Diane M. Carpenter

Rates of autoimmune diseases in Kaiser Permanente for use in vaccine adverse event safety studies

Safety monitoring following new vaccine introduction includes assessment of potential new onset autoimmune diseases (AID). As knowledge regarding AID background rates is limited, we evaluated the incidence of 11 AID in Northern California Kaiser Permanente. AID cases were identified using electronic records of members aged 10-62 years from 1998 to 2004, excluding those with AID diagnoses from 1996 to 1997. Using prespecified criteria, all identified cases of rare diseases were verified by medical record review, while a sample of cases was reviewed for common diseases; incidence rates were calculated based on the proportion of confirmed cases. Overall, the incidence of AID varied from 0.8/100,000 person-years (PY) for autoimmune hemolytic anemia (AIHA) to 54.1/100,000 PY for thyroiditis. Incidence rates in increasing order were AIHA, juvenile rheumatoid arthritis, Guillain-Barre Syndrome, idiopathic thromobocytopenia purpura, transverse myelitis, systemic lupus erythematosus, uveitis, multiple sclerosis, rheumatoid arthritis, Type 1 diabetes mellitus and thyroiditis; incidence rates also varied according to age and gender. These background incidence rates should prove useful for future observational vaccine safety studies and will help guide evaluation of potential vaccine AID events following introduction of new vaccines.

Perinatal substance abuse intervention in obstetric clinics decreases adverse neonatal outcomes.

OBJECTIVE: To evaluate the effect of Early Start, a managed care organizations obstetric clinic-based perinatal substance abuse treatment program, on neonatal outcomes.STUDY DESIGN: Study subjects were 6774 female Kaiser Permanente members who delivered babies between July 1, 1995 and June 30, 1998 and were screened by completing prenatal substance abuse screening questionnaires and urine toxicology screening tests. Four groups were compared: substance abusers screened, assessed, and treated by Early Start (“SAT,” n=782); substance abusers screened and assessed by Early Start who had no follow-up treatment (“SA,” n=348); substance abusers who were only screened (“S,” n=262); and controls who screened negative (“C,” n=5382).RESULTS: Infants of SAT women had assisted ventilation rates (1.5%) similar to control infants (1.4%), but lower than the SA (4.0%, p=0.01) and S groups (3.1%, p=0.12). Similar patterns were found for low birth weight and preterm delivery.CONCLUSION: Improved neonatal outcomes were found among babies whose mothers received substance abuse treatment integrated with prenatal care. The babies of SAT women did as well as control infants on rates of assisted ventilation, low birth weight, and preterm delivery. They had lower rates of these three neonatal outcomes than infants of either SA or S women.

Risk of rheumatoid arthritis following vaccination with tetanus, influenza and hepatitis B vaccines among persons 15–59 years of age

BACKGROUND Associations between vaccinations, particularly hepatitis B, and onset of rheumatoid arthritis (RA) have been reported, but examined in few large-scale studies. METHOD Onset of RA cases and dates of vaccination against hepatitis B, tetanus, and influenza were identified in a retrospective chart review of approximately 1 million Kaiser Permanente Northern California members ages 15-59 years from 1997 through 1999. In a cohort analysis, rates of new-onset RA were compared between vaccinated and unvaccinated within 90, 180, and 365 days. In a case-control analysis, rates of vaccination during exposure intervals (90, 180, 365, and 730 days) were compared between cases and controls using conditional logistic regression. RESULTS 378 RA cases were included in the cohort analysis; 37 additional cases were included in the case-control analysis. In the cohort analysis the relative risks of RA onset within 90, 180, or 365 days of hepatitis B vaccination were not significant (R.R.=1.44, p=0.53; R.R.=1.67, p=0.22; R.R.=1.23, p=0.59 respectively). We found a possible association between RA and influenza vaccine in the previous 180 and 365 days in the cohort analysis (R.R=1.36, p=0.03; R.R.=1.34, p=0.01 respectively), but in the case-control analysis, cases were no more likely than controls to have received any of the three vaccines. CONCLUSIONS In this large retrospective study we found no statistically significant association between exposure to hepatitis B vaccine and onset of RA. A possible association between RA and influenza vaccination in the cohort study was not borne out in the larger case-control analysis.

