Calcium plus vitamin D supplementation and the risk of postmenopausal weight gain

BACKGROUND: Obesity in the United States has increased significantly during the past several decades. The role of calcium in the maintenance of a healthy body weight remains controversial. METHODS: A randomized, double-blinded, placebo-controlled trial was performed with 36 282 postmenopausal women, aged 50 to 79 years, who were already enrolled in the dietary modification and/or hormone therapy arms of the Women's Health Initiative clinical trial. Women were randomized at their first or second annual visit to receive a dose of 1000 mg of elemental calcium plus 400 IU of cholecalciferol (vitamin D) or placebo daily. Change in body weight was ascertained annually for an average of 7 years. RESULTS: Women receiving calcium plus cholecalciferol supplements vs women receiving placebo had a minimal but consistent favorable difference in weight change (mean difference, -0.13 kg; 95% confidence interval, -0.21 to -0.05; P = .001). After 3 years of follow-up, women with daily calcium intakes less than 1200 mg at baseline who were randomized to supplements were 11% less likely to experience small weight gains (1-3 kg) and 11% less likely to gain more moderate amounts of weight (>3 kg) (P for interaction for baseline calcium intake = .008). CONCLUSION: Calcium plus cholecalciferol supplementation has a small effect on the prevention of weight gain, which was observed primarily in women who reported inadequate calcium intakes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611.     

Rapid infusion rituximab in combination with corticosteroid-containing chemotherapy or as maintenance therapy is well tolerated and can safely be delivered in the community setting

The increasing usage of rituximab in the management of non-Hodgkin lymphoma (NHL) has created huge logistical challenges with respect to the delivery of this time- and labor-intensive drug. To address these challenges, we developed and tested the feasibility of a 90-minute infusion schedule for rituximab (20% of the dose administered in the first 30 minutes, remaining 80% administered over 60 minutes). A safety analysis performed in 150 patients receiving rituximab with corticosteroid-containing chemotherapy and 56 patients receiving rituximab as maintenance therapy demonstrated that this schedule was well tolerated, with no grade 3 or 4 infusion reactions observed. In addition, no increase in minor reactions was noted. More than 1200 patients have been treated with this rapid rituximab infusion schedule in the province of British Columbia (BC), demonstrating its safety in the community setting. The adoption of this 90-minute schedule as standard practice has had a positive impact on resource utilization.     

Drinking water arsenic exposure and blood pressure in healthy women of reproductive age in Inner Mongolia, China

The extremely high exposure levels evaluated in prior investigations relating elevated levels of drinking water arsenic and hypertension prevalence make extrapolation to potential vascular effects at lower exposure levels very difficult. A cross-sectional study was conducted on 8790 women who had recently been pregnant in an area of Inner Mongolia, China known to have a gradient of drinking water arsenic exposure. This study observed increased systolic blood pressure levels with increasing drinking water arsenic, at lower exposure levels than previously reported in the literature. As compared to the referent category (below limit of detection to 20 microg of As/L), the overall population mean systolic blood pressure rose 1.29 mm Hg (95% CI 0.82, 1.75), 1.28 mm Hg (95% CI 0.49, 2.07), and 2.22 mm Hg (95% CI 1.46, 2.97) as drinking water arsenic concentration increased from 21 to 50, 51 to 100, and >100 microg of As/L, respectively. Controlling for age and body weight (n=3260), the population mean systolic blood pressure rose 1.88 mm Hg (95% CI 1.03, 2.73), 3.90 mm Hg (95% CI 2.52, 5.29), and 6.83 mm Hg (95% CI 5.39, 8.27) as drinking water arsenic concentration increased, respectively. For diastolic blood pressure effect, while statistically significant, was not as pronounced as systolic blood pressure. Mean diastolic blood pressure rose 0.78 mm Hg (95% CI 0.39, 1.16), 1.57 mm Hg (95% CI 0.91, 2.22) and 1.32 mm Hg (95% CI 0.70, 1.95), respectively, for the overall population and rose 2.11 mm Hg (95% CI 1.38, 2.84), 2.74 mm Hg (95% CI 1.55, 3.93), and 3.08 mm Hg (95% CI 1.84, 4.31), respectively, for the adjusted population (n=3260) at drinking water arsenic concentrations of 21 to 50, 51 to 100, and >100 microg of As/L. If our study results are confirmed in other populations, the potential burden of cardiovascular disease attributable to drinking water arsenic is significant.     

