RESULTS OF PROPHYLACTIC VACCINATION AGAINST PNEUMONIA AT CAMP WHEELER

1. 13,460 men, or about 80 per cent of the entire camp strength, were vaccinated against pneumonia with pneumococcus lipovaccine. 2. The dosage employed in all cases was 1 cc. of the lipovaccine containing approximately 10 billion each of Pneumococcus Types I, II, and III. 3. Both the local and general reactions produced by the vaccine were usually mild. Only 0.7 per cent of those who received the vaccine were sufficiently affected to need hospital care. None of these was seriously ill, and a majority of them returned to duty on the 2nd or 3rd day after admission. 4. Most of the troops inoculated were under observation for 2 or 3 months after vaccination. During this period there were 32 cases of Pneumococcus Type I, II, and III pneumonia among the vaccinated four-fifths of camp, and 42 cases of pneumonia of these types among the unvaccinated one-fifth of camp. If, however, all cases of pneumonia that developed within 1 week after vaccination are excluded from the vaccinated group, there remain only 8 cases of pneumonia produced by fixed types, and these were all secondary to severe attacks of influenza. This exclusion is justified by the fact that protective bodies do not begin to appear in the serum until the 8th day after injection of pneumococcus lipovaccine. 5. There is no evidence whatever that pneumococcus vaccine predisposes the individual even temporarily toward either pneumococcus or streptococcus pneumonia. 6. The weekly incidence rate for pneumonia (all types) among the vaccinated troops was conspicuously lower than that for the unvaccinated troops. 7. The pneumonia incidence rate per 1,000 men during the period of the experiment was twice as high for unvaccinated recruits as for vaccinated recruits, and nearly seven times as high for unvaccinated seasoned men as for vaccinated seasoned men. 8. Influenza causes a marked reduction in resistance to pneumonia even among vaccinated men. Of the 155 cases of pneumonia (all types) developing 1 week or more after vaccination, 133 were secondary to influenza. 9. The death rate for 155 cases of pneumonia (all types) that developed among vaccinated men 1 week or more after vaccination was only 12.2 per cent, whereas the death rate for 327 cases of all types that occurred among unvaccinated troops was 22.3 per cent. The death rate for primary pneumonia among vaccinated troops was 11.9 per cent. Among unvaccinated, it was 31.8 per cent, almost three times as great. On the other hand, the mortality rate in pneumonia secondary to influenza is about the same for the vaccinated and unvaccinated groups. 10. In conclusion, it must be admitted that the results of pneurnococcus vaccination at Camp Wheeler have not been so striking as those obtained at Camp Upton in 1918, largely on account of the influenza epidemic; but, although influenza obscured to some extent the effect of pneumococcus vaccination at Camp Wheeler, the results are sufficiently encouraging to justify its further application in civil as well as in military life.     

Progressively Reducing Regulatory Burden

Principles of dissolution science have been applied to allow waiver of in vivo bioequivalence studies for oral immediate release solid dosage forms, providing certain stipulations are met. This approach reduces regulatory burden without sacrificing product quality and performance requirements that assure continuing equivalence. These principles are broadly applicable to other dosage forms and routes of administration. In this article, we postulate a further opportunity, which relies on a determination of “optimal performance” for nonsolution orally administered drug products. The determination can be applied to certain highly soluble and rapidly dissolving drug products without further study, paving the way possibly for even further reductions in regulatory burden.     

Validation of an Event-Level,Male Sexual Pleasure Scale (EMSEXpleasure) Among Condom-Using Men in the U.S.

Sexual pleasure is a key determinant of condom use. We developed and validated a male, event-level sexual pleasure scale (EMSEXpleasure) among a sample of condom-using men in the U.S. in order to facilitate improved measurement of sexual pleasure. Based on an expert panel process, a 12-item scale was developed. An online sample of 169 men who have sex with men and 162 men who have sex with women were recruited. Factor analysis yielded a two-factor solution that matched domains identified a priori by the expert panel, general pleasure and condom-specific pleasure, indicating internal validity of the instrument. One item was deleted from the scale due to poor validity performance. The overall EMSEXpleasure scale, and each subscale, had high (> 0.8) Cronbach’s alpha coefficients, indicating internal reliability. The scale demonstrated convergent validity, with theoretically related constructs associated both with individual scale items and with scale totals. Overall relationship quality (b 3.0, 95% CI 2.0, 4.0), sexual relationship quality (b 2.9, 95% CI 2.0, 4.0), foreplay quality (b 7.5, 95% CI 2, 13), positive feelings about condoms (b 18.8, 95% CI 15, 23), and erection problems while using condoms (b ? 17.9, 95% CI ? 22, ? 14) were associated with the EMSEXpleasure scale in expected directions. The validated EMSEXpleasure event-level scale may be advantageous for future assessments of the ephemeral experience of sexual pleasure, including clinical trials of condoms and other interventions, because it can be used immediately after sex, potentially limiting recall error.     

