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Biomedical subjects

Patrick G O'Malley

Publications and source records attributed to Patrick G O'Malley.

At least 19 recordsLinked to original sources

Meta-analysis: the effect of statins on albuminuria.

BACKGROUND: Albuminuria is an independent risk factor for cardiovascular and renal disease with limited therapeutic options. Data on the effects of statins on albuminuria are conflicting. PURPOSE: To determine whether and to what degree statins affect albuminuria. DATA SOURCES: English-language and non-English-language studies found in PubMed, MEDLINE, EMBASE, BIOSIS, SciSearch, PASCAL, and International Pharmaceutical Abstracts (IPA) databases and the Cochrane Central Register of Controlled Trials that were published between January 1974 and November 2005. STUDY SELECTION: Randomized, placebo-controlled trials of statins reporting baseline and follow-up measurements of albuminuria or proteinuria measured by 24-hour urine collection or the urinary albumin-to-creatinine ratio. DATA EXTRACTION: Two investigators independently abstracted study quality, characteristics, and outcomes. DATA SYNTHESIS: Fifteen studies involving a total of 1384 patients and averaging 24 weeks in duration were included. Meta-analysis of the proportional reduction in proteinuria showed that statins reduced albuminuria (11 studies) and proteinuria (4 studies) in 13 of 15 studies. The reduction in excretion was greater among studies with greater baseline albuminuria or proteinuria: change of 2% (95% CI, -32% to 35%) for those with excretion less than 30 mg/d, -48% (CI, -71% to -25%) for those with excretion of 30 to 300 mg/d, and -47% (CI, -67% to -26%) for those with excretion more than 300 mg/d. Statistical heterogeneity was evident only in the group with excretion greater than 300 mg/d (excretion < 30 mg/d, I2 = 23% [P = 0.27]; excretion of 30 to 299 mg/d, I2 = 0% [P = 0.64]; excretion > or = 300 mg/d, I2 = 63% [P = 0.020]). LIMITATIONS: Published studies were not of high quality on average and varied markedly in effect size, as well as in characteristics of the cohorts. Unpublished studies showing no effect could impact these results. CONCLUSION: Statins may have a beneficial effect on pathologic albuminuria. The validity of this finding, and whether this effect translates into reduction of cardiovascular or end-stage renal disease, requires larger studies.

Albuminuria↗

Antidepressants and cognitive-behavioral therapy for symptom syndromes.

Somatic symptoms are common in primary care and clinicians often prescribe antidepressants as adjunctive therapy. There are many possible reasons why this may work, including treating comorbid depression or anxiety, inhibition of ascending pain pathways, inhibition of prefrontal cortical areas that are responsible for "attention" to noxious stimuli, and the direct effects of the medications on the syndrome. There are good theoretical reasons why antidepressants with balanced norepinephrine and serotonin effects may be more effective than those that act predominantly on one pathway, though head-to-head comparisons are lacking. For the 11 painful syndromes review in this article, cognitive-behavioral therapy is most consistently demonstrated to be effective, with various antidepressants having more or less randomized controlled data supporting or refuting effectiveness. This article reviews the randomized controlled trial data for the use of antidepressant and cognitive-behavior therapy for 11 somatic syndromes: irritable bowel syndrome, chronic back pain, headache, fibromyalgia, chronic fatigue syndrome, tinnitus, menopausal symptoms, chronic facial pain, noncardiac chest pain, interstitial cystitis, and chronic pelvic pain. For some syndromes, the data for or against treatment effectiveness is relatively robust, for many, however, the data, one way or the other is scanty.

Antidepressive Agents↗

Antioxidant vitamin intake and subclinical coronary atherosclerosis.

Numerous studies have evaluated the association between antioxidants and coronary atherosclerosis but have been limited by its study among individuals with advanced atherosclerosis. The authors studied 865 consecutive patients, 39-45 years of age, without known coronary artery disease and presenting for a periodic physical examination. Antioxidant intake was assessed with the Block Dietary Questionnaire, and coronary atherosclerosis was identified by measuring coronary artery calcification using electron beam computed tomography. The mean age was 42 (+/-2), 83% were male, and the prevalence of coronary artery calcification was 20%. Vitamin supplements were used by 56% of the participants, and the mean (+/-SD) daily intake (dietary plus supplemental) of vitamins A, C, and E were 1683 mg (+/-1245), 371 mg (+/-375), and 97 mg (+/-165), respectively. There was no significant correlation between coronary artery calcification score and individual vitamin or total antioxidant vitamin intake, even after adjusting for traditional cardiac risk factors. The highest quartile of vitamin E was positively associated with calcification (odds ratio=1.77; 95% confidence interval, 1.02-3.06). Antioxidant vitamin intake is not significantly related to coronary artery calcification, implying that there is no effect on the development of early coronary atherosclerosis. High doses of vitamin E may confer an increased risk of calcified atherosclerosis.

