Safety findings from CENTURION,a phase 3 consistency study of lasmiditan for the acute treatment of migraine

BackgroundLasmiditan (LTN) is a selective 5-HT_1F receptor agonist for the acute treatment of migraine in adults. We present detailed safety findings from the placebo-controlled, double-blind Phase 3 study, of LTN treatment across 4 attacks (CENTURION).MethodsPatients were randomized 1:1:1 to LTN 200 mg (LTN200), LTN100, or a control group that received placebo for 3 attacks and LTN50 for either the 3rd or 4th attack (1:1). Safety analyses were conducted for patients who took ≥1 dose of study drug and, in some cases, those who took all 4 doses.ResultsOverall, 1471 patients treated 4494 attacks. The incidences of treatment-emergent serious adverse events (SAEs) were - placebo, n=2 (0.4 %); LTN100, n=1 (0.2 %); LTN200, n=2 (0.4 %); no specific treatment-emergent SAE was reported in more than one patient. The most common treatment emergent adverse events (TEAEs) with lasmiditan were dizziness, paresthesia, fatigue, nausea, vertigo, and somnolence; the vast majority were mild or moderate in severity. The incidences of these TEAEs were highest during the first attack and decreased during subsequent attacks. For patients who experienced a common TEAE with the first attack, less than 45 % experienced the same event in subsequent attacks. Patients who did not experience an event in the 1st attack infrequently experienced the same event in subsequent attacks.The time of onset of the common TEAE ranged from ~40 min to 1 h (dependent upon TEAE) and, for individual TEAE, the onset was similar across attacks. Duration was dependent upon TEAE and attack. It was shortest for paresthesia (< 2 h for all attacks); it ranged from 1.8 to 5.5 h for other common TEAEs and was generally similar across attacks.Serotonin syndrome was reported for 2 patients post LTN dosing; there were no meaningful differences across treatment groups in suicidality; there was no evidence of an increase in motor vehicle accidents.ConclusionIn this blinded, controlled, multiple-attack study, LTN was associated with generally mild or moderate CNS-related TEAEs of short duration. TEAEs tended to decrease in frequency across the 4 attacks.Trial registration {"type":"clinical-trial","attrs":{"text":"NCT03670810","term_id":"NCT03670810"}}NCT03670810 Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01343-2.     

Asymptomatic total hip prosthesis: natural history determined using Tc- 99m MDP bone scans

A prospective study was performed with 97 patients who had undergone total hip replacement surgery and who were not experiencing pain or other symptoms or problems. The study was intended to determine the normal postoperative appearance of radionuclide scans of the hip following administration of technetium-99m methylene diphosphonate. Five areas of the prostheses were evaluated. Results showed that 6 months after implantation activity around the lesser trochanter and prosthesis shaft became insignificant. Activity around the acetabulum, greater trochanter, and prosthesis tip stabilized approximately 2 years after surgery; approximately 10% of patients in the study had persistent activity in these areas. Familiarity with this normal progression is fundamental to interpretation of postoperative bone scans in patients with total hip prosthesis.     

Does socioeconomic status affect mortality subsequent to hospital admission for community acquired pneumonia among older persons?

Background  

Low socioeconomic status has been associated with increased morbidity and mortality for various health conditions. The purpose of this study was twofold: to examine the mortality experience of older persons admitted to hospital with community acquired pneumonia and to test the hypothesis of whether an association exists between socioeconomic status and mortality subsequent to hospital admission for community-acquired pneumonia.     

Feasibility of a patient decision aid regarding disclosure of personal health information: qualitative evaluation of the Health Care Information Directive

Background  

Concerns regarding the privacy of health information are escalating owing both to the growing use of information technology to store and exchange data and to the increasing demand on the part of patients to control the use of their medical records. The objective of this study was to evaluate the Health Care Information Directive (HCID), a recently-developed patient decision aid that aims to delineate the level of health information an individual is willing to share.     

