Publications (31)241.72 Total impact
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Article: New statins also produce fatigue: spontaneous reporting as a complementary system to increase safety knowledge-reply.
JAMA internal medicine. 02/2013; 173(3):247-8. -
Article: Recruiting a special sample with sparse resources: Lessons from a study of Gulf War veterans.
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ABSTRACT: BACKGROUND: Recruitment is the most common failure point for clinical studies, with recruitment failure adversely affecting science, dollar costs, human capital, and the ethical risk-benefit trade-off to study participants. Added problems attend recruitment of special and/or challenging candidate populations, particularly in settings of sparse recruitment resources. Obstacles to study recruitment and participation of ill Gulf War veterans (GWVs) include health barriers, work and family obligations, mistrust of the medical/scientific community, and challenges to identifying/reaching potential participants. PURPOSE: We sought to identify and implement a minimal-cost multipronged recruitment approach for a small single-site (<50 participants) study of a special group, ill GWVs, with approaches substantially applicable to other recruitment settings and larger multisite studies. METHODS: Categories of recruitment approach included directed as well as general media, collaborations with support groups/interest groups, local free advertising resources (Craigslist and Backpage), physician outreach, Internet-based approaches, and referrals from study participants and screenees. We describe the subcategories and yield of each approach within each approach. RESULTS: Each approach contributed candidates to the final recruitment tally, with the largest fractional contribution by directed media (52%). Among the remainder, no other individual approach was clearly dominant (largest contribution: 13%). LIMITATIONS: Special population subsamples present special challenges; all approaches cited may not be useful in all settings and subpopulations. CONCLUSIONS: A multipronged suite of minimal-cost approaches led to successful recruitment to target for this single-site clinical trial for a special population with significant recruitment challenges. It additionally yielded a nation-wide corpus of several hundred individuals interested in participation in future studies of GWVs. While certain approaches produced disproportionate yield, it was not possible to predict these a priori. We suggest that this model, which incorporates a suite of approaches, and delineates backup approaches in the event of recruitment shortfall, may provide a template applicable to recruitment of other special samples in settings of limited resources and also is germane to cost-effective recruitment in studies more generally.Clinical Trials 01/2013; · 1.92 Impact Factor -
Article: Effects of statins on energy and fatigue with exertion: results from a randomized controlled trial.
Archives of internal medicine 08/2012; 172(15):1180-2. · 11.46 Impact Factor -
Article: Association between more frequent chocolate consumption and lower body mass index.
Archives of internal medicine 03/2012; 172(6):519-21. · 11.46 Impact Factor -
Article: The older the better: are elderly study participants more non-representative? A cross-sectional analysis of clinical trial and observational study samples.
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ABSTRACT: Study participants can differ from the target population they are taken to represent. We sought to investigate whether older age magnifies such differences, examining age-trends, among study participants, in self-rated level of activity compared to others of the same age. Cross-sectional examination of the relation of participant age to reported 'relative activity' (ie, compared to others of the same age), a bidirectionally correlated proxy for relative vitality, in exemplars of randomised and observational studies. University of California, San Diego (UCSD) PARTICIPANTS: 2404 adults aged 40-79 including employees of UCSD, and their partners (San Diego Population Study, observational study). 1016 adults (aged 20-85) not on lipid medications and without known heart disease, diabetes, cancer or HIV (UCSD Statin Study, randomised trial). Self-rated activity relative to others' age, 5-point Likert Scale, was evaluated by age decade, and related via correlation and regression to a suite of health-relevant subjective and objective outcomes. Successively older participants reported successively greater activity relative to others of their age (greater departure from the norm for their age), p<0.001 in both studies. Relative activity significantly predicted (in regression adjusted for age) actual activity (times/week exercised), and numerous self-rated and objective health-predictors. These included general self-rated health, CES-D (depression score), sleep, tiredness, energy; body mass index, waist circumference, serum glucose, high-density lipoprotein-cholesterol, triglycerides and white cell count. Indeed, some health-predictor associations with age in participants were 'paradoxical,' consistent with greater apparent health in older age-for study participants. Study participants may not be representative of the population they are intended to reflect. Our results suggest that departures from representativeness may be amplified with increasing age. Consequently, the older the age, the greater the disparity may be between what is recommended based on 'evidence, ' and what is best for the patient. UCSD Statin Study-Clinicaltrials.gov # NCT00330980 (http://ClinicalTrials.gov).BMJ open. 01/2012; 2(6). -
Article: Trans fat consumption and aggression.