Adult↗

Coronary calcium independently predicts incident premature coronary heart disease over measured cardiovascular risk factors: mean three-year outcomes in the Prospective Army Coronary Calcium (PACC) project.

OBJECTIVES: We sought to examine the independent predictive value of coronary artery calcium detection for coronary outcomes in a non-referred cohort of healthy men and women ages 40 to 50 years. BACKGROUND: Existing studies have suggested that coronary calcium might have incremental predictive value for coronary outcomes above standard coronary risk factors. However, additional data from non-referred and younger populations are needed. METHODS: Participants (n = 2,000; mean age 43 years) were evaluated with measured coronary risk variables and coronary calcium detected with electron beam tomography. Incident acute coronary syndromes and sudden cardiac death were ascertained via annual telephonic contacts, with follow-up (mean, 3.0 +/- 1.4 years; range, 1 to 6 years) in 99.2% of the cohort. RESULTS: Coronary calcium was found in 22.4% of men and 7.9% of women. A total of 9 acute events occurred in men at a mean age of 46 years, including 7 of 364 men with coronary calcium (1.95%) and 2 of 1,263 men without coronary calcium (0.16%; p < 0.0001 by log-rank). No events occurred in women. In these men, coronary calcium was associated with an 11.8-fold increased risk for incident coronary heart disease (CHD) (p = 0.002) in a Cox model controlling for the Framingham risk score. Among those with coronary artery calcification, the risk of coronary events increased incrementally across tertiles of coronary calcium severity (hazard ratio 4.3 per tertile). A family history of premature CHD was also predictive of incident events. The marginal cost effectiveness, assuming a 30% improvement in survival associated with primary prevention among at-risk men, was modeled to be 37,633 dollars per quality-adjusted life year saved. CONCLUSIONS: In young, asymptomatic men, the presence of coronary artery calcification provides substantial, cost-effective, independent prognostic value in predicting incident CHD that is incremental to measured coronary risk factors.

Adult↗

Cost-effectiveness of new tests to diagnose and treat coronary heart disease.

This article provides a review of the methods applied in defining cost-effectiveness as well as a review of the limited evidence base for defining incremental cost-effectiveness ratio of cardiovascular imaging when compared with an office-based risk assessment using the Framingham risk score. To date, there is a growing body of evidence that suggests that screening may be cost-effective in patients with an intermediate Framingham risk score. However, much of this evidence is derived from decision models or simulations that may not adequately represent the use of imaging evidence as it may be derived from "real world" or randomized trial data. Thus, we await additional evidence from large cohort studies or well-controlled clinical trials to define optimal economic efficiency strategies that may include the use of cardiovascular imaging in the screening of patients at risk for coronary heart disease.

Journal Article↗

Studying optimal healing environments: challenges and proposals.

The concept of optimal healing environments has strong face validity, but it is difficult to operationalize the complexity of the human dimensions that comprise the process of healing. Only rigorous evidence can justify the tremendous resources necessary to create optimal healing environments. This article outlines the current challenges of studying optimal healing environments from a clinical epidemiology perspective and discusses the major potential obstacles to include human resources, relationship-centered care competencies, dysfunctional educational and health care systems, research competencies, credibility, dispersed and unfocused current evidence base, and the actual logistical methodological difficulties. The concept of optimal healing environments is a paradigm shift in the delivery and study of medical care, and such an initiative will likely take decades to transition. However, there are feasible activities that can currently be undertaken to expedite this transition, chief of which is establishing a coalition of influential societies to forge an agenda on several fronts. Research activities presently should focus on validating and simplifying measurement tools for healing-related outcomes constructs, expanding the versatility and use of qualitative methods, as well as synthesizing research evidence to help clarify the current evidence base and the future research agenda.

Chronic Disease↗

Vitamin K1 intake and coronary calcification.

