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1.  Eyes wide open: an essay on developing an engaged awareness in global medicine and public health 
Background
There is a growing understanding of the role social determinants such as poverty, gender discrimination, racial prejudice, and economic inequality play on health and illness. While these determinants and effects may be challenging to identify in parts of high-income countries, they are patently obvious in many other areas of the world. How we react to these determinants and effects depends on what historical, cultural, ideological, and psychological characteristics we bring to our encounters with inequity, as well as how our feelings and thoughts inform our values and actions.
Discussion
To address these issues, we share a series of questions we have asked ourselves¿United States¿ citizens with experience living and working in Central America¿in relation to our encounters with inequity. We offer a conceptual framework for contemplating responses in hopes of promoting among educators and practitioners in medicine and public health an engaged awareness of how our every day work either perpetuates or breaks down barriers of social difference. We review key moments in our own experiences as global health practitioners to provide context for these questions.
Summary
Introspective reflection can help professionals in global medicine and public health recognize the dynamic roles that they play in the world. Such reflection can bring us closer to appreciating the forces that have worked both for and in opposition to global health, human rights, and well-being. It can help us recognize how place, time, environment, and context form the social determination of health. It is from this holistic perspective of social relations that we can work to effect fair, equitable, and protective environments as they relate to global medicine and public health.
doi:10.1186/s12914-014-0029-4
PMCID: PMC4422227  PMID: 25346040
Epidemiologic factors; Health knowledge; Attitudes; Practice; Internationality; Public health; Role; Professional; Social medicine
2.  Prescription patterns for children with juvenile idiopathic arthritis in Michigan Medicaid: a comparison by prescriber type 
Background
Due to a limited number and disparate distribution of pediatric rheumatologists in the US, a variety of physician types provide care to children with rheumatologic diseases. However, little is known about how that care may differ across prescribing physician groups. Our objective was to compare medication claims for children with juvenile idiopathic arthritis (JIA) by type of prescribing physician.
Methods
We performed a retrospective cohort study of children with JIA using Michigan Medicaid data for 7/1/2005-6/30/2007, employing descriptive and bivariate analyses by age, medication type, and prescriber type.
Results
Among 397 children, there was no difference in the frequency of medication claims for children with internist versus pediatric rheumatologist prescribers. Children with non-rheumatologist prescribers were less likely to have claims for disease modifying anti-rheumatic drugs (DMARDs) and biologic agents.
Conclusion
Differential use of DMARDs and biologic agents by rheumatologists indicates the importance of referring children with JIA for specialty care.
doi:10.1186/1546-0096-12-38
PMCID: PMC4164797  PMID: 25228851
Arthritis; Juvenile rheumatoid; Physician’s practice patterns; Drug therapy
3.  Remediation in the Context of the Competencies: A Survey of Pediatrics Residency Program Directors 
Background
The 6 competencies defined by the Accreditation Council for Graduate Medical Education provide the framework of assessment for trainees in the US graduate medical education system, but few studies have investigated their impact on remediation.
Methods
We obtained data via an anonymous online survey of pediatrics residency program directors. For the purposes of the survey, remediation was defined as “any form of additional training, supervision, or assistance above that required for a typical resident.” Respondents were asked to quantify 3 groups of residents: (1) residents requiring remediation; (2) residents whose training was extended for remediation purposes; and (3) residents whose training was terminated owing to issues related to remediation. For each group, the proportion of residents with deficiencies in each of the 6 competencies was calculated.
Results
In all 3 groups, deficiencies in medical knowledge and patient care were most common; deficiencies in professionalism and communication were moderately common; and deficiencies in systems-based practice and practice-based learning and improvement were least common. Residents whose training was terminated were more likely to have deficiencies in multiple competencies.
