Improved real-world glycaemic outcomes with liraglutide versus other incretin-based therapies in type 2 diabetes.

AIM: Liraglutide (LIRA) once-daily has provided greater A1C reductions than either exenatide (EXEN) twice-daily or sitagliptin (SITA) once-daily in head-to-head trials. The objective of this analysis is to compare the real-world clinical effectiveness of these agents in the USA. METHODS: Using the IMS Health (Alexandria, VA, USA) integrated claims database, A1C outcomes in patients aged ≥ 18 years with type 2 diabetes (T2D) who initiated either LIRA, EXEN or SITA (including SITA/metformin) were retrospectively compared. Patients included in the analysis had ≥ 1 prescription for LIRA, EXEN or SITA between January and December 2010 (index period) and persisted with their index treatment regimens for 6 months post-index. Outcomes included changes in A1C from baseline (45 days pre-index through 7 days post-index) to follow-up [6 months post-index (± 45)] and the proportion of patients reaching A1C<7%. Multivariable regression models adjusted for confounding factors (e.g. age, comorbidities, baseline A1C and background antidiabetic therapy). RESULTS: The predicted change in A1C from baseline was greater for LIRA patients compared with both SITA (-1.08 vs. -0.68%; treatment difference 0.40%, p < 0.0001) and EXEN (-1.08 vs. -0.75%; treatment difference 0.32%, p < 0.001). Predicted A1C goal achievement, derived from the multivariate logistic regression model, was higher with LIRA compared with both SITA [64.4% (95% confidence interval, CI: 63.5-65.3) vs. 49.4% (95% CI: 48.5-50.4); p < 0.0001] and EXEN [64.4% (95% CI: 63.5-65.3) vs. 53.6% (95% CI: 52.6-54.6); p < 0.0001]. CONCLUSIONS: In clinical practice, LIRA was associated with significantly greater reductions in A1C and improved glycaemic goal attainment compared with either EXEN or SITA among adult patients with T2D.

In vivo tyrosine hydroxylation in rat retina: effect of aspartame ingestion in rats pretreated with p-chlorophenylalanine.

Rats were pretreated with p-chlorophenylalanine (PCPA) to inhibit hepatic phenylalanine hydroxylase. Two days later, oral aspartame (APM; aspartylphenylalanine methylester) administration substantially increased serum phenylalanine (Phe) concentrations and the ratio, in serum, of Phe to the sum of its competitors for transport into brain and retina (the other large neutral amino acids). Smaller changes occurred in serum tyrosine (Tyr) concentrations and in the ratio, in serum, of Tyr to the sum of its competitors. P-chlorophenylalanine-pretreated rats showed normal increases in retinal Tyr hydroxylation rate after Tyr injection, indicating that the enzyme was functionally normal. APM (0, 500, 1000, 1500 mg/kg body wt) intubation of PCPA-pretreated rats produced a dose-related increment in retinal Phe concentrations (up to six times normal values), no changes in retinal Tyr concentration, and no changes in retinal Tyr hydroxylation rate. The results thus indicate that very large increments in retinal Phe concentrations produced by enormous doses of APM do not modify Tyr hydroxylation in vivo.

Assessing immunization performance of private practitioners in Maine: impact of the assessment, feedback, incentives, and exchange strategy.

