Contagiousness of varicella in vaccinated cases: a household contact study

Context  Limited data are available on the contagiousness of vaccinated varicella cases. Objectives  To describe secondary attack rates within households according to disease history and vaccination status of the primary case and household contacts and to estimate varicella vaccine effectiveness. Design, Setting, and Patients  Population-based, active varicella surveillance project in a community of approximately 320 000 in Los Angeles County, California, during 1997 and 2001. Varicella cases were reported by child care centers, private and public schools, and health care clinicians and were investigated to collect demographic, clinical, medical, and vaccination data. Information on household contacts' age, varicella history, and vaccination status was collected. Main Outcome Measures  Varicella secondary attack rate among household contacts; vaccine effectiveness using secondary attack rates in unvaccinated and vaccinated children and adolescents. Results  A total of 6316 varicella cases were reported. Among children and adolescents aged 1 to 14 years, secondary attack rates varied according to age and by disease and vaccination status of the primary case and exposed household contacts. Among contacts aged 1 to 14 years exposed to unvaccinated cases, the secondary attack rate was 71.5% if they were unvaccinated and 15.1% if they were vaccinated (risk ratio [RR], 0.21; 95% confidence interval [CI], 0.15-0.30). Overall, vaccinated cases were half as contagious as unvaccinated cases. However, vaccinated cases with 50 lesions or more were similarly contagious as unvaccinated cases whereas those with fewer than 50 lesions were only one third as contagious (secondary attack rate, 23.4%; RR, 0.32 [95% CI, 0.19-0.53]). Vaccine effectiveness for prevention of all disease was 78.9% (95% CI, 69.7%-85.3%); moderate disease, 92% (50-500 lesions) and 100% (clinician visit); and severe disease, 100%. Conclusions  Under conditions of intense exposure, varicella vaccine was highly effective in preventing moderate and severe disease and about 80% effective in preventing all disease. Breakthrough varicella cases in household settings were half as contagious as unvaccinated persons with varicella, although contagiousness varied with numbers of lesions.      

The burden of out-of-pocket payments for health care in Tbilisi, Republic of Georgia

Jacek Skarbinski, MD; H. Kenneth Walker, MD; Laurence C. Baker, PhD; Archil Kobaladze, MD,PhD; Zviad Kirtava, MD,PhD; Thomas A. Raffin, MD

JAMA. 2002;287:1043-1049.

Context  In the 1990s, the Republic of Georgia instituted health care reforms to convert the centralized, state-operated health care system inherited from the Soviet Union to a decentralized, market-driven system of health care delivery. Under the new system, 87% of health care expenditures are financed through out-of-pocket payments at the point of service.

Objective  To describe the effects of health care reforms on access to care and health care financing among ill residents of Tbilisi, Georgia.

Design, Setting, and Participants  A probability-proportionate-to-size cluster survey conducted in 1999 of 248 households containing 306 household members who had been ill in the past 6 months in Tbilisi, Georgia.

Main Outcome Measures  Reported health care utilization, out-of-pocket expenditures, and financing practices.

Results  Of sick household members, 51% used official health care services at hospitals and clinics; 49% did not use official services and sought advice from relatives or friends, used traditional medicines, or did nothing. Those with serious illness were more likely to seek care through official services (82%) than those with nonserious illness (27%). Ninety-three percent of respondents said costs were the major deterrent to obtaining health care. Ten percent of ill household members reported that they were unable to obtain health care because of high costs; 16% reported being unable to afford all the medications necessary to treat their illness. Sixty-one percent of ill household members used savings to pay for health care expenditures and 19% of those able to obtain care had to use strategies such as borrowing money or selling personal items to pay for health care. Total out-of-pocket health care expenditures (53%) were paid for by borrowing money or selling personal items. A significant portion of households with ill members (87%) reported an interest in purchasing health care insurance.

Conclusions  Economic disruption and health care reforms have led to access problems and out-of-pocket financing strategies that include reliance on personal savings, selling personal items, and borrowing money. Future reforms should consider an appropriate system for health care insurance risk pooling for the population of Tbilisi, Georgia.

