Hebrew version of the physical therapy patient satisfaction questionnaire: cross-cultural adaptation and psychometric properties.

PURPOSE: This study aimed at translating, culturally adjusting, and validating the Israeli version of the Physical Therapy Patient Satisfaction Questionnaire (PTPSQ-H). METHODS: Following the process of cross-cultural adaptation of self-report measures guidelines, we conducted a cross-cultural adaptation study among of adults completing outpatient physical therapy treatments. We formulated the PTPSQ-H using forward-backward translation procedures, a final review, and a pre-final version. The applied analyses were acceptability, reliability (measured by internal consistency; Cronbach's α), and factor analysis (exploring internal structure). Divergent validity was assessed by paralleling the PTPSQ-H with pain visual analogue scale (VAS), and a 5-point Likert scale evaluating the global perceived effect (GPE) of the physical therapy treatment. Preliminary analyses concluded that five items from the PTPSQ-H are irrelevant for the study population, thus these items were removed and the questionnaire was termed the PTPSQ-H[15]. RESULTS: The PTPSQ-H[15] exhibited high internal consistency (α = 0.883). Divergent validity was low for the GPE (r = 0.257, p < .0001) and insignificant for the VAS (r = -0.05, p = .480). A factor analysis indicated a significant two-factor structure related to "Overall Experience" and "Professional Impression", which explained nearly 60% of the total variance assuring its suitability to measure patient satisfaction. CONCLUSION: PTPSQ-H[15] was found to be a valid tool to measure physical therapy patient satisfaction.

Variation in Gut Microbiota Composition is Associated with Sleep Quality and Cognitive Performance in Older Adults with Insomnia.

Purpose: Insomnia, a chronic condition affecting 50% of older adults, is often accompanied by cognitive decline. The mechanism underlying this comorbidity is not fully understood. A growing literature suggests the importance of gut microbiota for brain function. We tested associations between sleep quality and cognitive performance with gut microbiota in older adults with insomnia. Patients and Methods: Seventy-two older adults with insomnia (age 73.2 ± 5.73 years, 56 females) provided stool samples for gut microbial sequencing. Microbiota profile was determined using the DADA2 bioinformatics pipeline. Cognition was assessed with the Cambridge Neuropsychological Test Automated Battery. Objective sleep quality was monitored by a two-week actigraphic recording, and participants completed the Insomnia Severity Index (ISI). We used partial canonical correspondence analysis (pCCA) to examine the relative contribution of insomnia, based on actigraphic sleep efficiency (SE) and ISI, and of cognitive status, based on the Multitasking test of Median Reaction Latency (MTTLMD) and the Spatial Working Memory Between Errors (SWMBE), to variance in microbiota composition. We used Pearson correlations to correlate insomnia and cognitive status parameters with microbiota amplicon sequence variants, genera, and families. Results: The pCCA revealed that sleep quality and cognitive performance explained a variation of 7.5-7.9% in gut microbiota composition in older adults with insomnia. Correlation analysis demonstrated that Lachnoclostridium (genus) correlates positively with SE (r=0.42; P=0.05) and negatively with MTTLMD (r=-0.29; P=0.03), whereas Blautia (genus) correlates negatively with MTTLMD (r=-0.31; P=0.01). Conclusion: Findings demonstrate the associations of sleep quality and cognitive performance with variance in gut microbiota composition and with specific genus abundance in older adults with insomnia. Further studies should validate the findings, determine causal relationships, and evaluate potential interventions for the comorbidity of insomnia and cognitive impairment in older adults with insomnia.

Hybrid Tele and In-Clinic Occupation Based Intervention to Improve Women's Daily Participation after Breast Cancer: A Pilot Randomized Controlled Trial.