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ABSTRACT: BACKGROUND: Dietary trans fatty acids (dTFA) are primarily synthetic compounds that have been introduced only recently; little is known about their behavioral effects. dTFA inhibit production of omega-3 fatty acids, which experimentally have been shown to reduce aggression. Potential behavioral effects of dTFA merit investigation. We sought to determine whether dTFA are associated with aggression/irritability. METHODOLGY/PRINICPAL FINDINGS: We capitalized on baseline dietary and behavioral assessments in an existing clinical trial to analyze the relationship of dTFA to aggression. Of 1,018 broadly sampled baseline subjects, the 945 adult men and women who brought a completed dietary survey to their baseline visit are the target of this analysis. Subjects (seen 1999-2004) were not on lipid medications, and were without LDL-cholesterol extremes, diabetes, HIV, cancer or heart disease. Outcomes assessed adverse behaviors with impact on others: Overt Aggression Scale Modified-aggression subscale (primary behavioral endpoint); Life History of Aggression; Conflict Tactics Scale; and self-rated impatience and irritability. The association of dTFA to aggression was analyzed via regression and ordinal logit, unadjusted and adjusted for potential confounders (sex, age, education, alcohol, and smoking). Additional analyses stratified on sex, age, and ethnicity, and examined the prospective association. Greater dTFA were strongly significantly associated with greater aggression, with dTFA more consistently predictive than other assessed aggression predictors. The relationship was upheld with adjustment for confounders, was preserved across sex, age, and ethnicity strata, and held cross-sectionally and prospectively. CONCLUSIONS/SIGNIFICANCE: This study provides the first evidence linking dTFA with behavioral irritability and aggression. While confounding is always a concern in observational studies, factors including strength and consistency of association, biological gradient, temporality, and biological plausibility add weight to the prospect of a causal connection. Our results may have relevance to public policy determinations regarding dietary trans fats. Clinicaltrials.gov # NCT00330980.PLoS ONE 01/2012; 7(3):e32175. · 4.09 Impact Factor -
Article: Brief report: approaches to 31P-MRS in awake, non-sedated children with and without autism spectrum disorder.
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ABSTRACT: We piloted a suite of approaches aimed to facilitate a successful series of up to four brain and muscle (31)Phosphorus-Magnetic Resonance Spectroscopy ((31)P-MRS) scans performed in one session in 12 awake, non-sedated subjects (ages 6-18), 6 with autism spectrum disorders (ASD) and 6 controls. We targeted advanced preparation, parental input, physical comfort, short scan protocols, allocation of extra time, and subject emotional support. 100% of subjects completed at least one brain scan and one leg muscle scan: 42 of 46 attempted scans were completed (91%), with failures dominated by exercise muscle scans (completed in 6/6 controls but 3/6 cases). One completed scan lacked usable data unrelated to subject/scan procedure (orthodonture affected a frontal brain scan). As a group, these methods provide a foundation for conduct and enhancement of future MR studies in pediatric subjects with ASD.Journal of Autism and Childhood Schizophrenia 10/2011; 42(6):1120-6. · 3.06 Impact Factor -
Article: Pondering the ponderous: are the "moral challenges" of bariatric surgery morally challenged?
The American journal of bioethics: AJOB 12/2010; 10(12):24-6. · 4.00 Impact Factor -
Article: What's in placebos: who knows? Analysis of randomized, controlled trials.