Conclusion
Although medical knowledge and patient care are reported most frequently, deficiencies in any of the 6 competencies can lead to the need for remediation in pediatrics residents. Residents who are terminated are more likely to have deficits in multiple competencies. It will be critical to develop and refine tools to measure achievement in all 6 competencies as the graduate medical education community may be moving further toward individualized training schedules and competency-based, rather than time-based, training.
doi:10.4300/JGME-D-12-00024.1
PMCID: PMC3613320  PMID: 24404228
4.  Investigation of Anticholinergic and Non-steroidal Anti-inflammatory Prodrugs which Reduce Chemically-induced Skin Inflammation 
As part of a continuous effort to develop efficient countermeasures against sulfur mustard injuries, several unique NSAID prodrugs have been developed and screened for anti-inflammatory properties. Presented herein are three classes of prodrugs which dually target inflammation and cholinergic dysfunction. Compounds 1–28 contain common NSAIDs linked either to choline bioisosteres or to structural analogs of acetylcholinesterase (AChE) inhibitors. These agents have shown utility as anti-vesicants and anti-inflammatory agents when screened in a mouse ear vesicant model (MEVM) against both 2-chloroethyl ethyl sulfide (CEES), a blistering agent, and 12-O-tetradecanoylphorbol-13-acetate (TPA), a common topical irritant. Many of the prodrugs have activity against CEES, with 5, 18, 22 and 27 reducing inflammation by more than 75 % compared to a control. Compounds 12, 13, 15 and 22 show comparable activity against TPA. Promising activity in the MEVM is related to half-lives of NSAID-release in plasma, moderate to high lipophilicity, and some degree of inhibition of AChE, a potential contributor to sulfur mustard-mediated tissue damage.
doi:10.1002/jat.1645
PMCID: PMC3770525  PMID: 21319177
5.  Barriers and facilitating factors for disease self-management: a qualitative analysis of perceptions of patients receiving care for type 2 diabetes and/or hypertension in San José, Costa Rica and Tuxtla Gutiérrez, Mexico 
BMC Family Practice  2013;14:131.
Background
The burden of cardiovascular disease is growing in the Mesoamerican region. Patients’ disease self-management is an important contributor to control of cardiovascular disease. Few studies have explored factors that facilitate and inhibit disease self-management in patients with type 2 diabetes and hypertension in urban settings in the region. This article presents patients’ perceptions of barriers and facilitating factors to disease self-management, and offers considerations for health care professionals in how to support them.
Methods
In 2011, 12 focus groups were conducted with a total of 70 adults with type 2 diabetes and/or hypertension who attended urban public health centers in San José, Costa Rica and Tuxtla Gutiérrez, Chiapas, Mexico. Focus group discussions were transcribed and coded using a content analysis approach to identify themes. Themes were organized using the trans-theoretical model, and other themes that transcend the individual level were also considered.
Results
Patients were at different stages in their readiness-to-change, and barriers and facilitating factors are presented for each stage. Barriers to disease self-management included: not accepting the disease, lack of information about symptoms, vertical communication between providers and patients, difficulty negotiating work and health care commitments, perception of healthy food as expensive or not filling, difficulty adhering to treatment and weight loss plans, additional health complications, and health care becoming monotonous. Factors facilitating disease self-management included: a family member’s positive experience, sense of urgency, accessible health care services and guidance from providers, inclusive communication, and family and community support.
Financial difficulty, gender roles, differences by disease type, faith, and implications for families and their support were identified as cross-cutting themes that may add an additional layer of complexity to disease management at any stage. These factors also relate to the broader family and societal context in which patients live.
Conclusions
People living with type 2 diabetes and hypertension present different barriers and facilitating factors for disease self-management, in part based on their readiness-to-change and also due to the broader context in which they live. Primary care providers can work with individuals to support self-management taking into consideration these different factors and the unique situation of each patient.
doi:10.1186/1471-2296-14-131
PMCID: PMC3846574  PMID: 24007205
Cardiovascular health; Trans-theoretical model; Health promotion; Primary care
6.  Hospitalizations for Intussusception Before and After the Reintroduction of Rotavirus Vaccine in the United States 
Objective
To determine whether hospital discharges for intussusception in children younger than 1 year have changed since the reintroduction of rotavirus vaccine in the United States.
Design
Serial cross-sectional analysis.
Setting
US hospitals.
Participants
Children younger than 1 year with a discharge diagnosis of intussusception identified in the Kids’ Inpatient Database, a series of nationally representative data sets of pediatric hospital discharges in the United States with 4 available years prior to vaccine reintroduction (1997, 2000, 2003, and 2006) and 1 year after (2009).
Main Exposures
Hospital discharge before vs after rotavirus vaccine reintroduction.
Outcome Measures
Total number and rate of hospital discharges for infants younger than 1 year with a diagnosis of intussusception (International Classification of Diseases, Ninth Revision, Clinical Modification code 560.0).