INTRODUCTION: A provider-based vaccination strategy that has strong supportive evidence of efficacy at raising immunization coverage level is known as Assessment, Feedback, Incentives, and Exchange. The Maine Immunization Program, and the Maine Chapter of the American Academy of Pediatrics collaborated on the implementation and evaluation of this strategy among private providers. METHODS: Between November 1994 and June 1996, the Maine Immunization Program conducted baseline immunization assessments of all private practices administering childhood vaccines to children 24 to 35 months of age. Coverage level assessments were conducted using the Clinic Assessment Software Application. Follow-up assessments were among the largest practices, delivering 80% of all vaccines. RESULTS: Of the 231 practices, 58 were pediatric and 149 were family practices. The median up-to-date vaccination coverages among all providers for 3 doses of diphtheria-tetanus-pertussis vaccine and 2 doses of oral polio vaccine, and 4 doses of diphtheria-tetanus-pertussis vaccine, 3 doses of oral polio vaccine, and 1 dose of measles-mumps-rubella vaccine at age 12 and 24 months were 90% and 78%, respectively, and did not vary by number of providers in a practice or by specialty. Urban practices had higher coverage than rural practices at 12 months (92% vs 88%). The median up-to-date coverage for 4 doses of diphtheria-tetanus-pertussis vaccine, 3 doses of oral polio vaccine, and 1 dose of measles-mumps-rubella vaccine at 24 months of age improved significantly among those practices assessed 1 year later (from 78% at baseline to 87% at the second assessment). On average, the assessments required 21/2 person-days of effort. CONCLUSIONS: We document the feasibility and impact of a public/private partnership to improve immunization delivery on a statewide basis. IMPLICATIONS: Other states should consider using public/private partnerships to conduct private practice assessments. More cost-effective methods of assessing immunization coverage levels in private practices are needed.

Prevalence of thyroid antibodies among healthy middle-aged women. Findings from the thyroid study in healthy women.

Autoimmune thyroiditis is the most common cause of subclinical hypothyroidism in North America, is more common in women than men, and is a risk factor for the development of coronary heart disease (CHD). We measured thyroid-stimulating hormone (TSH) and two thyroid antibodies, thyroid peroxidase and thyroglobulin, in stored sera of the participants (aged 44 to 54 years) of the Healthy Women Study. We selected 254 samples from the premenopausal baseline examination in 1983 to 1985 and from a follow-up examination that occurred an average of 5.7 years later (range, 3 to 7.7 years). At follow-up, 95 women remained premenopausal, 98 had ceased menstruating for at least 12 months, and 61 were taking postmenopausal hormone therapy. Overall, the prevalence of the thyroid antibodies in this healthy population was high at both time points (21 to 26%). Women with antibodies had higher TSH concentrations than did those with no antibodies (2.68 +/- 1.3 versus 1.51 +/- .73 mU/L, P < 0.001); this relationship was statistically significant even after excluding those with subclinical hypothyroidism (TSH > 6.0 mU/L). TSH and antibody levels did not differ by menopausal status or hormone therapy use at follow-up. Given the high prevalence of thyroid antibodies among healthy middle-aged women, long-term follow-up is warranted to ascertain whether the presence of antibodies is associated with subsequent excess risk of disease, in particular, CHD.

The status of immunization measurement and feedback in the United States.

BACKGROUND: A large body of scientific and programmatic data has demonstrated that provider measurement and feedback raises immunization coverage. Starting in 1995, Congress required that all states measure childhood immunization coverage in all public clinics, and federal grant guidelines encourage private practice measurements. OBJECTIVES: To determine state immunization measurement rates and examine risk factors for high rates. METHODS: Review of 1997 state reports, with correlation of measurement rates to birth cohort and provider numbers, public/private proportions, and vaccine distribution systems. RESULTS: Of the 9505 public clinics, 48% were measured; 4 states measured all clinics; 29 measured a majority. Measurement rates were highest for Health Department clinics (67%), lower for community/migrant health centers (39%), and lowest for other clinics (22%). Rates were highly correlated among categories of clinics (r>+0.308, P<.03), and the fewer the clinics, the higher the measurement rates (r = -0.351, P =. 01), but other factors were not significant. Of the 41,378 private practices, 6% were measured; no state measured all its practices; 1 measured a majority. Private practice measurement rates were not correlated to public clinic measurement rates or other factors examined. Of the 50,883 total providers, 14% were measured; no state measured all providers; 2 measured a majority. A trend toward higher measurement rates was found in states with fewer providers (r = -0. 266, P =.06). CONCLUSIONS: Three years after the congressional mandate, only a minority of public clinics and very few private practices had their immunization coverage measured. Greater efforts will be needed to assure implementation of the intervention. Arch Pediatr Adolesc Med. 2000;154:832-836

Changes in clinic vaccination coverage after institution of measurement and feedback in 4 states and 2 cities.