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ABSTRACT: No regulations govern placebo composition. The composition of placebos can influence trial outcomes and merits reporting. To assess how often investigators specify the composition of placebos in randomized, placebo-controlled trials. 4 English-language general and internal medicine journals with high impact factors. 3 reviewers screened titles and abstracts of the journals to identify randomized, placebo-controlled trials published from January 2008 to December 2009. Reviewers independently abstracted data from the introduction and methods sections of identified articles, recording treatment type (pill, injection, or other) and whether placebo composition was stated. Discrepancies were resolved by consensus. Most studies did not disclose the composition of the study placebo. Disclosure was less common for pills than for injections and other treatments (8.2% vs. 26.7%; P = 0.002). Journals with high impact factors may not be representative. Placebos were seldom described in randomized, controlled trials of pills or capsules. Because the nature of the placebo can influence trial outcomes, placebo formulation should be disclosed in reports of placebo-controlled trials.Annals of internal medicine 10/2010; 153(8):532-5. · 16.73 Impact Factor -
Article: Statins and muscle adverse effects: a complementary perspective.
Drug Safety 09/2010; 33(9):803; author reply 803-4. · 3.63 Impact Factor -
Article: Statin-associated muscle-related adverse effects: a case series of 354 patients.
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ABSTRACT: To characterize the properties and natural history of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin)-associated muscle-related adverse effects (MAEs). Patient-targeted postmarketing adverse-effect surveillance approach coupling survey design with an open-ended narrative. University-affiliated health care system. Three hundred fifty-four patients (age range 34-86 yrs) who self-reported muscle-related problems associated with statin therapy. Patients with perceived statin-associated MAEs completed a survey assessing statin drugs and dosages; characteristics of the MAEs; time course of onset, resolution, or recurrence; and impact on quality of life (QOL). Cases were assessed for putative drug adverse-effect causality by using the Naranjo adverse drug reaction probability scale criteria and were evaluated for inclusion in groups for which mortality benefit with statins has been shown. Patients reported muscle pain (93%), fatigue (88%), and weakness (85%). Three hundred patients (85%) met literature criteria for probable or definite drug adverse-effect causality. Ninety-four percent of atorvastatin usages (240/255) generated MAEs versus 61% of lovastatin usages (38/62, p<0.0001). Higher potency statins reproduced MAEs in 100% of 39 rechallenges versus 73% (29/40) with lower potency rechallenges (p<0.01). Time course of onset after statin initiation varied (median 14 wks); some MAEs occurred after long-term symptom-free use. Recurrence with rechallenge had a significantly shorter latency to onset (median 2 wks). The MAEs adversely affected all assessed functional and QOL domains. Most patients with probable or definite MAEs were in categories for which available randomized controlled trial evidence shows no trend to all-cause mortality benefit with statin therapy. This study complements available information on the properties and natural history of statin-associated MAEs, affirming dose dependence and strong QOL impact. The data indicating a dose-dependent relationship between MAE risk and recurrence suggest lower potency statins or discontinuation may bear consideration for ameliorating symptoms.Pharmacotherapy 06/2010; 30(6):541-53. · 2.90 Impact Factor -
Article: Mood food: chocolate and depressive symptoms in a cross-sectional analysis.
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ABSTRACT: Much lore but few studies describe a relation of chocolate to mood. We examined the cross-sectional relationship of chocolate consumption with depressed mood in adult men and women. A sample of 1018 adults (694 men and 324 women) from San Diego, California, without diabetes or known coronary artery disease was studied in a cross-sectional analysis. The 931 subjects who were not using antidepressant medications and provided chocolate consumption information were the focus of the analysis. Mood was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Cut points signaling a positive depression screen result (CES-D score, >or=16) and probable major depression (CES-D score, >or=22) were used. Chocolate servings per week were provided by 1009 subjects. Chocolate consumption frequency and rate data from the Fred Hutchinson Food Frequency Questionnaire were also available for 839 subjects. Chocolate consumption was compared for those with lower vs higher CES-D scores. In addition, a test of trend was performed. Those screening positive for possible depression (CES-D score >or=16) had higher chocolate consumption (8.4 servings per month) than those not screening positive (5.4 servings per month) (P = .004); those with still higher CES-D scores (>or=22) had still higher chocolate consumption (11.8 servings per month) (P value for trend, <.01). These associations extended to both men and women. These findings did not appear to be explained by a general increase in fat, carbohydrate, or energy intake. Higher CES-D depression scores were associated with greater chocolate consumption. Whether there is a causal connection, and if so in which direction, is a matter for future prospective study.Archives of internal medicine 04/2010; 170(8):699-703. · 11.46 Impact Factor -
Article: Doctoring the evidence: the case against lying to patients about placebos.