     

Mental health of Cambodian refugees 2 decades after resettlement in the United States

Context  Little is known about the long-term mental health of trauma-exposed refugees years after permanent resettlement in host countries. Objective  To assess the prevalence, comorbidity, and correlates of psychiatric disorders in the US Cambodian refugee community. Design, Setting, and Participants  A cross-sectional, face-to-face interview conducted in Khmer language on a random sample of households from the Cambodian community in Long Beach, Calif, the largest such community in the United States, between October 2003 and February 2005. A total of 586 adults aged 35 to 75 years who lived in Cambodia during the Khmer Rouge reign and immigrated to the United States prior to 1993 were selected. One eligible individual was randomly sampled from each household, with an overall response rate (eligibility screening and interview) of 87% (n = 490). Main Outcome Measures  Exposure to trauma and violence before and after immigration (using the Harvard Trauma Questionnaire and Survey of Exposure to Community Violence); weighted past-year prevalence rates of posttraumatic stress disorder (PTSD) and major depression (using the Composite International Diagnostic Interview version 2.1); and alcohol use disorder (by the Alcohol Use Disorders Identification Test). Results  All participants had been exposed to trauma before immigration. Ninety-nine percent (n = 483) experienced near-death due to starvation and 90% (n = 437) had a family member or friend murdered. Seventy percent (n = 338) reported exposure to violence after settlement in the United States. High rates of PTSD (62%, weighted), major depression (51%, weighted), and low rates of alcohol use disorder were found (4%, weighted). PTSD and major depression were highly comorbid in this population (n = 209; 42%, weighted) and each showed a strong dose-response relationship with measures of traumatic exposure. In bivariate analyses, older age, having poor English-speaking proficiency, unemployment, being retired or disabled, and living in poverty were also associated with higher rates of PTSD and major depression. Following multivariate analyses, premigration trauma remained associated with PTSD (odds ratio [OR], 2.08; 95% CI, 1.37-3.16) and major depression (OR, 1.56; 95% CI, 1.24-1.97); postmigration trauma with PTSD (OR, 1.65; 95% CI, 1.21-2.26) and major depression (OR, 1.45; 95% CI, 1.12-1.86); and older age with PTSD (OR, 1.76; 95% CI, 1.46-2.13) and major depression (OR, 1.47; 95% CI, 1.15-1.89). Conclusion  More than 2 decades have passed since the end of the Cambodian civil war and the subsequent resettlement of refugees in the United States; however, this population continues to have high rates of psychiatric disorders associated with trauma.      

Estimating the number of insecticide-treated nets required by African households to reach continent-wide malaria coverage targets

Context  African countries are scaling up malaria interventions, especially insecticide-treated nets (ITNs), for which ambitious coverage targets have been set. Objective  To estimate how many ITNs are available in African households that are at risk of malaria and how many ITNs are needed to reach targets for use by children younger than 5 years and pregnant women. Data Sources  Primary sources of data were the Multiple Indicator Cluster Surveys II, the Demographic and Health Surveys, or other nationally representative or large-scale household surveys that measured household possession and use of nets or ITNs among children younger than 5 years. Data Extraction  Data from 42 household surveys between 1999 and 2006 on net and ITN coverage (either household possession or use) and average numbers of nets and ITNs per household were compared with populations and households at risk. Data are included for 43 sub-Saharan African countries. Data Synthesis  For the median survey year 2003, the population-weighted mean proportion of households possessing at least 1 ITN was 6.7% (range among countries, 0.1%-71.0%) and was 23.8% (range, 5.0%-91.2%) for any type of net. Based on an average of 0.13 ITNs per household, we estimated that 53.6 million nets, of which 16.7 million were ITNs, were available in households at risk of malaria. Between 130 million and 264 million ITNs are required in 2007 to reach the 80% coverage target for about 133 million children younger than 5 years and pregnant women living in 123 million households in risk areas; the exact number depends on usage patterns (best estimate, assuming 55% of owned ITNs are used by the target groups, 192 million ITNs). Conclusion  To achieve the targeted ITN usage rates, numbers of ITNs available to African households must be dramatically increased.      

Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage

Context  Delayed cerebral vasospasm causes permanent neurological deficits or death in at least 15% of patients following otherwise successful treatment for ruptured intracranial aneurysm. Decreased bioavailability of nitric oxide has been associated with the development of cerebral vasospasm. Objective  To determine whether infusions of nitrite will prevent delayed cerebral vasospasm. Design, Setting, and Subjects  A total of 14 anesthetized cynomolgus monkeys had an autologous blood clot placed around the right middle cerebral artery. Cerebral arteriography was performed before clot placement and on days 7 and 14 to assess vasospasm. The study was conducted from August 2003 to February 2004. Interventions  A 90-mg sodium nitrite intravenous solution infused over 24 hours plus a 45-mg sodium nitrite bolus daily (n = 3); a 180-mg sodium nitrite intravenous solution infused over 24 hours (n = 3); or a control saline solution infusion (n = 8). Each was infused continuously for 14 days. Main Outcome Measures  Nitrite, S-nitrosothiol, and methemoglobin levels in blood and cerebrospinal fluid and degree of arteriographic vasospasm. Results  In control monkeys, mean (SD) cerebrospinal fluid nitrite levels decreased from 3.1 (1.5) µmol/L to 0.4 (0.1) µmol/L at day 7 and to 0.4 (0.4) µmol/L at day 14 (P = .03). All 8 control monkeys developed significant vasospasm of the right middle cerebral artery, which was complicated by stroke and death in 1 animal. Sodium nitrite infusions increased the nitrite and methemoglobin levels (<2.1% of total hemoglobin) in the blood and cerebrospinal fluid without evoking systemic hypotension. Nitrite infusion prevented development of vasospasm (no animals developed significant vasospasm; mean [SD] reduction in right middle cerebral artery area on day 7 after subarachnoid hemorrhage of 8% [9%] in nitrite-treated monkeys vs 47% [5%] in saline-treated controls; P<.001). There was a negative correlation between the concentration of nitrite in cerebrospinal fluid and the degree of cerebral vasospasm (P<.001). Pharmacological effects of nitrite infusion were also associated with the formation of S-nitrosothiol in cerebrospinal fluid. There was no clinical or pathological evidence of nitrite toxicity. Conclusion  Subacute sodium nitrite infusions prevented delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage.      

Symptoms of posttraumatic stress disorder and depression among children in tsunami-affected areas in southern Thailand

Context  On December 26, 2004, an undersea earthquake occurred off the northwestern coast of Sumatra, Indonesia. The tsunami that followed severely impacted all 6 southwestern provinces of Thailand, where approximately 20 000 children were directly affected. Objective  To assess trauma experiences and the prevalence of symptoms of posttraumatic stress disorder (PTSD) and depression among children in tsunami-affected provinces in southern Thailand. Design, Setting, and Participants  Population-based mental health surveys were conducted among children aged 7 to 14 years in Phang Nga, Phuket, and Krabi provinces from February 15-22, 2005 (2 months posttsunami), and September 7-12, 2005 (9 months posttsunami). Main Outcome Measures  Trauma experiences and symptoms of PTSD and depression as measured by a tsunami-modified version of the PsySTART Rapid Triage System, the UCLA PTSD Reaction Index, and the Birleson Depression Self-Rating Scale. Results  A total of 371 children (167 displaced and living in camps, 99 not displaced from villages affected by the tsunami, and 105 not displaced from unaffected villages) participated in the first survey. The prevalence rates of PTSD symptoms were 13% among children living in camps, 11% among children from affected villages, and 6% among children from unaffected villages (camps vs unaffected villages, P = .25); for depression symptoms, the prevalence rates were 11%, 5%, and 8%, respectively (P = .39). In multivariate analysis of the first assessment, having had a delayed evacuation, having felt one's own or a family member's life to have been in danger, and having felt extreme panic or fear were significantly associated with PTSD symptoms. Older age and having felt that their own or a family member's life had been in danger were significantly associated with depression symptoms. In the follow-up survey, 72% (151/210) of children from Phang Nga participated. Prevalence rates of symptoms of PTSD and depression among these children did not decrease significantly over time. Conclusions  This assessment documents the prevalence of mental health problems among children in tsunami-affected provinces in southern Thailand at 2 and 9 months posttsunami. Traumatic events experienced during the tsunami were significantly associated with symptoms of PTSD and depression. These data may be useful to target mental health services for children and may inform the design of these interventions.      