BACKGROUND: Since 1995, states and jurisdictions receiving federal immunization funds have been required to perform annual measurements of vaccination coverage in their public clinics, based on data from Georgia where clinic coverage increased after the institution of a measurement and feedback intervention. OBJECTIVE: To determine if clinic vaccination coverage improved in localities that used the Georgia intervention model. DESIGN: Retrospective examination of clinic vaccination coverage data. PARTICIPANTS: Children aged 19 to 35 months enrolled in clinics in localities that had applied the intervention for 4 years or longer. INTERVENTION: The Georgia intervention model: assessment of clinic vaccination coverage, feedback of the information to the clinic, incentives to clinics, and promotion of exchange of information among clinics (AFIX). MAIN OUTCOME MEASURE: Change in median clinic coverage rates, based on the primary (4-3-1) vaccine series, with comparison to results of the National Immunization Survey. RESULTS: Four states and 2 cities that had applied the AFIX intervention for 4 years or longer were identified. The number of clinic records reviewed annually was 4639 to 18000 in 73 to 116 clinics for states, and 714 to 5276 in 8 to 25 clinics for cities. Median clinic coverage rose in all localities: Missouri, 44% (1992) to 93% (1997); Louisiana, 61% (1992) to 83% (1997); Colorado, 55% (1993) to 75% (1997); Iowa, 71% (1994) to 89% (1997); Boston, Mass, 41% (1994) to 79% (1997); and Houston, Tex, 28% (1994) to 84% (1997). The increase in clinic coverage exceeded that of the general population in 5 localities and was identical in the sixth. The average annual coverage rise attributable to the intervention was +5 percentage points per year (Georgia, +6 per year). The average crude direct program cost was $49533 per locality per year. CONCLUSION: The Georgia intervention model (AFIX) can be reproduced elsewhere and is associated with improvements in clinic vaccination coverage.

Effect of 8-hydroxy-2-(di-n-propylamino)-tetralin on the tryptophan-induced increase in 5-hydroxytryptophan accumulation in rat brain.

The injection of 8-hydroxy-2-(di-n-propylamino)-tetralin [8-OH-DPAT]reduced 5-hydroxytryptophan accumulation in vivo in rat cerebral cortex, hypothalamus and brainstem. Brain tryptophan levels were unaffected. Dose-related increases in 5-hydroxytryptophan accumulation produced by single injections of L-tryptophan (0, 25, 75 mg/kg ip) were substantially diminished by pretreatment with 8-OH-DPAT. The drug did not affect the tryptophan-induced increments in brain tryptophan level. Since 8-OH-DPAT is known to reduce the activity of serotonin neurons in vivo, these results suggest that when serotonin neurons are relatively inactive, the ability of an injection of tryptophan to stimulate serotonin synthesis is greatly attenuated.

Persistently low natural killer cell activity and circulating levels of plasma beta endorphin: risk factors for infectious disease.

Beta endorphin levels were quantitated in plasma samples obtained from normal subjects (n = 81, 37% males and 63% females, age range 18-45 years) as a component of a prospective study examining the relationship of illness morbidity to natural killer cell activity and psychological indices of stress. The present study was designed to test whether beta endorphin levels contributed additionally to the explanation of illness outcome variance. In the larger study, persistently low NK (LNK) activity was associated prospectively with higher illness morbidity. The findings reported here suggest that the observed LNK activity might be affected by circulating levels of plasma beta endorphin, as lower endorphin levels predicted the LNK pattern, which in turn, predicted higher illness morbidity.

Evaluation of transthyretin as a monitor of protein-energy intake in preterm and sick neonatal infants.

