Efficacy and safety of mometasone furoate nasal spray in nasal polyposis

BACKGROUND: Studies have suggested that topical corticosteroids are effective in the treatment of nasal polyps; however, this has yet to be confirmed in a large, robust clinical trial. OBJECTIVE: To evaluate the efficacy and safety of mometasone furoate nasal spray (MFNS) for nasal polyposis. METHODS: A total of 354 subjects with bilateral nasal polyps and clinically significant congestion/obstruction participated in this multinational, randomized, double-blind, placebo-controlled study. Subjects received MFNS 200 microg once or twice daily or placebo for 4 months. Coprimary endpoints were (1) change from baseline to last assessment in physician-evaluated bilateral polyp grade score and (2) change from baseline averaged over month 1 in subject-assessed nasal congestion/obstruction. ANOVA was used for all efficacy endpoints, except for change in bilateral polyp grade score, for which baseline polyp grade was added as a covariate. RESULTS: Compared with placebo, MFNS 200 microg administered once or twice daily produced significantly greater reductions in bilateral polyp grade score (P < .001, P = .010, respectively) and congestion/obstruction (P = .001, P < .001), as well as improvement in loss of smell (P < .001, P = .036), anterior rhinorrhea (P < .001 for both), and postnasal drip (P < .001, P = .001) over month 1. MFNS 200 microg twice daily was superior to MFNS 200 microg once daily in reducing congestion/obstruction (P = .039), and there were more improvers in the MFNS 200 microg twice daily group (P = .035). MFNS was well tolerated in both groups. CONCLUSION: MFNS 200 mug, once or twice daily, was safe and significantly superior to placebo in reducing polyp grade (size and extent) and improving congestion/obstruction and return of sense of smell. MFNS is an effective medical treatment for nasal polyposis and may reduce or delay the need for surgery.     

Ventromedial hypothalamus vs. lateral hypothalamic D2 satiety receptors in the body weight increase induced by systemic sulpiride

Two experiments were conducted in order to see if dopamine satiety receptors in the lateral hypothalamus or satiety mechanisms in the ventromedial hypothalamus were involved in the hyperphagia and body weight increase induced by systemic sulpiride. In the first experiment, it was shown that systemic sulpiride (20 mg/kg) does not block the anorexia caused by intraperifornical injections of amphetamine. In the second experiment, sulpiride (20 mg/kg during 18 days) did not produce an additional increase in body weight in previously VMH-lesioned female rats. This last fact cannot be explained by a ceiling effect since insulin (5 U/day during 7 days) increased body weight in the same VMH rats in which sulpiride was not effective. These results do not support the hypothesis that systemic sulpiride reaches the perifornical dopamine D2 receptors to disinhibit feeding, but suggest instead an involvement of the ventromedial hypothalamus. This last suggestion is more in agreement with the hypothesis that sulpiride alters feeding and body weight gain through the induction of a functional gonadectomy.     

Duodenal ulcer

In 1958 the Yale freshman class gave blood samples as part of a study intended to determine the predictive value of plasma pepsinogen (PP) for the subsequent development of duodenal ulcer (DU). We report a long-term follow-up of this cohort. A selfadministered questionnaire designed to ascertain information about the development of peptic ulcers, and the presence of risk factors was mailed to 861 subjects with active addresses. A second questionnaire was mailed to each respondent's physician(s) to verify the diagnosis of DU. Completed questionnaires were returned, after three mailings, by 604 (70%) of the subjects. They reported 18 documented DUs, 15 since 1958, for an incidence of 1.1/1000 person years. Only smoking (P<0.05) and undergraduate physical inactivity (P<0.01) were identified as risk factors for DU. Family history; blood type; blood antigen secretor status; ingestion of coffee, alcohol, milk, salicylates, soda, or tea; and COPD were not identified as risk factors for DU. Patients with DU had higher mean PP values than those who did not (391.6±99.6 vs 346.6±106.7, mean ±sd) but this was not statistically significant (P>0.05). The predictive value of an elevated PP(>450) for the development of DU was 7.9%, but a low or normal PP predicted the absence of a DU in 97.5% of subjects over a 22-year span. We conclude that in a selected population followed for 22 years there is a low incidence of DU, supporting the general belief that duodenal ulcer is declining, that smoking and undergraduate physical inactivity are risk factors for duodenal ulcer, and that a low or normal PP may be useful as a predictor for a low susceptibility to duodenal ulcer disease.Dr. J. Chuong acknowledges the support of the Robert Wood Johnson Clinical Scholar Program, and the Daland Fellowship in Clinical Medicine of the American Philosophical Society.     

