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The prevalence and incidence of type 2 diabetes, representing >90% of all cases of diabetes, are increasing rapidly throughout the world. The International Diabetes Federation has estimated that the number [...]

Intellectual disability (ID) is a condition with a prevalence of 1% to 3%. (1-5) As a result, most pediatricians will be required to address and manage this condition on a [...]

Tumors are ugly. But the staff at Massachusetts General Hospital takes a snapshot of almost every one that crosses the doorstep. These snapshots are not photographs, but are rather whole [...]

Wouldn't it be helpfu to know which of our patients are likely to develop advanced AMD and resulting vision loss, and which are not? That way, we could tailor our [...]

Background: The Centers for Medicare & Medicaid Services considered whether to reimburse stool DNA testing for colorectal cancer screening among Medicare enrollees. Objective: To evaluate the conditions under which stool DNA testing could be cost-effective compared with the colorectal cancer screening tests currently reimbursed by the Centers for Medicare & Medicaid Services. Design: Comparative microsimulation modeling study using 2 independently developed models. Data Sources: Derived from literature. Target Population: A cohort of persons aged 65 years. A sensitivity analysis was also conducted, in which a cohort of persons aged 50 years was studied. Time Horizon: Lifetime. Perspective: Third-party payer. Intervention: Stool DNA test every 3 or 5 years in comparison with currently recommended colorectal cancer screening strategies. Outcome Measures: Life expectancy, lifetime costs, incremental cost-effectiveness ratios, and threshold costs. Results of Base-Case Analysis: Assuming a cost of $350 per test, strategies of stool DNA testing every 3 or 5 years yielded fewer life-years and higher costs than the currently recommended colorectal cancer screening strategies. Screening with the stool DNA test would be cost-effective at a per-test cost of $40 to $60 for stool DNA testing every 3 years, depending on the simulation model used. There were no levels of sensitivity and specificity for which stool DNA testing would be cost-effective at its current cost of $350 per test. Stool DNA testing every 3 years would be cost-effective at a cost of $350 per test if the relative adherence to stool DNA testing were at least 50% better than that with other screening tests. Results of Sensitivity Analysis: None of the results changed substantially when a cohort of persons aged 50 years was considered. Limitation: No pathways other than the traditional adenomacarcinoma sequence were modeled. Conclusion: Stool DNA testing could be a cost-effective alternative for colorectal cancer screening if the cost of the test substantially decreased or if its availability would entice a large fraction of otherwise unscreened persons to receive screening. Primary Funding Source: Agency for Healthcare Research and Quality.

Background: Resurgence of syphilis in Canada and worldwide requires laboratories to update their methods for molecular epidemiology investigation and surveillance. This study utilizes polymerase chain reaction diagnostic tests for syphilis, identifies macrolide resistance, and uses a molecular typing system to characterize Treponema pallidum clinical strains causing syphilis in Alberta and Northwest Territories, Canada. Methods: In total 449 specimens including genital swabs, whole blood, sera, and cerebrospinal fluid were obtained from 374 patients with suspect syphilis in Alberta and Northwest Territories. Molecular subtyping was based on genetic characterization of treponemal repeat genes, arp and tpr. Detection of macrolide resistance was accomplished by identification of the 23S rRNA gene mutation associated with the resistance pattern. Results: Forty-nine specimens obtained from 43 patients were found to be positive for T. pallidum DNA using bmp, tpp47 and polA polymerase chain reaction assays. Four molecular subtypes were identified, with one type, 14d, accounting for 70% of all cases and 83% of typeable strains. Seven patients (16%) were found to be infected by macrolide-resistant strains, of which 6 were men who have sex with men and 1 whose infection was acquired in China. Conclusions: A single molecular type of T. pallidum, characterized as 14d, caused the majority of the syphilis cases identified in this study. A more discriminatory typing method would be required to determine if these strains are clonal. Treatment of infectious syphilis with macrolide antibiotics should be restricted to patient populations where resistance is rare and clinical and serological follow up of patients is possible. DOI:10.1097/OLQ.0b013e318d73cel