In the past, weight and weight gain have been the two parameters used frequently in neonatal units to monitor nutrition among high-risk infants. Our investigation sought to assess how several anthropometric measures (weight, length, head circumference, arm:head circumference ratio, and tricep skinfold) and serum albumin, transthyretin, and transferrin concentrations reflect protein and energy intake. After monitoring 42 preterm and 40 sick infants over 3 consecutive weeks, we found that transthyretin concentration proved the only serum protein which accurately measured energy and protein intakes in less than 1 week from dietary manipulation. Among preterm infants, as protein and energy intakes rose, transthyretin concentration increased significantly (p less than 0.001). Preterm infants ingested 79 +/- 39 kcal/kg/day and 2.04 +/- 1.02 g protein/kg/day at the first assessment point after birth and rose to 103 +/- 34 kcal/kg/day and 2.64 +/- 0.94 g protein/kg/day. Likewise, transthyretin measured 10.83 +/- 3.91 mg/dl at the initial measurement and rose to 14.80 +/- 4.44 at the second measurement time. Although protein intakes measured slightly lower in the sick group, their intakes correlated to transthyretin concentration (assessment time 1, r = 0.39; time 2, r = 0.33; time 3, r = 0.33). Thus, transthyretin concentration in neonatal infants offers a rapid, accurate, and moderately inexpensive way to monitor protein-energy adequacy.

An outbreak of hepatitis A associated with an infected foodhandler.

OBJECTIVE: The recommended criteria for public notification of a hepatitis A virus (HAV)-infected foodhandler include assessment of the foodhandler's hygiene and symptoms. In October 1994, a Kentucky health department received a report of a catering company foodhandler with hepatitis A. Patrons were not offered immune globulin because the foodhandler's hygiene was assessed to be good and he denied having diarrhea. During early November, 29 cases of hepatitis A were reported among people who had attended an event catered by this company. Two local health departments and the Centers for Disease Control and Prevention, in collaboration with two state health departments, undertook an investigation to determine the extent of the outbreak, to identify the foods and event characteristics associated with illness, and to investigate the apparent failure of the criteria for determining when immune globulin (IG) should be offered to exposed members of the public. METHODS: Cases were IgM anti-HAV-positive people with onset of symptoms during October or November who had eaten foods prepared by the catering company. To determine the outbreak's extent and factors associated with illness, the authors interviewed all case patients and the infected foodhandler and collected information on menus and other event characteristics. To investigate characteristics of events associated with transmission, the authors conducted a retrospective analysis comparing the risk of illness by selected event characteristics. To evaluate what foods were associated with illness, they conducted a retrospective cohort study of attendees of four events with high attack rates. RESULTS: A total of 91 cases were identified. At least one case was reported from 21 (51%) of the 41 catered events. The overall attack rate was 7% among the 1318 people who attended these events (range 0 to 75% per event). Attending an event at which there was no on-site sink (relative risk [RR] = 2.3, 95% confidence interval [CI] 1.4, 3.8) or no on-site kitchen (RR = 1.9, 95% Cl 1.1, 2.9) was associated with illness. For three events with high attack rates, eating at least one of several uncooked foods was associated with illness, with RRs ranging from 8 to undefined. CONCLUSION: A large hepatitis A outbreak resulted from an infected foodhandler with apparent good hygiene and no reported diarrhea who prepared many uncooked foods served at catered events. Assessing hygiene and symptoms s subjective, and may be difficult to accomplish. The effectiveness of the recommended criteria for determining when IG should be provided to exposed members of the public needs to be evaluated.

Analysis of southern Ontario Actinobacillus (Haemophilus) pleuropneumoniae isolates by restriction endonuclease fingerprinting.

Isolates of Actinobacillus (Haemophilus) pleuropheumoniae were studied by restriction endonuclease fingerprinting (REF) analysis using the enzymes BamHI and HindIII. Restriction fragments were resolved by polyacrylamide gel electrophoresis and visualized by silver staining. Except for serotypes 1 and 9, reference strains of A. pleuropneumoniae serotypes 1 to 10 had clearly distinguishable REF profiles. Analysis of REF profiles of southern Ontario field isolates revealed limited heterogeneity amongst isolates of serotype 1 or serotype 5. The REF profiles of the serotype 7 isolates studied showed greater variation. Heterogeneity could not be correlated with the presence of plasmids nor with antibiotic resistance. Limited heterogeneity could also be detected amongst REF profiles of A. pleuropneumoniae isolates recovered from a closed herd suggesting that there is a small amount of genetic variation within clonal populations.

