A multicenter study to evaluate the pharmacokinetics and safety of liposomal bupivacaine for postsurgical analgesia in pediatric patients aged 6 to less than 17 years (PLAY).

STUDY OBJECTIVE: To evaluate the pharmacokinetics and safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery. DESIGN: Multicenter, open-label, phase 3, randomized trial (PLAY; NCT03682302). SETTING: Operating room. PATIENTS: Two separate age groups were evaluated (age group 1: patients 12 to <17 years undergoing spine surgery; age group 2: patients 6 to <12 years undergoing spine or cardiac surgery). INTERVENTION: Randomized allocation of liposomal bupivacaine 4 mg/kg or bupivacaine hydrochloride (HCl) 2 mg/kg via local infiltration at the end of spine surgery (age group 1); liposomal bupivacaine 4 mg/kg via local infiltration at the end of spine or cardiac surgery (age group 2). MEASUREMENTS: The primary and secondary objectives were to evaluate the pharmacokinetics (eg, maximum plasma bupivacaine concentrations [Cmax], time to Cmax) and safety of liposomal bupivacaine, respectively. MAIN RESULTS: Baseline characteristics were comparable across groups. Mean Cmax after liposomal bupivacaine administration was lower versus bupivacaine HCl in age group 1 (357 vs 564 ng/mL); mean Cmax in age group 2 was 320 and 447 ng/mL for spine and cardiac surgery, respectively. Median time to Cmax of liposomal bupivacaine occurred later with cardiac surgery versus spine surgery (22.7 vs 7.4 h). In age group 1, the incidence of adverse events (AEs) was comparable between liposomal bupivacaine (61% [19/31]) and bupivacaine HCl (73% [22/30]). In age group 2, 100% (5/5) and 31% (9/29) of patients undergoing spine and cardiac surgery experienced AEs, respectively. AEs were generally mild or moderate, with no discontinuations due to AEs or deaths. CONCLUSIONS: Plasma bupivacaine levels following local infiltration with liposomal bupivacaine remained below the toxic threshold in adults (~2000-4000 ng/mL) across age groups and procedures. AEs were mild to moderate, supporting the safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery. Clinical trial number and registry URL: ClinicalTrials.gov identifier: NCT03682302.

Impact of liposome bupivacaine on the adequacy of pain management and patient experiences following aesthetic surgery: Results from an observational study.

BACKGROUND: Despite the efficacy of opioid analgesics for postsurgical pain, they are associated with side effects that may complicate recovery. Liposome bupivacaine is a prolonged-release formulation of bupivacaine approved for intraoperative administration at the surgical site for postsurgical analgesia. OBJECTIVES: To evaluate the effect of a single intraoperative administration of liposome bupivacaine on postsurgical pain, opioid use and opioid-related side effects in subjects undergoing breast surgery and/or abdominoplasty. METHODS: In the present phase IV, multicentre, prospective observational study, subjects received a single intraoperative administration (266 mg) of liposome bupivacaine. Rescue analgesia was available to all subjects as needed. Outcome measures, assessed through postoperative day 3, included postsurgical pain intensity (11-point numerical rating scale), opioid consumption and overall benefit of analgesic score. Results were evaluated comparing investigators' previous experience with similar surgeries. RESULTS: Forty-nine subjects entered the study: 34 underwent breast surgery only and 15 underwent abdominoplasty with or without breast surgery (six underwent breast surgery in addition to abdominoplasty). Mean numerical rating scale pain scores remained ≤4.3 from discharge through postoperative day 3. Median daily oral opioid consumption was approximately 1.0 tablet postoperatively on the day of surgery and was approximately 2.0 tablets by postoperative day 3. Mean overall benefit of analgesic score ranged between 2.8 and 4.9 throughout the study. CONCLUSION: In this particular subject population, liposome bupivacaine was associated with low pain intensity scores and reduced opioid consumption compared with the investigators' previous experiences. Subjects' satisfaction with postsurgical analgesia was high, with a low burden of opioid-related side effects.