Background: Human papillomavirus type 16 (HPV16) is a common infection in the anogenital tract. HPV16 DNA detected in oral specimens has recently been identified as a risk factor for some oropharyngeal cancers. The reported prevalence of oral HPV infection from individual studies is highly variable. Methods: We systematically reviewed and abstracted data from published studies (n = 18) that detected oral HPV DNA in 4581 cancer-free subjects to determine the pooled prevalence (and 95% confidence intervals [CI]) of HPV16, carcinogenic HPV, and any HPV. Results: 1.3% (95% CI: 1.0-1.7%) of 3977 healthy subjects had oral HPV16, 3.5% (95% CI: 3.0-4.1) of 4441 subjects had carcinogenic HPV, and 4.5% (95% CI: 3.9-5.1) of 4070 subjects were positive for any HPV. Oral HPV16 accounted for 28% of all HPV detected in the oral region. Men (47 of 1017) and women (117 of 3690) had nearly exactly the same prevalence of any oral HPV detected (4.6% vs. 4.4%, respectively). Conclusions: HPV-16, a common anogenital infection, was rarely detected in oral specimens. However, a small but noteworthy proportion of healthy individuals have oral HPV infections with types known to cause cancer in the oral region. DOI: 10.1097/OLQ.0b013e3181c94a3b

Background: Genetic susceptibility testing for Alzheimer disease (AD) with APOE genotype disclosure is not recommended for clinical use but is available through direct-to-consumer (DTC) genetic testing companies. Little is known about whether APOE genotype disclosure would actually prompt changes in nutrition behaviors among at-risk individuals. Objective: We studied the effect of APOE genotype disclosure for AD risk assessment on dietary supplement use in adults with a family history of AD. Design: As part of a secondary analysis of data from the second Risk Evaluation and Education for Alzheimer's Disease Study, we examined the effect of genotype disclosure on health-behavior changes among 272 unaffected first-degree relatives of persons with AD. Results: Overall, 16% of all participants reported a change in dietary supplement use after AD risk assessment. Participants who learned that they had at least one copy of the risk-increasing [epsilon]4 allele ([epsilon]4+) had 4.75 times the odds of reporting a change in dietary supplement use than did their counterparts who had an absence of the risk-increasing [epsilon]4 allele ([epsilon]4-) (95% CI: 2.23, 10.10; P < 0.0001) after adjustment for age, sex, race, baseline supplement use, randomization arm, and educational level. There were no significant differences between APOE [epsilon]4+ and [epsilon]4- participants in changes in overall diet, exercise, or medications. Conclusions: In this sample of first-degree relatives receiving genetic susceptibility testing for AD, an APOE [epsilon]4+ genotype status was positively associated with dietary supplement use after risk disclosure. Such changes occurred despite the absence of evidence that supplement use reduces the risk of AD. Given the expansion of DTC genetic tests, this study highlights the need for future studies in disease risk communication. doi: 10.3945/ajcn.2009.28981.

Unexplained cardiac hypertrophy, the diagnostic criterion for hypertrophic cardiomyopathy (HCM), occurs in 1 in 500 adults. Insights into the genetic cause and molecular pathophysiology of HCM are reshaping clinical paradigms for diagnosis and treatment of this common myocardial disorder. Human genetic studies have established that dominant mutations in the proteins that make up the contractile apparatus (the sarcomere) cause HCM. With the current availability of clinical gene-based diagnostics, pathogenic mutations in affected patients can be defined, which can suggest a clinical course and allow definitive preclinical identification of family members at risk for HCM. Genetic discoveries have also fostered mechanistic investigations in model organisms that are engineered to carry human HCM mutations. Novel therapeutic targets have emerged from these fundamental studies and are currently under clinical assessment in humans. The combination of contemporary gene-based diagnosis with new strategies to attenuate disease development and progression is changing the natural history of lifelong cardiac symptoms, arrhythmias, and heart failure from HCM.

ABSTRACT The focus of genetics is shifting its contribution to common, complex disorders. New genetic risk factors will be discovered, which if undisclosed may allow adverse selection. However, this should [...]