Long-term outcome after intravenous thrombolysis of basilar artery occlusion

Context  Basilar artery occlusion (BAO) is an infrequent disease with high morbidity and mortality. Intra-arterial thrombolysis is advocated for treatment but is limited to use at specialized centers. Objective  To evaluate outcomes for patients with BAO treated with intravenous thrombolytic therapy. Design, Setting, and Participants  During 1995 to 2003, 50 consecutive patients with angiographically proven BAO were treated according to an institutional therapy protocol based on intravenous thrombolysis with recombinant tissue plasminogen activator (alteplase). Patients were treated at an urban university teaching hospital receiving all patients with ischemic stroke who were considered for thrombolysis in a catchment area of 1.5 million inhabitants in Helsinki, Finland. Intervention  Intravenous administration of alteplase (0.9 mg/kg) during a 1-hour infusion. Main Outcome Measures  Basilar artery recanalization determined by magnetic resonance angiography and clinical outcomes at 3 months and at 1 year or longer determined by modified Rankin Scale and Barthel Index scores. Results  Recanalization was studied in 43 patients and verified in 26 (52%) of all patients. By 3 months, 20 patients (40%) had died while 11 had good outcomes (modified Rankin Scale score, 0-2); 12 (24%) reached independence in activities of daily living (Barthel Index score, 95-100), and 6 (16%) were severely disabled (Barthel Index score, 0-50). In the long term (median follow-up 2.8 years), 15 patients (30%) reached good outcomes (modified Rankin Scale score, 0-2) while 23 (46%) died. Conclusions  Intravenous administration of alteplase for patients with BAO appears to be associated with rates of survival, recanalization, and independent functional outcome comparable with those reported with endovascular approaches. These data suggest that a randomized trial is needed to compare these approaches for treatment of BAO.      

Azithromycin for the secondary prevention of coronary heart disease events: the WIZARD study: a randomized controlled trial

Context  Several lines of evidence have implied an association between Chlamydia pneumoniae infection and atherogenesis. Objective  To determine the effect of 12 weeks of antibiotic therapy on coronary heart disease events in patients with stable coronary artery disease and known C pneumoniae exposure. Design, Setting, and Participants  Randomized, placebo-controlled trial of 7747 adults with previous myocardial infarction that had occurred at least 6 weeks previously (median, 2.6 years) and a C pneumoniae IgG titer of 1:16 or more. Patients were recruited from 271 clinical practices in North America, Europe, Argentina, and India, from October 10, 1997, to July 22, 2001. Intervention  The patients received either azithromycin (600 mg/d for 3 days during week 1, then 600 mg/wk during weeks 2-12; n = 3879) or placebo (n = 3868). Main Outcome Measures  The primary event was the first occurrence of death from any cause, nonfatal reinfarction, coronary revascularization, or hospitalization for angina. Patients were followed up until 1038 events accrued. Results  After a median of 14 months of follow-up, there was no significant risk reduction in the likelihood of a primary event with azithromycin vs placebo (7% [95% confidence interval, -5% to 17%], P = .23). Analysis of hazard ratios suggested early benefits of azithromycin on the primary event and on death or reinfarction, but these decreased over time. There were no significant risk reductions for any of the components of the primary end point including death (8%), recurrent myocardial infarction (7%), revascularization procedures (5%), or hospitalizations for angina (-1%). Adverse events related to study drug were reported by 13.2% of those randomized to receive azithromycin, predominantly a result of diarrhea, compared with 4.6% randomized to receive placebo, and resulted in discontinuation of drug in 1.6% of those taking azithromycin and 0.4% taking placebo. Conclusion  Among stable patients with previous myocardial infarction and with evidence of C pneumoniae exposure, a 3-month course of azithromycin did not significantly reduce the clinical sequelae of coronary heart disease.      

Early use of the pulmonary artery catheter and outcomes in patients with shock and acute respiratory distress syndrome: a randomized controlled trial

