An overview of the prevalence of 25‐hydroxy-vitamin D inadequacy amongst elderly patients with or without fragility fracture in the United Kingdom

ABSTRACT

Background: Many studies have investigated the prevalence of 25-hydroxy-vitamin D inadequacy throughout the world and found a high prevalence of 25-hydroxy-vitamin D inadequacy in older patients, particularly those with fragility fracture.

Scope: To review the findings from vitamin D audits from six units across the UK and compare with previously published data from around the world. Results from four units have been previously published (Belfast, Glasgow, London and Medway) and this paper presents new data from Southampton and Carshalton, and further sub-analysis of the data from Medway.

Findings: Three audits of patients attending metabolic bone clinics (Carshalton, Medway and Southampton) identified 954 patients, of which overall 49% had a prior fragility fracture. Mean 25‐hydroxy-vitamin D levels ranged from 47.7?nmol/L to 62.4?nmol/L. Of these patients 72.9–88.9% had a 25‐hydroxy-vitamin D level < 80?nmol/L, 68.8–83.3% < 70?nmol/L and 37.5–59.1% < 50?nmol/L. The mean age of patients ranged from 60.0 to 67.5 years. Sub-analysis of the data by fracture status revealed that patients with fracture had lower mean levels of 25‐hydroxy-vitamin D compared with patients without fracture. This was statistically significant in the sub-analysis of the Medway data (45.3?nmol/L versus 49.9?nmol/L, p < 0.005).

Three audits identified 330 patients with fragility fracture. Audits from Glasgow and Belfast specifically identified patients with fragility fracture. A subgroup of patients with fracture aged over 50 years from the Medway audit was also included in this group. Mean levels of 25‐hydroxy-vitamin D ranged from 40.0?nmol/L to 52.3?nmol/L. 83.7–96.4% of patients had a 25‐hydroxy-vitamin D level < 80?nmol/L, 73.3–89.7% < 70?nmol/L and 55.8–73.2% < 50?nmol/L. The mean age of patients ranged from 65.3 to 68.6 years.

The audits carried out in Belfast and Medway were also divided by supplementation status. Mean 25‐hydroxy-vitamin D levels were 48.1?nmol/L in Belfast and 40.5?nmol/L in Medway in the patients not receiving supplements and 53.8?nmol/L and 59.9?nmol/L, respectively in the patients receiving supplements. The difference was statistically significant in the Medway audit (?p < 0.0001), but not in the smaller Belfast audit (?p = 0.216). As would be expected, the prevalence of 25‐hydroxy-vitamin D inadequacy was higher in the patients not receiving supplements, for example at the 70?nmol/L threshold: 82.6% versus 67.1% in Belfast and 89.6% versus 72.7% in Medway.

Three audits specifically identified 694 patients with hip fracture (Belfast, Glasgow and London). Mean levels of 25‐hydroxy-vitamin D ranged from 24.7?nmol/L to 36.1?nmol/L. Of these patients 90.7–99.0% had a 25‐hydroxy-vitamin D level < 80?nmol/L, 88.4–98.0% < 70?nmol/L and 81.6–92.7% < 50?nmol/L. The mean age of patients ranged from 73.4 to 80.5 years.

Conclusion: Inadequate 25‐hydroxy-vitamin D levels are extremely common in the elderly and particularly so in patients with fragility fracture – specifically in those with hip fracture. Although the differing audit specifications and assay techniques used make direct comparisons difficult, the data do provide a snapshot of 25‐hydroxy-vitamin D status across the UK and are consistent with those previously observed elsewhere in Europe and the rest of the world.     

Evaluation of rotigotine transdermal patch for the treatment of depressive symptoms in patients with Parkinson’s disease

Objective: To evaluate the dopamine receptor agonist, rotigotine, for improving depressive symptoms in patients with Parkinson’s disease (PD).

Methods: Patients were randomized 1:1 to rotigotine or placebo, titrated for ≤7 weeks, and maintained at optimal/maximum dose for 8-weeks. Primary efficacy variable: 17- item Hamilton Depression Rating Scale (HAM-D 17) total score change from baseline to end-of-maintenance. Secondary variables: changes in Beck Depression Inventory-II, Unified Parkinson’s Disease Rating Scale (UPDRS) II (activities of daily living [ADL]) and III (motor) subscores, UPDRS II+III total, patient-rated Apathy Scale (AS), and Snaith-Hamilton Pleasure Scale.