Results
From 1997 to 2006, there was no change in the total number of hospital discharges for intussusception, with a small decrease in the rate of intussusception discharges (41.6 [95% CI, 36.7–46.5] to 36.5 [95% CI, 31.7–41.2] per 100 000 infants). Based on the trend, the predicted rate of discharges for intussusception in 2009 was 36.0 (95% CI, 30.2–41.8) per 100 000 infants. The measured rate of hospital discharges for intussusception in 2009 was 33.3 (95% CI, 29.0–37.6) per 100 000 infants.
Conclusion
The reintroduction of rotavirus vaccine since 2006 has not resulted in a detectable increase in the number of hospital discharges for intussusception among US infants.
doi:10.1001/archpediatrics.2011.1501
PMCID: PMC3442774  PMID: 22213609
8.  Association of variants in the carnosine peptidase 1 gene (CNDP1) with diabetic nephropathy in American Indians 
Molecular genetics and metabolism  2011;103(2):185-190.
CNDP1 is located on 18q22.3, where linkage with diabetic nephropathy has been observed in several populations, including Pima Indians. However, evidence for association between CNDP1 alleles and diabetic nephropathy is equivocal and population-dependent. This study investigated CNDP1 as a candidate for diabetic kidney disease in Pima Indians. Nineteen tag single nucleotide polymorphisms spanning the CNDP1 locus were selected using genotype data from Chinese individuals in the HapMap resource along with 2 variants previously associated with diabetic nephropathy. All variants were genotyped in 3 different samples including a diabetic end-stage renal disease (ESRD) case-control study, a family-based study of diabetic individuals who participated in the linkage study for nephropathy, and a cohort of diabetic individuals in whom longitudinal measures of glomerular filtration rates (GFR) were performed. There was no statistically significant evidence for association with diabetic ESRD. However, nominal evidence for association was found in the family study, where markers rs12957330 (Odds ratio [OR]=0.29 per copy of G allele; p=0.04) and rs17817077 (OR=0.46 per copy of G allele; p=0.05) were associated with diabetic nephropathy. In addition, markers rs12964454, rs7244647, and rs7229005 were associated with changes in GFR (−8.5 ml/min per copy of the G allele; p=0.04; 18.8 ml/min per copy of the C allele; p=0.03; and −13.4 ml/min per copy of the C allele; p=0.001, respectively). These findings provide nominal evidence supporting a role between CNDP1 variants and diabetic kidney disease.
doi:10.1016/j.ymgme.2011.02.010
PMCID: PMC3101283  PMID: 21393041
kidney disease; single nucleotide polymorphism; proteinuria
9.  Career shift phenomenon among doctors in tacloban city, philippines: lessons for retention of health workers in developing countries 
Background
At the height of the global demand for nurses in the 1990s, a phenomenon of grave concern arose. A significant number of medical doctors in the Philippines shifted careers in order to seek work as nurses overseas. The obvious implications of such a trend require inquiry as to the reasons for it; hence, this cross-sectional study. The data in the study compared factors such as personal circumstances, job satisfaction/dissatisfaction, perceived benefits versus costs of the alternative job, and the role of social networks/linkages among doctors classified as career shifters and non-shifters.
Methodology
A combined qualitative and quantitative method was utilized in the study. Data gathered came from sixty medical doctors practicing in three major hospitals in Tacloban City, Philippines, and from a special nursing school also located in the same city. Respondents were chosen through a non-probability sampling, specifically through a chain referral sampling owing to the controversial nature of the research. A set of pre-set criteria was used to qualify doctors as shifters and non-shifters. Cross-tabulation was carried out to highlight the differences between the two groups. Finally, the Wilcoxon-Mann-Whitney test was utilized to assess if these differences were significant.
Results
Among the different factors investigated, results of the study indicated that the level of job satisfaction or dissatisfaction and certain socio-demographic factors such as age, length of medical practice, and having children to support, were significantly different among shifters and non-shifters at p ≤ 0.05. This suggested that such factors had a bearing on the intention to shift to a nursing career among physicians.