Missed opportunities to improve immunization status among high-risk children in the WIC program.

An investigation of a recent pertussis outbreak in Idaho showed that WIC participants were less well immunized than non-WIC participants. Conducting immunization status assessment and referral to a provider for vaccination (A/R) in WIC has been shown to significantly improve immunization. WIC files were abstracted to obtain immunization and visit histories. More frequent A/R at WIC has potential to improve the immunization status of preschool age WIC participants.

Vaccination coverage and physician distribution in the United States, 1997.

BACKGROUND: How many physicians are needed in the United States and how they should be allocated geographically and among specialties has been the subject of intense debate, a debate that has often focused more on costs to third-party payers and government than on benefits to health. Child health is a central aspect of public health, and immunization is one of its most cost-effective and easily measured interventions. OBJECTIVE: To examine the association of immunization rates and delivery characteristics with the distribution of child health physicians in the United States in 1997. DESIGN: Cross-sectional ecological study, using the state as the unit of analysis, immunization rates and delivery characteristics (from the National Immunization Survey) as the main outcome measures, concentration of the principal physician specialties providing routine care to children (pediatric, family, and general physicians from the American Medical Association Masterfile) as the main risk factor, while controlling for demographic and economic factors (from the Bureau of the Census and other sources). RESULTS: Of the 96 689 physicians providing routine care to children, 37% were pediatric, 49% family, and 14% general physicians. Higher rates of vaccination, private sector vaccination, and increased numbers of public and private vaccination sites were all associated with the concentration of pediatricians but not of family or general physicians. The distribution of pediatricians was strongly associated with the distribution of residency positions. CONCLUSIONS: Pediatrician distribution is a strong correlate to immunization rates and delivery characteristics. Opportunities to affect pediatrician distribution may exist with allocation of residency positions.

Thermogenic drugs for the treatment of obesity: screening using obese rats and mice.

The thermogenic activity of ephedrine, ethinyloestradiol and triiodothyronine were compared by incorporating the drugs into the diets fed to groups of adult rats and mice. The animals used were normal lean mice, hypothalamic obese mice, dietary-induced obese mice and rats, and genetically obese mice and rats. Food intake and body weight were monitored throughout and oxygen consumption measurements were made. Finally, the animals were killed and their carcasses analysed. Generally, ethinyloestradiol reduced body weight by causing anorexia. Triiodothyronine increased oxygen consumption but also increased food intake such that in most cases body weight did not change; it killed the genetically obese animals, but reduced fat in the hypothalamic and dietary induced obese animals. The animals treated with ephedrine lost body weight and body fat without increasing food intake, and had elevated oxygen consumptions. This experiment not only demonstrated marked differences between the various laboratory animal models of obesity, but also that ephedrine is a potential slimming agent. It is relatively safe and has been used by us to obtain successful breeding using the genetically obese male animals which are normally sterile.

Exposure to protein aeroallergens in egg processing facilities.

Proteinaceous materials in the air can be highly allergenic and result in a range of immunologically mediated respiratory effects, including asthma. We report on the largest evaluation of exposure to date of airborne egg protein concentrations in an egg breaking and processing plant that had cases of occupational asthma. Personal air samples for egg protein were analyzed in duplicate on each PTFE filter using two analytical methods: (1) a commercial assay for non-specific total protein, and (2) indirect competitive inhibition assay using an ELISA method to quantify specific egg protein components. The highest concentrations were found in the egg washing room (mean exposure 644 microg/m3) and breaking room (255 microg/m3), which were also the areas where the risk of being sensitized was the greatest. There was excellent quantitative agreement between the airborne concentrations of total protein and sum of the specific protein antigens (ovalbumin, ovomucoid, and lysozyme). The correlation coefficient of the log-transformed data from the two methods was 0.88 (p < 0.0001). Size-selective sampling also indicated that most of the aerosol was capable of reaching the small airways. The methods described can be utilized to evaluate employee exposure to egg proteins. Exposure documentation, coupled with recommended exposure reduction strategies, could facilitate prevention of future employee sensitization and allergic respiratory responses by identifying high-exposure jobs and evaluating control measures.

