Home medication management practices and associated factors among patients with selected chronic diseases in a community pharmacy in Uganda

ABSTRACT: BACKGROUND: Chronic diseases are rapidly increasing and are currently the major cause of death and disability worldwide. Patients with chronic diseases experience many challenges including medicine-related problems. However, there is limited information about the home management of medicines among these patients. This study therefore was to determine home medication management practices and associated factors among patients with chronic diseases seeking care in a community pharmacy in Uganda. METHODS: A cross-sectional study was conducted in a community pharmacy in Kampala from June to July 2010. A total of 207 consenting chronic disease patients or caregivers of children with chronic disease were consecutively sampled. The patients were visited at home to evaluate their drug management practices and to check their medical forms for disease types and drugs prescribed. An interviewer-administered questionnaire and an observation checklist were used to collect the data. RESULTS: Overall home medication management was inappropriate for 70% (n = 145) of the participants (95% CI = 63.3-76.2) and was associated with perceived severity of disease (not severe OR =0.40, moderately severe OR = 0.35), duration of disease >5 years (OR = 2.15), and health worker not assessing for response to treatment (OR = 2.53). About 52% (n = 107) had inappropriate storage which was associated with inadequate information about the disease (OR = 2.39) and distance to the health facility >5 kilometres (OR = 2.82). Fifteen percent (n = 31) had no drug administration schedule and this was associated with increasing age (OR = 0.97), inadequate information about the disease (OR = 2.96), and missing last appointment for medical review (OR = 6.55). About 9% (n = 18) had actual medication duplication; 1.4% (n = 3) had expired medicines; while 18.4% (n = 38) had drug hoarding associated with increasing number of prescribers (OR = 1.34) and duration of disease (OR = 2.06). About 51% (n = 105) had multiple prescribers associated with perceiving the disease to be non severe (OR = 0.27), and having more than one chronic disease (OR = 2.37). CONCLUSIONS: Patients with chronic disease have poor home management of medicines. In order to limit the occurrence of poor outcomes of treatment or drug toxicity, health providers need to strengthen the education of patients with chronic disease on how to handle their medicines at home.

From Lydia Pinkham to Queen Levitra:Direct-to-consumer advertising and medicalisation

The medicalisation of life problems has been occurring for well over a century and has increased over the past 30 years, with the engines of medicalisation shifting to biotechnology, managed care, and consumers. This paper examines one strand of medicalisation during the last century: direct-to-consumer advertising (DTCA) of pharmaceuticals. In particular, it examines the roles that physicians and the Food and Drug Administration (FDA) have played in regulating DTCA in the US. Two advertising exemplars, the late 19 century Lydia E. Pinkham's Vegetable Compound (for 'women's complaints') and contemporary Levitra (for erectile dysfunction) are used to examine the parallels between the patent medicine era and the DTCA era. DTCA re-establishes the direct and independent relationship between drug companies and consumers that existed in the late 19 century, encouraging self-diagnosis and requests for specific drugs. The extravagant claims of Lydia Pinkham's day are constrained by laws, but modern-day advertising is more subtle and sophisticated. DTCA has facilitated the impact of the pharmaceutical industry and consumers in becoming more important forces in medicalisation. © 2008 The Authors.

Lead in rice: Analysis of baseline lead levels in market and field collected rice grains

In a large scale survey of rice grains from markets (13 countries) and fields (6 countries), a total of 1578 rice grain samples were analysed for lead. From the market collected samples, only 0.6% of the samples exceeded the Chinese and EU limit of 0.2 μg g− 1 lead in rice (when excluding samples collected from known contaminated/mine impacted regions). When evaluating the rice grain samples against the Food and Drug Administration's (FDA) provisional total tolerable intake (PTTI) values for children and pregnant women, it was found that only people consuming large quantities of rice were at risk of exceeding the PTTI from rice alone. Furthermore, 6 field experiments were conducted to evaluate the proportion of the variation in lead concentration in rice grains due to genetics. A total of 4 of the 6 field experiments had significant differences between genotypes, but when the genotypes common across all six field sites were assessed, only 4% of the variation was explained by genotype, with 9.5% and 11% of the variation explained by the environment and genotype by environment interaction respectively. Further work is needed to identify the sources of lead contamination in rice, with detailed information obtained on the locations and environments where the rice is sampled, so that specific risk assessments can be performed.

The effect of inhaled IFN-β on worsening of asthma symptoms caused by viral infections. a randomized trial

Rationale: Ex vivo, bronchial epithelial cells from people with asthma are more susceptible to rhinovirus infection caused by deficient induction of the antiviral protein, IFN-b. Exogenous IFN-b restores antiviral activity.