Conclusion
Taken in the context of the medical profession, it was the level of job satisfaction/dissatisfaction that was the immediate antecedent in the intention to shift careers among medical doctors. Personal factors, specifically age, support of children, and the length of medical practice gained explanatory power when they were linked to job satisfaction or dissatisfaction. On the other hand, factors such as perceived benefits and costs of the alternative job and the impact of social networks did not differ between shifters and non-shifters. It would then indicate that efforts to address the issue of physician retention need to go beyond economic incentives and deal with other sources of satisfaction or dissatisfaction among practicing physicians. Since this was an exploratory study in a particular locale in central Philippines, similar studies in other parts of the country need to be done to gain better understanding of this phenomenon at a national level.
doi:10.1186/1447-056X-10-13
PMCID: PMC3204289  PMID: 21977902
Career-shift; doctors; nurses; immigration/emigration/migration; retention; health workers; job satisfaction/dissatisfaction
10.  Preferential benefits of nifedipine GITS in systolic hypertension and in combination with RAS blockade: further analysis of the ‘ACTION' database in patients with angina 
Journal of Human Hypertension  2010;25(1):63-70.
A retrospective analysis of the database from A Coronary Disease Trial Investigating Outcome with Nifedipine (ACTION) evaluated the effectiveness of nifedipine gastrointestinal therapeutic system (GITS) (i) in combination with renin angiotensin system (RAS) blockers and (ii) in patients with isolated systolic hypertension (ISH). Analysed on an intention-to-treat basis, treatment groups were compared by the log-rank test without adjustment for covariates and hazard ratios with 95% CIs were obtained using Cox proportional hazards models. Of 7665 randomized patients, 1732 patients were receiving RAS blockade at baseline, the addition of nifedipine GITS significantly reduced any cardiovascular (CV) event (−20% P<0.05), the composite of death, any CV event and revascularization (−16% P<0.05) and coronary angiography (−22% P<0.01). These benefits were achieved with relatively small differences in systolic (3.2 mm Hg) and diastolic blood pressure (BP) (2.3 mm Hg). In 2303 patients (30.0%) who had ISH at baseline (1145 nifedipine GITS and 1158 placebo), nifedipine significantly reduced the primary efficacy end point (−18% P<0.03), any CV event (−22% P<0.01) and new heart failure (−40% P<0.01). The benefits were associated with between-group differences in achieved BP of 4.7 and 3.3 mm Hg for systolic and diastolic BP, respectively. In summary, the lowest CV event rates were seen in those receiving (i) the combination of RAS blockade and nifedipine GITS and (ii) in those specifically treated for ISH.
doi:10.1038/jhh.2010.19
PMCID: PMC3016863  PMID: 20182454
ACE inhibitor; angiotensin receptor blockers; combination drug therapy; coronary artery disease; isolated systolic hypertension; nifedipine
11.  ACE inhibition and AT1 receptor blockers: efficacy and duration in hypertension 
Heart  2000;84(Suppl 1):i39-i41.
doi:10.1136/heart.84.suppl_1.i39
PMCID: PMC1766526  PMID: 10956321
12.  The biocide tributyltin reduces the accumulation of testosterone as fatty acid esters in the mud snail (Ilyanassa obsoleta). 
Environmental Health Perspectives  2003;111(4):426-430.
Imposex, the development of male sex characteristics by female gonochoristic snails, has been documented globally and is causally associated with exposure to the ubiquitous environmental contaminant tributyltin (TBT). Elevated testosterone levels in snails also are associated with TBT, and direct exposure to testosterone has been shown to cause imposex. We discovered previously that the mud snail (Ilyanassa obsoleta)biotransforms and retains excess testosterone primarily as fatty acid esters. The purpose of this study was to determine whether TBT interferes with the esterification of testosterone, resulting in the elevated free (unesterified) testosterone levels associated with imposex. Exposure of snails to environmentally relevant concentrations of TBT (> or = 1.0 ng/L as tin) significantly increased the incidence of imposex. Total (free + esterified) testosterone levels in snails were not altered by TBT; however, free testosterone levels increased with increasing exposure concentration of TBT. TBT-exposed snails were given [14C]]testosterone to measure the production of [14C]testosterone-fatty acid esters. The production of testosterone-fatty acid esters decreased with increasing exposure concentration of TBT. These results indicate that TBT elevates free testosterone levels in snails by decreasing the production or retention of testosterone-fatty acid esters. These findings were confirmed among field-sampled snails where individuals collected from a high-tin-affected site exhibited a greater incidence of imposex, higher free testosterone levels, and lower testosterone-fatty acid ester levels when compared with individuals sampled from a low-tin-affected site. Decreased testosterone-fatty acid esterification among TBT-treated snails was not caused by direct inhibition of the acyl coenzyme A:testosterone acyltransferase (ATAT) enzyme responsible for testosterone esterification, nor by suppressed ATAT protein expression. The target of TBT may be a co-contributor to the testosterone fatty esterification process or a factor in the enhanced hydrolysis of the testosterone-fatty acid pool.