Role of dopamine D1 and D2 receptors in CRF-induced disruption of sensorimotor gating

Corticotropin-releasing factor (CRF), a neuropeptide released during stress, has been reported to modulate startle behavior, including reducing the threshold for acoustic startle responding and reducing prepulse inhibition (PPI). The central mechanisms mediating CRF system regulation of startle and PPI are still unclear. Some antipsychotic drugs attenuate CRF-induced deficits in PPI in rats and mice. Here we tested the hypothesis that indirect activation of DA(1)-receptors (D(1)) and DA(2)-receptors (D(2)) contributes to the effects of CRF on PPI. We compared the effect of central administration of h/r-CRF (0.2-0.6 nmol) on PPI in mice with either a D(1) or D(2) receptor null mutation (knockout, KO) or in mice pretreated with D(1) or D(2) receptor antagonists SCH23390 (1 mg/kg) or haloperidol (1 mg/kg). D(1) and D(2) KO mice exhibited no significant differences in their sensitivity to CRF-induced disruptions of PPI. Similarly, neither SCH23390 nor haloperidol pretreatment altered the CRF-induced disruption in PPI, although both increased PPI at baseline. CRF-induced increases in startle also remained unchanged by any of the DA receptor manipulations. These results indicate that neither D(1)- nor D(2)-receptor activation is necessary for CRF to exert its effects on acoustic startle and PPI in mice.     

Diabetes abolishes sildenafil-induced cGMP-dependent protein kinase-I expression and cardioprotection

The selective phosphodiesterase type 5 inhibitor sildenafil has been demonstrated to produce cardioprotection; however, diabetes is known to abolish cardioprotective signaling. We tested the hypothesis that sildenafil-induced cGMP-dependent protein kinase-I (PKG-I) expression and cardioprotection are attenuated by diabetes. Barbiturate-anesthetized dogs (n = 38) were instrumented for measurement of hemodynamics and subjected to 60-minute occlusion of the left anterior descending coronary artery and 3-hour reperfusion. Dogs were randomly assigned to receive 0.9% saline (control) or intravenous sildenafil (0.7 or 1.4 mg/kg) in the absence or presence of diabetes (3 weeks after administration of alloxan and streptozotocin). No differences in hemodynamics or coronary collateral blood flow (radioactive microspheres) were observed between groups before and during ischemia and reperfusion, except that infusion of sildenafil produced transient decreases in left ventricle systolic pressure. Sildenafil significantly (P < 0.05) reduced infarct size (16 +/- 2% of the left ventricular area at risk; triphenyltetrazolium staining) as compared to control (31 +/- 39%). Diabetes alone did not alter infarct size (31 +/- 2%) but abolished the protective effect of sildenafil (0.7 mg/kg: 26 +/- 3%; 1.4 mg/kg: 26 +/- 3%). Sildenafil increased PKG-I expression (immunohistochemistry and Western blotting) in the absence but not the presence of diabetes. The results indicate that diabetes abolishes cardioprotection by sildenafil and implicates PKG-I in the signal transduction pathway activated by this drug.     

A mixed methods study investigating the quality of urinary and faecal continence assessment and management in residential aged care: Challenges,implications and solutions

Objective

Incontinence is one of the main reasons for institutionalisation into residential aged care. It is linked with increased falls, skin breakdown, depression, social isolation and impaired quality of life. Studies over the past decade have demonstrated poor-quality incontinence care, which has led to ongoing development of best practice guidelines and educational resources. This study investigated current practices, and staff and resident experiences with continence assessment and management, in comparison with best practice guidelines.