Electronic Patient Registries Improve Diabetes Care and Clinical Outcomes in Rural Community Health Centers

ABSTRACT:  Context: Diabetes care is challenging in rural areas. Research has shown that the utilization of electronic patient registries improves care; however, improvements generally have been described in combination with other ongoing interventions. The level of basic registry utilization sufficient for positive change is unknown. Purpose: The goal of the current study was to examine differential effects of basic registry utilization on diabetes care processes and clinical outcomes according to level of registry use in a rural setting. Methods: Patients with diabetes (N = 661) from 6 Federally Qualified Health Centers in rural West Virginia were entered into an electronic patient registry. Data from pre- and post-registry were compared among 3 treatment and control groups that had different levels of registry utilization: low, medium, or high (for example, variations in the use of registry-generated progress notes examined at the point-of-care and in the accuracy of registry-generated summary reports to track patients' care). Data included care processes (annual exams, screens to promote wellness, education, and self-management goal-setting) and clinical outcomes (HbA1c, LDL, HDL, cholesterol, triglycerides, blood pressure). Findings: The registry assisted in significantly improving 12 of 13 care processes and 3 of 6 clinical outcomes (HbA1c, LDL, cholesterol) for patients exposed to at least medium levels of registry utilization, but not for the controls. For example, the percent of patients who had received an annual eye exam at follow-up was 11%, 34%, and 38% for the low, medium, and high utilization groups, respectively; only the latter groups improved. Conclusions: As an initial step to achieving control of diabetes, basic registry utilization may be sufficient to drive improvements in provider-patient care processes and in patient outcomes in rural clinics with few resources.     

Cardiovascular risk factors and hyperinsulinemia in elderly men: The Honolulu Heart Program

Associations of cardiovascular risk factors, including several measures of adiposity, with hyperinsulinemia were assessed in 3562 elderly (71 to 93 years of age) Japanese American men from the Honolulu Heart Program who were examined between 1991 and 1993. In addition, cardiovascular risk factors measured 25 years earlier were also examined in relation to hyperinsulinemia. Hyperinsulinemia was defined as fasting insulin 95th percentile (20 μU/mL) among the subset of subjects (n = 504) who were nonobese and free of clinical diabetes and glucose intolerance. When this definition was applied to the entire population, the prevalence of hyperinsulinemia declined cross-sectionally with age (P < 0.001) from 24.2% in men aged 71 to 74 years to 16.4% in men aged 85 to 93 years. Factors having a positive and independent association with hyperinsulinemia included body mass index (BMI), triglycerides, glucose, hematocrit, use of diabetic medication, heart rate, and hypertension. The association with physical activity was negative. Triglycerides, BMI, diabetic medication, hypertension, and smoking levels measured 25 years earlier were also associated independently with hyperinsulinemia. Associations were similar in nondiabetic subjects. Three measures of adiposity (BMI, waist circumference, and subscapular skinfold thickness) were independently related to hyperinsulinemia cross-sectionally. However, associations involving a difference between the 80th and 20th percentiles in each adiposity measure appeared strongest for BMI (odds ratio (OR) = 4.5, 95% confidence interval (CI) = 3.7 to 5.6) and waist circumference (OR = 4.1, 95% CI = 3.3–5.1) and slightly weaker for subscapular skinfold thickness (OR = 2.1, 95% CI = 1.8–2.5). These findings suggest that features of an insulin resistance syndrome including dyslipidemia, glucose intolerance, hypertension, and obesity, assessed both cross-sectionally and 25 years previously, are associated independently with hyperinsulinemia in elderly Japanese American men.     

Bacillus anthracis Protective Antigen Kinetics in Inhalation Spore-Challenged Untreated or Levofloxacin/Raxibacumab-Treated New Zealand White Rabbits

Inhaled Bacillus anthracis spores germinate and the subsequent vegetative growth results in bacteremia and toxin production. Anthrax toxin is tripartite: the lethal factor and edema factor are enzymatic moieties, while the protective antigen (PA) binds to cell receptors and the enzymatic moieties. Antibiotics can control B. anthracis bacteremia, whereas raxibacumab binds PA and blocks lethal toxin effects. This study assessed plasma PA kinetics in rabbits following an inhaled B. anthracis spore challenge. Additionally, at 84 h post-challenge, 42% of challenged rabbits that had survived were treated with either levofloxacin/placebo or levofloxacin/raxibacumab. The profiles were modeled using a modified Gompertz/second exponential growth phase model in untreated rabbits, with added monoexponential PA elimination in treated rabbits. Shorter survival times were related to a higher plateau and a faster increase in PA levels. PA elimination half-lives were 10 and 19 h for the levofloxacin/placebo and levofloxacin/raxibacumab groups, respectively, with the difference attributable to persistent circulating PA-raxibacumab complex. PA kinetics were similar between untreated and treated rabbits, with one exception: treated rabbits had a plateau phase nearly twice as long as that for untreated rabbits. Treated rabbits that succumbed to disease had higher plateau PA levels and shorter plateau duration than surviving treated rabbits.     