Duration of benzodiazepine clinical activity: Lack of direct relationship with plasma half-life

The anxiolytic activity and tolerance of two dosage schedules of prazepam, a long plasma half-life benzodiazepine, were compared under double-blind conditions in two groups of 10 inpatients each who met Research Diagnostic Criteria for Generalized Anxiety Disorder and presented chronic and severe symptomatology. Patients received prazepam 40 mg per day on one of two dosage schedules: 1) divided dosage (DD) - 10 mg in the morning and at noon and 20 mg in the evening; or 2) single dosage (SD) - 40 mg in the evening. The 3 weeks of therapy were preceded and followed by 1 week of wash-out for baseline and follow-up assessments, which were performed weekly with the Hamilton Anxiety Scale, Clinical Global Impression, rating of morning drowsiness and evening worsening of symptoms, and patient self-rating of anxiety by means of a visual analogue scale performed both in the morning and in the afternoon. The results showed a clear superiority of the DD over the SD schedule: better anxiolytic efficacy on the Hamilton Anxiety Scale (P<0.0005) and on both morning and afternoon visual analogue scales (P<0.01 andP<0.0002); less morning drowsiness (P<0.0001); and steadier anxiolytic effect during the daytime, as globally rated by the investigator (P<0.0001) or measured by morning-afternoon differences on the visual analogue scale (P<0.005). These results suggest that plasma pharmacokinetics alone may not be sufficient to predict the duration of benzodiazepine anxiolytic activity.     

Difficulties in navigating the intersection of generalist and specialist palliative care services: A cross-sectional study of bereaved family's experiences of care at home in New Zealand

A generalist–specialist model of palliative care is well established as a framework for the provision of community care in resource-rich countries. However, evidence is lacking regarding how the model is experienced by family carers and the extent to which access to both generalist and specialist palliative care is equitable. A cross-sectional postal survey was undertaken to explore bereaved family's experiences of generalist palliative care and its intersection with hospice services in the last 3 months of life. A modified version of the Views of Informal Carers—Evaluation of Services survey was sent to 4,778 bereaved family. Data were collected between February 2017 and October 2018. Chi-square was utilised to identify factors that impacted on experiences of generalist palliative care; analysis of free text data comprising 45,823 words was undertaken using a directed content analysis approach. Eight hundred and twenty-six questionnaires were returned (response rate = 21%). Seventy per cent of people (n = 579) spent some time at home in the last 3 months prior to death. People who received support from hospice were more likely to receive support from multiple other services. Those who received no community services were less likely to feel supported by their general practitioner, less likely to spend the last 2 days of life or die at home. Feeling supported had a strong association with services working well together, being involved in decision-making and being aware of the poor prognosis. The provision of palliative care is complicated by a lack of integration with specialist palliative care and may be the basis of continuing inequities in the provision of community care at the end of life. The assumption at a policy level that “generalists” are willing and able to play a key role in palliative care provision needs to be further challenged.     

Prevalence and predictors of symptoms of Perinatal Mood and anxiety Disorders among a sample of Urban Black Women in the South

Maternal and Child Health Journal - Data are scarce regarding the prevalence and predictors of perinatal mood and anxiety disorders (PMADs) among Black women. The purpose of this study was to...     

A Randomized Study of Nutritional Supplementation in Patients with Unilateral Wet Age-Related Macular Degeneration

The purpose of this study is evaluate the efficacy and safety of medicinal products containing the original Age-Related Eye Disease group (AREDS) formulation at doses approved in Europe (EU, control group; n = 59) with a product that adds DHA, lutein, zeaxanthin, resveratrol and hydroxytyrosol to the formula (intervention group; n = 50). This was a multicenter, randomized, observer-blinded trial conducted in patients aged 50 years or older diagnosed with unilateral exudative Age related Macular Degeneration AMD. At month 12, the intervention did not have a significant differential effect on visual acuity compared with the control group, with an estimated treatment difference in Early Treatment Diabetic Retinopathy Study (ETDRS) of −1.63 (95% CI −0.83 to 4.09; p = 0.192). The intervention exhibited a significant and, in most cases, relevant effect in terms of a reduction in some inflammatory cytokines and a greater improvement in the fatty acid profile and serum lutein and zeaxantin concentration. In patients with unilateral wet AMD, the addition of lutein, zeaxanthin, resveratrol, hydroxytyrosol and DHA to the AREDS EU recommended doses in the short-term did not have a differential effect on visual acuity compared to a standard AREDS EU formula but, in addition to improving the fatty acid profile and increasing carotenoid serum levels, may provide a beneficial effect in improving the proinflammatory and proangiogenic profile of patients with AMD.