A genealogical study of Alzheimer disease in the Saguenay region of Quebec

We performed an analysis of inbreeding and kinship among the ascending genealogies of 205 autopsy-confirmed Alzheimer disease (AD) subjects recruited in the Saguenay area of Québec. We hypothesized that if some traits pertaining to the disease were determined by inherited factors, and if the corresponding genes were not too frequent in the population, it might be possible to detect some clusters of patients related to common ancestors and presenting a level of kinship and/or inbreeding higher than is observed in the unaffected population of the same age. In view of the heterogeneity of the disease, we also verified if some of the factors investigated could be associated more specifically with subsets of cases based on age of onset and on apolipoprotein E (APOE) genotype. Results were compared with those obtained on 205 controls matched for gender, place and year of birth. We found that late-onset AD cases with an APOE-epsilon 4 were significantly more inbred than controls and that this increase was explained by the high level of inbreeding of a few cases whose parents were related at the first-cousin level. This could possibly indicate the implication of a recessive element in a small subset of AD cases in the Saguenay population. We also found that late-onset epsilon 4+ cases were significantly more closely related among themselves than with controls. This increase in kinship may be attributable to the presence of the epsilon 4 allele or to some other unidentified genetic factor possibly acting in conjunction with APOE-epsilon 4.     

Twenty-five-year experience with rastelli repair for transposition of the great arteries

OBJECTIVE: Our purpose was to describe the outcome of the Rastelli repair in D -transposition of the great arteries and to determine the risk factors associated with unfavorable events. METHODS: From March 1973 to April 1998, 101 patients with D -transposition of the great arteries and ventricular septal defect underwent a Rastelli type of repair. Median age and weight were 3.1 years (10th to 90th percentiles 0.3-9.9 years) and 12.8 kg (5.9-28.2). Pulmonary stenosis was present in 73 patients and pulmonary atresia in 18; 10 patients had no left ventricular outflow tract obstruction. RESULTS: There were 7 early deaths (7%) and no operative deaths in the last 7 years of the study. Risk factors for early death, by univariable analysis, included straddling tricuspid valve (P =.04) and longer aortic crossclamping times (P =.04). At a median follow-up of 8.5 years, there were 17 late deaths and 1 patient had undergone heart transplantation. Forty-four patients had reoperations for conduit stenosis, 11 for left ventricular outflow tract obstruction, and 28 had interventional catheterization to relieve conduit stenosis. Nine patients had late arrhythmias, and there were 5 sudden deaths. Overall freedom from death or transplantation (Kaplan-Meier) was 82%, 80%, 68%, and 52% at 5, 10, 15, and 20 years, respectively. Freedom from death or reintervention (catheterization or surgical treatment) was 53%, 24%, and 21% at 5, 10, and 15 years of follow-up, respectively. CONCLUSIONS: The Rastelli repair can be performed with low early mortality. However, substantial late morbidity and mortality are associated with conduit obstruction, left ventricular outflow tract obstruction, and arrhythmia.     

A Model of Shared Mycobacteriology Testing Services: Lessons Learned

Objective

The need for public health laboratories (PHLs) to prioritize resources has led to increased interest in sharing diagnostic services. To address this concept for tuberculosis (TB) testing, the New York State Department of Health Wadsworth Center and the Rhode Island State Health Laboratories assessed the feasibility of shared services for the detection and characterization of Mycobacterium tuberculosis complex (MTBC).

Methods

We assessed multiple aspects of shared services including shipping, testing, reporting, and cost. Rhode Island State Health Laboratories shipped MTBC-positive specimens and isolates to Wadsworth Center. Average turnaround times were calculated and cost analysis was performed.

