns of time of onset and in-hospital death

Paraneoplastic Acral Vascular Syndrome

Introduction Cases of rheumatologic phenomena coinciding with malignancy have been well-documented in the medical literature. These syndromes may be associated with common autoimmune markers, potentially masking the underlying diagnosis of malignancy. The association between malignancy and its coinciding rheumatologic manifestations is poorly understood. These paraneoplastic symptoms are more prevalent in high-stage adenocarcinomas of the lung, breast, and ovary. Possible mechanisms may include cytokine derangements, blood hyperviscosity, and circulatory disruption. While some evidence suggests that control of the primary tumor alleviates its associated paraneoplastic symptoms, other proposed therapies include heparin, prednisone, aspirin, and vasodilatory agents. Efficacy is limited due to association of these syndromes with high-grade malignancy. We describe the case of a patient presenting with para neoplastic acral vascular syndrome (PAVS) in association with primary ovarian carcimona.1.2 Case The patient is a 57-year-old female with a history ofHashimoto\u27s thyroiditis and migraines, who presents with an ulcerating rash of the fingertips and a tender discoloration of the plantar aspect of both feet. The rash began four weeks prior to presentation as a purple discoloration of the fingertips, progressing to a desquamating, palmar rash with distal phalangeal ulceration and necrosis of the fingertips. Almost simultaneously, the patient experienced purple discoloration of the soles of her feet bilaterally and described a sensation of standing on marbles. She denies similar episodes in the past as well as sick contacts. She reports experiencing excessive stress in preparing for her daughter\u27s wedding, exposure to a new type of dryer sheet, and a recent manicure/pedicure. The patient was recently treated with two medrol dose packs, minocydine, nitroglycerin paste (which had to be discontinued due to hypotension), and aspirin. Following treatment, the patient had no relief of symptoms

Variation in patient information and rehabilitation regimens after flexor tendon repair in the United Kingdom

Introduction There is clinical uncertainty regarding the optimal method of rehabilitation following flexor tendon repair. Many splint designs and rehabilitation regimens are reported in the literature; however, there is insufficient evidence to support the use of any one regimen. The aim of this study was to describe rehabilitation guidelines used in the United Kingdom (UK) following zone I/II flexor tendon repair. Methods Using a cross-sectional design, hand units in the UK were invited to complete a short survey and to upload their flexor tendon rehabilitation guidelines and patient information material. Approval was granted by the British Association of Hand Therapists. Data were extracted in duplicate, using a pre-piloted form, and analysed using descriptive statistics. Results Thirty-five hand units responded (21%), providing 52 treatment guidelines. Three splinting regimens were described, and all involved early active mobilisation: (i) long dorsal-blocking splint (DBS); (ii) short DBS; and (iii) relative motion flexion splint. Duration of full-time splint wear ranged from 4 to 6 weeks. There were variations in splint design and composition of home exercise programmes, particularly for the long DBS. Where reported, recommended return to driving ranged from 8 to 12 weeks, and return to light work activities ranged from 5 to 10 weeks. Discussion Treatment guidelines varied across UK hand therapy departments, suggesting that patients receive differing advice about how to protect, move and use their hand after zone I/II flexor tendon repair. The disparity in splint wear duration, home exercise frequency and prescribed functional restrictions raises potential financial and social implications for patients. Future research should explore rehabilitation burden in addition to clinical outcomes

Impact of Renal Impairment on Beta-Blocker Efficacy in Patients With Heart Failure.

BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS: Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS: Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction

Multiparametric MRI Changes Persist Beyond Recovery in Concussed Adolescent Hockey Players

Objective: To determine whether multiparametric MRI data can provide insight into the acute and long-lasting neuronal sequelae after a concussion in adolescent athletes. Methods: Players were recruited from Bantam hockey leagues in which body checking is first introduced (male, age 11–14 years). Clinical measures, diffusion metrics, resting-state network and region-to-region functional connectivity patterns, and magnetic resonance spectroscopy absolute metabolite concentrations were analyzed from an independent, age-matched control group of hockey players (n 5 26) and longitudinally in concussed athletes within 24 to 72 hours (n 5 17) and 3 months (n 5 14) after a diagnosed concussion. Results: There were diffusion abnormalities within multiple white matter tracts, functional hyperconnectivity, and decreases in choline 3 months after concussion. Tract-specific spatial statistics revealed a large region along the superior longitudinal fasciculus with the largest decreases in diffusivity measures, which significantly correlated with clinical deficits. This region also spatially intersected with probabilistic tracts connecting cortical regions where we found acute functional connectivity changes. Hyperconnectivity patterns at 3 months after concussion were present only in players with relatively less severe clinical outcomes, higher choline concentrations, and diffusivity indicative of relatively less axonal disruption. Conclusions: Changes persisted well after players’ clinical scores had returned to normal and they had been cleared to return to play. Ongoing white matter maturation may make adolescent athletes particularly vulnerable to brain injury, and they may require extended recovery periods. The consequences of early brain injury for ongoing brain development and risk of more serious conditions such as second impact syndrome or neural degenerative processes need to be elucidated

Nutritional and Exercise-Focused Lifestyle Interventions and Glycemic Control in Women with Diabetes in Pregnancy: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Diabetes disrupts one in six pregnancies, bestowing immediate and long-term health risks to mother and child. Diet and exercise are commonly prescribed to control dysglycemia, but their effectiveness across sub-populations and types of diabetes (type-1; type-2; or gestational diabetes mellitus, GDM) is uncertain. Therefore, a systematic review and meta-analysis on the effect of diet and/or exercise on glycemia in pregnant women with diabetes was conducted. Random effects models were used to evaluate effect sizes across studies and anticipated confounders (e.g., age, ethnicity, BMI). Of the 4845 records retrieved, 26 studies (8 nutritional supplements, 12 dietary, and 6 exercise interventions) were included. All studies were conducted in patients with GDM. Overall, supplement- and exercise-based interventions reduced fasting glucose (−0.30 mmol/L; 95% CI = −0.55, −0.06; p = 0.02; and 0.10 mmol/L; 95% CI = −0.20, −0.01; p = 0.04); and supplement- and diet-based interventions reduced HOMA-IR (−0.40; 95% CI = −0.58, −0.22; p < 0.001; and −1.15; 95% CI = −2.12, −0.17; p = 0.02). Subgroup analysis by confounders only confirmed marginal changed effect sizes. Our results suggest a favorable role of certain nutritional supplements, diet, and exercise practices on glycemia in women with GDM and underline a lack of evidence in ~20% of other diabetes-related pregnancies (i.e., women with pre-existing diabetes)

Physical activity and breast cancer survival

Physical activity improves quality of life after a breast cancer diagnosis, and a beneficial effect on survival would be particularly welcome. Four observational studies have now reported decreased total mortality among physically active women with breast cancer; the two largest have also reported decreased breast cancer specific mortality. The estrogen pathway and the insulin pathway are two potential mechanisms by which physical activity could affect breast cancer survival. Randomized trials are ongoing but trials of lifestyle factors are notoriously challenging to perform. Women with breast cancer have little to lose and may possibly gain from moderate exercise

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives