Importance of the physical exam: double-blind randomized controlled trial of radiologic interpretation of ventral hernias after selective clinical information.

PURPOSE: Increasingly, radiologic imaging is obtained as part of the pathway in diagnosing ventral hernias. Often, radiologists receive incomplete or incorrect clinical information from clinicians. OBJECTIVE: The aim of the study is to determine if clinical exam findings alter radiological interpretation of ventral hernias on CT. METHODS: This is a single-institution double-blind, randomized trial. All patients with a recent abdominal/pelvic CT scan seen in various surgical clinics were enrolled. A surgeon blinded to the CT scan findings performed a standardized physical examination and assessed for the presence of a ventral hernia. Seven independent radiologists blinded to the study design reviewed the scans. Each radiologist received one of three types of clinical exam data per CT: accurate (correct), inaccurate (purposely incorrect), or none. Allocation was random and stratified by the presence of clinical hernia. The primary outcome was the proportion of radiologic hernias detected, analyzed by chi square. RESULTS: 115 patients were enrolled for a total of 805 CT scan reads. The proportion of hernias detected differed by up to 25% depending on if accurate, no, or inaccurate clinical information was provided. Inaccurate clinical data in patients with no hernia on physical exam led to a significant difference in the radiologic hernia detection rate (54.3% versus 35.7%, p = 0.007). No clinical data in patients with a hernia on physical exam led to a lower radiologic hernia detection rate (75.0% versus 93.8%, p = 0.001). CONCLUSIONS: The presence and accuracy of clinical information provided to radiologists impacts the diagnosis of abdominal wall hernias in up to 25% of cases. Standardization of both clinical and radiologic examinations for hernias and their reporting are needed. TRIAL REGISTRATION: Clinicaltrials.gov, Number NCT03121131, https://clinicaltrials.gov/ct2/show/NCT03121131.

Optomechanical design and construction of a vacuum-compatible optical parametric oscillator for generation of squeezed light.

With the recent detection of gravitational waves, non-classical light sources are likely to become an essential element of future detectors engaged in gravitational wave astronomy and cosmology. Operating a squeezed light source under high vacuum has the advantages of reducing optical losses and phase noise compared to techniques where the squeezed light is introduced from outside the vacuum. This will ultimately provide enhanced sensitivity for modern interferometric gravitational wave detectors that will soon become limited by quantum noise across much of the detection bandwidth. Here we describe the optomechanical design choices and construction techniques of a near monolithic glass optical parametric oscillator that has been operated under a vacuum of 10(-6) mbar. The optical parametric oscillator described here has been shown to produce 8.6 dB of quadrature squeezed light in the audio frequency band down to 10 Hz. This performance has been maintained for periods of around an hour and the system has been under vacuum continuously for several months without a degradation of this performance.

Squeezed quadrature fluctuations in a gravitational wave detector using squeezed light.

Squeezed states of light are an important tool for optical measurements below the shot noise limit and for optical realizations of quantum information systems. Recently, squeezed vacuum states were deployed to enhance the shot noise limited performance of gravitational wave detectors. In most practical implementations of squeezing enhancement, relative fluctuations between the squeezed quadrature angle and the measured quadrature (sometimes called squeezing angle jitter or phase noise) are one limit to the noise reduction that can be achieved. We present calculations of several effects that lead to quadrature fluctuations, and use these estimates to account for the observed quadrature fluctuations in a LIGO gravitational wave detector. We discuss the implications of this work for quantum enhanced advanced detectors and even more sensitive third generation detectors.

Community-based cardiovascular Risk Factors Intervention Strategies (CORFIS) in managing hypertension: A pragmatic non-randomised controlled trial.

BACKGROUND: Hypertension is the number one cardiovascular risk factor in Malaysia. This study aimed to evaluate the effectiveness of a Community-Based Cardiovascular Risk Factors Intervention Strategies (CORFIS) in the management of hypertension in primary care. METHODS: This is a pragmatic, non-randomized controlled trial. Seventy general practitioners (GPs) were selected to provide either CORFIS (44 GPs) or conventional care (26 GPs) for 6 months. A total of 486 hypertensive patients were recruited; 309 were in the intervention and 177 in the control groups. Primary outcome was the proportion of hypertensive patients who achieved target blood pressure (BP) of <140/90mmHg (for those without diabetes mellitus) and <130/80mmHg (with diabetes mellitus). Secondary outcomes include change in the mean/median BP at 6-month as compared to baseline. RESULTS: The proportion of hypertensive patients who achieved target BP at 6-month was significantly higher in the CORFIS arm (69.6%) as compared to the control arm (57.6%), P=0.008. Amongst those who had uncontrolled BP at baseline, the proportion who achieved target BP at 6-month was also significantly higher in the CORFIS arm (56.6%) as compared to the control arm (34.1%), p<0.001. There was no difference in the patients who had already achieved BP control at baseline. There were significant reductions in SBP in the CORFIS arm (median -9.0mmHg; -60 to 50) versus control (median -2mmHg; -50 to 48), p=0.003; as well as in DBP (CORFIS arm: median -6.0mmHg; ranged from -53 to 30 versus control arm: median 0.0mmHg; ranged from -42 to 30), p<0.001. CONCLUSIONS: Patients who received CORFIS care demonstrated significant improvements in achieving target BP.

Pharmaceutical care issues encountered by post-menopausal osteoporotic women prescribed bisphosphonates.

WHAT IS KNOWN AND OBJECTIVE: Pharmacists have been involved in providing comprehensive interventions to osteoporosis patients, but pharmaceutical care issues (PCIs) encountered during such interventions have not been well documented. Therefore, the aim of this study was to document PCIs encountered by post-menopausal osteoporotic women prescribed bisphosphonates. METHODS: A randomized controlled study was conducted from September 2005-February 2009 in the University Malaya Medical Centre, Malaysia. This main intervention study measured the effects of pharmaceutical care on medication adherence, persistence, quality of life, knowledge and patient satisfaction. However, this manuscript is part of the main intervention study and focuses only on the PCIs encountered. INCLUSION CRITERIA: post-menopausal women diagnosed with osteoporosis (T-score≤-2·5/low-trauma fracture) and prescribed weekly alendronate/risedronate. EXCLUSION CRITERIA: those with metabolic bone disease and could not communicate in English. The PCIs identified were collected via personal interviews or telephone calls, and each participant was followed-up for a period of 2 years. All PCIs were discussed with and confirmed by a physician. RESULTS AND DISCUSSION: Of the 198 participants recruited, 64 (32·3%) experienced adverse effects because of bisphosphonates whereas one participant (0·5%) refused to start bisphosphonates because of fear of adverse effects. Most adverse effects [50 (74·6%)] were reported during the first 3 months of therapy with gastrointestinal problems being the main issue [23 (11·6%)]. Of the nine participants (4·5%) who discontinued bisphosphonates, only three agreed to take another medication. From the 97 PCIs identified, 77 issues could be classified as drug-related problems [according to the Pharmaceutical Care Network Europe Classification v6·2]. There were 87 causes, 178 interventions and 77 outcomes. The main problem and cause of the PCIs encountered were adverse drug events (83·1% and 74·7% respectively), whereas the main intervention provided was patient counselling (41·0%). All problems were solved (98·5%) except for one because of the lack of cooperation of a patient. After 2 years, 36 participants (20%) were no longer persistent with therapy, 19 (10·6%) did not have clinic follow-up and 53 (26·8%) did not have a bone mineral density scan. WHAT IS NEW AND CONCLUSION: The main PCIs identified were related to the use of bisphosphonates and its adverse effects. The study showed that the presence of a clinical pharmacist has enabled patients to voice their medication-related issues and to allow appropriate recommendations and actions to be taken to resolve these issues.

Effects of pharmaceutical care on adherence and persistence to bisphosphonates in postmenopausal osteoporotic women.

WHAT IS KNOWN AND OBJECTIVE: Studies have shown that comprehensive interventions by pharmacists can improve adherence and persistence to osteoporosis therapy, but the association between adherence and bone turnover markers (BTMs) has never been studied. Therefore, the aim of this study was to evaluate the effects of pharmaceutical care on medication adherence (and its effects on BTMs), as well as persistence of postmenopausal osteoporotic women to prescribed bisphosphonates. METHODS: A randomized controlled trial was conducted from 2005 to 2009 in the University Malaya Medical Centre, Malaysia. INCLUSION CRITERIA: postmenopausal osteoporotic women diagnosed with osteoporosis with a T-score ≤ -2·5 or who had a low-trauma fracture and prescribed weekly alendronate/risedronate. Intervention participants received counselling on osteoporosis, risk factors, lifestyle modifications, goals of therapy, side effects and the importance of adherence. Adherence was assessed at months 3, 6 and 12, and persistence at month 12. Feedback on BTMs was provided at months 4 and 7. The control group received no counselling. Two BTMs were used: serum C-terminal cross-linking telopeptide of type I collagen (CTX-I) and serum osteocalcin (OC). MAIN OUTCOMES MEASURED: medication adherence, BTMs and persistence. RESULTS AND DISCUSSION: Intervention participants who received pharmaceutical care reported significantly higher medication adherence at 6 (P = 0·015) and 12 months (P = 0·047) compared with the control group; but this effect was not shown by the BTMs. This is probably due to the long effect of bisphosphonates in bone. A significant difference was found between serum CTX-I and OC in identifying non-responders to anti-resorptive therapy (P < 0·001), indicating the usefulness of BTMs as an objective marker. However, pharmaceutical care did not affect persistence to osteoporosis therapy within a 1-year period [log rank (Mantel-Cox) χ² = 0·496, P = 0·481]. The proportion of participants who were persistent with bisphosphonate therapy after 12 months was 89·8% and 87·0% in the control and intervention group respectively. WHAT IS NEW AND CONCLUSION: The provision of pharmaceutical care improved medication adherence but not persistence. BTMs were not appropriate objective measures for assessing adherence to weekly bisphosphonates but were useful for identifying non-responders to treatment within 3-6 months, much earlier than using bone mineral density. The study indicates that pharmacists have a role in improving medication adherence, but its long-term effect on persistence warrants further studies with longer duration.

A systematic review of interventions by healthcare professionals on community-dwelling postmenopausal women with osteoporosis.

UNLABELLED: A systematic review was conducted to evaluate evidence concerning the effect of non-drug interventions by healthcare professionals on community-dwelling postmenopausal osteoporotic women. Evidence available indicates that such interventions are effective in improving the quality of life, medication compliance, and calcium intake, but effect on other outcomes is less conclusive. INTRODUCTION: The purpose of this study is to conduct a systematic review to evaluate evidence concerning the effect of non-drug interventions by healthcare professionals on community-dwelling postmenopausal osteoporotic women. METHODS: Randomized controlled trials (RCTs) published in English between year 1990 and 2009 were identified. Types of patient outcome used as assessment included quality of life (QOL), bone mineral density (BMD), medication compliance and persistence, knowledge level, and lifestyle modification. RESULTS: Twenty four RCTs met the inclusion criteria. Seven studies assessed interventions by physiotherapists, six by physicians, seven by nurses, three by multi-disciplinary teams and one by dietitians. Variability in the types and intensity of interventions made comparison between each study difficult. Collectively, these studies provided some evidence to show that interventions by healthcare professionals improved the QOL medication compliance and calcium intake of patients but its effects on BMD, medication persistence, knowledge, and other lifestyle modifications were less conclusive. CONCLUSIONS: From this review, it was found that some outcome measures of such non-drug interventions still required further studies. Future studies should use validated instruments to assess the outcomes, with focus on common definitions of interventions and outcome measures, more intensive one-to-one interventions, appropriate control groups, adequate randomization procedures, and also provide information on effect size.

Development and validation of the osteoporosis patient satisfaction questionnaire (OPSQ).

OBJECTIVES: To develop and validate the Osteoporosis Patient Satisfaction Questionnaire (OPSQ) and to assess the opinion of postmenopausal osteoporotic women towards pharmaceutical care. METHODS: A 16-item instrument was designed. Each response consists of a five-point Likert-like scale with higher scores indicating greater satisfaction. The face and content validity was established via consultation with an endocrinologist and three pharmacists as well as feedback from participants in a preliminary study. Postmenopausal osteoporotic women taking bisphosphonates were recruited and randomly allocated to the intervention (n=90) and control groups (n=90). Pharmaceutical care was provided at month 2 to the intervention group while the control group received standard pharmacy services. The OPSQ was administered at month 6 (end of the intervention period), to assess patients' satisfaction. Factor analysis was performed using varimax rotation. Internal reliability was established using Cronbach's alpha. Construct validity was performed by using the Mann-Whitney U test. RESULTS: The internal reliability of the OPSQ produced a Cronbach's alpha of 0.86. Factor analysis identified one component in the OPSQ, which measured patient satisfaction. The intervention group showed significantly better overall OPSQ score than the control group (91.89+/-7.22% versus 84.32+/-7.48%, p<0.001). This indicates that the OPSQ was able to differentiate between participants who received pharmaceutical care from those who did not. CONCLUSIONS: The 16-item OPSQ developed in this study has high internal reliability and is a valid instrument for assessing osteoporotic women's satisfaction with pharmaceutical care service in Malaysia.

An observational study of drug administration errors in a Malaysian hospital (study of drug administration errors).

BACKGROUND AND OBJECTIVE: Drug administration errors were the second most frequent type of medication errors, after prescribing errors but the latter were often intercepted hence, administration errors were more probably to reach the patients. Therefore, this study was conducted to determine the frequency and types of drug administration errors in a Malaysian hospital ward. METHODS: This is a prospective study that involved direct, undisguised observations of drug administrations in a hospital ward. A researcher was stationed in the ward under study for 15 days to observe all drug administrations which were recorded in a data collection form and then compared with the drugs prescribed for the patient. RESULTS: A total of 1118 opportunities for errors were observed and 127 administrations had errors. This gave an error rate of 11.4 % [95% confidence interval (CI) 9.5-13.3]. If incorrect time errors were excluded, the error rate reduced to 8.7% (95% CI 7.1-10.4). The most common types of drug administration errors were incorrect time (25.2%), followed by incorrect technique of administration (16.3%) and unauthorized drug errors (14.1%). In terms of clinical significance, 10.4% of the administration errors were considered as potentially life-threatening. Intravenous routes were more likely to be associated with an administration error than oral routes (21.3% vs. 7.9%, P < 0.001). CONCLUSION: The study indicates that the frequency of drug administration errors in developing countries such as Malaysia is similar to that in the developed countries. Incorrect time errors were also the most common type of drug administration errors. A non-punitive system of reporting medication errors should be established to encourage more information to be documented so that risk management protocol could be developed and implemented.

The validity and reliability of the Malaysian Osteoporosis Knowledge Tool in postmenopausal women.

OBJECTIVES: To design a valid and reliable questionnaire, the Malaysian Osteoporosis Knowledge Tool (MOKT), to assess the knowledge of postmenopausal osteoporotic women in Malaysia, on osteoporosis and its treatment. METHODS: A 40-item instrument was designed and tested in this study. The scores ranged from 1 to 40, which were then converted into percentage. This was administered to 88 postmenopausal osteoporotic women who were taking alendronate (patient group) and 43 pharmacists (professional group). The MOKT was administered again to the patient group after 1 month. RESULTS: Flesch reading ease was 57, which is satisfactory, while the mean difficulty factor+/-S.D. was 0.73+/-0.25, indicating that the MOKT is moderately easy. Internal consistency of the instrument was good with Cronbach's alpha=0.82. The test and retest scores showed no significant difference for 38 out of the 40 items, indicating that the questionnaire has achieved a stable reliability. Level of knowledge on osteoporosis and its treatment was good with a mean score+/-S.D. of 69.0+/-13.9 and 81.6+/-9.5 in the patient and professional group, respectively. The difference in knowledge scores between the two groups was statistically significant (p<0.001). CONCLUSIONS: In conclusion, the 40-item questionnaire (MOKT) is a reliable and valid instrument for measuring knowledge on osteoporosis in the Malaysian setting. Therefore, it can be used to identify individuals in need of educational interventions and to assess the effectiveness of education efforts as part of osteoporosis management.