Context  Many physicians believe that the pulmonary artery catheter (PAC) is useful for the diagnosis and treatment of cardiopulmonary disturbances; however, observational studies suggest that its use may be harmful. Objective  To determine the effects on outcome of the early use of a PAC in patients with shock mainly of septic origin, acute respiratory distress syndrome (ARDS), or both. Design, Setting, and Patients  A multicenter randomized controlled study of 676 patients aged 18 years or older who fulfilled the standard criteria for shock, ARDS, or both conducted in 36 intensive care units in France from January 30, 1999, to June 29, 2001. Intervention  Patients were randomly assigned to either receive a PAC (n = 335) or not (n = 341). The treatment was left to the discretion of each individual physician. Main Outcome Measures  The primary end point was mortality at 28 days. The principal secondary end points were day 14 and 90 mortality; day 14 organ system, renal support, and vasoactive agents–free days; hospital, intensive care unit, and mechanical ventilation–free days at day 28. Results  The 2 groups were similar at baseline. There were no significant differences in mortality with or without the PAC at day 14: 49.9% vs 51.3% (mortality relative risk [RR], 0.97; 95% confidence interval [CI], 0.84-1.13; P = .70); day 28: 59.4% vs 61.0% (RR, 0.97; 95% CI, 0.86-1.10; P = .67); or day 90: 70.7% vs 72.0% (RR, 0.98; 95% CI, 0.89-1.08; P = .71). At day 14, the mean (SD) number of days free of organ system failures with or without the PAC (2.3 [3.6] vs 2.4 [3.5]), renal support (7.4 [6.0] vs 7.5 [5.9]), and vasoactive agents (3.8 [4.8] vs 3.9 [4.9]) did not differ. At day 28, mean (SD) days in hospital with or without the PAC (0.9 [3.6] vs 0.9 [3.3]), in the intensive care unit (3.4 [6.8] vs 3.3 [6.9]), or mechanical ventilation use (5.2 [8.5] vs 5.0 [8.5]) did not differ. Conclusion  Clinical management involving the early use of a PAC in patients with shock, ARDS, or both did not significantly affect mortality and morbidity.      

Medicine residents' understanding of the biostatistics and results in the medical literature

Context  Physicians depend on the medical literature to keep current with clinical information. Little is known about residents' ability to understand statistical methods or how to appropriately interpret research outcomes. Objective  To evaluate residents' understanding of biostatistics and interpretation of research results. Design, Setting, and Participants  Multiprogram cross-sectional survey of internal medicine residents. Main Outcome Measure  Percentage of questions correct on a biostatistics/study design multiple-choice knowledge test. Results  The survey was completed by 277 of 367 residents (75.5%) in 11 residency programs. The overall mean percentage correct on statistical knowledge and interpretation of results was 41.4% (95% confidence interval [CI], 39.7%-43.3%) vs 71.5% (95% CI, 57.5%-85.5%) for fellows and general medicine faculty with research training (P < .001). Higher scores in residents were associated with additional advanced degrees (50.0% [95% CI, 44.5%-55.5%] vs 40.1% [95% CI, 38.3%-42.0%]; P < .001); prior biostatistics training (45.2% [95% CI, 42.7%-47.8%] vs 37.9% [95% CI, 35.4%-40.3%]; P = .001); enrollment in a university-based training program (43.0% [95% CI, 41.0%-45.1%] vs 36.3% [95% CI, 32.6%-40.0%]; P = .002); and male sex (44.0% [95% CI, 41.4%-46.7%] vs 38.8% [95% CI, 36.4%-41.1%]; P = .004). On individual knowledge questions, 81.6% correctly interpreted a relative risk. Residents were less likely to know how to interpret an adjusted odds ratio from a multivariate regression analysis (37.4%) or the results of a Kaplan-Meier analysis (10.5%). Seventy-five percent indicated they did not understand all of the statistics they encountered in journal articles, but 95% felt it was important to understand these concepts to be an intelligent reader of the literature. Conclusions  Most residents in this study lacked the knowledge in biostatistics needed to interpret many of the results in published clinical research. Residency programs should include more effective biostatistics training in their curricula to successfully prepare residents for this important lifelong learning skill.      