A randomized controlled trial of three low-dose gonadotrophin protocols for unexplained infertility

This randomized controlled trial assessed which of three low-intensity ovulation induction protocols was associated with the highest rate of cycle completion among infertile women undergoing intrauterine insemination (IUI) with their husband's spermatozoa. Sixty-three women aged < or = 42 years with normospermic partners participated in the study. The primary diagnosis of infertility was unexplained in 89% of subjects, endometriosis in 6% and tubal factor in 5%. Women were assigned to three groups according to recombinant FSH dosage: group A received two ampoules (75 IU FSH per ampoule) on cycle day 4, and one ampoule on days 6 and 8 (total four ampoules); group B received two ampoules on days 4, 6 and 8 (total six ampoules); group C received two ampoules on days 4, 6, 8 and 10 (total eight ampoules). Daily ultrasound investigations began on cycle day 9-12 and human chorionic gonadotrophin (HCG) 5000 IU was administered when one or two follicles > or = 18 mm were seen. IUI was scheduled for the next day. HCG was given and/or ovulation shown to have occurred in 88 of 109 cycles attempted (81%) with no differences among the three dose groups. Two singleton pregnancies occurred (2.3% per ovulatory cycle and 1.8% per cycle start). There were no significant differences among the three regimes in terms of cycle parameters, suggesting that an individualized and more intensive approach to ovarian stimulation is necessary for many women with unexplained infertility.      

The effectiveness of ovulation induction and intrauterine insemination in the treatment of persistent infertility: a meta-analysis

A systematic review was conducted to evaluate the effectiveness of intrauterine insemination (IUI) with or without ovarian stimulation using gonadotrophin in the treatment of persistent infertility. Relevant randomized controlled trials were identified by a diverse strategy including a hand search of 43 core journals from 1966 to the present. Two approaches to meta-analysis were used to summarize data. First, using a standard Mantel-Haenszel approach, eight trials comparing FSH/IUI with FSH/timed intercourse for unexplained infertility were combined. The common odds ratio for pregnancy was 2.37 [95% confidence interval (CI), 1.43, 3.90], suggesting a significant improvement with IUI following ovulation induction in this patient group. Although the data were statistically homogeneous, clinically important heterogeneity was present. Second, across all diagnostic groups, the independent effects of treatment with follicle stimulating hormone (FSH), clomiphene citrate, IUI, as well as the diagnoses of male factor and endometriosis were assessed using stepwise logistic regression. Based on 5214 cycles reported in 22 trials, the odds ratio for pregnancy associated with FSH use was 2.35 (95% CI, 1.87, 2.94) for IUI, 2.82 (95% CI, 2.18, 3.66) for male factor, 0.48 (95% CI, 0.37, 0.61), and for endometriosis 0.45 (95% CI, 0.27, 0.76). This summary of the best available evidence may prove useful in counselling couples who are considering FSH and/or IUI therapy.      

Esophageal motility: assessment with synchronous video tape fluoroscopy and manometry

Synchronous video tape fluoroscopy and manometry of the esophagus was performed in 11 subjects (seven men and four women; mean age, 49 years). Four had normal and seven had abnormal esophageal motility (diffuse esophageal spasm, n = 4; nonspecific esophageal motility disorder, n = 3) that was shown by previous manometry. A digital timer appeared on the video tape recording and marked the manometric tracing synchronously. Alternate 5-mL and 10-mL barium boluses were recorded for a total of 10 swallows per patient. Video tape examinations were reviewed prospectively, and the status of primary peristalsis and presence and severity of tertiary activity were noted. A total of 98 swallows (58 normal, 40 abnormal) were correlated, and a 96% agreement was found in assessing primary peristalsis. Overall results of fluoroscopic examinations of each subject during all swallows showed complete agreement with those of manometry; segregating the swallows into groups of five showed 92% concordance. Severe tertiary activity was invariably seen with abnormal primary peristalsis at fluoroscopy.