BACKGROUND: Women after breast cancer (BC) cope with decreased daily participation and quality of life (QOL) due to physical, cognitive, and emotional symptoms. This study examined a hybrid occupation-based intervention, Managing Participation with Breast Cancer (MaP-BC), to improve daily participation in their meaningful activities. METHODS: Thirty-five women after BC phase were randomly allocated to the MaP-BC intervention (n = 18) or control (n = 17) group (standard care only). Assessments were administered at baseline (T1), 6-week (T2), and 12-week (T3) post-T1. MAIN OUTCOME: perceived performance and performance-satisfaction with meaningful activities according to the Canadian Occupational Performance Measure. SECONDARY OUTCOMES: retained activity levels (Activity Card Sort), QOL (Functional Assessment of Cancer Therapy-Breast), cognitive abilities (Montreal Cognitive Assessment and Behavior Rating Inventory of Executive Function), and upper-extremity functioning (Disability of Arm, Shoulder, Hand). Results showed significant interaction (group x time) effects for the primary outcome in performance, F(2,66) = 29.54, p = 0.001, ɳP2 = 0.472, and satisfaction, F(2,66) = 37.15, p = 0.000, ɳP2 = 0.530. The intervention group improved more in performance, t = 5.51, p = 0.0001, d = 1.298, and satisfaction, t = -5.32, p = 0.0001, d = 1.254, than the control group between T1 and T2. Secondary outcomes demonstrated within-group improvements. CONCLUSION: MaP-BC, a comprehensive occupation-based hybrid intervention tailored to women's functional daily needs after BC, improved participation in meaningful activities within a short period.

Relationship between Occupational Identity Post-Stroke and Outcomes of a Self-Management Participation-Focused Intervention: A Preliminary Investigation.

Self-management programs are used to assist stroke survivors to manage their condition and participation. This study was designed to examine correlations between occupational identity and outcomes of participation-focused self-management program using the Occupational Performance History Interview for the occupational identity and participation and self-efficacy as outcome measures. Spearman's rho correlations were calculated between occupational Identity and the program's outcomes. Results showed moderate significant positive correlations with self-efficacy for self-management and self-efficacy for participation scales at baseline; few were found at post-intervention and follow-up. Non-significant correlations were found between occupational identity and the change in outcome measures from baseline to post-intervention and to follow-up. Findings suggest occupational identity is strongly related to self-efficacy after stroke, and less related to intervention outcomes. However, other factors may possibly affect the effectiveness of self-management programs for a stroke population. Exploration of these factors might help develop programs better tailored to each stroke survivor.

Examining the feasibility and effectiveness of a culturally adapted participation-focused stroke self-management program in a day-rehabilitation setting: A randomized pilot study.

Background: Stroke survivors find it difficult to participate in daily activities, despite their improvement throughout the rehabilitation process. Thus, it has been questioned whether day-rehabilitation services provide adequate preparation for participation and reintegration into the community. Self-management programs can improve survivors' self-efficacy to manage their condition and participation. Improving Participation After Stroke Self-Management program (IPASS) is an occupational therapy-based group intervention developed in the United States, which has been effective in improving participation outcomes.Objective: To evaluate the feasibility and effectiveness of the IPASS adapted for an Israeli population of individuals admitted to a day-rehabilitation center after stroke.Methods: A single-center, randomized, assessor-blind study was conducted. Eligible participants were randomized to receive the IPASS (intervention group), in addition to standard individual therapy or standard care only (control group). Feasibility was based on attendance rate and a feedback questionnaire. Effectiveness was evaluated with the Functional Independence Measure (FIM), the Reintegration to Normal Living Index (RNLI) and self-efficacy questionnaires.Results: Sixty participants were included, of which 39 completed baseline and post-intervention evaluations. The intervention group improved significantly in the FIM scores (p < .01), as compared to the control group (p > .05). Moderate effect sizes (≥0.35) were found for the FIM and RNLI, and large effect sizes (≥0.65) for two subcategories in the participation self-efficacy questionnaire.Conclusions: The results support the feasibility of the adapted IPASS, and show a trend for positive effects in improving participation and self-efficacy in managing participation in home and community activities, for an Israeli post-stroke population.