PMCID: PMC1241423  PMID: 12676594
13.  Inquiry into the potential value of an information pamphlet on consent to surgery to improve surgeon-patient communication 
Quality in Health Care : QHC  1998;7(2):65-69.
OBJECTIVES: To find out how patients recently undergoing surgery experienced the consenting process and the response of these patients to a pamphlet on consent to surgery. To test the reaction of health professionals to the pamphlet. DESIGN: A pilot pamphlet was produced and a questionnaire was sent to patients inquiring about their consenting experience, and how the pamphlet might have helped them through the consent procedure. A pamphlet and a questionnaire were also sent to a random sample of the health professionals serving these patients. SUBJECTS: Patients and health professionals. RESULTS: 61% of patients returned the questionnaire. Knowledge about the consent procedure was shown to be limited. 49% were unaware that they had the right to insist that the surgeon could only perform the specified operation and nothing more. 83% were unaware that they could add something in writing to the consent form before signing. 28% of health professionals returned their questionnaire, most of whom thought that the pamphlet provided a useful contribution to surgeon-patient communication. CONCLUSION: Evidence shows that patients are not well informed about consenting to surgery and further information would provide much needed guidance on understanding their role in the consent procedure. The low response from the health professional study is perhaps an indication that at present this is an issue which is not seen as a priority.
PMCID: PMC2483596  PMID: 10180792
14.  The NHS patient information lottery: it is whom you see rather than what you need. 
OBJECTIVE: To examine the current scale of provision of patient information materials by consultant surgeons in UK NHS and private sector hospitals. DESIGN: Secondary analysis of the responses of 12,555 surgical patients to surveys evaluating surgical services provided by specific consultants. SETTING: 7 NHS Trusts and one private sector hospital distributed throughout the UK. MAIN OUTCOME MEASURES: Provision of information materials by hospital, surgeon, and case-mix. Comparison of this service with patients' evaluations of surgeons' verbal communication in the outpatient clinic. RESULTS: Great variation exists between surgeons of the same specialty, and between hospital surgical directorates as a whole in the routine provision of supportive information materials to patients undergoing surgery. This variation cannot be explained solely by clinical need. Patients treated in private hospitals were less likely to receive information materials compared to patients treated within the NHS. CONCLUSIONS: Provision of printed information materials to patients by clinicians appears to be arbitrary. With the prospect of national performance frameworks in the foreseeable future, it is reasonable to assume that not only will the content of patient information be determined by quality standards but, in addition, its availability will be decided by clinical need rather than the clinician's preferences or interests.
PMCID: PMC2503436  PMID: 10858690
15.  Clinical pharmacokinetics of doxazosin in a controlled-release gastrointestinal therapeutic system (GITS) formulation 
Aims
A controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin mesylate, a long-acting selective α1-adrenoceptor antagonist, was developed to enhance the pharmacokinetic profile and simplify the titration schedule by precisely controlling drug delivery rate, permitting an initial dose of 4 mg once daily, compared with standard doxazosin, which is initiated at 1 mg day−1 and titrated to a higher therapeutically effective dose. The aim of the present work was to evaluate the pharmacokinetics and bioavailability of doxazosin GITS with respect to the effect of food, age and gender, and multiple dosing. In addition, in vitro performance was assessed in conditions simulating the gastrointestinal environment.
Methods
A three-way crossover study in 24 subjects assessed the comparative bioavailability of doxazosin GITS under fed and fasting conditions and doxazosin standard under fasting condition. A multiple-dose, two-way crossover study in 35 subjects assessed the comparative pharmacokinetics and bioavailability of doxazosin GITS and doxazosin standard 4 and 8 mg upon multiple dosing. A multiple-dose, four-parallel–group study was conducted to determine the steady-state pharmacokinetics and bioavailability of doxazosin GITS 4 mg in 41 young and elderly male and female subjects. The release-rate profiles of doxazosin GITS were determined in artificial gastric fluid (pH =1.2), intestinal fluid (pH =7.5), and water. The effect of agitation on the dissolution characteristics of doxazosin GITS in artificial gastric fluid was studied at stirring rates of 50, 75, and 100 rev min−1.