Background Human papillomavirus (HPV) DNA testing has shown higher sensitivity than cytology for detecting cervical lesions, but it is uncertain whether the higher sensitivity is dependent on the age of the woman being screened. We compared the age-specific performance of primary HPV DNA screening with that of conventional cytology screening in the setting of an organized population-based cervical cancer screening program in Finland. Methods From January 1, 2003, to December 31, 2005, randomized invitations were sent to women aged 25-65 years for routine cervical cancer screening by primary high-risk HPV DNA testing (n = 54207) with a Hybrid Capture 2 assay followed by cytology triage for women who were HPV DNA positive or by conventional cytology screening (n = 54218). In both screening arms, cytology results of low-grade squamous intraepithelial lesion or worse triggered a referral for colposcopy. Relative rates (RRs) of detection to assess test sensitivity, specificity, and positive predictive values (PPVs) with 95% confidence intervals (CIs) were calculated for the histological endpoints of cervical intraepithelial neoplasia (CIN) grade 1 or higher (CIN 1+), CIN grade 2 or higher (CIN 2+), and CIN grade 3 or higher (CIN 3+). All statistical tests were two-sided. Results The overall frequency of colposcopy referrals was 1.2% in both screening arms. Women younger than 35 years were referred more often in the HPV DNA screening vs the conventional screening arm (RR = 1.27, 95% CI = 1.01 to 1.60). The prevalence of histologically confirmed CIN or cancer was 0.59% in the HPV DNA screening arm vs 0.43% in the conventional screening arm. The relative rates of detection for CIN 1, CIN 2, and CIN 3+ for HPV DNA screening with cytology triage vs conventional screening were 1.44 (95% CI = 0.99 to 2.10), 1.39 (95% CI = 1.03 to 1.88), and 1.22 (95% CI = 0.78 to 1.92), respectively. The specificity of the HPV DNA test with cytology triage was equal to that of conventional screening for all age groups (99.2% vs 99.1% for CIN 2+, P = .13). Among women aged 35 years or older, the HPV DNA test with cytology triage tended to have higher specificity than conventional screening. The PPVs for HPV DNA screening with cytology triage were consistently higher than those for conventional screening. In both screening arms, the test specificities increased with increasing age of the women being screening, whereas the highest PPVs were observed among the youngest women being screened. Overall, 7.2% of women in the HPV DNA screening arm vs 6.6% of women in the conventional screening arm were recommended for intensified follow-up, and the percentages were highest among 25- to 29-year-olds (21.9% vs 10.0%, respectively). Conclusions Primary HPV DNA screening with cytology triage is more sensitive than conventional screening. Among women aged 35 years or older, primary HPV DNA screening with cytology triage is also more specific than conventional screening and decreases colposcopy referrals and follow-up tests. J Natl Cancer Inst 2009;101:1612-1623 DOI: 10.1093/jnci/djp367

The thinking about autism and Lyme disease is moving so quickly, it can make your head spin. Last year, and again this year, doctors at the Lyme-Induced Autism (LIA) Foundation's [...]

Embryonic research and genetic testing continue to raise concerns. (1) With controversy comes debate and, sometimes, distortion of facts through the use of loaded terms and concepts that call to [...]

Over the last several years there have been a huge number of advances in our understanding of the biology and natural history of human papillomavirus (HPV). A PubMed search indicates [...]

Background: HIV-1 genotypic and phenotypic susceptibility testing (GPT) optimizes antiretroviral selection, but its effect on survival is unknown. Objective: To evaluate the association between GPT and survival. Design: Cohort study. Setting: 10 U.S. HIV clinics. Patients: 2699 HIV-infected patients eligible for GPT (plasma HIV RNA level >1000 copies/mL) seen from 1999 through 2005. Measurements: Demographic characteristics, clinical factors, GPT use, all-cause mortality, and crude and adjusted hazard ratios (HRs) for the association of GPT with survival. Results: Patients were followed for a median of 3.3 years; 915 (34%) had GPT. Patients who had GPT had lower mortality rates than those who did not (2.0 vs. 2.7 deaths per 100 person-years). In standard Cox models, GPT was associated with improved survival (adjusted HR, 0.69 [95% CI, 0.51 to 0.94]; P = 0.017) after controlling for demographic characteristics, [CD4.sup.+] cell count, HIV RNA level, and intensity of clinical follow-up. In subgroup analyses, GPT was associated with improved survival for the 2107 highly active antiretroviral therapy (HAART)-experienced patients (2.2 vs. 3.2 deaths per 100 person-years for patients who had GPT vs. those who did not have GPT; adjusted HR, 0.60 [CI, 0.43 to 0.82]; P = 0.002) and for the 921 triple antiretroviral class-experienced patients (2.1 vs. 3.1 deaths per 100 person-years; adjusted HR, 0.61 [CI 0.40 to 0.93]; P = 0.022). Marginal structural models supported associations between GPT and improved survival in the overall cohort (adjusted HR, 0.54; P = 0.001) and in the HAART-experienced group (adjusted HR, 0.56; P = 0.003). Limitations: Use of GPT was not randomized. Residual confounding may exist. Conclusion: Use of GPT was independently associated with improved survival among HAART-experienced patients. Primary Funding Source: Centers for Disease Control and Prevention.