Objectives: To compare the efficacy and safety of inhaled IFN-b with placebo administered to people with asthma after onset of cold symptoms to prevent or attenuate asthma symptoms caused by respiratory viruses.

Methods: A total of 147 people with asthma on inhaled corticosteroids (British Thoracic Society Steps 2–5), with a history of virus-associated exacerbations, were randomized to 14-day treatment with inhaled IFN-b (n = 72) or placebo (n = 75) within 24 hours of developing cold symptoms and were assessed clinically, with relevant samples collected to assess virus infection and antiviral responses.

Measurements and Main Results: A total of 91% of randomized patients developed a defined cold. In this modified intention-to-treat population, asthma symptoms did not get clinically significantly worse
(mean change in six-item Asthma Control Questionnaire ,0.5) and IFN-b treatment had no significant effect on this primary endpoint, although it enhanced morning peak expiratory flow recovery (P = 0.033), reduced the need for additional treatment, and boosted innate immunity as assessed by blood and sputum biomarkers. In an exploratory analysis of the subset ofmore difficult-to-treat, Step 4-5 peoplewith asthma (n = 27 IFN-b; n = 31 placebo), Asthma Control Questionnaire-6 increased significantly on placebo; this was prevented by IFN-b (P = 0.004).

Conclusions: Although the trial did not meet its primary endpoint, it suggests that inhaled IFN-b is a potential treatment for virus-induced deteriorations of asthma in difficult-to-treat people with asthma and supports the needforfurther, adequately powered, trialsin this population. Clinical trial registered with www.clinicaltrials.gov (NCT 01126177).

The TORCH (towards a revolution in COPD health) survival study protocol

Only long-term home oxygen therapy has been shown in randomised controlled trials to increase survival in chronic obstructive pulmonary disease (COPD). There have been no trials assessing the effect of inhaled corticosteroids and long-acting bronchodilators, alone or in combination, on mortality in patients with COPD, despite their known benefit in reducing symptoms and exacerbations. The "TOwards a Revolution in COPD Health" (TORCH) survival study is aiming to determine the impact of salmeterol/fluticasone propionate (SFC) combination and the individual components on the survival of COPD patients. TORCH is a multicentre, randomised, double-blind, parallel-group, placebo-controlled study. Approximately 6,200 patients with moderate-to-severe COPD were randomly assigned to b.i.d. treatment with either SFC (50/500 microg), fluticasone propionate (500 microg), salmeterol (50 microg) or placebo for 3 yrs. The primary end-point is all-cause mortality; secondary end-points are COPD morbidity relating to rate of exacerbations and health status, using the St George's Respiratory Questionnaire. Other end-points include other mortality and exacerbation end-points, requirement for long-term oxygen therapy, and clinic lung function. Safety end-points include adverse events, with additional information on bone fractures. The first patient was recruited in September 2000 and results should be available in 2006. This paper describes the "TOwards a Revolution in COPD Health" study and explains the rationale behind it.

Gastroretentive Extended-Release Floating Granules Prepared Using a Novel Fluidized Hot Melt Granulation (FHMG) Technique

The objective of this work was to investigate the feasibility of using a novel granulation technique, namely, fluidized hot melt granulation (FHMG), to prepare gastroretentive extended-release floating granules. In this study we have utilized FHMG, a solvent free process in which granulation is achieved with the aid of low melting point materials, using Compritol 888 ATO and Gelucire 50/13 as meltable binders, in place of conventional liquid binders. The physicochemical properties, morphology, floating properties, and drug release of the manufactured granules were investigated. Granules prepared by this method were spherical in shape and showed good flowability. The floating granules exhibited sustained release exceeding 10 h. Granule buoyancy (floating time and strength) and drug release properties were significantly influenced by formulation variables such as excipient type and concentration, and the physical characteristics (particle size, hydrophilicity) of the excipients. Drug release rate was increased by increasing the concentration of hydroxypropyl cellulose (HPC) and Gelucire 50/13, or by decreasing the particle size of HPC. Floating strength was improved through the incorporation of sodium bicarbonate and citric acid. Furthermore, floating strength was influenced by the concentration of HPC within the formulation. Granules prepared in this way show good physical characteristics, floating ability, and drug release properties when placed in simulated gastric fluid. Moreover, the drug release and floating properties can be controlled by modification of the ratio or physical characteristics of the excipients used in the formulation.