Results: Of 380 patients randomized, 149/184 (81.0%) rotigotine-treated and 164/196 (83.7%) placebo-treated patients completed the study. Patients: mean (±SD) age 65.2 (±8.5) years; time since PD-diagnosis 2.74 (±3.08) years; 42.6% male. The treatment difference (LS mean [95% CI]) in change from baseline HAM-D 17 was ?1.12 (?2.56, 0.33; p = 0.1286). UPDRS II, III, II+III and AS scores improved numerically with rotigotine versus placebo. Common adverse events with higher incidence with rotigotine: nausea, application/instillation site reactions, vomiting, and pruritus. Forty-one (10.8%) patients discontinued owing to adverse events (25 rotigotine/16 placebo).

Conclusions: No statistically significant improvement in depressive symptoms were observed with rotigotine versus placebo. ADL, motor function, and patient-rated apathy improved numerically.

ClinicalTrials.gov: NCT01523301     

Examination of Setarud (IMOD™) in the management of patients with severe sepsis

BACKGROUND AND THE PURPOSE OF THE STUDY: Analysis of current immunomodulating strategies indicates that monovalent approaches are unlikely to restore immunostasis or achieve complete therapy of sepsis. Setarud (IMOD) as a mixture of urtica, carotenoids, urea, and selenium has been recently patented for its potential in reduction of Tumor Necrosis Factor alpha (TNF-α) and Interferon-γ and Interleukin-2 levels. The aim of this study was to examine efficacy of IMOD in the management of patients with severe sepsis. METHODS: Twenty patients with severe sepsis and acute physiology and chronic health evaluation (APACHE) score of more than 20 were randomized to receive standard treatment of severe sepsis (control group) or standard treatment plus IMOD (IMOD group). The group treated with IMOD for 14 days was according to the pilot study and regarding the stability of patient's conditions in the ICU. Of course patients in both groups received standard treatment and all were monitored for 28 days. Blood samples were analyzed for interleukins (IL-1, IL-2, IL-6), plasminogen activator inhibitor (PAI-1), TNF-α, total thiol molecules (TTM), nitric oxide (NO), total antioxidant power (TAP), and lipid peroxidation (LPO). Daily APACHE, Sequential Organ Failure Assessment (SOFA), and Simplified Acute Physiology Score (SAPS) were calculated. RESULTS AND MAJOR CONCLUSION: Comparing with controls, IMOD was significantly effective in improving SAPS, SOFA, and APACHE scores, and reduction of mortality rate. Among tested inflammatory biomarkers, IMOD significantly improved TTM and TNF-α values. It is concluded that IMOD might be added as a safe adjutant to standard treatment of severe sepsis.     

What’s the role of topiramate in the management of patients with hyperkinetic movement disorders?

Topiramate (TPM) is an O-alkyl sulfamate derivative of the naturally occurring monosaccharide D-fructose with an epileptic activity. However, it has been suggested that, in addition to its use in epilepsy, TPM could also be used in the treatment of neurological disorders, psychiatric conditions and hyperkinetic movement disorders. The clinical applications of TPM in hyperkinetic movement disorders is consistent with the multiple pharmacodynamic mechanisms e.g., the modulation of both γ-aminobutyric acidergic or glutamatergic neurotransmission and the modulation of voltage-gated ion channels or intracellular signalling pathways. The purpose of the present review is to describe the mechanisms of action of TPM and its clinical efficacy in patients with hyperkinetic movement disorders.     

Evaluation of susceptibility locus for response to interferon-α based therapy in chronic hepatitis B patients in Chinese

In 2009, three independent genome-wide association studies reported that genetic variation in the interleukin 28B gene to be associated with the response to interferon-α/ribavirin therapy in hepatitis C virus genotype 1 infected patients. We carried out the present study to assess whether such polymorphisms also affect the therapy effect of another interferon-α responsive illness as chronic hepatitis B. Five hundred and twelve interferon-α treatment-naïve HBeAg seropositive chronic hepatitis B patients were enrolled in the present retrospective nested case-control study. All patients received PEG-IFN-α-2a based treatment and were examined for the therapy efficacy. SNP rs8099917 was genotyped using the MassArray system (Sequenom). Interestingly, the frequency of G allele of rs8099917 was significantly higher in response group than in non response group (8.3% vs. 3.9%, p = 0.003, OR = 0.44, 95%CI = 0.25-0.79). The genotype distributions of this SNP also differed significantly between two groups (p = 0.003). Our study suggested that the G allele of rs8099917 was associated with higher rate of response in HBeAg seropositive chronic hepatitis B patients treated with interferon α.     