Objective: To assess the frequency of HPV-DNA detection, human papillomavirus (HPV) seropositivity, presence of cervical lesions, and its relationship with certain socio-demographic factors in women from Girardot, Colombia from 2006 to 2007. Methods: Nine hundred fifty-three women attending their regular Pap smear control voluntarily provided cervical cells and blood samples for HPV-DNA analysis and ELISA detection of anti-L1 peptides and virus-like particles (VLPs) antibodies after answering a questionnaire regarding sexual behaviors, number of births, smoking habits, and socio-demographic background. Results: Twenty-six of the 953 women being examined (2.73%) presented cervical cell abnormalities. A frequency of 36.62% (95% CI: 33.52%-39.7%) HPV seropositivity was detected with peptide 18301, 35.36% (95% CI: 32.3%-38.4%) with 18283, and 32.95% (95% CI: 29.9%-36%) with 18294, whereas VLPs detected a 43% seropositivity (95% CI: 39.8%-46.2%). Antibody frequency found with all peptides was significantly higher in women having cervical abnormalities (atypical squamous cells of undetermined significance and high-grade squamous intraephitelial lesions) compared with those having normal cytologies. Peptide 18283 reported a significantly higher seropositivity (35.71%) in women >44 years old, whereas peptides 18301 and 18294 evidenced a significantly lower seropositivity in those who had never given birth. HR-HPV-DNA was detected in 157 (20.50%) of 766 cervical samples amplifying positively for the [beta]-globin housekeeping gene. Conclusion: Peptides 18283, 18294, and 18301 were more specific and more sensitive than VLPs for detecting women with HR-HPV-DNA positive cervical lesions. Therefore, they could be useful in the design of a serological test for detecting HR-HPV-infected women having cervical lesions at a risk of progressing to cervical cancer.

Background Primary cervical screening with both human papillomavirus (HPV) DNA testing and cytological examination of cervical cells with a Pap test (cytology) has been evaluated in randomized clinical trials. Because the vast majority of women with positive cytology are also HPV DNA positive, screening strategies that use HPV DNA testing as the primary screening test may be more effective. Methods We used the database from the intervention arm (n = 6257 women) of a population-based randomized trial of double screening with cytology and HPV DNA testing to evaluate the efficacy of 11 possible cervical screening strategies that are based on HPV DNA testing alone, cytology alone, and HPV DNA testing combined with cytology among women aged 32-38 years. The main outcome measures were sensitivity for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) within 6 months of enrollment or at colposcopy for women with a persistent type-specific HPV infection and the number of screening tests and positive predictive value (PPV) for each screening strategy. All statistical tests were two-sided. Results Compared with screening by cytology alone, double testing with cytology and for type-specific HPV persistence resulted in a 35% (95% confidence interval [CI] = 15% to 60%) increase in sensitivity to detect CIN3+, without a statistically significant reduction in the PPV (relative PPV = 0.76, 95% CI = 0.52 to 1.10), but with more than twice as many screening tests needed. Several strategies that incorporated screening for high-risk HPV subtypes were explored, but they resulted in reduced PPV compared with cytology. Compared with cytology, primary screening with HPV DNA testing followed by cytological triage and repeat HPV DNA testing of HPV DNA-positive women with normal cytology increased the CIN3+ sensitivity by 30% (95% CI = 9% to 54%), maintained a high PPV (relative PPV = 0.87, 95% CI = 0.60 to 1.26), and resulted in a mere 12% increase in the number of screening tests (from 6257 to 7019 tests). Conclusions Primary HPV DNA-based screening with cytology triage and repeat HPV DNA testing of cytology-negative women appears to be the most feasible cervical screening strategy.

Within the medical, legal and bioethical literature, there has been an increasing concern that the information derived from genetic tests may be used to unfairly discriminate against individuals seeking various kinds of insurance; particularly health and life insurance. Consumer groups, the general public and those with genetic conditions have also expressed these concerns, specifically in the context of life insurance. While it is true that all insurance companies may have an interest in the information obtained from genetic tests, life insurers potentially have a very strong incentive to (want to} use genetic information to rate applicants, as individuals generally purchase their own cover and may want to take out very large policies. This paper critically focuses on genetic information in the context of life insurance. We consider whether genetic information differs in any relevant way from other kinds of non-genetic information required by and disclosed to life insurance companies by potential clients. We will argue that genetic information should not be treated any differently from other types of health information already collected from those wishing to purchase life insurance cover.