Comparison between prototype hybrid capture 3 and hybrid capture 2 human papillomavirus DNA assays for detection of high-grade cervical intraepithelial neoplasia and cancer

We compared the performance of a prototype version of the Hybrid Capture 3 (HC3) human papillomavirus (HPV) DNA assay to the current generation Hybrid Capture 2 (HC2) assay, both of which target 13 oncogenic HPV types, for the detection of cervical intraepithelial neoplasia grade 3 and cancer (CIN3+) with cervicovaginal lavage specimens collected at enrollment into a 10-year cohort study at Kaiser Permanente (Portland, Oreg.). HC3 results for a risk-stratified sample (n = 4,364) were compared to HC2 results for the entire cohort (n = 20,810) with receiver operating characteristics curves, and the optimal cut points for both tests (relative light units [RLU]/positive control [PC]) for the detection of CIN3+ were determined. Specimens were also tested for HPV16 and HPV18 with separate HC3 type-specific probes. The optimal cut point for detecting CIN3+ was 1.0 RLU/PC for HC2, as previously shown, and was 0.6 RLU/PC for HC3. At the optimal cut points, HC3 and HC2 had similar screening performance characteristics for CIN3+ diagnosed at the enrollment visit. In analyses that included cases CIN3+ at enrollment and those diagnosed during early follow-up, HC3 had nonsignificantly higher sensitivity and equal specificity for the detection of CIN3+ compared to HC2; this increase in sensitivity was primarily the result of increased detection of CIN3+ in women who were 30 years of age or older and were cytologically negative (P = 0.006). We also compared the performance of the hybrid capture tests to MY09/11 L1 consensus primer PCR results (n = 1,247). HC3 was less likely than HC2 to test positive for specimens that tested positive by PCR for any untargeted types (P < 0.001). HC3 was less likely than HC2 to test positive for untargeted PCR-detected single infections with HPV53 (P = 0.001) and HPV66 (P = 0.01). There was good agreement between test positivity by PCR and by single type-specific HC3 probes for HPV16 (kappa = 0.76; 95% confidence interval [CI] = 0.71 to 0.82) and for HPV18 (kappa = 0.73; 95% CI = 0.68 to 0.79). In conclusion, we suggest that HC3 (>/=0.6 RLU/PC) may be slightly more sensitive than and equally specific test as HC2 (>/=1.0 RLU/PC) for the detection of CIN3+ over the duration of typical screening intervals.     

A framework for improving the quality of cancer care: the case of breast and cervical cancer screening.

This commentary presents a conceptual framework, Quality in the Continuum of Cancer Care (QCCC), for quality improvement studies and research. Data sources include review of relevant literature (cancer care, quality improvement, organizational behavior, health services evaluation, and research). The Detecting Early Tumors Enables Cancer Therapy (DETECT) project is used to apply the QCCC model to evaluate the quality of secondary prevention. Cancer care includes risk assessment, primary prevention, screening, detection, diagnosis, treatment, recurrence surveillance, and end-of-life care. The QCCC model represents a systematic approach for assessing factors that influence types of cancer care and the transitions between them, the factors at several levels (community, plan and practice setting) that potentially impact access and quality, and the strategies groups and organizations can consider to reduce potential failures. Focusing on the steps and transitions in care where failures can occur can facilitate more organized systems and medical practices that improve care, establish meaningful measures of quality that promote improved outcomes, and enhance interdisciplinary research.     

Differential effectiveness of methylphenidate and Adderall in school-age youths with attention-deficit/hyperactivity disorder.

OBJECTIVE: To compare the effectiveness of a single dose of Adderall (q.d.) with that of 2 daily doses of methylphenidate (b.i.d.; MPH) as a treatment for attention-deficit/hyperactivity disorder (ADHD) in youths ranging in age from 5 to 17 years. Forty-two youths treated with MPH were compared with 42 youths treated with Adderall. Subjects were matched for age, sex, and DSM-IV diagnostic subtype. METHOD: Youths were assigned to the Adderall or MPH condition by their prescribing physician. All youths were evaluated under 5 conditions, including baseline, placebo, 5 mg, 10 mg, and 15 mg. The best dose was assigned prior to breaking the medication blind and was assigned by the consensus of the psychologist and psychiatrist. Subjective ratings by both teachers and parents were examined for dosage level effects and medication type effects. RESULTS: Best dose was always superior to baseline and placebo conditions. No differences between MPH and Adderall were observed on either teacher or parent ratings of behavior. CONCLUSIONS: Both MPH and Adderall have been shown to be effective treatments for children with ADHD. Both medications appear to improve teachers' and parents' ratings of behavior. Single-dose treatments of Adderall appear to be as effective as 2 daily doses of MPH and therefore increase the possibility of managing treatment without involving the school in medication administration. In addition, youths who have previously been unsuccessfully treated with MPH because of adverse side effects or poor response may be successfully treated with Adderall.     