Thyroid function and perimenopausal lipid and weight changes: the Thyroid Study in Healthy Women (TSH-W).

We designed a prospective observational trial to study the relationship of thyroid function to cholesterol and weight changes at menopause. Subjects were participants in the ongoing Healthy Women Study, a prospective study of cardiovascular risk factor change through menopause. Healthy premenopausal women were recruited from a random sample of licensed drivers in selected ZIP codes of Allegheny County, Pennsylvania. Participants had to be 42-50 years of age, have menstruated within the last 3 months, not have had surgical menopause, have diastolic blood pressure < 100 mm Hg, and not be taking medications (including insulin, estrogen, lipid-lowering drugs, or thyroid or antihypertensive medications) at the baseline examination. The substudy included three groups of women who were premenopausal at baseline and were categorized according to change noted at follow-up regarding menopausal status and use of hormone replacement therapy (HRT). The groups comprised 95 women who remained premenopausal, 96 postmenopausal women not on HRT, and 61 postmenopausal women using HRT. The main outcome measures were baseline and follow-up measurements for serum levels of thyroid-stimulating hormone (TSH), thyroid peroxidase, and thyroglobulin, as well as serum cholesterol, total high-density lipoprotein (HDL) cholesterol, triglycerides, and calculated low-density lipoprotein (LDL) cholesterol, height, and weight. Covariates included cigarette smoking and alcohol intake. The prevalence of thyroid antibodies in this healthy population was high at both time points (range 27%-31%) and did not differ by menopausal status. The presence of thyroid antibodies was associated with increased TSH concentration. Women with antibodies at both time points had lower levels of total and LDL cholesterol compared with those with no antibodies, significant only for those women who remained premenopausal during the follow-up period. Thyroid function during menopause in this healthy population is unlikely to account for the observed changes in levels of serum lipoprotein and body weight. The presence of thyroid antibodies may be associated with lower total and LDL cholesterol, possibly through an underlying inflammatory disorder.

Intussusception among infants given an oral rotavirus vaccine.

BACKGROUND: Intussusception is a form of intestinal obstruction in which a segment of the bowel prolapses into a more distal segment. Our investigation began on May 27, 1999, after nine cases of infants who had intussusception after receiving the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) were reported to the Vaccine Adverse Event Reporting System. METHODS: In 19 states, we assessed the potential association between RRV-TV and intussusception among infants at least 1 but less than 12 months old. Infants hospitalized between November 1, 1998, and June 30, 1999, were identified by systematic reviews of medical and radiologic records. Each infant with intussusception was matched according to age with four healthy control infants who had been born at the same hospital as the infant with intussusception. Information on vaccinations was verified by the provider. RESULTS: Data were analyzed for 429 infants with intussusception and 1763 matched controls in a case-control analysis as well as for 432 infants with intussusception in a case-series analysis. Seventy-four of the 429 infants with intussusception (17.2 percent) and 226 of the 1763 controls (12.8 percent) had received RRV-TV (P=0.02). An increased risk of intussusception 3 to 14 days after the first dose of RRV-TV was found in the case-control analysis (adjusted odds ratio, 21.7; 95 percent confidence interval, 9.6 to 48.9). In the case-series analysis, the incidence-rate ratio was 29.4 (95 percent confidence interval, 16.1 to 53.6) for days 3 through 14 after a first dose. There was also an increase in the risk of intussusception after the second dose of the vaccine, but it was smaller than the increase in risk after the first dose. Assuming full implementation of a national program of vaccination with RRV-TV, we estimated that 1 case of intussusception attributable to the vaccine would occur for every 4670 to 9474 infants vaccinated. CONCLUSIONS: The strong association between vaccination with RRV-TV and intussusception among otherwise healthy infants supports the existence of a causal relation. Rotavirus vaccines with an improved safety profile are urgently needed.