Efficacy of Compression Gloves in the Rehabilitation of Distal Radius Fractures: Randomized Controlled Study.

OBJECTIVE: The aim of this study was to examine the outcomes of wearing made-to-measure compression gloves after distal radius fracture. DESIGN: In a randomized controlled trial, adults who were about 6 wks post distal radius fracture were recruited and divided into a comparison control group (n = 15), who received standard rehabilitation twice a week for half an hour, and an intervention group (n = 17), who additionally used compression gloves. All treatments were conducted at a single rehabilitation clinic. Outcomes assessed were wrist and finger range of motion, grip strength, swelling, pain, and activities of daily living (using the Patient Rating Wrist Evaluation). The intervention group underwent additional objective dynamic assessments of range of motion with and without the gloves. RESULTS: The intervention group demonstrated reduced swelling, pain, and analgesic use; increased wrist range of motion; better scores for specific hand functions; and greater participation in activities of daily living compared with the comparison group. CONCLUSION: This randomized controlled trial shows that using compression gloves during the rehabilitation phase after distal radius fracture improves daily functioning and reduces adverse symptoms. These improvements, which are important in their own right, are also expected to aid in preventing the development of chronic conditions and disability. EVIDENCE LEVEL II: Un-blinded prospective comparative study.

Interaction Between the Haptoglobin Genotype and Vitamin E on Cardiovascular Disease in Diabetes.

PURPOSE OF REVIEW: Despite compelling evidence regarding the importance of oxidant stress in the development of vascular complications and observational studies suggesting that vitamin E may be protective from these complications, multiple clinical trials have failed to show benefit from vitamin E supplementation in the prevention of vascular complications in diabetes. One possible explanation for this failure of vitamin E may have been inappropriate patient selection. This review seeks to provide the clinical evidence and mechanistic basis for why a subset of individuals defined by their haptoglobin (Hp) genotype may derive cardiovascular protection by vitamin E supplementation. RECENT FINDINGS: Clinical trial data from the HOPE, ICARE, and WHS studies is presented showing a pharmacogenomic interaction between the Hp genotype and vitamin E on the development of CVD. Specifically, in individuals with diabetes and the Hp2-2 genotype, vitamin E has been shown to be associated with an approximately 35% reduction in CVD. Cardioprotection by vitamin E in individuals with the Hp2-2 genotype appears to be mediated in part by an improvement in HDL functionality as demonstrated in three independent trials in both type 1 diabetes and type 2 diabetes. Vitamin E may provide benefit in reducing CVD in Hp2-2 individuals with diabetes. However, in order for this pharmacogenomic algorithm to be accepted as a standard of care and used clinically, an additional large prospective study will need to be performed.

Effect of Magnesium Oxide Supplementation on Nocturnal Leg Cramps: A Randomized Clinical Trial.