Results

Testing turnaround times were similar at both PHLs; however, the availability of conventional drug susceptibility testing (DST) results for Rhode Island primary specimens and isolates were extended by approximately four days of shipping time. An extended molecular testing panel was performed on every specimen submitted from Rhode Island State Health Laboratories to Wadsworth Center, and the total cost per specimen at Wadsworth Center was $177.12 less than at Rhode Island State Health Laboratories, plus shipping. Following a mid-study review, Wadsworth Center provided testing turnaround times for detection (same day), species determination of MTBC (same day), and molecular DST (2.5 days).

Conclusion

The collaboration between Wadsworth Center and Rhode Island State Health Laboratories to assess shared services of TB testing highlighted a successful model that may serve as a guideline for other PHLs. The provision of additional rapid testing at a lower cost demonstrated in this study could potentially improve patient management and result in significant cost and resource savings if used in similar models across the country.Public health laboratories (PHLs) are essential for disease prevention and control. They serve as a first line of defense by rapidly recognizing and averting the spread of communicable diseases. In addition, they play a critical role in providing specialized tests for low-incidence, high-risk diseases, such as tuberculosis (TB), rabies, and botulism.¹ Due to recent economic constraints, many PHLs have suffered financial pressures, including budget and staffing cuts. In some cases, PHLs have reduced or eliminated certain tests, creating a potential risk to the public''s health. As an alternative to the discontinuation of services, one suggested approach was the investigation of shared services with other PHLs in different jurisdictions through testing directories and pilot projects with assistance and support from the Centers for Disease Control and Prevention (CDC) and the Association of Public Health Laboratories (APHL).^2,3TB, which is caused by the bacteria Mycobacterium tuberculosis, is a disease for which PHLs play an important role by providing diagnostics that contribute to prevention. Despite an overall decline in cases, TB continues to be a significant burden on social, public health, and economic systems in the United States.⁴ Maintaining a comprehensive and efficient laboratory system is critical to the continued decline of TB rates and overall prevention and control of TB in the United States. However, providing comprehensive TB testing services is becoming increasingly expensive per case identified. Additionally, retaining technical proficiency remains a challenge, especially as many experienced personnel are lost to retirement and are difficult to replace.⁵In 2013, a total of 9,582 new TB cases were reported in the United States, with an incidence rate of 3.0 cases per 100,000 population. Only four states reported more than 500 cases of TB: California, Texas, New York, and Florida, accounting for half of all TB cases in the United States. The TB incidence rate in New York State (NYS) is 4.4 per 100,000 population.⁴ The overall number of TB cases in NYS has decreased slightly over time, while the number of drug-resistant TB (DR TB) cases has remained steady during the past five years. Additionally, the percentage of multidrug-resistant TB (MDR TB) cases in NYS has increased from 1.3% to 3.6% during the past five years.⁶ In contrast, the TB incidence rate in Rhode Island is 2.6 per 100,000 population, and the overall number of TB cases has remained constant; DR TB and MDR TB cases in Rhode Island are rare.^4,7 Given the low number of TB-positive specimens received each year in Rhode Island State Health Laboratories, developing an extensive, increasingly molecular-based, testing program for TB may not be cost effective. In contrast, a high proportion of specimens received each year by the NYS Department of Health Wadsworth Center are Mycobacterium tuberculosis complex (MTBC) positive, including DR TB and MDR TB cases, and an extensive testing program has been implemented.We assessed the feasibility of shared services for the detection and characterization of MTBC between Wadsworth Center and Rhode Island State Health Laboratories during a 10-month time period. Multiple aspects critical to the implementation of shared services were examined, including shipping, testing, reporting, and cost. During this project, Wadsworth Center provided services to Rhode Island State Health Laboratories for rapid detection of MTBC, MTBC species identification, rapid detection of mutations associated with rifampin and isoniazid resistance, and conventional drug susceptibility testing (DST). Importantly, this partnership allowed Wadsworth Center to assess its ability to share its extended testing capabilities with another PHL, determine if the additional services provided were beneficial to patient treatment and outcomes, and identify any potential issues with this testing approach.