Methods

This concurrent mixed methods study was conducted in a 120-bed residential aged care home. Secondary analysis of data from clinical records provided a snapshot of how continence was assessed and managed. Semistructured interviews with four staff and five residents explored their experiences to understand the impact of current practice on resident emotional well-being. Mixing methods allowed for comparison between quantitative and qualitative findings, enabling a deeper understanding.

Results

Findings from the two data sets were highly congruent and identified: (1) lack of communication with residents and family members about continence needs; (2) heavy reliance on product usage and limited other conservative strategies; (3) staff frustration at inability to respond to calls in a timely manner; and (4) positive staff–resident relationships protect resident emotional well-being.

Conclusions

Current practices are not consistent with best practice guidelines, which raises the question as to why nothing has changed. We argue that a stronger focus on implementation underpinned by a relationship-centred approach is required to improve continence care practices among residential care staff, and the quality of life for adults living with incontinence.     

A pharmacist-led intervention to improve the management of opioids in a general practice: a qualitative evaluation of participant interviews

Background Opioid prescribing has escalated, particularly long-term in chronic noncancer pain. Innovative models of care have been recommended to augment regulatory and harm-minimisation strategies and to review the safety and benefits of opioids for the individual patient. Medication stewardship and pharmacist integration are evolving approaches for general practice. Aim To explore enablers, barriers, and outcomes of a pharmacist-led intervention to improve opioid management in general practice, from the perspectives of general practitioners (GPs) and practice personnel. Method The study was part of a mixed-methods investigation into a general practice pharmacist pilot. Qualitative data relevant to opioids were analysed. Data from 13 semi-structured interviews were coded, analysed iteratively and thematically, and interpreted conceptually through the framework of Opioid Stewardship fundamentals proposed by the National Quality Forum. Results Seven themes and 14 subthemes aligned with stewardship fundamentals. Participants considered organisational policy, supported by leadership and education, fostered collaboration and consistency and improved practice safety. Patient engagement with individualised resources, ‘agreements’ and ‘having the conversation’ with the pharmacist enabled person-centred opioid review and weaning. GPs reported greater accountability and reflection in their practices, in the broader context of opioid prescribing and dilemmas in managing patients transitioning through care. Receiving feedback on practice deprescribing outcomes encouraged participants’ ongoing commitment. Patient communication was deemed an early barrier; however, learnings were applied when transferring the model to other high-risk medicines. Conclusion Improved opioid management was enabled through implementing pharmacist-led coordinated stewardship. The findings offer a practical application of guideline advice to individualise opioid deprescribing.

     

Pregnancy, sleep disordered breathing and treatment with nasal continuous positive airway pressure

OBJECTIVE: To investigate the tolerance, compliance and problems associated with usage of nasal continuous positive airway pressure (CPAP) by pregnant women with sleep disordered breathing (SDB). PATIENTS AND METHOD: Twelve pregnant women diagnosed with SDB received polysomnography (PSG) at entry, CPAP titration, repeat PSG at 6 months gestation (GA) and home monitoring of cardio-respiratory variables at 8 months GA. Compliance was verified by the pressure at the mask. Results from the Epworth sleepiness scale, fatigue scale and visual analogue scales (VAS) for sleepiness, fatigue, and snoring were compared over time. RESULTS: All of the subjects had full term pregnancies and healthy infants. Nightly compliance was at least 4 h initially and 6.5 h at 6 months GA. Nasal CPAP significantly improved all scales compared to entry. VAS scores remained lower at 6 months GA compared to entry. Re-adjustment of CPAP pressure was needed in six subjects at 6 months GA. CONCLUSION: Nasal CPAP is a safe and effective treatment of SDB during pregnancy.