Do variations in disease prevalence limit the usefulness of population-based hospitalization rates for studying variations in hospital admissions?

BACKGROUND: Studies of geographic variation in hospitalizations commonly examine age- and gender-adjusted population-based hospitalization rates (ie, the numbers of persons hospitalized relative to what is expected given the age/gender distributions in the area population). OBJECTIVE: To determine whether areas identified as extreme using population-based hospitalization rates remain extreme when ranked by disease-based hospitalization rates (the numbers of persons hospitalized relative to what is expected given the amount of disease in the area). DESIGN: The authors examined 1997 Medicare data on both inpatient admissions and outpatient visits of patients 65 years and older in each of 71 small areas in Massachusetts for 15 medical conditions. For each area, the number of people having each condition was calculated as the sum of those hospitalized plus those treated as outpatients only. The authors used hierarchical Bayesian modeling to estimate area-specific population-based hospitalization rates, disease-based hospitalization rates (DHRs), and disease prevalence. MAIN OUTCOME MEASURE: The extent to which the same areas were identified as extreme based on population-based hospitalization rates versus DHRs. RESULTS: Area-specific population-based hospitalization rates, DHRs, and disease prevalence varied substantially. Areas identified as extreme using population-based hospitalization rates often were not extreme when ranked by DHRs. For 11 of the 15 conditions, 5 or more of the 14 areas ranked in top and bottom deciles by population-based hospitalization rates were more likely than not (ie, with probability > or = 0.50) to be at least 2 deciles less extreme when ranked by DHRs. CONCLUSION: Differences in disease prevalence can limit the usefulness of population-based hospitalization rates for studying variations in hospital admissions.     

Seasonal variations in acute toxoplasmosis in pregnant women in the Rh?ne-Alpes region (France)

Clin Microbiol Infect 2012; 18: E401-E403 ABSTRACT: To search for seasonal variations we analysed data on 1998 acute toxoplasmic infections diagnosed between 1988 and 2009 in pregnant women. Two distinctive transmission profiles were observed: one in rural areas, which was strongly influenced by seasons with significantly fewer infections in the first half of the year but maximal risks at the end of summer and end of autumn, and a stable urban distribution with only moderate peaks. Further studies on individual risks and environmental and climatic factors are needed to understand what prevention message should be given to susceptible pregnant women.     

Estimation of seasonal variations in risk factor profiles and mortality from coronary heart disease

OBJECTIVE: Seasonal variations in coronary heart disease (CHD) and related risk factors have been reported previously. However, no studies to date quantify the contribution of seasonal variations in risk factors to actual mortality in both men and women using a single database of sufficient size and follow-up. METHODS: We investigated the database from the Western Austrian Vorarlberg Health Monitoring and Promotion Programme (VHM&PP) including over 450,000 repeated measurements of 149,650 individuals between 1985 and 1999. RESULTS: Of a total of 1266 deaths from CHD (ICD-9 410-414), 353 deaths occurred between December and February (27.9%), in contrast to 275 (21.7%) between June and August. While the frequency of deaths through acute myocardial infarction (ICD-9 410) was similar over the seasons, chronic forms of CHD (ICD-9 414) occurred significantly (p < 0.001) more frequently in winter. Total cholesterol, blood pressure and body mass index showed pronounced seasonal variations with average levels significantly higher during the winter months in all age groups and both sexes, giving an estimated increase in score risk of 6.8% in men and 3.6% in women. However by contrast, use of single time point risk factor data tended to over-estimate subsequent 10 year mortality if measured in winter and the converse in summer. CONCLUSION: For the first time, this study quantifies the contribution of seasonal risk factor variation to CHD mortality. The consistent effect across demographic groups suggests that this is a real physiological phenomenon and not an artefact of living conditions. Interpretation of standard risk scores should take account of this seasonal fluctuation in subsequent investigation and follow-up.     

Sample sizes for time-to-event endpoints: Should you insure against chance variations in accrual?

This note addresses the questions of whether one should safeguard against a potential loss of power due to random variations of the accrual time, how this "insurance" can be formulated, and how much the sample size needs to be increased to obtain it.     

Can hospital structural and financial characteristics explain variations in mortality caused by acute myocardial infarction?

Each year 1 in 160 people in the United States suffers from acute myocardial infarction (AMI). Of these more than 1.5 million cases annually, 500,000 end in fatalities. This study's purpose was to describe and evaluate the role hospital characteristics play in rates of mortality caused by AMI in acute-care California hospitals. Characteristics evaluated include structural characteristics--i.e., teaching status, percentage of board-certified physicians, registered nurse hours per patient day (RN hours/patient day), volume of cases, technological resource availability, and urban density; and financial characteristics--profit status and total operating expenses per patient day. Although part of a larger investigation correlating mortality and length of stay, this article reports only the results for significant influences on mortality.     

Analysis of sequence variations in the LDL receptor gene in Spain: general gene screening or search for specific alterations?