Results
In vitro studies demonstrated that release rates for the GITS tablet are independent of pH in the range of 1.2 (gastric) to 7.5 (intestinal), and of stirring rates simulating gastrointestinal motility. Clinical pharmacology studies showed that doxazosin GITS had a lower maximum plasma concentration, prolonged time to reach maximum plasma concentration, and a higher minimum plasma concentration compared with doxazosin standard. Thus, the GITS formulation results in a more gradual absorption of doxazosin, and a reduced plasma doxazosin concentration peak-to-trough fluctuation ratio. The relative bioavailability of doxazosin GITS is approximately 60%. With a high-fat meal, the maximum plasma concentration and area under the concentration-time curve were 31% and 18% higher, respectively (P <0.05). Bioequivalence was established between the dose strengths of two 4 mg doxazosin GITS tablets and one 8 mg doxazosin GITS tablet. For both young adult and elderly subjects, and males and females, the pharmacokinetics of doxazosin GITS once daily for 7 days were comparable. Doxazosin GITS was well tolerated in the subjects studied, including young and elderly males and females.
Conclusions
The GITS formulation of doxazosin enhances the pharmacokinetic profile compared with doxazosin standard, allowing more gradual absorption of doxazosin, and a reduced plasma doxazosin peak-to-trough concentration ratio. Thus, doxazosin GITS therapy can be initiated at a therapeutic dose of 4 mg with reduced haemodynamic side-effects.
doi:10.1046/j.1365-2125.1999.00067.x
PMCID: PMC2014349  PMID: 10594469
benign prostatic hyperplasia; controlled-release; doxazosin GITS; doxazosin; gastrointestinal therapeutic system; hypertension; pharmacodynamics; pharmacokinetics
18.  Comparison of patients' needs for information on prostate surgery with printed materials provided by surgeons. 
Quality in Health Care  1995;4(1):18-23.
OBJECTIVES--To identify strengths, weaknesses, and omissions in existing leaflets and factsheets on prostatectomy given by surgeons to patients. DESIGN--Comparison of content of leaflets and factsheets with patients' needs and discontents in a questionnaire survey as part of the national prostatectomy audit. SETTING--All NHS and independent hospitals performing prostatectomy in four health regions. SUBJECTS--87 surgeons, 53 of whom used printed material to inform patients about their operations; a total of 25 different factsheets being used. 5361 men undergoing prostatectomy were sent a closed response questionnaire about their treatment; 4226 men returned it completed. A random sample of 2000 patients was asked for further comments, of whom 807 supplied pertinent comments. MAIN MEASURES--Content of the 25 factsheets compared with patients' needs identified in the questionnaires. RESULTS--Much of the information distributed had considerable shortcomings: it lacked uniformity in form and content, topics of relevance to patients were omitted, terminology was often poor, and patients' experience was at variance with what their surgeons said. For example, only one factsheet discussed the potential consequences of malignancy. Patients wanted more information on prostate cancer (1250(29%)) and some thought that the explanation of biopsy results was inadequate (29(4%)). Only six factsheets discussed the possible changes in sexual sensation after transurethral resection of the prostate, stating that patients would feel no change. However, 1490(35%) patients reported a change and 500(12%) were worried about it. CONCLUSION--Current standards of printed information do not meet the needs and requirements of patients undergoing prostatectomy.
PMCID: PMC1055261  PMID: 10142031
19.  A comparative assessment of the duration of action of amlodipine and nifedipine GITS in normotensive subjects. 
1 This study in normotensive subjects compared the duration and consistency of action of amlodipine (5 mg) and nifedipine GITS (60 mg) by assessment of the attenuation of pressor responses to noradrenaline and angiotensin II. 2 Both drugs significantly attenuated pressor responses to both vasoconstrictors at 6 and 24 h post-dose with rightward shifts of up to 2.3-fold in the dose-response curves. 3 There was significantly less pharmacokinetic variability with amlodipine: for example, intra-subject variability was 33% with amlodipine and 59% with nifedipine GITS. 4 There were no significant differences in the pressor dose ratios up to 48 h post-dose with amlodipine whereas there was a significant and progressive reduction in the pressor dose ratios with nifedipine. 5 These results suggest that both drugs are broadly comparable as once daily treatments but amlodipine displayed less intra- and inter-subject variability and provided a significantly more sustained effect with a reserve of pharmacological activity up to 48 h post-dose.