Importance: Magnesium supplements are widely marketed for prophylaxis of nocturnal leg cramps (NLC) despite no evidence of significant benefit. Objective: To determine whether magnesium oxide is better than placebo for NLC prophylaxis. Design, Setting, and Participants: A randomized, double-blind, placebo-controlled clinical trial of 2 weeks eligibility screening followed by 4 weeks of treatment was conducted in northern Israel, from February to October 2013. An intention-to-treat data analysis was performed from March 22, 2014, to April 17, 2016. We used a volunteer sample of community-dwelling individuals experiencing NLC, 21 years or older, with 4 or more documented episodes of NLC during 2 weeks of screening. Interventions: Capsules containing either magnesium oxide or a similar-looking placebo to be taken orally, once daily at bedtime for a period of 4 weeks. Main Outcomes and Measures: The primary outcome was the difference in the mean number of NLC per week between the screening and treatment phases. Secondary outcomes included severity and duration of NLC, quality of life, and quality of sleep. Results: Of the 166 volunteers, 72 (43%) were excluded, of whom 15 declined to participate and 57 did not meet the inclusion criteria. Of the 94 individuals (39% male; mean [SD] age, 64.9 [11.1] years) randomly assigned to magnesium oxide (48) or placebo (46), 6 did not complete the study protocol (3 in each group). Mean (SD) change of NLC was -3.41 (4.05) (from 7.84 [5.68] to 4.44 [5.66]) and -3.03 (4.53) (from 8.51 [5.20] to 5.48 [4.93]) per week in the magnesium oxide and placebo groups, respectively, a difference between groups of 0.38 (0.48) NLC per week (P = .67 in an intention-to-treat analysis). There were no between-group differences in the severity and duration of NLC, quality of life, or quality of sleep. Conclusions and Relevance: Oral magnesium oxide was not superior to placebo for older adults experiencing NLC. The decrease in the mean number of NLC per week, from the screening to the treatment phase in both groups, is probably a placebo effect that may explain the wide use of magnesium for NLC. Trial Registration: clinicaltrials.gov Identifier: NCT01709968.

Effects of anti-TNF-α treatment on lipid profile in rheumatic diseases: an analytical cohort study.

BACKGROUND: The aim was to assess the influence of long-term treatment with tumor necrosis factor alpha (TNF-α) inhibitors on total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and atherogenic index (AI) in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) patients. METHODS: A retrospective cohort study was conducted on RA, PsA, and AS patients treated with TNF-α inhibitors for at least 270 days between 2001 and 2011. Levels of TC, TG, LDL, and HDL and the AI were compared with baseline values at 0-6, 6-12, 12-18, and 18-24 months. Patients were further subdivided into three groups according to their HMG CoA reductase inhibitor (statin) treatment status in order to assess their effect on the results. RESULTS: The records of 311 patients (152 RA, 90 PsA, and 69 AS) were reviewed. TC and TG increased following treatment with TNF-α inhibitors, from 180.85 ± 2.12 mg/dl and 116.00 ± 3.55 mg/dl at baseline to 188.12 ± 2.35 mg/dl (p = 0.02) and 132.02 ± 4.63 mg/dl at 0-6 months (p < 0.01), respectively, and to 184.88 ± 2.09 mg/dl (p = 0.02) and 129.36 ± 4.32 mg/dl at 18-24 months (p < 0.01), respectively. AI increased following treatment with TNF-α inhibitors, from -0.032 ± 0.017 at baseline to 0.004 ± 0.019 at 18-24 months (p < 0.01). LDL decreased significantly in patients who were treated with statins before and during the entire study period, from 119.97 ± 2.86 mg/dl at baseline to 104.02 ± 3.57 mg/dl at 18-24 months (p < 0.01), in contrast to an increase in LDL values in patients who did not receive statins during the study. CONCLUSIONS: TNF-α inhibitor treatment was associated with a significant increase in TC and TG levels and the AI. Adding statins to the treatment was associated with a significant decrease in LDL levels.

Factors associated with adherence to glaucoma pharmacotherapy in the primary care setting.