HISTORIQUE: Malgré l'efficacité des opioïdes pour soulager la douleur postchirurgicale, des effets secondaires peuvent compliquer le rétablissement. La bupivacaïne liposomique est une formulation à libération prolongée approuvée pour l'administration peropératoire d'une analgésie postchirurgicale au site opératoire. OBJECTIFS: Évaluer l'effet de l'administration peropératoire d'une seule dose de bupivacaïne liposomique sur la douleur postchirurgicale, ainsi que sur l'utilisation d'opioïdes et leurs effets secondaires chez des sujets subissant une chirurgie mammaire, une abdominoplastie ou les deux interventions. MÉTHODOLOGIE: Dans le cadre de la présente étude d'observation prospective et multicentrique de phase IV, les sujets se sont fait administrer une seule dose peropératoire de bupivacaïne liposomique (266 mg). Tous les sujets pouvaient recevoir une analgésie de secours, au besoin. Les mesures des résultats, évaluées jusqu'au troisième jour postopératoire, incluaient l'intensité de la douleur postchirurgicale (sur une échelle numérique de onze points), la consommation d'opioïdes et les bienfaits globaux du score analgésique. Les chercheurs ont évalué les résultats en les comparant à leur expérience de chirurgies similaires. RÉSULTATS: Quarante-neuf sujets ont participé à l'étude : 34 ont subi seulement une chirurgie mammaire et 15, une abdominoplastie accompagnée ou non d'une chirurgie mammaire (six ont subi une chirurgie mammaire en plus de l'abdominoplastie). Les scores de douleur moyens sur l'échelle numérique ne dépassaient pas 4,3 entre le congé et le troisième jour postopératoire. La consommation quotidienne médiane d'opioïdes par voie orale après l'opération était d'environ 1,0 comprimé le jour de la chirurgie et d'environ 2,0 comprimés le troisième jour postopératoire. Les avantages globaux moyens du score analgésique se situaient entre 2,8 et 4,9 tout au long de l'étude. CONCLUSION: Au sein de cette population de sujets, la bupivacaïne liposomique s'associait à de faibles scores d'intensité de la douleur et à une consommation réduite d'opioïdes par rapport aux expériences passées des chercheurs. Les sujets étaient très satisfaits de l'analgésie postchirurgicale et présentaient un faible fardeau d'effets secondaires liés aux opioïdes.

Impact of postsurgical opioid use and ileus on economic outcomes in gastrointestinal surgeries.

OBJECTIVES: To assess the incidence and economic impact of postoperative ileus (POI) following laparotomy (open) and laparoscopic procedures for colectomies and cholecystectomies in patients receiving postoperative pain management with opioids. METHODS: Using the Premier research database, we retrospectively identified adult inpatients discharged between 2008 and 2010 receiving postsurgical opioids following laparotomy and laparoscopic colectomy and cholecystectomy. POI was identified through ICD-9 diagnosis codes and postsurgical morphine equivalent dose (MED) determined. RESULTS: A total of 138,068 patients met criteria, and 10.3% had an ileus. Ileus occurred more frequently in colectomy than cholecystectomy and more often when performed by laparotomy. Ileus patients receiving opioids had an increased length of stay (LOS) ranging from 4.8 to 5.7 days, total cost from $9945 to $13,055 and 30 day all-cause readmission rate of 2.3 to 5.3% higher compared to patients without ileus. Patients with ileus received significantly greater MED than those without (median: 285 vs. 95 mg, p < 0.0001) and were twice as likely to have POI. MED above the median in ileus patients was associated with an increase in LOS (3.8 to 7.1 days), total cost ($8458 to $19,562), and readmission in laparoscopic surgeries (4.8 to 5.2%). Readmission rates were similar in ileus patients undergoing open procedures regardless of MED. CONCLUSIONS: Use of opioids in patients who develop ileus following abdominal surgeries is associated with prolonged hospitalization, greater costs, and increased readmissions. Furthermore, higher doses of opioids are associated with higher incidence of POI. Limitations are related to the retrospective design and the use of administrative data (including reliance on ICD-9 coding). Yet POI may not be coded and therefore underestimated in our study. Assessment of pre-existing disease and preoperative pain management was not assessed. Despite these limitations, strategies to reduce opioid consumption may improve healthcare outcomes and reduce the associated economic impact.