Pharmacists’ satisfaction with their involvement in the management of COVID-19 patients in Saudi Arabia

IntroductionThe Coronavirus Disease 2019 (COVID-19) is a public health emergency and during this unprecedented situation, health care providers across the globe are at the frontline in the fight against this disease. Countries that have been severely hit by the pandemic are using pharmacists to help triage patients. In order to ensure the continuity of these services, it is of paramount importance that pharmacists be formally involved and engaged in the management of this pandemic. In response to the underlying knowledge deficit, this study was undertaken as the first of its kind in the entirety of Saudi Arabia.MethodsThis study is a questionnaire based cross-sectional study that was carried out for a period of five months from March 2020 to July 2020 to assess the role of working pharmacists in the management of the COVID-19 pandemic under different health care settings across Saudi Arabia.ResultsA total of 398 responses were recorded, in which 51.1% of the respondents were not involved in any learning or awareness activities involving health care providers (HCPs) or patients. The majority of respondents (62.9%) were not involved in creating or evaluating therapeutic plans for COVID19 patients, and 55% were not involved in therapeutic mentoring of COVID19 patients. Only a very low percentage of respondents were participating in COVID19-related research within their institution. Only 37% of respondents reported being satisfied with their role and contribution in the management of COVID-19.ConclusionThe present study reveals that pharmacists are underutilized in the management of COVID-19 patients in Saudi Arabia. As such, the findings emphasize the importance of enhancing the role and contribution of pharmacists in patient care management across all hospitals and especially under health care crisis conditions. The establishment of a crisis standard of care guideline for all HCPs, including pharmacists, would help in improving patient overall care under crisis conditions like the present COVID-19 pandemic.     

Does impairment of renal and hepatic function influence the metabolism of thrombolytics in patients with myocardial infarction?

Thrombolytic agents activate plasminogen and induce a systemic fibrinolytic and anticoagulant state. Two thrombolytic drugs are used frequently in practice: streptokinase (SK) and alteplase (t-PA). Streptokinase mainly undergoes renal elimination with a half-life of 11-17 min, while alteplase is eliminating by the liver with a half-life of 4-6 min. Our goal was to examine whether renal and hepatic function influence the elimination and metabolism of thrombolytics and the efficacy of percutaneous coronary intervention (PCI) after using alteplase or streptokinase. 416 patients with myocardial infarction (MI) were treated from January 2001 to December 2003 (228 male and 189 female). Alteplase was used in 9 men and 6 women (mean age: 53.88 +/- 9.61 vs. 65.33 +/- 9.87 years, p = 0.07). Patients who underwent rescue PCI after administration of alteplase had slightly higher hepatic enzyme levels/alanine transaminase (ALT): 47.85 vs. 41.4 U/l; gamma-glutamyl transpeptidase (GGT): 69.5 vs. 44.8 U/l/. All patients treated with alteplase survived, rescue PCI was done in 8 cases. Streptokinase was used in 36 men and 28 women (mean age: 63.33 +/- 10.51 vs. 63 +/- 12.03 years, p = 0.9). We did not find a difference between serum creatinine levels of patients who received streptokinase and underwent PCI as compared to those who had not. Rescue PCI was done in 16 cases. 12 patients died in this group. In conclusion we have not found a significant correlation between the use of the thrombolytics and hepatic or renal function; this could indicate that such a slight impairment of liver and renal function does not influence pharmacokinetic properties of thrombolytics.     

“Not a good look”: Impossible Dilemmas for Young Women Negotiating the Culture of Intoxication in the United Kingdom

This paper investigates young women's alcohol consumption in the United Kingdom within a widespread culture of intoxication in relation to recent debates about postfeminism and contemporary femininity. Young women are faced with an “impossible dilemma,” arising from the contradiction between a hedonistic discourse of alcohol consumption and postfeminist discourse around attaining and maintaining the “right” form of hypersexual heterosexual femininity. Drawing on a recent interview study with 24 young white working-class and middle-class women in the South-West of England, we explore how young women inhabit the dilemmas of contemporary femininity in youth drinking cultures, striving to achieve the “right” form of hypersexual femininity and an “optimum” level of drunkenness.     