The American journal of bioethics: AJOB 12/2009; 9(12):34-6. · 4.00 Impact Factor -
Article: Association not causation.
Archives of internal medicine 07/2009; 169(11):1079. · 11.46 Impact Factor -
Article: Statin-associated adverse cognitive effects: survey results from 171 patients.
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ABSTRACT: To characterize the adverse cognitive effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Patient survey-based analysis. One hundred seventy-one patients (age range 34-86 yrs) who self-reported memory or other cognitive problems associated with statin therapy while participating in a previous statin effects study. Patients completed a survey assessing statin-associated, cognitive-specific adverse drug reaction (ADR) characteristics, relation of the ADR to specific statin and dose (or potency), and time course of symptom onset and recovery. Visual analog scales were used to assess the effect of the cognitive ADRs on seven quality-of-life domains. Demographic and clinical data were also collected. To target cognitive ADRs with a probable or definite causal relationship to statins, the Naranjo adverse drug reaction probability scale was used: 128 patients (75%) experienced cognitive ADRs determined to be probably or definitely related to statin therapy. Of 143 patients (84%) who reported stopping statin therapy, 128 (90%) reported improvement in cognitive problems, sometimes within days of statin discontinuation (median time to first-noted recovery 2.5 wks). Of interest, in some patients, a diagnosis of dementia or Alzheimer's disease reportedly was reversed. Nineteen patients whose symptoms improved or resolved after they discontinued statin therapy and who underwent rechallenge with a statin exhibited cognitive problems again (multiple times in some). Within this vulnerable group, a powerful relationship was observed between potency of the statin and fraction of trials with that agent resulting in cognitive ADRs (p<0.00001). Quality of life was significantly adversely affected for each of the seven assessed domains (all p<0.00000001). Findings from the survey suggest that cognitive problems associated with statin therapy have variable onset and recovery courses, a clear relation to statin potency, and significant negative impact on quality-of-life. Administration of a patient-targeted questionnaire is a feasible approach that provides a useful complement to other ADR surveillance approaches.Pharmacotherapy 07/2009; 29(7):800-11. · 2.90 Impact Factor -
Article: Amyotrophic lateral sclerosis-like conditions in possible association with cholesterol-lowering drugs: an analysis of patient reports to the University of California, San Diego (UCSD) Statin Effects Study.
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ABSTRACT: While cases of amyotrophic lateral sclerosis (ALS) or ALS-like conditions have arisen in apparent association with HMG-CoA reductase inhibitors ('statins') and/or other lipid-lowering drugs (collectively termed 'statins' in this paper for brevity), additional information is needed to understand whether the connection may be causal. The University of California, San Diego (UCSD) Statin Effects Study is a patient-targeted adverse event surveillance project focused on lipid-lowering agents, whose aim is to capitalize on patient reporting to further define characteristics and natural history of statin adverse effects (AEs), and to ascertain whether a patient-targeted surveillance system might lead to presumptive identification of previously unrecognized AEs. ALS was a candidate 'new' AE identified through this process. The aim of the analysis presented here was to examine characteristics and natural history of reported statin-associated ALS-like conditions with attention to factors that may bear on the issue of causality. For the present analysis, we focused on cases of statin-associated ALS that were reported to our study group prior to publication of a possible statin-ALS association. Of 35 identified subjects who had contacted the UCSD Statin Effects Study group to report ALS or an ALS-like condition, 18 could not be reached (e.g. contact information was no longer valid). Six were unable to participate (e.g. due to progression of their disease). Of the 11 who could be contacted and were able to participate, one declined to give informed consent. The remaining ten, with either a formal or probable diagnosis of ALS in the context of progressive muscle wasting/weakness arising in association with