Development and validation of a risk score to identify patients at high risk for opioid-related adverse drug events.

BACKGROUND: Opioid-related adverse drug events (ORADEs) are common causes of hospitalization and increased health care costs. OBJECTIVES: To (a) estimate rates of specific adverse drug events (ADEs) among gastrointestinal (GI) surgery patients receiving postoperative opioids; (b) examine the utility of a risk-scoring model in categorizing patients at high risk of experiencing ORADEs; and (c) quantify potential clinical/economic benefits of targeting high-risk GI surgical patients for opioid-sparing regimens in terms of hospitalization cost, length of stay (LOS), and 30-day readmission rates. METHODS: Using a retrospective design based on an administrative database, patients with an inpatient surgical procedure between January 1, 2010, and December 31, 2010, were included. GI surgical patients aged greater than 18 years followed from admission through 30 days postdischarge were characterized as high or low risk using clinical/demographic characteristics and were evaluated for several outcomes. Using multivariate logistic regression, the ORADE incidence, total hospitalization cost, LOS, and 30-day readmissions were compared for high-risk and low-risk patients. RESULTS: In 87.8% (n = 3,235) of the surgical population, there was a strong concordance between risk assignment and ORADE incidence. Among the remaining 12.2% (n = 449) of patients, 5.5% (n = 202) were low risk with an ORADE, and 6.7% (n = 247) were high risk without an ORADE. Overall, 20.6% (n = 344) of high-risk patients experienced ≥1 ORADE (mean cost: $31,988; LOS: 12.1 days) compared with only 5.3% (n = 107) of low-risk patients (mean cost: $25,216; LOS: 8.0 days). High-risk patients had higher hospitalization costs and longer LOS than low-risk patients, respectively (mean cost: $19,234 vs. $13,036; mean LOS: 6.8 days vs. 3.3 days). These differences correspond to 47.0% higher costs for high-risk patients and an LOS approximately twice as long compared with low-risk patients. CONCLUSIONS: Patient clinical/demographic characteristics influence the risk of developing ORADEs. Risk assessment tools can effectively identify high-risk patients, thereby enabling interventions that can reduce ORADEs, decrease hospital costs, and improve postsurgical experiences for patients.

Effect of bromocriptine-QR (a quick-release formulation of bromocriptine mesylate) on major adverse cardiovascular events in type 2 diabetes subjects.