Elucidating Risk Factors for Androgen Deficiency Associated with Daily Opioid Use

BACKGROUND Opioids can suppress testosterone in men, which can lead to extensive morbidity. Identifying risk factors for androgen deficiency in men using daily opioids could improve monitoring and safety. METHODS In a retrospective cohort study, we used Kaiser Permanente Northern California databases to identify men on stable doses of opioids. These subjects had no diagnoses of cancer or endocrine disorders except treated primary hypothyroidism. Subjects were divided into those using long-acting opioids and short-acting opioids. Total testosterone was measured in blood drawn in the morning while the subjects were on their regular dose of opioid. The association between opioid duration of action and androgen deficiency, controlling for dose, body mass index, age, diabetes, hyperlipidemia, and hypertension, was assessed using logistic regression. RESULTS The study included 1585 men. Men on long-acting opioids were more likely to be androgen deficient than men on short-acting opioids (57% vs 35%, P < 0.001; odds ratio [OR] 3.39; 95% confidence interval [CI], 2.39-4.77). As dose increased, the odds of androgen deficiency increased; however, dose was more strongly associated with androgen deficiency in men on short-acting opioids (OR 1.16; 95% CI, 1.09-1.23, for each 10-mg increase in dose) than in men on long-acting opioids (OR 1.01; 95% CI, 1.01-1.02). CONCLUSION Use of long-acting opioids is a key risk factor in the development of androgen deficiency. Dose was significantly associated with androgen deficiency, but more so for men on short-acting than on long-acting opioids.

Skin Disorders Associated with Obesity in Children and Adolescents: A Population‐Based Study

Obesity in children is a major public health concern in the United States. The objectives of the current study were to determine the prevalence of various groups of cutaneous disorders in obese children and adolescents and to compare the use of dermatology services in obese subjects with that those with a normal body mass index (BMI). This was a retrospective, population‐based study at the Kaiser Permanente Northern California Managed Healthcare System. The main outcome measures were the relative risk of cutaneous disorders associated with insulin resistance, androgen excess, bacterial infection, fungal infection, viral infection, inflammation, mechanical changes, and other skin conditions (hidradenitis, hyperhidrosis) in three weight groups (normal, overweight, obese) and the number of dermatology visits. A total of 248,775 subjects were included. Bivariate analyses showed a higher proportion of insulin resistance disorders, bacterial infection, fungal infection, inflammatory disorders, mechanical changes, and other skin conditions in obese subjects than in subjects with a normal BMI (p < 0.001). Disorders of androgen excess and viral infection were significantly less common in obese subjects (p < 0.001). Obese subjects had significantly lower odds of having at least one dermatology encounter than subjects with a normal BMI (odds ratio = 0.92, 95% confidence interval 0.88, 0.96, p = 0.003). Early onset obesity is associated with cutaneous disorders characterized by hyperproliferation, inflammation, bacterial and fungal infection, and mechanical changes but lower rates of disorders of androgen excess and viral infection. The use of dermatology services was not greater in obese patients. Heightened recognition and further analysis of adipose tissue as an endocrine organ that is capable of affecting the skin is warranted.

Association Between Commonly Prescribed Opioids and Androgen Deficiency in Men: A Retrospective Cohort Analysis

Abstract Objective. Androgen deficiency is common among men who use opioids daily for chronic pain. In previous studies, we found that long-acting opioids are associated with greater odds of androgen suppression than equipotent doses of short-acting opioids. Here we examined whether specific commonly prescribed opioids were associated with greater odds of androgen deficiency compared to hydrocodone. Design. Retrospective cohort study. Setting and Patients. Within a large, integrated health care delivery system, this study was comprised of men ages 18–80 on a stable regimen of a single opioid for chronic non-cancer pain. Methods. Morning serum total testosterone levels were measured in subjects prescribed one opioid for at least 90 days. The association between individual opioids and androgen deficiency was assessed with logistic regression, controlling for dose, obesity, age, hypertension, hyperlipidemia, and diabetes, using hydrocodone as a referent. Results. This study included 1,159 men. Men on fentanyl (odds ratio [OR] 25.7, 95% CI 2.82–234.97), methadone (OR 7.33, 95% CI 3.29–16.33), or oxycodone (OR 3.15, 95% CI 1.87–5.33) were more likely to be androgen deficient than men on hydrocodone. Increases in dose affected the odds of androgen deficiency differently for different opioids. Increased doses of hydrocodone (OR 1.18 per 10-mg increase in drug, 95% CI 1.09–1.28) and oxycodone (OR 1.01, 95% CI 1.00–1.02) were associated with increased odds of androgen deficiency. Conclusions. Our results suggest that certain opioids are associated with increased odds of androgen deficiency compared with hydrocodone. Transdermal fentanyl, methadone and oxycodone were associated with higher odds of androgen deficiency than hydrocodone.