BACKGROUND: Familial hypercholesterolemia (FH) is a frequent form of autosomal-dominant hypercholesterolemia that predisposes to premature coronary atherosclerosis. FH is caused by sequence variations in the gene coding for the LDL receptor (LDLR). This gene has a wide spectrum of sequence variations, and genetic diagnosis can be performed by 2 strategies. METHODS: Point variations and large rearrangements were screened along all the LDLR gene (promoter, exons, and flanking intron sequences). RESULTS: We screened a sample of 129 FH probands from the Valencian Community, Spain, and identified 54 different LDLR sequence variations. The most frequent (10% of cases) was 111insA, and 60% of the variants had a frequency as low as 1%. A previously described method for detection of known sequence variations in the Spanish population by DNA array analysis allowed the identification of only approximately 50% of patients with a variant LDLR gene and approximately 40% of the screened samples. CONCLUSION: Our results indicate that the adequate procedure to identify LDLR sequence variations in outbreed populations should include screening of the entire gene.     

Weight variations in the prophylactic therapy of primary headaches: 6–month follow–up

We conducted a study on 367 patients (86% female, 14% male; mean age 37±15 years) suffering from migraine with and without aura and chronic tension–type headache to evaluate the incidence of weight gain, an undesirable side effect observed during prophylactic therapy in primary headaches. Patients treated with amitriptyline (20 and 40 mg), pizotifen (1 mg), propranolol (80–160 mg), atenolol (50–100 mg), verapamil (160–240 mg), valproate (600 mg) and gabapentin (900–1200 mg) were evaluated after a period of 3 and 6 months. In particular, 89 patients were assessed (78% female, 22% male) at 6 months, of whom 10 were in treatment with amitriptyline 20 mg, 19 with amitriptyline 40 mg, 7 with pizotifen (1 mg), 13 with propranolol (80–160 mg), 4 with verapamil (160 mg), 10 with valproate (600 mg), 15 with atenolol (50 mg) and 11 with gabapentin (900–1200 mg). The control group consisted of 97 patients with migraine (79% female, 21% male; mean age 35±16 years) without indication for prophylactic therapy. Weight variations ≥1 kg were considered. After 6 months of therapy, the percentage of patients with weight gain was 86% with pizotifen (6/7; mean weight increase 4.4±2.5 kg), 60% with amitriptyline 20 mg (6/10; 3.1±1.6), 47% with amitriptyline 40 mg (9/19; 5.4±2.7), 25% with valproate 600 mg (2/8, 3.0±2.8 kg), 25% with verapamil (1/4, 2.5 kg), 20% with atenolol (3/15, 1.7±0.6 kg), 9% with gabapentin (1/11, 1.5 kg) and 8% with propranolol (1/13; 6 kg). We conclude that propranolol, gabapentin, atenolol, verapamil and valproate affect body weight in a modest percentage of patients at 6 months. A greater mean weight gain at 6 months was found in patients treated with pizotifen, amitriptyline, and, in one patient out of 13, with propranolol.     

Pancreatic Steatosis and Its Relationship to β-Cell Dysfunction in Humans: Racial and ethnic variations

OBJECTIVE

To evaluate racial/ethnic differences in pancreatic triglyceride (TG) levels and their relationship to β-cell dysfunction in humans.

RESEARCH DESIGN AND METHODS

We studied black, Hispanic, and white adults who completed three research visits: screening and an oral glucose tolerance test; frequently sampled intravenous glucose tolerance tests for evaluation of β-cell function and insulin resistance; and proton magnetic resonance spectroscopy for evaluation of pancreatic and hepatic TG levels.

RESULTS

Pancreatic TG levels were higher in Hispanics and whites than in blacks (P = 0.006). Hepatic TG levels were highest in Hispanics (P = 0.004). Compensatory insulin secretion and disposition index were higher in blacks (P = 0.003 and P = 0.024, respectively). Insulin sensitivity was comparable between Hispanics and blacks and was lower than in whites (P = 0.005). In blacks, compensatory insulin secretion increased steeply with small increments in pancreatic TG levels (R² = 0.45, slope = 247). In whites, the range of pancreatic TG levels was higher, and the slope was less steep than in blacks (R² = 0.27, slope = 27). In Hispanics, pancreatic TG levels were similar to those of whites, but compensatory insulin secretion was described by a combination of pancreatic and hepatic TG levels and visceral fat mass ( R² = 0.32).

