Sex dependent influence of a functional polymorphism in steroid 5‐α‐reductase type 2 (SRD5A2) on post‐traumatic stress symptoms

A non‐synonymous, single nucleotide polymorphism (SNP) in the gene coding for steroid 5‐α‐reductase type 2 (SRD5A2) is associated with reduced conversion of testosterone to dihydrotestosterone (DHT). Because SRD5A2 participates in the regulation of testosterone and cortisol metabolism, hormones shown to be dysregulated in patients with PTSD, we examined whether the V89L variant (rs523349) influences risk for post‐traumatic stress disorder (PTSD). Study participants (N = 1,443) were traumatized African‐American patients of low socioeconomic status with high rates of lifetime trauma exposure recruited from the primary care clinics of a large, urban hospital. PTSD symptoms were measured with the post‐traumatic stress symptom scale (PSS). Subjects were genotyped for the V89L variant (rs523349) of SRD5A2. We initially found a significant sex‐dependent effect of genotype in male but not female subjects on symptoms. Associations with PTSD symptoms were confirmed using a separate internal replication sample with identical methods of data analysis, followed by pooled analysis of the combined samples (N = 1,443, sex × genotype interaction P < 0.002; males: n = 536, P < 0.001). These data support the hypothesis that functional variation within SRD5A2 influences, in a sex‐specific way, the severity of post‐traumatic stress symptoms and risk for diagnosis of PTSD. © 2013 Wiley Periodicals, Inc.     

Gluten-free diet does not appear to induce endoscopic remission of eosinophilic esophagitis in children with coexistent celiac disease

BACKGROUND:

Celiac disease and eosinophilic esophagitis are usually considered to be separate gastrointestinal diseases; however, it appears that they may coexist more often than would be expected. It is unknown whether eosinophilic esophagitis in patients with celiac disease responds to a gluten-free diet.

OBJEVTIVES:

To examine the clinical, endoscopic and histological features of children with both conditions to evaluate whether eosinophilic esophagitis responds to a gluten-free diet.

METHODS:

From January 1, 2009, to June 30, 2011, the medical records of children <18 years of age diagnosed with eosinophilic esophagitis and/or celiac disease were reviewed. Patients with clinical, endoscopic and histological diagnoses of both diseases were identified and included. These findings were analyzed, as were laboratory results, treatment and follow-up.

RESULTS:

During the study period, there were 206 celiac disease patients, 86 eosinophilic esophagitis patients and nine (4.4% of total celiac) patients with both diagnoses. Gluten-free diet was the primary treatment for both conditions in seven of nine (78%) cases. In six of these seven (86%) patients, no endoscopic or histological improvement of eosinophilic esophagitis was observed, while in one patient, histological remission of esophageal eosinophilia occurred while on a gluten-free diet.

CONCLUSION:

The prevalence of eosinophilic esophagitis in patients with celiac disease was 4.4%, confirming a higher than expected prevalence of eosinophilic esophagitis compared with the general population. In patients with celiac disease, a gluten-free diet did not appear to induce remission of coexistent endoscopic and histological features of eosinophilic esophagitis.     

Randomized controlled trial of health maintenance reminders provided directly to patients through an electronic PHR

BACKGROUND

Provider and patient reminders can be effective in increasing rates of preventive screenings and vaccinations. However, the effect of patient-directed electronic reminders is understudied.

OBJECTIVE

To determine whether providing reminders directly to patients via an electronic Personal Health Record (PHR) improved adherence to care recommendations.

DESIGN

We conducted a cluster randomized trial without blinding from 2005 to 2007 at 11 primary care practices in the Partners HealthCare system.

PARTICIPANTS

A total of 21,533 patients with access to a PHR were invited to the study, and 3,979 (18.5%) consented to enroll.

INTERVENTIONS

Patients in the intervention arm received health maintenance (HM) reminders via a secure PHR “eJournal,” which allowed them to review and update HM and family history information. Patients in the active control arm received access to an eJournal that allowed them to input and review information related to medications, allergies and diabetes management.

MAIN MEASURES

The primary outcome measure was adherence to guideline-based care recommendations.

KEY RESULTS

Intention-to-treat analysis showed that patients in the intervention arm were significantly more likely to receive mammography (48.6% vs 29.5%, p = 0.006) and influenza vaccinations (22.0% vs 14.0%, p = 0.018). No significant improvement was observed in rates of other screenings. Although Pap smear completion rates were higher in the intervention arm (41.0% vs 10.4%, p < 0.001), this finding was no longer significant after excluding women’s health clinics. Additional on-treatment analysis showed significant increases in mammography (p = 0.019) and influenza vaccination (p = 0.015) for intervention arm patients who opened an eJournal compared to control arm patients, but no differences for any measure among patients who did not open an eJournal.

CONCLUSIONS

Providing patients with HM reminders via a PHR may be effective in improving some elements of preventive care.