Considerations in the sterile manufacture of polymeric microneedle arrays

We describe, for the first time, considerations in the sterile manufacture of polymeric microneedle arrays. Microneedles (MN) made from dissolving polymeric matrices and loaded with the model drugs ovalbumin (OVA) and ibuprofen sodium and hydrogel-forming MN composed of "super-swelling" polymers and their corresponding lyophilised wafer drug reservoirs loaded with OVA and ibuprofen sodium were prepared aseptically or sterilised using commonly employed sterilisation techniques. Moist and dry heat sterilisation, understandably, damaged all devices, leaving aseptic production and gamma sterilisation as the only viable options. No measureable bioburden was detected in any of the prepared devices, and endotoxin levels were always below the US Food & Drug Administration limits (20 endotoxin units/device). Hydrogel-forming MN were unaffected by gamma irradiation (25 kGy) in terms of their physical properties or capabilities in delivering OVA and ibuprofen sodium across excised neonatal porcine skin in vitro. However, OVA content in dissolving MN (down from approximately 101.1 % recovery to approximately 58.3 % recovery) and lyophilised wafer-type drug reservoirs (down from approximately 99.7 % recovery to approximately 60.1 % recovery) was significantly reduced by gamma irradiation, while the skin permeation profile of ibuprofen sodium from gamma-irradiated dissolving MN was markedly different from their non-irradiated counterparts. It is clear that MN poses a very low risk to human health when used appropriately, as evidenced here by low endotoxin levels and absence of microbial contamination. However, if guarantees of absolute sterility of MN products are ultimately required by regulatory authorities, it will be necessary to investigate the effect of lower gamma doses on dissolving MN loaded with active pharmaceutical ingredients and lyophilised wafers loaded with biomolecules in order to avoid the expense and inconvenience of aseptic processing.

Molecular predictors of response to antiangiogenesis therapies

Angiogenesis is a crucial component of tumor growth and metastasis. Targeting the vascular endothelial growth factor pathway represents therapeutic potentials for treating cancer. To date, 3 Food and Drug Administration-approved agents targeting angiogenesis have been developed, bevacizumab, sunitinib, and sorafenib. However, no validated biomarkers are available to identify those patients who are likely to benefit from antiangiogenesis therapy. Molecular biomarker research in antiangiogenesis inhibition is an actively growing field. Although current data are extremely promising, it is still uncertain which biomarker(s) can reliably predict their efficacy. With increasing numbers of inhibitors being developed, the need for biomarkers is more critical than ever. This review will focus on translational research that strives to identify molecular biomarkers (tissue, circulating and genomic) for approved antiangiogenesis therapies that can indicate benefit, resistance, and toxicity.

Angle-closure glaucoma: impact, etiology, diagnosis, and treatment.

PURPOSE OF REVIEW:

Recent studies underscore the importance of angle-closure glaucoma (ACG) as a cause of world blindness. A major contribution in assessing the true impact of this disease has been an article estimating the number of persons with occludable angles, angle closure, and blindness from ACG in China as 28.2 million, 9.1 million, and 1.7 million, respectively. Although these numbers are based on data from Singapore and Mongolia, which may be applied to China only with caution, they emphasize the blinding potential of ACG, which is three times as likely to be associated with blindness as open-angle glaucoma (OAG).

RECENT FINDINGS:

Recent reports in the Chinese literature on ACG prevalence suffer from definitional problems that would appear to lead to systematic overestimates of ACG prevalence and underestimates of OAG prevalence. Nonetheless, data from studies by Chinese investigators further emphasize the strong association between ACG and blindness, with fully 16% of subjects with ACG blind in one report-a far higher proportion than for OAG in China and elsewhere. The importance of topiramate as a cause of secondary angle closure has recently been understood, in part, because of a series of 19 such cases reported by investigators at the Food and Drug Administration.

SUMMARY:

Angle closure in this setting appears to be caused by uveal effusion and anterior rotation of the ciliary body with resultant closure of the angle. The condition is not always responsive to laser iridectomy, and elimination of the causative agent appears to be critical. Ultrasonic biomicroscopy is a potential new diagnostic modality for ACG, allowing the measurement of novel parameters, such as the angle opening distance (AOD) at 500 microm (AOD 500). The efficacy of such parameters in improving screening for ACG can only be established by prospective studies of potentially at-risk eyes. A number of novel treatments for AC and angle closure have recently been proposed, including cataract extraction, paracentesis, and argon laser iridoplasty. As with proposed new diagnostic modalities, the efficacy of these treatments remains to be demonstrated with prospective studies, ideally organized in a controlled, randomized fashion.

Microneedle-mediated delivery of donepezil: Potential for improved treatment options in Alzheimer's disease

Transdermal drug delivery is an attractive route of drug administration, however there are relatively few marketed transdermal products. To increase delivery across the skin, strategies to enhance skin permeability are widely investigated, with microneedles demonstrating particular promise. Hydrogel-forming microneedles are inserted into the skin, and following dissolution of a drug loaded reservoir and movement of the drug through the created channels, the microneedle array is removed intact, and can then be readily and safely discarded. This study presents the formulation and evaluation of an integrated microneedle patch containing the Alzheimer's drug, donepezil hydrochloride. The integrated patch consisted of hydrogel-forming microneedles in combination with a donepezil hydrochloride containing film. Formulation and characterisation of plasticised films, prepared from poly(vinylpyrrolidone) or poly (methyl vinyl ether co-maleic anhydride/acid) (Gantrez(®)) polymers, is presented. Furthermore, in vitro permeation of donepezil hydrochloride across neonatal porcine skin from the patches was investigated, with 854.71 μg ± 122.71 μg donepezil hydrochloride delivered after 24 h, using the optimum patch formulation. Following administration of the patch to an animal model, plasma concentrations of 51.8 ± 17.6 ng/mL were obtained, demonstrating the success of this delivery platform for donepezil hydrochloride.

Clinical Application of Poly(ADP-Ribose) Polymerase Inhibitors in High-Grade Serous Ovarian Cancer

: High-grade serous ovarian cancer is characterized by genomic instability, with one half of all tumors displaying defects in the important DNA repair pathway of homologous recombination. Given the action of poly(ADP-ribose) polymerase (PARP) inhibitors in targeting tumors with deficiencies in this repair pathway by loss of BRCA1/2, ovarian tumors could be an attractive population for clinical application of this therapy. PARP inhibitors have moved into clinical practice in the past few years, with approval from the Food and Drug Administration (FDA) and European Medicines Agency (EMA) within the past 2 years. The U.S. FDA approval of olaparib applies to fourth line treatment in germline BRCA-mutant ovarian cancer, and European EMA approval to olaparib maintenance in both germline and somatic BRCA-mutant platinum-sensitive ovarian cancer. In order to widen the ovarian cancer patient population that would benefit from PARP inhibitors, predictive biomarkers based on a clear understanding of the mechanism of action are required. Additionally, a better understanding of the toxicity profile is needed if PARP inhibitors are to be used in the curative, rather than the palliative, setting. We reviewed the development of PARP inhibitors in phase I-III clinical trials, including combination trials of PARP inhibitors and chemotherapy/antiangiogenics, the approval for these agents, the mechanisms of resistance, and the outstanding issues, including the development of biomarkers and the rate of long-term hematologic toxicities with these agents.

IMPLICATIONS FOR PRACTICE: The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib has recently received approval from the Food and Drug Administration (FDA) and European Medicines Agency (EMA), with a second agent (rucaparib) likely to be approved in the near future. However, the patient population with potential benefit from PARP inhibitors is likely wider than that of germline BRCA mutation-associated disease, and biomarkers are in development to enable the selection of patients with the potential for clinical benefit from these agents. Questions remain regarding the toxicities of PARP inhibitors, limiting the use of these agents in the prophylactic or adjuvant setting until more information is available. The indications for olaparib as indicated by the FDA and EMA are reviewed.

Enhancement of the Cytotoxic Effect of Anticancer Agent by Cytochrome c Functionalised Hybrid Nanoparticles in Hepatocellular Cancer Cells

Treatment of hepatocellular cancer with chemotherapeutic agents has limited successin clinical practice and their efficient IC50 concentration would require extremely highdoses of drug administration which could not be tolerated due to systemic side effects.In order to potentiate the efficacy of anticancer agents we explored the potentialof co-treatment with pro-apoptotic Cytochrome c which activates the apoptoticpathway downstream of p53 that is frequently mutated in cancer. To this end weused hybrid iron oxide-gold nanoparticles as a drug delivery system to facilitate theinternalisation of Cytochrome c into cultured HepG2 hepatocellular carcinoma cells.Our results showed that Cytochrome c can be easily conjugated to the gold shell ofthe nanoparticles which are readily taken up by the cells. We used Cytochrome cin concentration (0.2μgmL-1) below the threshold required to induce apoptosis onits own. When the conjugate was administered to cells treated by doxorubicin, itsignificantly reduced its IC50 concentration from 9μgmL-1 to 3.5μgmL-1 as detectedby cell viability assay, and the efficiency of doxorubicin on decreasing viability ofHepG2 cells was significantly enhanced in the lower concentration range between0.01μgmL-1 to 5μgmL-1. The results demonstrate the potential of the application oftherapeutic proteins in activating the apoptotic pathway to complement conventionalchemotherapy to increase its efficacy. The application of hybrid iron oxide-goldnanoparticles can also augment the specificity of drug targeting and could serve as amodel drug delivery system for pro-apoptotic protein targeting and delivery.