BACKGROUND: Primary open-angle glaucoma is a leading cause of irreversible blindness. OBJECTIVES: To identify factors associated with adherence to glaucoma pharmacotherapy in the primary care setting, focusing on physicians' role. METHODS: Patients were recruited from primary care clinics and telephone-interviewed using a structured questionnaire that addressed patient-, medication-, environment- and physicians-related factors. Patients' data on pharmacy claims were retrieved to calculate the medication possession ratio for measuring adherence. RESULTS: Seven hundred thirty-eight glaucoma patients were interviewed. The multivariate analysis identified eight variables that were associated independently with adherence. Barriers to adherence were found to be low income, believing that 'It makes no difference to my vision whether I take the drops or not' and relying on someone else for drop instillation (exp(B) = 1.91, P = 0.002; exp(B) = 2.61, P < 0.0001; exp(B) = 2.17, P = 0.001, respectively). Older age, having a glaucoma patient among close acquaintances, taking a higher number of drops per day, taking a prostaglandin drug and reporting that the ophthalmologist had discussed the importance of taking eye drops as prescribed, were found to promote adherence (exp(B) = 0.96, P < 0.0001; exp(B) = 0.54, P = 0.014; exp(B) = 0.81, P = 0.001; exp(B) = 0.37, P < 0.0001; exp(B) = 0.60, P = 0.034, respectively). No association was found between the patient's relationship with the family physician and adherence to glaucoma treatment. CONCLUSION: Adherence to glaucoma pharmacotherapy is associated with patient-related, medication-related, physician-related and environmental factors. Ophthalmologists have a significant role in promoting adherence. However, the potential role of family physicians is unfulfilled and unrecognized.

Can cognitive remediation improve mobility in patients with Parkinson's disease? Findings from a 12 week pilot study.

BACKGROUND: Patients with Parkinson's disease (PD) suffer from impaired gait and mobility. These changes in motor function have been associated with cognitive deficits that also commonly co-occur in PD, especially executive function (EF) and attention. OBJECTIVE: We hypothesized that a cognitive remediation program would enhance gait and mobility. METHODS: The 18 PD patients in this study were assessed at baseline and again one and four weeks after completion of a 12 week long, home-based computerized cognitive training program. Subjects were asked to "play" computer games designed to improve EF and attention for 30 minutes a day, three times per week for 12 weeks, while seated. The Timed Up and Go (TUG), gait speed, and stride time variability quantified mobility. A previously validated, computerized neuropsychological battery quantified global cognitive function and its sub-domains. RESULTS: Compared to pre-training values, global cognitive scores and time to complete the TUG significantly improved after the training. TUG components of turning speed and duration also improved. Other TUG components, gait speed, and variability did not change after training. CONCLUSIONS: These initial findings suggest that computerized cognitive training can improve cognitive function and has a beneficial carryover effect to certain aspects of mobility in patients with PD. Additional studies are required to replicate these findings and more fully assess the underlying mechanisms. Nonetheless, the present results underscore the motor-cognitive link in PD and suggest that computerized cognitive training may be applied as a therapeutic option to enhance mobility in patients with PD.

[Mediterranean diet in cancer patients and cancer free adult Arabs in Israel--a case-control study].

BACKGROUND: Although several studies have investigated the association of the Mediterranean diet (MD) with overall risk of specific cancers, data on overall cancer risk are sparse, especially in Arab populations. OBJECTIVES: To compare between the score of MD in cancer patients and cancer-free adult Israeli Arabs in order to identify risk factors amenable to intervention. METHODS: A case control study was conducted in northern Israel, involving 200 Arab subscribers of a regional Health Maintenance Organization (HMO). RESULTS: An inverse association was found (p = 0.000) between Mediterranean diet score and cancer, with OR = 0.4, 95% CI = 0.260-0.612. CONCLUSIONS: Greater adherence to Mediterranean diet is associated with lower prevalence of cancer. The adoption of this dietary pattern also seems to moderate the prevalence of obesity and risks of chronic diseases.

Incidence of cancer among diabetic and non-diabetic adult Israeli Arabs.

BACKGROUND: A worldwide epidemic of type 2 diabetes mellitus (T2DM) is in progress. This disease carries a heavy socioeconomic burden. OBJECTIVES: To compare the incidence rate of overall and site-specific cancers among Israeli Arabs with T2DM to that of Israeli Arabs without. METHODS: A retrospective cohort study of all adult Arab members of Clalit Health Care Services in northern Israel was conducted over a 10 year period (1999-2008). RESULTS: During the study period 752 and 2045 incident cases of cancer were diagnosed among 13,450 adults with diabetes and 74,484 without, respectively. The follow-up time involved 817,506 person-years. Diabetes was associated with a standard incidence ratio (SIR) of 3.27 (95% CI 1.49-5.05) and 2.87 (95% CI 1.25-4.50) for pancreatic cancer in men and women, respectively. A significantly reduced SIR (0.67, 95% CI 0.36-0.99) was observed for esophageal, stomach and intestinal cancers in men. CONCLUSIONS: Our findings support an association between T2DM and increased risk of cancer of the pancreas in Arab men and women. A significantly reduced risk of all other cancers was observed only in Arab men. Our findings underscore the need for effective diabetes and cancer prevention and intervention programs.