Is the Health Utilities Index responsive in total hip arthroplasty patients?

OBJECTIVE: The purpose is to examine the responsiveness of the Health Utilities Index Mark 2 (HUI2), Mark 3 (HUI3), and other generic and disease-specific measures in osteoarthritis patients undergoing total hip arthroplasty (THA). METHODS: Ninety patients (mean age=68.13; SD=8.15) on a waiting list for THA completed measures that included the standard gamble, HUI2, HUI3, SF-36, Harris Hip Scale, WOMAC, and MACTAR. before and after THA. Responsiveness statistics (effect size, standardized response mean, Guyatt's responsiveness statistic, paired-sample t-tests, and relative efficiency statistic) were calculated. RESULTS: The disease-specific measures were more responsive than the generic measures. Rankings of the degree of responsiveness varied depending on the responsiveness statistic used. CONCLUSIONS: Disease-specific measures are the most responsive in THA patients. However, the SF-36, HUI2, and HUI3 had summary scores and domain/attributes scores that were also responsive and provided additional information. Among the generic measures, HUI3 was the most responsive.     

Comparison of the safety and immunogenicity of concomitant and sequential administration of an adult formulation tetanus and diphtheria toxoids adsorbed combined with acellular pertussis (Tdap) vaccine and trivalent inactivated influenza vaccine in adults

The annual contact for influenza vaccination provides an opportunity to ensure that adults have received other recommended vaccines such as Tdap. Healthy 19-64 year-olds were randomized to receive concomitant administration of Tdap and influenza vaccines or influenza vaccine followed (in 4-6 weeks by) Tdap. 720 participants were enrolled. No clinically relevant between-group differences were observed in the rates or severities of erythema, swelling, or pain at the Tdap injection site. Injection-site pain was the most commonly reported adverse event (66.6% concomitant administration group versus 60.8% sequential administration group); most pain was graded as mild and resolved by day 3. Seroprotection and seroresponse rates for all influenza strains were comparable between the two groups. For diphtheria and tetanus, seroprotection rates and post-vaccination GMTs were non-inferior in the concomitant administration group compared to the sequential administration group. A trend for lower antibody responses to pertussis antigens PT, FHA, and FIM was observed after concomitant administration and, for PRN, this difference failed the non-inferiority criteria. While there is a small diminution in antibody response to tetanus and pertussis antigens, concomitant administration of Tdap and influenza vaccine was well tolerated and immunogenic and may offer practical advantages including convenience, compliance, and cost-savings.     

Predisposition to nephropathy in Polynesians is associated with family history of renal disease, not diabetes mellitus.

AIMS: Familial clustering of diabetes and nephropathy suggests that either common environmental or inherited mechanisms are important in developing diabetic nephropathy. If an inherited mechanism is important, the albumin excretion rate might be increased in those at future risk. This study aimed to determine whether people with a family history of diabetes or people with a family history of renal disease were most at risk. METHODS: In a two-by-two factorial study of urinary albumin in non-diabetic Polynesians, 90 people with a first degree relative (FDR) with end-stage renal failure (ESRF) and diabetes (group 1) were compared with 90 people with a FDR with non-diabetic ESRF (group 2), with 90 people with a FDR with diabetes but no known nephropathy (group 3) and 90 people with no known relatives with either diabetes or nephropathy (group 4). Groups were matched for ethnicity and age. RESULTS: Subjects with a family history of ESRF (groups 1 and 2) had an increased mean albumin-creatinine ratio (1.25 vs. 1.00 mg/mmol, P = 0.01), but in subjects with a family history of diabetes (groups 1 and 3), the mean ratios were not significantly different from those without a family history of diabetes (1.06 vs. 1.17 mg/mmol; P = 0.2). In those with a family history of nephropathy, fasting blood glucose and systolic blood pressure were increased, while fasting insulin and 2 h insulin concentrations were lower. A family history of diabetes was associated with an increased fasting blood glucose and 2-h blood glucose. By multiple linear regression, the mean systolic blood pressure (P = 0.02), the 2-h glucose concentration (P = 0.05), a family history of renal failure (P = 0.04), female sex (P = 0.0001) and the total cholesterol (P = 0.01) were each independently associated with microalbuminuria, while a family history of diabetes was not (P = 0.09). CONCLUSIONS: These data suggest that among Polynesians there is no specific inherited tendency to diabetic nephropathy per se. The risk of nephropathy does not appear to be associated with the degree of familial risk of diabetes itself. Rather, the risk of diabetic nephropathy may be the result of a familial risk of nephropathy from any cause and is associated with diabetes through relative hypoinsulinaemia and hyperglycaemia.