OBJECTIVES: The activity of matrix Gla-protein (MGP), a potent inhibitor of vascular calcification, is dependent on carboxylation using vitamin K as a co-factor. In animals, low intake of total vitamin K has been shown to accelerate vascular calcification via the MGP mechanism. This has led to the hypothesis that low levels of dietary vitamin K intake may be a risk factor for accelerated vascular calcification in humans due to decreased MGP activity. Additionally, some authors have suggested that current recommended daily intake values for vitamin K might be insufficient to fully inhibit vascular calcification via the MGP mechanism. The aim of this study was to examine the relationship between dietary vitamin K1 (the most prevalent dietary form of vitamin K) intake and premature coronary artery calcification (CAC) in an asymptomatic screening population. METHODS: We conducted a prospective study of 807 consecutive active-duty US Army personnel, 39-45 years of age, without known coronary heart disease. Vitamin K1 intake was measured with the Block Dietary Questionnaire and CAC was identified using electron-beam computed tomography (EBCT). RESULTS: We found no significant correlation between CAC score and vitamin K1 intake (r = 0.132, P = 0.106). Multivariate analysis with adjustment for cardiac risk factors showed no association between dietary vitamin K1 intake and CAC. CONCLUSIONS: Dietary vitamin K1 (phylloquinone) intake appears to be unrelated to premature coronary calcification in a screening population. Further investigation into the relationship of vascular calcification and other forms of vitamin K1 (menaquinones) is indicated.

Adult↗

Treatment of fibromyalgia with cyclobenzaprine: A meta-analysis.

OBJECTIVE: To systematically review the effectiveness of cyclobenzaprine in the treatment of fibromyalgia. METHODS: Articles describing randomized, placebo-controlled trials of cyclobenzaprine in people with fibromyalgia were obtained from Medline, EMBase, Psyclit, the Cochrane Library, and Federal Research in Progress Database. Unpublished literature and bibliographies were also reviewed. Outcomes, including global improvement, treatment effects on pain, fatigue, sleep, and tender points over time, were abstracted. RESULTS: Five randomized, placebo-controlled trials were identified. The odds ratio for global improvement with therapy was 3.0 (95% confidence interval [95% CI] 1.6-5.6) with a pooled risk difference of 0.21 (95% CI 0.09-0.34), which calculates to 4.8 (95% CI 3.0-11) individuals needing treatment for 1 patient to experience symptom improvement. Pain improved early on, but there was no improvement in fatigue or tender points at any time. CONCLUSION: Cyclobenzaprine-treated patients were 3 times as likely to report overall improvement and to report moderate reductions in individual symptoms, particularly sleep.

Amitriptyline↗

Cost-effectiveness of using electron beam computed tomography to identify patients at risk for clinical coronary artery disease.

BACKGROUND: The use of electron beam computed tomography (EBCT) to screen for coronary artery calcification (CAC) has been widely promulgated, although the cost effectiveness of this practice is unknown. METHODS: We constructed a decision tree to determine the marginal cost per additional patient who was "at risk" (>10% 10-year risk of coronary heart disease) identified with the addition of EBCT to the Framingham Risk Index (FRI) in a screening population with no cardiac symptoms. We also determined the marginal cost per quality adjusted life year (QALY) saved, assuming a 30% improvement in life expectancy associated with primary prevention. A consecutive screening cohort of 39- to 45-year-old men and women was used for demographic and risk factor data. Estimates of the relevant input costs were made on the basis of published literature when available. RESULTS: Compared with using FRI alone, the strategy of incorporating EBCT detects patients who are "at risk" at a cost of 9789 dollars/additional case and a marginal cost of 86,752 dollars/QALY. The marginal cost per QALY is highly sensitive to the gain in life expectancy from early intervention (10,000-1,700,000 dollars/QALY for a relative risk reduction in mortality of 50% or 25%, respectively), the utility of being "at risk" (18,000 dollars/QALY to dominated for a utility of 1.0-<0.98, similar to other asymptomatic chronic illnesses), and the added prognostic value of EBCT (60,000 dollars/QALY to dominated in a wide range). CONCLUSION: The use of EBCT to improve cardiovascular risk prediction in a population with no cardiac symptoms who are at low absolute risk is expensive, even using favorable assumptions. If the utility of being "at risk" is comparable with other asymptomatic disease states, EBCT may in aggregate have a detrimental effect on the quality of life of screening populations.

Bayes Theorem↗

Alcohol intake is not associated with subclinical coronary atherosclerosis.