lipid-lowering drug therapy, completed a mail or phone survey eliciting information about ALS symptom onset and change in association with drug use/modification and development of statin-associated AEs. We reviewed findings in the context of literature on statin antioxidant/pro-oxidant balance, as well as ALS mechanisms involving oxidative stress and mitochondrial dysfunction. All ten subjects reported amelioration of symptoms with drug discontinuation and/or onset or exacerbation of symptoms with drug change, rechallenge or dose increase. Three subjects initiated coenzyme Q10 supplementation; all reported initial benefit. All subjects reportedly developed statin AEs (not indicative of ALS) prior to ALS symptom onset, strongly disproportionate to expectation (p < 0.001). Since this reflects induction of pro-oxidant effects from statins, these findings lend weight to a literature-supported mechanism by which induction by statins of oxidative stress with amplification of mitochondrial dysfunction, arising in a vulnerable subgroup, may propel mechanisms underlying both AEs and, more rarely, ALS. A theoretical foundation and preliminary clinical observations suggest that statins (and other lipid-lowering drugs) may rarely be associated with ALS in vulnerable individuals in whom pro-oxidant effects of statins predominate. Our observations have explanatory relevance extending to ALS causes that are not statin associated and to statin-associated neurodegenerative conditions that are not ALS. They suggest means for identification of a possible vulnerable subgroup. Indeed whether statins may, in contrast, confer ALS protection when antioxidant effects predominate merits examination.Drug Safety 01/2009; 32(8):649-61. · 3.63 Impact Factor -
Article: Correction for Golomb, "Reply to Blazer et al.: Flawed challenges to 'Acetylcholinesterase inhibitors and Gulf War illnesses',".
Proceedings of the National Academy of Sciences 12/2008; 105(47):E94. · 9.68 Impact Factor -
Article: Lipid lowering: what and when to monitor.
The Lancet 09/2008; 372(9638):516-7. · 38.28 Impact Factor -
Article: Re: Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease.
Neurology 07/2008; 70(24):2349; author reply 2349-50. · 8.31 Impact Factor -
Article: Reduction in blood pressure with statins: results from the UCSD Statin Study, a randomized trial.
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ABSTRACT: Some studies have suggested reductions in blood pressure (BP)with statin treatment, particularly in persons with hypertension. Randomized trial evidence is limited. We performed a randomized, double-blind, placebo-controlled trial with equal allocation to simvastatin, 20 mg; pravastatin sodium,40 mg; or placebo for 6 months. Nine hundred seventy-three men and women without known cardiovascular disease or diabetes mellitus, with low-density lipoprotein cholesterol screening levels of 115 to 190 mg/dL, had assessment of systolic and diastolic BP (SBP and DBP, respectively). Blood pressure values were compared for placebo vs statins by intention-to-treat (ITT) analysis. Additional analyses were performed that (1) were confined to subjects with neither high baseline BP (SBP>140 mm Hg or DBP>90 mm Hg) nor receiving BP medications, to exclude groups in whom BP medications or medication changes may have influenced results, and (2) separately evaluated simvastatin and pravastatin (vs placebo). The time course of BP changes after statin initiation and the effect of stopping statins on BP were examined. Statins modestly but significantly reduced BP relative to placebo,by 2.2 mm Hg for SBP (P=.02) and 2.4 mm Hg for DBP (P<.001) in ITT analysis. Blood pressure reductions ranged from 2.4 to 2.8 mm Hg for both SBP and DBP with both simvastatin and pravastatin, in those subjects with full follow-up, and without potential for influence by BP medications (ie, neither receiving nor meriting BP medications). Reductions in SBP and DBP occurred with hydrophilic and lipophilic statins and extended to normotensive subjects. These modest effects may contribute to the reduced risk of stroke and cardiovascular events reported on statins. Trial Registration clinicaltrials.gov Identifier: NCT00330980.Archives of Internal Medicine 05/2008; 168(7):721-7. · 11.46 Impact Factor
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2003–2013
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University of California, San Diego
- Department of Medicine
San Diego, CA, USA
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