Multi-purpose utility of circulating plasma DNA testing in patients with advanced cancers.

Tumor genomic instability and selective treatment pressures result in clonal disease evolution; molecular stratification for molecularly targeted drug administration requires repeated access to tumor DNA. We hypothesized that circulating plasma DNA (cpDNA) in advanced cancer patients is largely derived from tumor, has prognostic utility, and can be utilized for multiplex tumor mutation sequencing when repeat biopsy is not feasible. We utilized the Sequenom MassArray System and OncoCarta panel for somatic mutation profiling. Matched samples, acquired from the same patient but at different time points were evaluated; these comprised formalin-fixed paraffin-embedded (FFPE) archival tumor tissue (primary and/or metastatic) and cpDNA. The feasibility, sensitivity, and specificity of this high-throughput, multiplex mutation detection approach was tested utilizing specimens acquired from 105 patients with solid tumors referred for participation in Phase I trials of molecularly targeted drugs. The median cpDNA concentration was 17 ng/ml (range: 0.5-1600); this was 3-fold higher than in healthy volunteers. Moreover, higher cpDNA concentrations associated with worse overall survival; there was an overall survival (OS) hazard ratio of 2.4 (95% CI 1.4, 4.2) for each 10-fold increase in cpDNA concentration and in multivariate analyses, cpDNA concentration, albumin, and performance status remained independent predictors of OS. These data suggest that plasma DNA in these cancer patients is largely derived from tumor. We also observed high detection concordance for critical 'hot-spot' mutations (KRAS, BRAF, PIK3CA) in matched cpDNA and archival tumor tissue, and important differences between archival tumor and cpDNA. This multiplex sequencing assay can be utilized to detect somatic mutations from plasma in advanced cancer patients, when safe repeat tumor biopsy is not feasible and genomic analysis of archival tumor is deemed insufficient. Overall, circulating nucleic acid biomarker studies have clinically important multi-purpose utility in advanced cancer patients and further studies to pursue their incorporation into the standard of care are warranted.

Does video feedback analysis improve CPR performance in phase 5 medical students?

Background The use of simulation in medical education is increasing, with students taught and assessed using simulated patients and manikins. Medical students at Queen’s University of Belfast are taught advanced life support cardiopulmonary resuscitation as part of the undergraduate curriculum. Teaching and feedback in these skills have been developed in Queen’s University with high-fidelity manikins. This study aimed to evaluate the effectiveness of video compared to verbal feedback in assessment of student cardiopulmonary resuscitation performance Methods Final year students participated in this study using a high-fidelity manikin, in the Clinical Skills Centre, Queen’s University Belfast. Cohort A received verbal feedback only on their performance and cohort B received video feedback only. Video analysis using ‘StudioCode’ software was distributed to students. Each group returned for a second scenario and evaluation 4 weeks later. An assessment tool was created for performance assessment, which included individual skill and global score evaluation. Results One hundred thirty eight final year medical students completed the study. 62 % were female and the mean age was 23.9 years. Students having video feedback had significantly greater improvement in overall scores compared to those receiving verbal feedback (p = 0.006, 95 % CI: 2.8–15.8). Individual skills, including ventilation quality and global score were significantly better with video feedback (p = 0.002 and p < 0.001, respectively) when compared with cohort A. There was a positive change in overall score for cohort B from session one to session two (p < 0.001, 95 % CI: 6.3–15.8) indicating video feedback significantly benefited skill retention. In addition, using video feedback showed a significant improvement in the global score (p < 0.001, 95 % CI: 3.3–7.2) and drug administration timing (p = 0.004, 95 % CI: 0.7–3.8) of cohort B participants, from session one to session two. Conclusions There is increased use of simulation in medicine but a paucity of published data comparing feedback methods in cardiopulmonary resuscitation training. Our study shows the use of video feedback when teaching cardiopulmonary resuscitation is more effective than verbal feedback, and enhances skill retention. This is one of the first studies to demonstrate the benefit of video feedback in cardiopulmonary resuscitation teaching.