BACKGROUND: Bromocriptine-QR (a quick-release formulation of bromocriptine mesylate), a dopamine D2 receptor agonist, is a US Food and Drug Administrration-approved treatment for type 2 diabetes mellitus (T2DM). A 3070-subject randomized trial demonstrated a significant, 40% reduction in relative risk among bromocriptine-QR-treated subjects in a prespecified composite cardiovascular (CV) end point that included ischemic-related (myocardial infarction and stroke) and nonischemic-related (hospitalization for unstable angina, congestive heart failure [CHF], or revascularization surgery) end points, but did not include cardiovascular death as a component of this composite. The present investigation was undertaken to more critically evaluate the impact of bromocriptine-QR on cardiovascular outcomes in this study subject population by (1) including CV death in the above-described original composite analysis and then stratifying this new analysis on the basis of multiple demographic subgroups and (2) analyzing the influence of this intervention on only the "hard" CV end points of myocardial infarction, stroke, and CV death (major adverse cardiovascular events [MACEs]). METHODS AND RESULTS: Three thousand seventy T2DM subjects on stable doses of ≤2 antidiabetes medications (including insulin) with HbA1c ≤10.0 (average baseline HbA1c=7.0) were randomized 2:1 to bromocriptine-QR (1.6 to 4.8 mg/day) or placebo for a 52-week treatment period. Subjects with heart failure (New York Heart Classes I and II) and precedent myocardial infarction or revascularization surgery were allowed to participate in the trial. Study outcomes included time to first event for each of the 2 CV composite end points described above. The relative risk comparing bromocriptine-QR with the control for the cardiovascular outcomes was estimated as a hazard ratio with 95% confidence interval on the basis of Cox proportional hazards regression. The statistical significance of any between-group difference in the cumulative percentage of CV events over time (derived from a Kaplan-Meier curve) was determined by a log-rank test on the intention-to-treat population. Study subjects were in reasonable metabolic control, with an average baseline HbA1c of 7.0±1.1, blood pressure of 128/76±14/9, and total and LDL cholesterol of 179±42 and 98±32, respectively, with 88%, 77%, and 69% of subjects being treated with antidiabetic, antihypertensive, and antihyperlipidemic agents, respectively. Ninety-one percent of the expected person-year outcome ascertainment was obtained in this study. Respecting the CV-inclusive composite cardiovascular end point, there were 39 events (1.9%) among 2054 bromocriptine-QR-treated subjects versus 33 events (3.2%) among 1016 placebo subjects, yielding a significant, 39% reduction in relative risk in this end point with bromocriptine-QR exposure (P=0.0346; log-rank test) that was not influenced by age, sex, race, body mass index, duration of diabetes, or preexisting cardiovascular disease. In addition, regarding the MACE end point, there were 14 events (0.7%) among 2054 bromocriptine-QR-treated subjects and 15 events (1.5%) among 1016 placebo-treated subjects, yielding a significant, 52% reduction in relative risk in this end point with bromocriptine-QR exposure (P<0.05; log-rank test). CONCLUSIONS: These findings reaffirm and extend the original observation of relative risk reduction in cardiovascular adverse events among type 2 diabetes subjects treated with bromocriptine-QR and suggest that further investigation into this impact of bromocriptine-QR is warranted. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique Identifier: NCT00377676.

Statins and prostate cancer diagnosis and grade in a veterans population.

BACKGROUND: Although prostate cancer is commonly diagnosed, few risk factors for high-grade prostate cancer are known and few prevention strategies exist. Statins have been proposed as a possible treatment to prevent prostate cancer. METHODS: Using electronic and administrative files from the Veterans Affairs New England Healthcare System, we identified 55,875 men taking either a statin or antihypertensive medication. We used age- and multivariable-adjusted Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer incidence among patients taking statins (n = 41,078) compared with patients taking antihypertensive medications (n = 14,797). We performed similar analyses for all lipid parameters including total cholesterol examining each lipid parameter as a continuous variable and by quartiles. All statistical tests were two-sided. RESULTS: Compared with men taking an antihypertensive medication, statin users were 31% less likely (HR = 0.69, 95% CI = 0.52 to 0.90) to be diagnosed with prostate cancer. Furthermore, statin users were 14% less likely (HR = 0.86, 95% CI = 0.62 to 1.20) to be diagnosed with low-grade prostate cancer and 60% less likely (HR = 0.40, 95% CI = 0.24 to 0.65) to be diagnosed with high-grade prostate cancer compared with antihypertensive medication users. Increased levels of total cholesterol were also associated with both total (HR = 1.02, 95% CI = 1.00 to 1.05) and high-grade (HR = 1.06, 95% CI = 1.02 to 1.10) prostate cancer incidence but not with low-grade prostate cancer incidence (HR = 1.01, 95% CI = 0.98 to 1.04). CONCLUSIONS: Statin use is associated with statistically significantly reduced risk for total and high-grade prostate cancer, and increased levels of serum cholesterol are associated with higher risk for total and high-grade prostate cancer. These findings indicate that clinical trials of statins for prostate cancer prevention are warranted.

