Randomized,double‐blind,placebo‐controlled study of safety and efficacy of miltefosine in antihistamine‐resistant chronic spontaneous urticaria

Background Chronic spontaneous urticaria (CSU), a mast cell‐driven condition, is debilitating, common, and hard to treat. Miltefosine, a lipid raft modulator, can inhibit mast cell responses in vivo. Objective To study the safety and efficacy of systemic miltefosine treatment in CSU patients resistant to standard‐dosed antihistamines. Methods In this investigator‐initiated multicentre, randomized, double‐blind, placebo‐controlled study, CSU patients were treated for 4 weeks with daily doses of up to 150‐mg miltefosine (n = 47) or placebo (n = 26). Disease activity was assessed using the urticaria activity score. Safety and tolerability of miltefosine were also assessed. Results After 4 weeks of treatment, Urticaria Activity Score (UAS7) levels were substantially more reduced in miltefosine‐treated patients (?6.3 vs. ?3.5 in placebo‐treated patients; P = 0.05). Also, the number of weals, but not the intensity of pruritus, was significantly reduced in miltefosine‐treated patients vs. placebo‐treated patients (P = 0.02). In general, adverse events were frequent in both groups (miltefosine: 88%, placebo: 65% of patients) but mostly mild to moderate in severity. We did not observe any serious adverse events. Conclusions The results of this study indicate that miltefosine is an effective and safe treatment option for CSU patients who do not respond to standard‐dosed antihistamines.     

Delayed first medical contact to reperfusion time increases mortality in rural emergency medical services patients with ST-elevation myocardial infarction

Background

ST-elevation myocardial infarction (STEMI) guidelines recommend an emergency medical services (EMS) first medical contact (FMC) to percutaneous coronary intervention (PCI) time of ≤90 min. The primary objective of this study was to evaluate the association between FMC to PCI time and mortality in rural STEMI patients.

Methods

We conducted a cohort study of patients ≥18 years old with STEMI activations from January 2016 to March 2020. Data were obtained from a rural North Carolina Regional STEMI Data Registry, which included eight rural EMS agencies and three PCI centers, the National Cardiovascular Data Registry, and the EMS electronic health record. Prehospital and in-hospital time intervals were digitally abstracted. The outcome of index hospitalization mortality was compared between patients who did and did not meet FMC to PCI time goal using Fisher's exact tests. Negative predictive value (NPV) for index hospitalization death was calculated with 95% confidence intervals (CIs). A receiver operating characteristic curve was constructed and an optimal FMC to PCI time goal was identified by maximizing NPV to prevent index hospitalization death.

Results

Among 365 rural EMS STEMI patients, 30.1% (110/365) were female with a mean ± SD age of 62.5 ± 12.7 years. PCI was performed within the 90-min time goal in 60.5% (221/365) of patients. Among these patients, 3% (11/365) died during initial STEMI hospitalization, with 1.4% (3/221) mortality in the group that met the 90-minute time goal compared to 5.6% (8/144) in patients exceeding the time goal (p = 0.03). Meeting the 90-min time goal yielded a 98.6% (95% CI 96.1%–99.7%) NPV for index death. A 78-min FMC to PCI time was the optimal cut point, yielding a NPV for index mortality of 99.3% (95% CI 96.1%–100%).

Conclusions

Death among rural patients with STEMI was four times more likely when they did not receive PCI within 90 min.     

Diagnosis of a preputial cavity abscess with bedside ultrasound in the emergency department

Bedside ultrasound has become an important diagnostic tool for emergency physicians. Clinical investigators have demonstrated that evaluating soft tissue infections with ultrasound is useful for the detection of subcutaneous abscesses. Bedside ultrasound of a preputial cavity abscess in the Emergency Department has not been previously described in the English medical literature. A preputial cavity abscess, a rare complication of balanoposthitis, is a collection of pus between the foreskin and the distal penis. This case report describes the use of ultrasound to diagnose a penile abscess and reviews the related literature.     

Comparison of continuous and discrete measurements of dyspnea during exercise in patients with COPD and normal subjects

STUDY OBJECTIVES: The objectives of this study were as follows: (1) to compare results of the discrete and the continuous methods for measuring breathlessness; (2) to examine test-retest reliability; (3) and to test the hypothesis that patients with COPD have higher slopes and lower x-intercepts and absolute thresholds for power production, oxygen consumption (O(2)), and minute ventilation as independent variables and breathlessness ratings as the dependent variable, as compared with healthy subjects. DESIGN: Visit 1 (familiarization) and visit 2 and visit 3 (2 days apart) with randomized assignment of the discrete and continuous methods for subjects rating breathlessness during cycle ergometry. SETTING: Cardiopulmonary exercise laboratory in a university medical center. PARTICIPANTS: Twenty-four patients with COPD (mean age, 66 +/- 8 years [+/- SD]) and 24 healthy subjects (mean age, 66 +/- 10 years). INTERVENTIONS: None. Measurements and results: Ratings of breathlessness on the Borg scale on cue with subjects moving and pressing the computer mouse button to indicate a rating (discrete method) or by moving the position of the mouse to adjust a vertical bar to indicate a change in breathlessness (continuous method). There were no significant differences in results between visit 2 and visit 3. Although peak exercise variables were similar with the discrete and continuous methods, both groups provided significantly more ratings of breathlessness with the continuous method. Patients with COPD exhibited higher slopes, lower x-intercepts, and lower absolute thresholds (breathlessness rating >/==" BORDER="0"> 0.5 ["just noticeable"] on the Borg scale) for power production and O(2)-breathlessness compared with healthy subjects (p < 0.05). CONCLUSIONS: Elderly patients with COPD and healthy subjects are able to use the continuous method successfully. Reliability is excellent for both methods. The continuous method provides a greater number of breathlessness ratings over the course of exercise, and allows the clinician to calculate an absolute threshold and just-noticeable differences. Regression parameters and absolute thresholds discriminate between patients with COPD and healthy subjects.     

Effects of exercise training program on functional capacity and quality of life in patients with peripheral arterial occlusive disease. Evaluation of a pilot project

BACKGROUND: In patients with peripheral arterial occlusive disease (PAOD) stage II, exercise training seems to be important to reduce symptoms and improve functional capacity. We evaluated the effects of an out-patient treatment program on walking distance (standardized treadmill testing), training exercise capacity, and disease specific quality of life (PAVK-86 questionnaire). METHODS AND RESULTS: Thirty-one patients aged 70 +/- 2 with intermittent claudicatio in stage IIa/IIb according to Fontaine (n = 18/13) underwent a supervised 12 week exercise training and education outpatient program. During course of intervention, patients demonstrated improvements in pain-free training walking distance (p < 0.001) and repetitions of tiptoe standing (p < 0.05). In standardized treadmill testing, pain-free walking distance was improved by 182% (129 +/- 19 m-->364 +/- 53 m; p < 0.001), and maximum walking distance by 76% (311 +/- 42 m-->546 +/- 63 m; p < 0.01). Before training, mean subscale scores of the PAVK-86 demonstrated distinct impairments concerning pain and functional status. After 12 weeks of intervention, with exception of the subscale complaints, all dimensions of quality of life assessed have improved significantly. The highest effect size was observed for the subscales pain, mood, and functional status. Improvement in the subscale anxiety and pain-free walking distance (treadmill test) correlated significantly (r = 0.46) as well as improvement in the subscale mood and maximum walking distance (r = 0.45). CONCLUSION: In patients with PAOD stage II considerable effects on functional capacity and important dimensions of quality of life can be achieved by a short exercise and education program.