Sequence analysis of HLA class II genes from insulin-dependent diabetic individuals

To examine the nature of HLA-linked genetic susceptibility to insulin-dependent diabetes mellitus (IDDM), we compared HLA class II gene sequences from IDDM patients and control individuals. Genomic libraries were constructed from two siblings with IDDM, typed serologically as DR3,w6 and DR3,4. These libraries represent the HLA haplotypes (DR3, DR4) most frequently associated with IDDM, as well as one haplotype found less often. Individual genomic clones were identified and assigned to specific loci and haplotypes. The nucleotide sequence was then determined from the variable second exon from the HLA-DQ, DQß, and DRß genes from all three haplotypes. Sequence variation within the DQ genes could not be correlated with the disease. For all three haplotypes, the DQ sequence from the IDDM patient was identical to the DR-matched control sequence. Similarly, for the DR3 haplotype, the DQß sequences matched all control DR3 alleles. The DQß sequence from the DR4 haplotype was identical to the predominant DR4 allele (DQß 3.2) but differed at four amino acid residues from the other major DR4 DQß sequence (DQß3.1) found rarely among IDDM patients. Sequence analysis of the DQß gene from the DRw6 haplotype revealed a new allele that differed from the DQß allele from a control DR6 allele at two residues. The DRß genes from these three haplotypes also did not show any sequence features uniquely associated with IDDM, although the frequency of certain allelic variants in all three of these haplotypes may be altered in the IDDM population. A particular group of amino acids was found to be shared between the DRß-1 alleles from the DR4 and DRw6 haplotypes and may be involved in genetic susceptibility to IDDM.     

Comparison of cognitive performance among different age groups in patients with obstructive sleep apnea

The aim of this study was to evaluate the effect of obstructive sleep apnea syndrome on the cognitive performance of young and middle-aged patients. Patients were divided into two groups, one consisting of 30 patients less than 50 years of age and the other consisting of 28 patients 50 years and over. Normal subjects were similarly divided into two groups, composed of 17 younger and 24 older controls. Patients and controls were examined with all-night polysomnography and subsequently underwent cognitive testing via attention–alertness tests. Comparing young to middle-aged patients, there were statistically significant differences in cognitive performance, especially in attention tests. Younger patients’ cognitive performance was similar to their age-matched controls, while middle-aged patients showed cognitive decline in comparison with their age-matched controls. Although we studied only two age groups using 50 years of age as a cut-off, we could demonstrate that cognitive deterioration of untreated sleep apnea patients is age dependent, and several factors may contribute to this effect including brain hypoxia, sleep fragmentation, or comorbidities. Aging patients with sleep apnea demonstrate cognitive decline, while younger patients with the same disease severity are (somehow) able to compensate for this effect.     

National survey of elements and radioactivity in municipal incinerator ashes

An analytical survey of fly ashes, bottom ashes and mixtures of the two for 36 elements, soluble salts and radioactivity was conducted. The ashes were taken from approximately one-fourth of the municipal solid waste incinerators presently operating in the United States. The concentrations of a number of toxic elements such as As, Cd, Cr, Cu, Hg, Ni, Pb, Sb, and Zn in specific ashes were high. The levels of radioactivity were not significant from a health standpoint. A number of ashes were exceedingly high in organic matter, indicating grossly inadequate conditions during incineration. Soluble salt content was appreciable in the ashes. The possible sources of elements in refuse and their behavior and fate during refuse incineration are discussed with respect to their chemical forms and properties and incinerator operating parameters. Variability of metal concentrations in ash with time of sampling and their solubilization in landfills are also considered.     

Modelling health expenditure at the household level in Greece

Health expenditure data are known to be afflicted by restricted range, zero values, skewness and kurtosis. Several methods for modelling such data have been suggested in the literature to cope with these problems. This paper compares the performance of several alternative estimators, including two-part models and generalised linear models. The dependent variable is household expenditure on health care in Greece, a country where out-of-pocket health expenditure is higher than anywhere else in the European Union, whether as a proportion of GDP, as a share of all health spending, or in per capita terms. To facilitate comparison of model performance, household health expenditure is examined in two different specifications: expenditure on all health care (where zero values are rare) and expenditure on hospital services alone (where zero values are common). In the case of expenditure on all health care, three of the estimators performed almost equally well in terms of three alternative model performance indicators: a modified two-part model with non-linear least squares in the second part, a constant-variance generalised linear model and a variance-proportional-to-mean generalised linear model. In the case of expenditure on hospital services, the constant-variance generalised linear model out-performed the rest. The findings suggest that no estimator is best under all circumstances, while most alternative estimators are likely to produce relatively similar results. The paper concludes by discussing implications for further research.