CONCLUSIONS

In a multiethnic sample of adults with mild obesity and without diabetes, we found striking ethnic differences in the levels of pancreatic TGs and in the relationship between pancreatic TGs and β-cell dysfunction. Our data implicate pancreatic TG content measured by proton magnetic resonance spectroscopy as a noninvasive novel biomarker for pancreatic β-cell dysfunction, especially in the Hispanic population.Diet-induced obesity (1) dramatically increases the risk—by >40-fold in certain populations (2)—for type 2 diabetes. A better understanding of the underlying mechanisms by which overnutrition-induced obesity causes diabetes could lead to the discovery of novel preemptive interventions.One putative mechanism is pancreatic steatosis with β-cell lipotoxicity (3). We define steatosis as high levels of triglyceride (TG) droplets in the cytosol of nonadipose cells and lipotoxicity as organ dysfunction caused by steatosis. It is important to note that cytosolic TG droplets are not toxic themselves but byproducts of their exaggerated metabolism are toxic and cause lipotoxic β-cell dysfunction, at least in animal models. In the Zucker diabetic fatty (ZDF) rat, a standard genetic model of obesity-related diabetes, pancreatic steatosis heralds the transition from insulin resistance with compensated hyperinsulinemia to β-cell failure and frank diabetes. In this model, excess of cytosolic TG marks excessive levels of ceramide and other toxic metabolites that activate inducible nitric oxide synthase to cause progressive β-cell apoptosis and failure (4–6). A key question is to what extent can this mechanistic hypothesis be translated to common obesity-related diabetes in humans?Localized proton magnetic resonance spectroscopy (¹H MRS) was developed as a noninvasive clinical research tool to conduct translational research testing steatosis and lipotoxicity hypotheses with precise in vivo quantification of cytosolic TGs within parenchymal cells of human skeletal muscle (7), liver (8), and heart muscle (9,10). This research has implicated skeletal muscle and liver steatosis as a cause of insulin resistance (11,12) and cardiac steatosis as a cause of obesity-related cardiomyopathy (13). More recently, we validated localized ¹H MRS as a measure of pancreatic TG levels (14). Insulin-secreting β-cells cannot be differentiated from non–insulin-secreting parenchymal cells of the human pancreas with ¹H MRS. However, in the ZDF rat, we documented that the accumulation of TGs in pancreatic tissue as measured by ¹H MRS closely parallels the development of β-cell failure both in time course and magnitude (14). We then demonstrated that pancreatic TG content is highly reproducible when healthy human subjects are studied repeatedly and that pancreatic TG level increases with increasing stages of human obesity and glucose intolerance even before the development of type 2 diabetes (14).The goal of this study was to test whether pancreatic TG constitutes a novel biomarker of early (prediabetic) β-cell dysfunction in human subjects representing the three major race/ethnic groups in the United States. African Americans and Hispanic Americans are known to have higher rates of type 2 diabetes than white Americans, even after adjustment for BMI (15). Moreover, Hispanic Americans are known to have higher rates of hepatic steatosis than other groups (8,12). However, ethnic differences in pancreatic steatosis—and its relationship to β-cell dysfunction—have not been studied previously.     

Are regional variations in end-of-life care intensity explained by patient preferences?: A Study of the US Medicare Population

OBJECTIVE: We sought to test whether variations across regions in end-of-life (EOL) treatment intensity are associated with regional differences in patient preferences for EOL care. RESEARCH DESIGN: Dual-language (English/Spanish) survey conducted March to October 2005, either by mail or computer-assisted telephone questionnaire, among a probability sample of 3480 Medicare part A and/or B eligible beneficiaries in the 20% denominator file, age 65 or older on July 1, 2003. Data collected included demographics, health status, and general preferences for medical care in the event the respondent had a serious illness and less than 1 year to live. EOL concerns and preferences were regressed on hospital referral region EOL spending, a validated measure of treatment intensity. RESULTS: A total of 2515 Medicare beneficiaries completed the survey (65% response rate). In analyses adjusted for age, sex, race/ethnicity, education, financial strain, and health status, there were no differences by spending in concern about getting too little treatment (39.6% in lowest spending quintile, Q1; 41.2% in highest, Q5; P value for trend, 0.637) or too much treatment (44.2% Q1, 45.1% Q5; P = 0.797) at the end of life, preference for spending their last days in a hospital (8.4% Q1, 8.5% Q5; P = 0.965), for potentially life-prolonging drugs that made them feel worse all the time (14.4% Q1, 16.5% Q5; P = 0.326), for palliative drugs, even if they might be life-shortening (77.7% Q1, 73.4% Q5; P = 0.138), for mechanical ventilation if it would extend their life by 1 month (21% Q1, 21.4% Q5; P = 0.870) or by 1 week (12.1% Q1, 11.7%; P = 0.875). CONCLUSIONS: Medicare beneficiaries generally prefer treatment focused on palliation rather than life-extension. Differences in preferences are unlikely to explain regional variations in EOL spending.     

Why do pulse pressure variations fail to predict the response to fluids in acute respiratory distress syndrome patients ventilated with low tidal volume?

Respiratory-associated variations in stroke volume and pulse pressure are frequently used to predict the response to fluid administration. However, it has been demonstrated that low tidal volume ventilation may limit their use in patients with acute respiratory distress syndrome (ARDS). In this issue, a trial investigates the value of pulse pressure variation to predict fluid responsiveness in a large series of patients with ARDS ventilated according to current guidelines.