Impact of medication therapy management in patients with Parkinson’s disease

Background Since the new German Apothekenbetriebsordnung was released, medication therapy management (MTM) has increased in importance. MTM is intended to improve the quality of life of patients. Objectives The aim of this study was to improve the quality of life of patients with Parkinson’s disease through an MTM by a community pharmacist. Setting The patients were recruited in cooperation with the Deutsche Parkinson Vereinigung e.V. (dPV) in Germany. Methods All patients were evaluated at baseline (t0) and after a follow-up of 4 months (t1). During the intervention period, the pharmacists implemented an MTM with standardized pharmaceutical care. Main outcome measure The effects of the interventions were measured by the Unified Parkinson Disease Rating Scale (UPDRS) and the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS). Results In this study, 90 patients with Parkinson’s disease were included. The most common intervention was to find a therapy for untreated comorbidities. The UPDRS or MDS-UPDRS improved significantly after the intervention period by a median change rate of 1 (p < 0.05) or rather 2 (p < 0.05) compared to the baseline. Conclusion The study shows that the quality of life in Parkinson’s disease patients improved significantly through MTM.     

Pharmacological management of behavioral disturbances in patients with Alzheimer’s disease

ABSTRACT

Neuropsychiatric symptoms (NPS) inevitably occur during the course of Alzheimer’s disease (AD) including psychosis, aggression, and depression. The effectiveness of pharmacological treatments for NPS has been limited because of their lack of efficacy, discontinuation due to undesirable adverse events, or poor adherence. In recent consensus guidelines, non-pharmacological treatments for NPS have been prioritized as first-line management strategies. Pharmacological treatments for severe NPS should be administrated as a second-line approach, and have been suggested to be started at a lower dosage followed by titration to a minimum effective dosage and for a limited time period. However, recent studies have shown that some patients receiving pharmacological treatments do not exhibit treatment efficacy in comparison with placebo. The concurrence of several sub-symptoms in NPS makes it difficult to target one symptom exclusively. Therefore, the current review focuses on a strategy for such refractory NPS in patients with AD. Recent randomized controlled trials have shown that the severity of NPS gradually reduces in a time-dependent manner regardless of active treatments. Therefore, clinicians should consider potential causes of NPS sub-symptoms from multifactorial aspects and select alternative treatments (e.g. neuromodulation or relocation into specialized care units) during the long-term disease course.     

Ocular effects of pegylated interferon-α in patients with chronic hepatitis B

Abstract

Purpose: To evaluate the early retinal changes and its reflection on the visual field examination in chronic hepatitis B (CHB) patients using pegylated interferon-α (PEGIFN-α) monotherapy.

Patients and methods: Thirty eyes of fifteen patients with CHB were examined prospectively for changes in the fundus examination and visual field examination (both Humphrey Perimetry and Frequency Doubling Perimetry). The patients were examined before and in 3 months intervals after starting the PEGIFN-α treatment. The changes in the fundus examination were noted and the visual field examinations, retinal nerve fiber thickness, Schirmer scores and color vision before and at 3 months of the treatment were compared. The statistical evaluation was performed with paired-t test, using SPSS 16.0 Inc. (Chicago, IL).

Results: The mean age of the 15 patients (seven male, eight female) was 52.5?±?12.4 years. There was no significant retinal change in none of the patients. Neither the visual field examination with Humphrey Field Analyzer nor the Frequency Doubling Perimetry results has demonstrated any significant change during 3 months follow-up. There was a statistically significant increase in the retinal nerve fiber layer (RNFL) thickness; while Schirmer test scores for dry eye assessment was significantly decreased.

Conclusion: PEGIFN-α monotherapy, which is used for treatment of CHB, may cause some changes in the thickness of RNFL that may necessitate the close follow-up for further morphological changes of the optic disc in these patients.     

Inotropes for the management of acute heart failure patients with renal dysfunction. Still an option?

Introduction: Renal dysfunction is highly prevalent in patients with acute heart failure (AHF). These patients are more vulnerable in worsening of kidney function and have also higher mortality rates.

Areas covered: Recent developments in the understanding of bidirectional interaction between heart and kidney are reviewed in the context of the potential impact of inotropes on renal function. Key clinical trials reporting the use of inotropes in AHF patients with renal dysfunction are discussed in this review.

Expert opinion: Inotropes may be indicated on a short-term basis and under close monitoring in AHF with renal dysfunction mostly in cases of low output heart failure that can provoke renal hypoperfusion. Dopamine administration with low dose of i.v. furosemide has been recently compared with high dose of i.v. furosemide alone, demonstrating lower rates of worsening renal function and electrolyte disturbances. Moreover, small clinical trials have shown that the novel inodilator levosimendan seems to be superior to dobutamine or placebo in improving renal function in patients with acutely decompensated heart failure. The impact of novel inotropes on kidney function is still unclear. Randomized clinical trials are required in order to identify the role of inotropes in the management and/or prevention of acute cardiorenal syndrome.