PMCID: PMC1364661  PMID: 12959273
20.  A clinical pharmacological assessment of doxazosin and enalapril in combination. 
This study in 12 normotensive males investigated potential pharmacokinetic and pharmacodynamic interaction mechanisms resulting from the combination of enalapril and doxazosin. Blood pressure reductions were consistently greater with the combination but there was no evidence of a significant pharmacodynamic interaction (as determined by heart rate changes, renal function tests or by pressor responsiveness indices) and there was no evidence of a pharmacokinetic interaction with either drug. Responsiveness to each drug i.e. blood pressure reduction per unit drug concentration was not significantly altered in the combination regimen. In conclusion, these results suggest that the combination of enalapril and doxazosin produces a usefully additive hypotensive effect but there was no evidence of synergism i.e an effect which was more than additive.
PMCID: PMC1364667  PMID: 12959279
21.  R-verapamil: pharmacokinetics and effects on PR interval, blood pressure and heart rate. 
1. This study in healthy normotensive male volunteers investigated the pharmacokinetics and the effects on electrocardiographic PR interval, blood pressure and heart rate of single oral doses of the single isomer R-verapamil (250, 500 and 1000 mg) in comparison to placebo and 240 mg racemic verapamil. 2. After 500 and 1000 mg R-verapamil there were significant prolongations in PR interval, maximal at 1-2 h after dosing and coincident with peak plasma drug concentrations, but these were not significantly different from the maximum prolongation obtained with 240 mg racemic verapamil. 3. After 1000 mg R-verapamil there was a significant hypotensive effect, particularly on standing. 4. Single doses of 500 and 1000 mg R-verapamil produced peak plasma drug concentrations in the range 1000-3000 ng ml-1. If this concentration range is appropriate for adjuvant cancer chemotherapy it can be predicted that similar steady state concentrations will occur with a dosage regimen of 300 mg 3 times daily.
PMCID: PMC1364570  PMID: 8398588
23.  Haemodynamic and hormonal responses to oral enalapril in salt depleted normotensive man. 
A combination of dietary sodium restriction (40 mmol day-1) and frusemide pretreatment has been used to activate the renin angiotensin system (RAS) in order to characterise the haemodynamic and hormonal responses to enalapril in young normotensives. Enalapril significantly reduced supine blood pressure with a mean maximum fall of 19 +/- 7.6, compared with 6.5 +/- 6.8 mm Hg with placebo. Similar but greater responses were seen in erect blood pressure. Mean maximal plasma ACE inhibition (78 +/- 5.7%) was associated with a significant increase in PRA from 5.2 +/- 2.1 ngAI ml-1 h-1 to a peak of 29.1 +/- 6 ngAI ml-1 h-1. This simple well tolerated regimen produced consistent RAS activation and gave readily measurable falls in blood pressure following enalapril. This model may be used to undertake detailed assessments of ACE inhibition, renin inhibition and angiotensin receptor blockade.
PMCID: PMC1381578  PMID: 8471406
24.  NHS provision for the treatment of ankle fractures: a patient satisfaction study. 
From a clinical audit of the treatment given to 1005 patients suffering from ankle fractures, 507 patients of 626 taken randomly from 15 hospitals were contacted and asked to complete a questionnaire describing and evaluating their experiences. The design of the study aimed in a number of ways to reduce respondents' tendency towards a positive response in completing satisfaction scales. The very high response rate, commentaries and variations in opinions about specific service criteria indicate that the results have a high degree of validity. The generally high rates of satisfaction reported here reflect very well on existing NHS provision for a specific procedure, with the exception of certain hospitals' arrangements for waiting, and the provision of certain types of information. Against general indicators of satisfaction with the management of pain relief in hospitals, that in ankle fracture treatments appears to be exceptionally high. However, it would be valuable to discover why younger patients appear to be strikingly more critical than older patients across the entire range of issues. The inquiry aims to compare findings with studies of other orthopaedic services using a similar elementary methodology as a routine component of clinical audit.
PMCID: PMC1294482  PMID: 8315626
25.  Patient compliance. 
BMJ : British Medical Journal  1992;305(6866):1434.
PMCID: PMC1883945  PMID: 1301053

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