Cardiovascular benefit of magnitude of low-density lipoprotein cholesterol reduction: a comparison of subgroups by age.

BACKGROUND: We examined the effect of the magnitude of low-density lipoprotein cholesterol (LDL-C) reduction across subjects of various ages in a retrospective cohort study. METHODS AND RESULTS: We selected 20,132 male veterans at high risk for an acute cardiovascular event and who had 2 or more LDL-C measurements before their first documented acute myocardial infarction, revascularization, death, or censoring date. LDL-C reduction was categorized as no reduction (<10 mg/dL; reference), small reduction (between 10 and 40 mg/dL), moderate reduction (between 40 and 70 mg/dL), or large reduction (> or =70 mg/dL). The primary outcome was combined acute myocardial infarction or revascularization. The first and last LDL-C levels in the databases were used to calculate the LDL-C reduction in patients who experienced no outcome or who died. Within each age quartile and in a subgroup of patients > or =80 years of age, a Cox proportional hazards model was used to determine hazard ratios for each category of LDL-C reduction compared with the reference category, with adjustment for age, body mass index, current smoking status, medications, and comorbidities. In all age groups, the magnitude of LDL-C reduction was proportional to the magnitude of cardiovascular risk reduction. Risk reduction for the combined outcome in patients who achieved a large LDL-C reduction was similar in all age quartiles, with multivariate-adjusted hazard ratios of approximately 0.30. CONCLUSIONS: In a cohort of veterans at high risk for cardiovascular events, patients of all ages, including those 80 years or older, benefitted the most from large reductions in LDL-C.

Lack of cholesterol awareness among physicians who smoke.

Cigarette use is a known risk factor for the development of coronary artery disease (CAD) as it adversely affects HDL cholesterol levels and promotes thrombogenesis. Smoking may also be associated with behavioral characteristics that potentiate the risk of CAD. A lack of cholesterol knowledge would indicate an aversion to a prevention-oriented lifestyle. Thus, our goal was to determine the association between tobacco use and knowledge of self-reported cholesterol among male physicians. Using the 1982 and follow-up questionnaires from the physician health study, we report the changes in the frequencies of awareness of self-reported total cholesterol and cardiovascular risk factors among the 22,067 participants. We classified physicians as being aware of their cholesterol if they reported a cholesterol level and unaware if the question was left unanswered. In 1997, 207 physicians were excluded, as the recorded cholesterol was not interpretable, leaving 21,860 for our follow up analyses. Using unadjusted logistic models, we determined the odds ratios (OR) and 95% confidence intervals (CI) of not reporting a cholesterol level in either 1982 or 1997 for each specified risk factor. We then evaluated whether the lack of cholesterol awareness at both time points was associated with the use of tobacco throughout the study. After 14-years of follow up, cholesterol awareness increased from 35.9 to 58.6 percent. During this period, the frequency of hypertension and hyperlipidemia treatment increased (13.5 to 40.5% and 0.57% to 19.6% respectively), as did the diagnosis of diabetes (2.40 to 7.79%). Behavioral characteristics such as a sedentary lifestyle and obesity also increased (27.8 to 42% and 43.5 to 53.5%, respectively), however the proportion of current smokers deceased from 11.1 to 4.05%. The percentages of individuals being unaware of their cholesterol decreased in all risk factor groups. However, individuals were likely to be unaware of their cholesterol at both time points if they were current smokers (1982 OR 1.44, CI 1.4-1.7; 1997 OR 1.71, CI 1.48-1.97), past smokers (1982 OR 1.12, CI 1.05-1.18; 1997 OR 1.13, CI 1.06-1.20), overweight (BMI 25 kg/m2) or sedentary. In addition, physicians who never quit smoking were likely to be unaware of their cholesterol throughout the study (OR 1.42, CI 1.21-1.67). Cholesterol awareness in general and among those with CAD risk factors improved after 14-years of follow-up. However, the likelihood of being unaware was greater among smokers at both time points. Therefore, smokers do not appear to take advantage of other preventive strategies that would minimize their risk of developing CAD.