Hospitalizations of patients treated with anti-tumor necrosis factor-α agents -- a retrospective cohort analysis.

OBJECTIVE: To assess the association between treatment with anti-tumor necrosis factor-α (TNF-α) agents and the occurrence of hospitalizations, their causes and complications, compared to treatment with traditional disease-modifying antirheumatic drugs in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). METHODS: A retrospective cohort study was conducted of patients with RA, AS, and PsA treated with anti-TNF-α agents between April 2002 and December 2007. Patients were assessed during the period of anti-TNF-α treatment (Group B) and compared to an equivalent period before initiation of anti-TNF-α therapy (Group A). All hospitalization charts were reviewed and diagnoses, comorbidities, concomitant medications, and clinical course were analyzed. Statistical analysis was performed using multivariate mixed Poisson regression. RESULTS: In the study period of 57 months, 735 hospitalization events of 327 patients were analyzed. Statistically significant decreases were seen in the total number of hospitalization events as well as hospitalizations due to exacerbation of rheumatic diseases in Group B compared to Group A (44.4 vs 74.2 and 21.9 vs 47.5 per 100 patient-years, respectively; p < 0.0001). More infectious events (7.4 in Group B compared to 4.6 per 100 patient-years in Group A; p = 0.043) were associated with anti-TNF-α treatment, older age, and underlying disease, because patients with RA had higher rates of infections compared to patients with PsA and patients with AS. CONCLUSION: The overall effect of anti-TNF-α therapy was a significant decline in total hospitalization events. The decrease was more prominent in patients with RA than in patients with AS and patients with PsA, and reflected the significant decrease in hospitalizations due to rheumatic disease exacerbation. The decrease was more pronounced than the observed increase in infectious events.

Obesity and risk taking. A male phenomenon.

There is a growing tendency to regard overeating as an addiction, with obesity as its primary symptom. We propose that similar to other addictions, obesity is associated with excessive risk-taking in men, though not in women. To examine this suggestion we conducted two studies, one involving a sample of overweight and normal-weight students, and the other involving obese adults drawn from a dataset of health care clients, and a control sample of normal-weight adults. In both of these studies, we found that overweight and obese men took more risk in a laboratory task than normal-weight men, while overweight and obese women did not differ from normal-weight women in this respect. At the same time, obese women (but not overweight women) displayed higher impulsivity levels than normal-weight women. These findings shed light on the cognitive characteristics of obesity in men, and accent the importance of taking gender into account when developing research paradigms and treatment methods for obesity.

[Diabetes mellitus and cancer: the different expression of these diseases in Israeli Arabs and Jews].

BACKGROUND: The Arab population of Israel is a separate ethnic group from the Jewish population, embracing a different lifestyle and different nutritional habits and environmental exposures. These variations may lead to dissimilar expressions of certain diseases in the Arab Israeli as compared with the Jewish population. In recent years, the Arab population in Israel has experienced rapid and marked changes toward westernization in lifestyle, and significant increases in the incidence rate of both diabetes mellitus (DM) and cancer This is combined with an increase in known risk factors common to both illnesses. METHODS: Review of recent publications and official health statistics provided the sources of information for this review. RESULTS: Studies show that in recent decades the incidence rate of DM in the Israeli Arab population has increased by 9.1 per 1000 persons annually and of cancer by 1.3 per 1000 person annually among males and by 1.2 per 1000 person among females. In contrast, these rates have decreased in the Jewish population. CONCLUSIONS: Lifestyle change in recent decades (westernization) in the Israeli Arab population has led to a marked increase in the incidence rate of DM and cancer in this group. The most influential risk factors are unhealthy diet, physical inactivity and tobacco smoking. By understanding these processes, effective intervention efforts can be initiated in order to reverse these trends.