The impact of obesity on the folliculosebaceous unit

The impact of obesity on the folliculosebaceous unit To the Editor: Yang et al reported on the association of higher bodymass index (BMI)with greater severity of hair loss in 189 men with androgenetic alopecia (AGA). The explanation for this association is unclear, although products released from enlarged fat cells including peptide hormones and cytokines, among others, may lead to manifestations of metabolic syndrome, which is linked to AGA. In addition, other evidence suggests that enlarged fat cells influence the physiology of the folliculosebaceous unit. Hirsutism, which is excess terminal hair in areas where the hair is typically fine, is significantly correlated with BMI independent of age and testosterone level in adults. We recently reported on skin disorders associated with obesity in children and adolescents in a population-based cohort from Kaiser Permanente Northern California. We found that early onset obesity was associated with cutaneous disorders characterized by hyperproliferation, inflammation, bacterial and fungal infection, and mechanical changes. We present here the results of a subgroup analysis of our larger cohort. We hypothesized that early onset obesity might be associated with alterations of the folliculo-sebaceous unit manifested as hirsutism and alopecia. Briefly, subjects aged 5 to17 years with at least 1 recorded BMI value in 2009 were eligible. Diagnoses of inflammatory alopecia were excluded. Subjects were classified as normal BMI, overweight, and obese according to ageand sex-specific criteria established by the Centers for Disease Control and Prevention. A total of 248,775 subjects were included in the analysis. Alopecia was not significantly associated with BMI (normal BMI, 0.34%; overweight, 0.42%; obese, 0.42%; P 1⁄4 .085). However, rates of hirsutism were significantly higher in subjects who were overweight or obese than in those of normal weight (normal BMI, 0.06%; overweight, 0.15%; obese, 0.17%; P \ .0001). Among girls with diagnosed hirsutism, the rate of polycystic ovary syndrome (PCOS) was higher (31%) than in girls with diagnosed alopecia (PCOS prevalence 2.8%). Conversion of vellus or fine caliber hairs to thicker terminal hairs has been described to occur as a result of hormonal, androgen-mediated signals on the face, axilla, and chest, whereas these same androgen signals lead to miniaturization of the hair

Impact of Maternal Substance Abuse on Neonatal Assisted Ventilation

The purpose of this study was to assess the relationship between maternal drug use during pregnancy, which was identified by positive toxicology screening tests, and subsequent neonatal assisted ventilation. The study population consisted of 38,762 women and their babies who were born alive in 1995 or 1996 at 7 Northern California Kaiser Permanente hospitals with neonatal intensive care nurseries (NICUs). Data available on each mother-infant pair included demographics, toxicology screen results (including specific drugs for which each screen was positive), NICU admission status, and neonatal assisted ventilation use. Overall, 4.2% of mothers (n=1642) had at least one positive toxicology test during their pregnancy. Of the 11 drugs tested for, the following 5 were considered most harmful to the fetus and were used either singly or in combinations by 965 of the women who ever tested positive: alcohol (n=197 women ever tested positive, 0.5% of the total), amphetamines (n=161, 0.4%), methamphetamines (n=183, 0.5%), cocaine (n=91, 0.2%), and tetrahydrocannabinol (THC) (n=666, 1.7%). Women were counted once for each drug for which they ever tested positive. In this 2-year cohort, 2.7%(n=1034) of all babies required assisted ventilation. Significantly more babies of mothers ever found positive for any of the 5 most harmful drugs required assisted ventilation (5.4%) than those who did not test positive(2.6%; Chi square test, p=0.001). This finding was driven by the results for intermediate low birthweight babies between 1500 and 2499 grams, in which 26.3% of babies whose mothers tested positive for one of the 5 most harmful drugs required assisted ventilation compared to 13.2% of the babies whose mothers did not test positive for any of those drugs (p=0.001). These results suggest that babies of mothers who tested positive for alcohol, amphetamines, methamphetamines, cocaine or THC during pregnancy are significantly more likely to require assisted ventilation than babies of mothers who do not test positive for those drugs, particularly in the intermediate low birthweight category. The morbidity experienced by these babies and the costs of associated neonatal services are enormous. Identifying drug-using women early in pregnancy and providing rehabilitation programs might lower morbidity and neonatal services costs considerably.