Cost impact of diagnostic imaging for lower extremity peripheral vascular occlusive disease.

OBJECTIVE: The evaluation of peripheral vascular disease in the primary care setting is routinely performed by contrast-enhanced magnetic resonance angiography (CE-MRA) and digital subtraction angiography (DSA). However, limited data are available on the relative costs and clinical outcomes following these diagnostic procedures. The objective of this study is to assess and compare costs associated with diagnostic imaging in peripheral vascular occlusive disease (PAOD). METHODS: US veterans (n = 19,209) with CE-MRA or DSA for the assessment of PAOD from fiscal year (FY) 1999 to FY 2004. Main outcome measure(s) using the Department of Veterans Affairs' (VA) costing algorithms, cost, and log-cost of interventions (e.g., revascularization, stent, angioplasty), amputations or mortality rates within 30/90 days and 1 year of DSA or CE-MRA were compared, and adjusted for patient characteristics and disease severity using multivariate regression. Imaging modality selection bias was evaluated with propensity score, instrumental variables, and Heckman methods using untransformed costs and log-costs with smearing retransformation. RESULTS: Initial CE-MRA imaging was significantly more likely among patients with prior renal disease or bypass surgery [odds ratio (OR) > 2; P < 0.001], and less likely among patients with prior amputation, peripheral vascular disease (PVD), claudication, or other cardiovascular disease (OR < 0.7; P < 0.001). After adjusting for endogenous choice of initial imaging modality, 30-day treatment costs were US$3500-$4300 lower (P < 0.001) for patients with initial CE-MRA. Eighty-two percent of DSA imaging patients had no additional procedures or events within 30 days, and 65% at 90 days. Less than 3.2% (3.6%) of patients had any repeat imaging within 30 (90) days of initial imaging. CONCLUSIONS: Relative to DSA, CE-MRA imaging was associated with substantial treatment episode savings, beyond the US$950 direct savings in imaging cost per procedure. Substituting CE-MRA for DSA among those not planning or requiring any follow-up procedures within 30 days, could have reduced outpatient imaging costs by up to 55%, and reduced VA system costs by US$13.2 million over the six-year period.

The association between statins and cancer incidence in a veterans population.

BACKGROUND: Meta-analyses of trials of 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors or statins for cardiovascular disease prevention have failed to show any statistically significant benefit of statins for cancer prevention. However, these trials included relatively young participants, who develop few cancers, and their follow-up periods may have been too short to detect an association between statin use and cancer incidence. We investigated this association in a population of veterans. METHODS: We identified patients using antihypertensive medications but no cholesterol-lowering medications (n = 25,594) and patients using statins (n = 37,248) who were enrolled in the Veterans Affairs New England Healthcare System between January 1, 1997, and December 31, 2005. Age- and multivariable-adjusted Cox proportional hazards models were used to calculate the hazard ratio (HR) and its 95% confidence interval (CI) for cancer incidence, excluding nonmelanoma skin cancer, among patients taking statins compared with patients taking antihypertensive medications and among patients grouped by statin dose (as equivalent simvastatin dose). All statistical tests were two-sided. RESULTS: The absolute incidence of total cancers was 9.4% among statin users and 13.2% among nonusers (difference = 3.8%, 95% CI = 3.3% to 4.3%, P(difference) < .001). Statin users had a statistically significant lower risk for total cancer than nonusers after adjustment for age (HR = 0.76, 95% CI = 0.73 to 0.80) and multiple potential confounders (HR = 0.74, 95% CI = 0.70 to 0.78). After multivariable adjustment, a statistically significantly decreased risk of all cancers was also associated with increasing statin use (P(trend) < .001). CONCLUSIONS: Patients using statins may be at lower risk for developing cancer. Additional observational studies and randomized trials of statins for cancer prevention are warranted.