Utilisation of non-steroidal anti-inflammatory drugs (NSAIDs) through community pharmacies in Malaysia.

This study was conducted to evaluate the use of non-steroidal anti-inflammatory drugs (NSAIDs) by consumers who obtained these drugs from community pharmacies. Factors that influenced community pharmacists in their choice of NSAIDs were also determined. Personal interviews were conducted on consumers who visited the 25 participating community pharmacies throughout Malaysia. Of the 389 respondents, 49% requested for an NSAID by name, 42% asked the pharmacist to recommend a medication and 9% had a doctor's prescription. NSAIDs were mainly purchased for joint/shoulder pain and the most commonly dispensed was diclofenac. Elderly respondents were more likely to be dispensed a selective COX-2 inhibitor than those below 60. NSAIDs were recommended based mainly on the pharmacist's perception of their efficacy, cost and safety. Community pharmacists play an important role in assisting patients in choosing the most appropriate NSAID for their health problems.

Phenotypic consequences of lung-specific inducible expression of FGF-3.

Members of the fibroblast growth factor (FGF) family play a critical role in embryonic lung development and adult lung physiology. The in vivo investigation of the role FGFs play in the adult lung has been hampered because the constitutive pulmonary expression of these factors often has deleterious effects and frequently results in neonatal lethality. To circumvent these shortcomings, we expressed FGF-3 in the lungs under the control of the progesterone antagonist-responsive binary transgenic system. Four binary transgenic lines were obtained that showed ligand-dependent induction of FGF-3 with induced levels of FGF-3 expression dependent on the levels of expression of the GLp65 regulator as well as the dose of the progesterone antagonist, RU486, administered. FGF-3 expression in the adult mouse lung resulted in two phenotypes depending on the levels of induction of FGF-3. Low levels of FGF-3 expression resulted in massive free alveolar macrophage infiltration. High levels of FGF-3 expression resulted in diffuse alveolar type II cell hyperplasia. Both phenotypes were reversible after the withdrawal of RU486. This system will be a valuable means of investigating the diverse roles of FGFs in the adult lung.

Induction of mammary gland hyperplasia in transgenic mice over-expressing human Cdc25B.

Cdc25 A and B are dual-specificity phosphatases which have been implicated in neoplastic transformation. Although Cdc25A and Cdc25B have been found to be over-expressed in many cancer cell lines and primary tumors, the physiological roles of Cdc25A and B in vivo are largely undefined. To investigate the roles of these proteins in the oncogenic transformation of the mammary gland we used the mouse mammary tumor virus (MMTV) promoter to target over-expression of the Cdc25B transgene in the mammary glands of transgenic mouse lines. Here we report that the over-expression of Cdc25B enhances the proliferation of mammary epithelial cells resulting in the formation of precocious alveolar hyperplasia. At the molecular level, marked increases in cyclin D1 protein have been found in transgenic mammary epithelial cells. The accelerated growth rate of the mammary epithelial cells could also be attributed to the increased levels of cyclin E/cdk2 activity. In addition, a pronounced decrease in apoptosis was also observed during the involution of mammary gland. The reduction of apoptosis during involution correlated well with the reduced expression of c-myc and p53, both of which have been implicated in apoptosis. Taken together, our results clearly indicate that the deregulated expression of Cdc25B generates mammary gland hyperplasia.

Identification of three chitin synthase genes in the dimorphic fungal pathogen Sporothrix schenckii.

Degenerate PCR primers were used to amplify a 600-bp conserved gene region for chitin synthases from genomic DNA of Sporothrix schenckii, a dimorphic fungal pathogen of humans and animals. Three chitin synthase gene homologs were amplified as shown by DNA sequence analysis and by Southern blotting experiments. Based on differences among the predicted amino acid sequences of these homologs, each was placed within one of three different chitin synthase classes. Phylogenies constructed with the sequences and the PAUP 3.1.1 program showed that S. schenckii consistently clustered most closely with Neurospora crassa in each of the three chitin synthase classes. These findings are significant because the phylogenies support by a new method the grouping of the imperfect fungus S. schenckii with the Pyrenomycetes of the Ascomycota.