Risk factors for parvovirus B19 infection in pregnancy

Context  Parvovirus B19 infection during pregnancy has been associated with fetal death. However, the incidence of and risk factors for infection in pregnant women have not been well studied. Objectives  To estimate a pregnant woman's risk of infection with parvovirus B19 in epidemic and endemic situations and to study risk factors for infection. Design  Population-based cohort study conducted between November 1992 and June 1994. Setting  Three regions in Denmark. Participants  A total of 30,946 pregnant women from a consecutive and population-based screening. Main Outcome Measures  Specific IgG antibodies in serum samples obtained in the first trimester of pregnancy and from the newborn infant to assess past infection and seroconversion. Information on family structure, educational background, socioeconomic status, and pregnancy outcome was obtained from national registers. Results  Based on 30,946 serum samples, 65.0% of pregnant women had evidence of past infection. Annual seroconversion rates among susceptible women during endemic and epidemic periods were 1.5% (95% confidence interval [CI], 0.2%-1.9%) and 13.0% (95% CI, 8.7%-23.1%), respectively. Baseline seropositivity was significantly correlated with increasing number of siblings, having a sibling of the same age, number of own children, and occupational exposure to children. Risk of acute infection increased with the number of children in the household as follows: 0 children odds ratio (OR), 1 (reference); 1 child OR, 3.17 (95% CI, 2.24-4.49); 2 children OR, 5.47 (95% CI, 3.55-8.45); 3 or more children OR, 7.54 (95% CI, 3.80-14.94). Having children aged 6 to 7 years resulted in the highest rate of seroconversion among mothers (6.8%; OR, 4.07; 95% CI, 1.89-8.73). Compared with other pregnant women, nursery school teachers had a 3-fold increased risk of acute infection (OR, 3.09; 95% CI, 1.62-5.89). Population-attributable risk of seroconversion was 55.4% for number of own children and 6.0% for occupational exposure. Conclusions  The risk of infection is high for susceptible pregnant women during epidemics and associated with the level of contact with children. Nursery school teachers have the highest occupational risk, but most infections seem to be the result of exposure to the woman's own children.      

Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis

Context  Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. Objective  To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. Data Sources  Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. Study Selection  All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. Data Extraction  Individual records were provided on each of 154 211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13 210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. Data Synthesis  Within each age group considered (40-59, 60-69, and 70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. Conclusions  In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.      

Definitions and measurement of chronic health conditions in childhood: a systematic review

Context  Changes in the prevalence of chronic health conditions in childhood have considerable societal consequences for health care planning and for employment. To obtain valid and reliable estimates of the prevalence of chronic health conditions, a clear definition is needed. Objective  To present an overview of all definitions and operationalizations that have been applied to measure the prevalence of chronic health conditions in childhood. Data Sources  PubMed and the Web of Science were searched for articles published up to December 2006. Also, references were searched by hand for related articles. Study Selection  Non–English- and non–Dutch-language articles were excluded. Of 7252 articles found, 64 articles that stated a conceptual definition and/or operationalization of chronic health conditions in children (aged 0-18 years) were included. Data Extraction  Data on the (1) definition; (2) operationalization in terms of source of information, method of information retrieval, and study population; and (3) resulting prevalence rate were extracted by 2 independent reviewers. Data Synthesis  A large range of definitions were in use, of which 4 were cited by many authors. Various operationalizations of the concepts that were measured were identified. Chronic health conditions in childhood prevalence estimates ranged from 0.22% to 44%, depending on these operationalizations. Conclusions  The wide variability in reported prevalence rates of chronic health conditions in childhood can be explained by considerable diversity in the concepts and operationalizations used. International consensus about the conceptual definition of chronic health conditions in childhood is needed.      

Pregnancy in the sixth decade of life: obstetric outcomes in women of advanced reproductive age

Context  As a result of oocyte donation, women in their sixth decade of life are now able to conceive and carry pregnancies to term. However, little is known about pregnancy outcomes in this population. Objective  To describe pregnancy outcomes in women aged 50 years or older who conceived after in vitro fertilization with donor oocytes. Design and Setting  Retrospective analysis of cycles conducted at a US university assisted reproduction program during calendar years 1991-2001. Patients  Seventy-seven postmenopausal women with no chronic medical conditions (mean [SD] age, 52.8 [2.9] years; range, 50-63 years) who underwent 121 embryo transfer procedures (89 fresh and 32 frozen). Pregnancy outcomes were ascertained by chart review and telephone follow-up. Main Outcome Measures  Maternal and neonatal outcomes. Results  There were 55 clinical pregnancies for a total pregnancy rate of 45.5%. The live birth rate was 37.2%. Of the 45 live births, 31 were singletons, 12 were twins, and 2 were triplets, for which the mean (SD) gestational ages at delivery were 38.4 (2.1) weeks, 35.8 (2.8) weeks, and 32.2 weeks, respectively. Mean (SD) birth weights were 3039 g (703 g), 2254 g (581 g), and 1913 g, respectively. Apgar scores at 1 and 5 minutes were 8.2 (0.9) and 9.1 (0.5), respectively. Of singletons, 68% were delivered by cesarean, and all multiples were delivered by cesarean. Mild preeclampsia was noted in 25% of patients and severe preeclampsia in 10%. Gestational diabetes required diet modification in 17.5%, and 2.5% required insulin. Conclusions  Appropriately screened women aged 50 years or older can successfully conceive via oocyte donation and experience similar pregnancy rates, multiple gestation rates, and spontaneous abortion rates as younger recipients. During pregnancy, they appear at increased risk of preeclampsia and gestational diabetes. A majority can expect to deliver via cesarean. However, there does not appear to be any definitive medical reason for excluding these women from attempting pregnancy on the basis of age alone.      