Performance of a rheumatoid arthritis records-based index of severity.

OBJECTIVE: To assess the performance of a rheumatoid arthritis (RA) records-based index of severity (RARBIS) developed by a Delphi panel process in a cohort of patients with RA. METHODS: We reviewed the medical records of 120 RA patients from the New England Veteran's Administration (VA) Healthcare System and collected data on markers of RA disease severity. Markers were refined through a Delphi panel process before developing the RARBIS based on chart review. The RARBIS includes 5 subscales on surgery, radiography, extraarticular manifestations, clinical status, and laboratory values. Factors that were regarded by the Delphi panel as highly related to severity of RA were assigned higher points on the index. We assessed the validity of the RARBIS by comparing it to the intensity of the actual RA treatment that these patients received: low, neither biologic nor disease modifying antirheumatic drug (DMARD) use; moderate, therapy with DMARD such as hydroxychloroquine, gold, or sulfasalazine; high, treatment with stronger DMARD such as methotrexate, azathioprine, leflunomide, and cyclosporine; and very high, use of any biologics. RESULTS: The RARBIS had a range of 0 to 8. All subscales except extraarticular manifestations were statistically significantly related to intensity of RA treatment (chi-square test p

Characteristics associated with differences in reported versus measured total cholesterol among male physicians.

We studied 4,543 male physicians to assess accuracy of self-reported cholesterol level. The rate of accurate reporting improved over 14 years (25% to 62%), while failing to report a cholesterol level decreased. Overweight, current or past smoking, and physical inactivity were significantly associated with not reporting or inaccurately reporting cholesterol level. Though an increasing proportion of physicians accurately reported their cholesterol level over time, those at increased risk for developing cardiovascular disease tended to underestimate or fail to report their cholesterol level. Knowledge may be a critical factor in empowering physicians and patients to advocate for and adopt healthier lifestyles. EDITORS' STRATEGIC IMPLICATIONS: Rates of sedentary behavior and obesity in the U.S. continue to rise. In this promising study with a large sample, a longitudinal design, and multi-method assessments, we find that--even among this sample of highly educated medical professionals--those individuals who are at greatest cardiovascular risk might require different types of monitoring, motivational interventions, or health education.

Predictors of 14-year changes in the total cholesterol to high-density lipoprotein cholesterol ratio in men.

BACKGROUND: Although the ratio of total to high-density lipoprotein cholesterol (TC/HDL) is a powerful predictor of cardiovascular disease (CVD), few studies have investigated which factors are associated with changes in this ratio over time. We examined predictors of a change in TC/HDL ratio over a period of 14 years among 4451 men free of CVD from the Physicians' Health Study. METHODS: Baseline and updated physician characteristics and CVD risk factors were included in multivariate linear and logistic regression models to determine factors associated with a change in the TC/HDL ratio or of having a ratio of > or =5 on follow-up. RESULTS: After a mean follow-up of 14 years, mean total cholesterol decreased by 7 mg/dL, HDL increased by 1 mg/dL, and the ratio decreased by 0.37. In multivariate logistic analyses, physicians were more likely to have a TC/HDL ratio of > or =5 at follow-up if they maintained a weight of > or =25 kg/m2 (OR, 1.69 [1.35-2.12]), gained weight (OR, 2.01 [1.55-2.62]), or became inactive (OR, 1.43 [1.11-1.83]). However, older physicians and those who consumed alcohol or received treatment for hyperlipidemia were more likely to have a ratio of <5. CONCLUSIONS: Although pharmacologic treatment for hyperlipidemia had the greatest favorable impact on the ratio over time, our data also show that maintaining an ideal weight and exercise have beneficial effects. We therefore advocate a renewed fervor for raising public awareness of the benefits of healthy lifestyle behaviors and pharmacologic treatments that are associated with long-term maintenance of favorable cholesterol levels.