Cardiovascular effects of a chlorpheniramine/paracetamol combination in hypertensive patients who were sensitive to the pressor effect of pseudoephedrine.

Twelve hypertensive patients who were classified as pseudoephedrine-sensitive in a preliminary trial were selected for further investigation with single doses of pseudoephedrine 60 mg, a combination of chlorpheniramine 4 mg with paracetamol 650 mg and placebo. A double-blind, randomised, crossover study design was followed. Treatment with pseudoephedrine produced significant effects on all the four variables measured (systolic, diastolic and mean arterial blood pressure, and heart rate). Effects of the chlorpheniramine/paracetamol combination were found to be not significantly different from placebo. It was concluded that the combination may be useful as a medication for 'colds' in hypertensive patients, since it does not induce cardiovascular effects such as those observed with pseudoephedrine.

A controlled clinical trial on the cardiovascular effects of single doses of pseudoephedrine in hypertensive patients.

Twenty hypertensive patients received single oral doses of pseudoephedrine 60 mg or placebo in a double-blind, randomised, crossover trial. Systolic, diastolic, mean arterial blood pressure, and heart rate were measured at 5 min intervals for 30 min prior to and 210 min after the administration of pseudoephedrine or placebo. Statistically significant differences between the two treatments were observed with changes in systolic blood pressure (P less than 0.03) and heart rate (P less than 0.01) but not in diastolic (P greater than 0.03) and mean arterial blood pressure (P greater than 0.1). Minor differences in the number of reported side effects between the two treatments were not statistically significant.

Pharmacokinetics of non-prescription sympathomimetic agents.

The pharmacokinetics of non-prescription sympathomimetic agents are discussed with respect to absorption from the gastrointestinal tract, volumes of distribution, metabolism and renal excretion. Where specific data are not available, postulations are made with inference from the chemical structures of these agents, or from studies with other drugs. No studies on hypertensive patients have been found, but attempts are made to correlate any possible changes in the pharmacokinetics of these sympathomimetic agents to hypertensive patients as a high proportion of the elderly population is hypertensive. Sympathomimetic agents with lesser polar hydroxyl groups, for example, are thought to be more lipophilic and are more readily absorbed from the gastrointestinal tract, have higher volumes of distribution, and are more extensively metabolized. Major metabolic pathways include oxidation, deamination, demethylation, and conjugation. Most of these agents are excreted primarily through the kidneys and due to their basic nature, the rate of excretion is dependent on urinary pHs. Any alteration in kidney functions such as in the aged is, therefore, expected to have some clinical significance on the pharmacokinetics of these agents.

Non-prescription sympathomimetic agents and hypertension.

In recent years, considerable attention has been focused on the pressor effects of nonprescription sympathomimetic agents. The impact and usage of these agents especially ephedrine, pseudoephedrine, phenylpropanolamine and phenylephrine, in hypertensive patients has been the topic of constant debates. The present review is an attempt to report and evaluate all the clinical trials and cases of pressor reactions associated with these 4 agents. The study protocols used in these clinical trials are examined and comments made on any diversion from the standard design. Many factors are found to cause the discrepancies in the data available. It is concluded that ephedrine and phenylpropanolamine are best avoided by hypertensive patients due to higher probability of causing pressor reactions. Data on pseudoephedrine and phenylephrine appear to indicate non-significant effects on blood pressure of normotensive subjects when used at the recommended oral dose as nasal decongestants. Phenylephrine is also commonly employed in nasal and eye drops and the limited data available appear to support its usage in hypertensive patients. However, it is noted that most of the clinical trials involve normotensive subjects and the majority of the results could not be verified due to inadequacies in the study design. This paucity and inconclusive information on hypertensive patients warrants further investigations with emphasis on the study protocols used.