Erectile dysfunction and subsequent cardiovascular disease

Context  The risk factors for cardiovascular disease and erectile dysfunction are similar. Objective  To examine the association of erectile dysfunction and subsequent cardiovascular disease. Design, Setting, and Participants  Men aged 55 years or older who were randomized to the placebo group (n = 9457) in the Prostate Cancer Prevention Trial at 221 US centers were evaluated every 3 months for cardiovascular disease and erectile dysfunction between 1994 and 2003. Proportional hazards regression models were used to evaluate the association of erectile dysfunction and cardiovascular disease. In an adjusted model, covariates included age, body mass index, blood pressure, serum lipids, diabetes, family history of myocardial infarction, race, smoking history, physical activity, and quality of life. Main Outcome Measures  Erectile dysfunction and cardiovascular disease. Results  Of the 9457 men randomized to placebo, 8063 (85%) had no cardiovascular disease at study entry; of these men, 3816 (47%) had erectile dysfunction at study entry. Among the 4247 men without erectile dysfunction at study entry, 2420 men (57%) reported incident erectile dysfunction after 5 years. After adjustment, incident erectile dysfunction was associated with a hazard ratio of 1.25 (95% confidence interval [CI], 1.02-1.53; P = .04) for subsequent cardiovascular events during study follow-up. For men with either incident or prevalent erectile dysfunction, the hazard ratio was 1.45 (95% CI, 1.25-1.69; P<.001). For subsequent cardiovascular events, the unadjusted risk of an incident cardiovascular event was 0.015 per person-year among men without erectile dysfunction at study entry and was 0.024 per person-year for men with erectile dysfunction at study entry. This association was in the range of risk associated with current smoking or a family history of myocardial infarction. Conclusions  Erectile dysfunction is a harbinger of cardiovascular clinical events in some men. Erectile dysfunction should prompt investigation and intervention for cardiovascular risk factors.      

Sirolimus-eluting stents vs paclitaxel-eluting stents in patients with coronary artery disease: meta-analysis of randomized trials

Context  Placement of sirolimus-eluting stents or paclitaxel-eluting stents has emerged as the predominant percutaneous treatment strategy in patients with coronary artery disease (CAD). Whether there are any differences in efficacy and safety between these 2 drug-eluting stents is unclear. Objective  To compare outcomes of sirolimus-eluting and paclitaxel-eluting coronary stents on the basis of data generated by randomized head-to-head clinical trials. Data Sources  PubMed and the Cochrane Central Register of Controlled Trials, conference proceedings from major cardiology meetings, and Internet-based sources of information on clinical trials in cardiology from January 2003 to April 2005. Study Selection  Randomized trials comparing the sirolimus-eluting stent with the paclitaxel-eluting stent in patients with CAD reporting the outcomes of interest (target lesion revascularization, angiographic restenosis, stent thrombosis, myocardial infarction [MI], death, and the composite of death or MI) during a follow-up of at least 6 months. Data Extraction  Two reviewers independently identified studies and abstracted data on sample size, baseline characteristics, and outcomes of interest. Data Synthesis  Six trials, including 3669 patients, met the selection criteria. No significant heterogeneity was found across trials. Target lesion revascularization, the primary outcome of interest, was less frequently performed in patients who were treated with the sirolimus-eluting stent (5.1%) vs the paclitaxel-eluting stent (7.8%) (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.49-0.84; P = .001). Similarly, angiographic restenosis was less frequently observed among patients assigned to the sirolimus-eluting stent (9.3%) vs the paclitaxel-eluting stent (13.1%) (OR, 0.68; 95% CI, 0.55-0.86; P = .001). Event rates for sirolimus-eluting vs paclitaxel-eluting stents were 0.9% and 1.1%, respectively, for stent thrombosis (P = .62); 1.4% and 1.6%, respectively, for death (P = .56); and 4.9% and 5.8%, respectively, for the composite of death or MI (P = .23). Conclusions  Patients receiving sirolimus-eluting stents had a significantly lower risk of restenosis and target vessel revascularization compared with those receiving paclitaxel-eluting stents. Rates of death, death or MI, and stent thrombosis were similar.      