Electronic supplementary material

The online version of this article (doi:10.1007/s11606-011-1859-6) contains supplementary material, which is available to authorized users.KEY WORDS: health maintenance reminders, personal health record, preventive care, clinical decision support, Patient Gateway     

The efficacy and tolerability of MK-0633, a 5-lipoxygenase inhibitor, in chronic asthma

Leukotriene B4 (LTB(4)) is a potent inflammatory mediator in asthma, and is increased in more severe asthma. Targeting LTB(4), in addition to cysteinyl leukotrienes, could be beneficial in asthma. This was a randomized, double-blind trial of once-daily MK-0633, a potent 5-lypoxygenase inhibitor, 10?mg, 50?mg, and 100?mg, and placebo in patients 18-70 years with a history of chronic asthma, and FEV(1) ≥45 and ≤85% predicted. There was a 6-week main period and optional 18-week and 34-week periods (52 weeks total), the latter two comparing only MK-0633 100?mg and placebo. The primary endpoint was the change from baseline in FEV(1) over the last 4 weeks of the 6-week primary treatment period. Secondary endpoints included symptom scores, β-agonist use, peak expiratory flow (PEF), asthma quality of life questionnaire (AQLQ), asthma control questionnaire (ACQ), asthma attacks, exacerbations, days with asthma control, post-β-agonist FEV(1), and blood eosinophils. MK-0633 100?mg was significantly more effective than placebo for the change from baseline in FEV(1) (0.20?L vs. 0.13?L; p?=?0.004). The other MK-0633 doses were not significantly more effective than placebo. MK-0633 (at various doses) was also more effective than placebo for β-agonist use, AQLQ, AM and PM PEFR, ACQ, and post-β-agonist FEV(1) (p?相似文献   

A Binational Study of Patient-Initiated Changes to Antiretroviral Therapy Regimen Among HIV-positive Latinos Living in the Mexico–U.S. Border Region

Research is lacking on factors associated with antiretroviral therapy (ART) sub-optimal adherence among U.S. Latinos, who are disproportionately affected by HIV and face substantial health care barriers. We examined self-reported, patient-initiated changes to ART (i.e., made small/major changes from the antiretroviral drugs prescribed) among HIV-positive Latinos. Trained interviewers administered surveys to 230 participants currently on ART in San Diego, U.S. and Tijuana, Mexico. We identified factors independently associated with ART changes. Participants were Spanish-language dominant (86%), mean age of 41 years, male (77%), and born in Mexico (93%). Patient-initiated changes to ART were reported in 43% of participants. Being female, having ≥1 sexual partner (past 3 months), ≤6 years since HIV diagnosis and poor health were associated with increased odds of ART changes. Findings raise concern about sub-optimal adherence among this binational population. Longitudinal studies are needed to further explore adherence barriers and avenues for intervention.     

Glucocorticoid effects on changes in bone mineral density and cortical structure in childhood nephrotic syndrome

The impact of glucocorticoids (GC) on skeletal development has not been established. The objective of this study was to examine changes in volumetric bone mineral density (vBMD) and cortical structure over 1 year in childhood nephrotic syndrome (NS) and to identify associations with concurrent GC exposure and growth. Fifty‐six NS participants, aged 5 to 21 years, were enrolled a median of 4.3 (0.5 to 8.1) years after diagnosis. Tibia peripheral quantitative computed tomography (pQCT) scans were obtained at enrollment and 6 and 12 months later. Sex, race, and age‐specific Z‐scores were generated for trabecular vBMD (TrabBMD‐Z), cortical vBMD (CortBMD‐Z), and cortical area (CortArea‐Z) based on >650 reference participants. CortArea‐Z was further adjusted for tibia length‐for‐age Z‐score. Quasi‐least squares regression was used to identify determinants of changes in pQCT Z‐scores. At enrollment, mean TrabBMD‐Z (?0.54 ± 1.32) was significantly lower (p = 0.0001) and CortBMD‐Z (0.73 ± 1.16, p < 0.0001) and CortArea‐Z (0.27 ± 0.91, p = 0.03) significantly greater in NS versus reference participants, as previously described. Forty‐eight (86%) participants were treated with GC over the study interval (median dose 0.29 mg/kg/day). On average, TrabBMD‐Z and CortBMD‐Z did not change significantly over the study interval; however, CortArea‐Z decreased (p = 0.003). Greater GC dose (p < 0.001), lesser increases in tibia length (p < 0.001), and lesser increases in CortArea‐Z (p = 0.003) were independently associated with greater increases in CortBMD‐Z. Greater increases in tibia length were associated with greater declines in CortArea‐Z (p < 0.01); this association was absent in reference participants (interaction p < 0.02). In conclusion, GC therapy was associated with increases in CortBMD‐Z, potentially related to suppressed bone formation and greater secondary mineralization. Conversely, greater growth and expansion of CortArea‐Z (ie, new bone formation) were associated with declines in CortBMD‐Z. Greater linear growth was associated with impaired expansion of cortical area in NS. Studies are needed to determine the fracture implications of these findings. © 2013 American Society for Bone and Mineral Research.     

Discordance Between Patient and Surgeon Satisfaction After Total Joint Arthroplasty

We surveyed 331 patients undergoing total hip or knee arthroplasty pre-operatively, and patients and surgeons were both surveyed 6 and 12 months post-operatively. We identified variables (demographic factors, operative factors and patient expectations) as possible predictors for discordance in patient–surgeon satisfaction. At 12 months, 94.5% of surgeons and 90.3% of patients recorded satisfaction with the outcome. The discordance between patient and surgeon satisfaction was mainly due to patient dissatisfaction–surgeon satisfaction. In an adjusted analysis, the strongest predictors of discordance in patient–surgeon satisfaction were unmet patient expectations and the presence of complications. Advice to potential joint arthroplasty candidates regarding the decision to proceed with surgery should be informed by patient reported outcomes, rather than the surgeon's opinion of the likelihood of success.