BACKGROUND: The inverse relation between alcohol intake and clinical coronary artery disease (CAD) is well established, although the mechanisms remain speculative. We studied the relation between alcohol intake and subclinical CAD to assess the possible role of alcohol in atherogenesis. METHODS: We conducted a prospective study of 731 consecutive, consenting, active-duty US Army personnel (39 to 45 years of age) without known CAD who were undergoing a routine physical examination. Each participant was surveyed with the validated Block dietary questionnaire, which included detailed information on alcohol intake as wine, beer, or liquor. Subclinical CAD was determined by means of electron beam computed tomography to quantify coronary artery calcification (CAC). RESULTS: The mean age was 42 (+/-2); 83% were male, 71% were white, and 82% were college graduates. The prevalence of CAC was 18.6% (mean CAC score = 12 +/- 69). Twenty-two percent drank alcohol daily, with an average of 2.4 drinks per day. Systolic blood pressure was correlated with number of drinks per day (r = 0.10, P = .025). Among drinkers, HDL was weakly correlated with daily alcohol consumption (r = 0.10, P = .025). There was no relation between the CAC score and the alcohol intake as measured by drinks per day (OR, 1.02; 95% CI, 0.64 to 1.63; 1.13, 0.59 to 2.15; 1.26, 0.69 to 2.59, for less than 1, 1 to 2, and more than 2 drinks per day, respectively). Stratified analyses based on type of alcohol and multivariate analyses indicated no independent relation between any type or quantity of alcohol intake and the presence or extent of coronary calcification. CONCLUSIONS: Alcohol intake does not appear to be inversely related to subclinical CAC, implying that previous observations of a protective effect of alcohol on clinical CAD may involve factors related to plaque stability rather than atherogenesis.

Adult↗

The presence of psychiatric disorders reduces the likelihood of neurologic disease among referrals to a neurology clinic.

OBJECTIVES: This study aims to explore the prevalence and impact of psychiatric disorders on the likelihood of an organic, neurological explanation for symptoms among neurology referrals. METHODS: Consecutive new adult neurology referrals were screened for psychiatric disorders (PRIME-MD) prior to evaluation by neurologists, blinded to these results. Diagnoses were stratified into three categories: no neurological diagnosis, neurological-headache, and neurological-nonheadache. RESULTS: Of 235 patients enrolled, 79 (34%) received no neurological diagnosis, 54 (23%) headache and 102 (43%) a neurological diagnosis. Overall, 39% had an underlying psychiatric disorder. Patients with psychiatric disorders were less likely to have a neurological diagnosis (RR: 0.66, 95% CI: 0.48-0.90): 25% of patients with a neurological diagnosis had an underlying psychiatric disorder, compared to 43% among those with no diagnosis and 57% among those with headaches. CONCLUSION: Psychiatric disorders are common among neurology referrals, particularly those with headaches and are associated with a decreased likelihood of an underlying neurological process.

Adolescent↗

Association between C-reactive protein and hypertension in healthy middle-aged men and women.

OBJECTIVE: To ascertain whether C-reactive protein (CRP), an inflammatory marker related to increased cardiovascular risk, is associated with blood pressure in a sample of healthy, middle-aged people. METHODS AND RESULTS: A case-control study among 904 participants, 39-50 years old, from a cardiovascular risk screening study. Participants with systolic blood pressure > or =140 mmHg or diastolic blood pressure > or =90 mmHg (n=120) were considered as case participants and all others as control participants (n=784). Exposure was defined using quintiles of high-sensitivity CRP among control participants. A continuous increase in blood pressure was observed across CRP quintiles. Systolic blood pressure increased 1.17 mmHg [95% confidence interval (CI), 0.60-1.74] and diastolic blood pressure 1.04 mmHg (95% CI, 0.64-1.45) from one quintile to the next. The prevalence of hypertension was 13.3% and it increased with CRP exposure: Q1, 8.9%; Q2, 11.9%; Q3, 12.2%; Q4, 14.3%; and Q5, 18.6%. After adjustment for sex, obesity, race, serum insulin level and family history of coronary heart disease, odds ratios for hypertension increased progressively across CRP quintiles. Participants in the highest CRP quintile were 2.35 times more likely to have hypertension than those in the lowest quintile (P=0.03, trend test P=0.04). CONCLUSION: These results are consistent with a continuous, independent association between serum CRP and elevated blood pressure.

Adult↗

Subclinical calcified atherosclerosis in men and its association with a family history of premature coronary heart disease in first- and second-degree relatives.

The authors examined the associations between coronary artery calcification and a family history of premature coronary heart disease in either first-degree (immediate family) or second-degree (grandparents, aunts, uncles) relatives in 1619 asymptomatic healthy men ages 40-50 years. The prevalence of any coronary artery calcification was 19.3% in participants (n=1102) with no family history, 26.6% in those with a first-degree family history (n=203; 12.5%), 26.5% in those with a second-degree family history (n=215, 13.3%), and 30.3% with both (n=99, 6.1%, p=0.003). After controlling for the Framingham risk score, body mass index, and ethnicity, all categories of family history were significant predictors of coronary artery calcification. The odds ratios for coronary artery calcification associated with a first- (1.49; p=0.026) and second-degree (1.41; p=0.049) family history of coronary heart disease were similar. Clinical coronary risk assessments should broadly include an assessment of premature coronary heart disease in both first- and second-degree relatives.

Adult↗