Thyroid status, cardiovascular risk, and mortality in older adults

Context  Previous studies have suggested that subclinical abnormalities in thyroid-stimulating hormone levels are associated with detrimental effects on the cardiovascular system. Objective  To determine the relationship between baseline thyroid status and incident atrial fibrillation, incident cardiovascular disease, and mortality in older men and women not taking thyroid medication. Design, Setting, and Participants  A total of 3233 US community-dwelling individuals aged 65 years or older with baseline serum thyroid-stimulating hormone levels were enrolled in 1989-1990 in the Cardiovascular Health Study, a large, prospective cohort study. Main Outcome Measures  Incident atrial fibrillation, coronary heart disease, cerebrovascular disease, cardiovascular death, and all-cause death assessed through June 2002. Analyses are reported for 4 groups defined according to thyroid function test results: subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism. Results  Individuals with overt thyrotoxicosis (n = 4) were excluded because of small numbers. Eighty-two percent of participants (n = 2639) had normal thyroid function, 15% (n = 496) had subclinical hypothyroidism, 1.6% (n = 51) had overt hypothyroidism, and 1.5% (n = 47) had subclinical hyperthyroidism. After exclusion of those with prevalent atrial fibrillation, individuals with subclinical hyperthyroidism had a greater incidence of atrial fibrillation compared with those with normal thyroid function (67 events vs 31 events per 1000 person-years; adjusted hazard ratio, 1.98; 95% confidence interval, 1.29-3.03). No differences were seen between the subclinical hyperthyroidism group and euthyroidism group for incident coronary heart disease, cerebrovascular disease, cardiovascular death, or all-cause death. Likewise, there were no differences between the subclinical hypothyroidism or overt hypothyroidism groups and the euthyroidism group for cardiovascular outcomes or mortality. Specifically, individuals with subclinical hypothyroidism had an adjusted hazard ratio of 1.07 (95% confidence interval, 0.90-1.28) for incident coronary heart disease. Conclusion  Our data show an association between subclinical hyperthyroidism and development of atrial fibrillation but do not support the hypothesis that unrecognized subclinical hyperthyroidism or subclinical hypothyroidism is associated with other cardiovascular disorders or mortality.      

History and molecular genetics of Lynch syndrome in family G: a century later

Context  In 1895, Aldred Scott Warthin, MD, PhD, initiated one of the most thoroughly documented and longest cancer family histories ever recorded. The unusually high incidence and segregation of cancers of the colon, rectum, stomach, and endometrium in Dr Warthin’s family G was later followed up by his colleagues, most recently by Henry Lynch, MD. Described today as a Lynch syndrome family, family G was last documented in 1971, prior to the modern era of molecular diagnostics. Objective  To update family G. Design, Setting, and Participants  Historical prospective cohort study of family G members from 1895 to 2000. Main Outcome Measures  The primary outcomes were the frequencies and types of cancers, ages at diagnosis, and presence of the T to G transversion at the splice acceptor site of exon 4 of the mutS homolog 2, colon cancer, nonpolyposis type 1 (E coli) (MSH2) gene in family G members. A secondary analysis compared cancer-specific incidence rates in family G with published national and regional cancer incidence rates through the standardized incidence ratio (SIR). Results  Family G now has 929 known descendants of the original progenitor first reported in 1913. Cancers of the colon and rectum (SIR, 3.20; 95% confidence interval [CI], 2.39-4.19) and endometrium (SIR, 3.51; 95% CI, 1.92-5.89) continue to predominate in family G. Five of 40 tested members of family G carry the MSH2 T to G mutation; as a result, 15 of their living relatives are at increased risk of developing 1 or more colorectal or Lynch syndrome–associated cancers. In contrast, 97 living members of family G can now be excluded as mutation carriers. Conclusion  Within the last decade, molecular diagnostic testing has transformed the care of family G and other Lynch syndrome families in which a pathogenic mutation has been identified.