Vitamin E reduces cardiovascular disease in individuals with diabetes mellitus and the haptoglobin 2-2 genotype.

AIMS: Individuals with both diabetes mellitus (DM) and the Haptoglobin (Hp) 2-2 genotype are at increased risk of cardiovascular disease. As the antioxidant function of the Hp 2-2 protein is impaired, we sought to test the pharmacogenomic hypothesis that antioxidant vitamin E supplementation would provide cardiovascular protection to Hp 2-2 DM individuals. MATERIALS & METHODS: We determined the Hp genotype on DM participants from two trials (HOPE and ICARE) and assessed the effect of vitamin E by Hp genotype on their common prespecified outcome, the composite of stroke, myocardial infarction and cardiovascular death. Data was analyzed with a fixed-effect model. These results were input into a simulation model, the Evidence Based Medicine Integrator, in order to estimate their long-term implications in a real-world population from Kaiser Permanente (CA, USA). RESULTS: Meta-analysis of the two trials demonstrated a significant overall reduction in the composite end point in Hp 2-2 DM individuals with vitamin E (odds ratio: 0.58; 95% CI: 0.40-0.86; p = 0.006). There was a statistically significant interaction between the Hp genotype and vitamin E on the composite end point. In these trials, Hp typing of 69 DM individuals and treating those with the Hp 2-2 with vitamin E prevented one myocardial infarct, stroke or cardiovascular death. Lifelong administration of vitamin E to Hp 2-2 DM individuals in the Kaiser population would increase their life expectancy by 3 years. CONCLUSION: A pharmacogenomic strategy of screening DM individuals for the Hp genotype and treating those with Hp 2-2 with vitamin E appears to be highly clinically effective.

Correction of HDL dysfunction in individuals with diabetes and the haptoglobin 2-2 genotype.

OBJECTIVE: Pharmacogenomics is a key component of personalized medicine. The Israel Cardiovascular Events Reduction with Vitamin E Study, a prospective placebo-controlled study, recently demonstrated that vitamin E could dramatically reduce CVD in individuals with diabetes and the haptoglobin (Hp) 2-2 genotype (40% of diabetic individuals). However, because of the large number of clinical trials that failed to demonstrate benefit from vitamin E coupled with the lack of a mechanistic explanation for why vitamin E should be beneficial only in diabetic individuals with the Hp 2-2 genotype, enthusiasm for this pharmacogenomic paradigm has been limited. In this study, we sought to provide such a mechanistic explanation based on the hypothesis that the Hp 2-2 genotype and diabetes interact to promote HDL oxidative modification and dysfunction. RESEARCH DESIGN AND METHODS: Hb and lipid peroxides were assessed in HDL isolated from diabetic individuals or mice with the Hp 1-1 or Hp 2-2 genotypes. HDL function was assessed based on its ability to promote cholesterol efflux from macrophages. A crossover placebo-controlled study in Hp 2-2 diabetic humans and in Hp 1-1 and Hp 2-2 diabetic mice assessed the ability of vitamin E to favorably modify these structural and functional parameters. RESULTS-Hb and lipid peroxides associated with HDL were increased and HDL function was impaired in Hp 2-2 diabetic individuals and mice. Vitamin E decreased oxidative modification of HDL and improved HDL function in Hp 2-2 diabetes but had no effect in Hp 1-1 diabetes. CONCLUSIONS: Vitamin E significantly improves the quality of HDL in Hp 2-2 diabetic individuals.