Long-term comparative safety analysis of the risks associated with adding or switching to a sulfonylurea as second-line Type 2 diabetes mellitus treatment in a US veteran population.

AIM: To examine the risks of all-cause mortality and cardiovascular events associated with adding vs switching to second-line therapies in a comparative safety study of people with Type 2 diabetes mellitus. METHODS: We conducted a retrospective cohort study using an as-treated analysis of people served by the Veterans Health Administration who were on metformin and subsequently augmented this treatment or switched to other oral glucose-lowering treatments between 1998 and 2012. This study included 145 250 people with long follow-up. Confounding was addressed through several strategies, involving weighted propensity score models with rich confounder adjustment and strict inclusion criteria, coupled with an incident-user design. RESULTS: Second-line use of sulfonylureas was related to higher mortality (hazard ratio 1.39, 95% CI 1.14, 1.70) and cardiovascular risks (hazard ratio 1.19, 95% CI 1.09, 1.30) compared with thiazolidinedione therapy. Differential hazards were associated with discontinuing or not discontinuing metformin; switching to sulfonylurea therapy was associated with a higher risk of all-cause mortality and cardiovascular events compared with all other therapies. Furthermore, add-on sulfonylurea therapy was associated with an elevated risk for both outcomes when compared with thiazolidinedione add-on therapy. CONCLUSIONS: The results of the present study may inform decisions on whether to augment or discontinue metformin; when considering the long-term risks, switching to a sulfonylurea appears unfavourable compared with other therapies. Instead, adding a thiazolidinedione to existing metformin therapy appears to be superior to adding or switching to a sulfonylurea.

Older Veteran Experiences of using Technology during a Multicomponent Telerehabilitation Program: A Convergent Mixed Methods Study.

Less than half of U.S. veterans meet physical activity guidelines. Even though changing physical activity can be challenging, prior studies have demonstrated that it is possible. Older adults are using technology to aid in such behavior change. However, research that explores the mechanisms of how technology can aid in behavior change is lacking, especially among older veterans. Thus, the purpose of this secondary, convergent mixed methods study was to explore how older veterans engaged with technologies that were used during a multicomponent telerehabilitation program. The study included veterans aged ≥60 years with ≥3 chronic medical conditions and physical function limitation. Quantitative data were collected during the primary randomized controlled trial, and qualitative data were collected via individual interviews following completion of the telerehabilitation program. Data were merged and then analyzed by high vs. low technology engagement groups. Key similarities and differences between groups were identified in five domains: satisfaction with the virtual environment, coping self-efficacy, perceptions of Annie (automated text messaging platform), experiences using the activity monitor, and self-management skills. Findings can help inform the successful integration of similar technologies into physical rehabilitation programs. Further study is warranted to understand additional factors and mechanisms that influence technology engagement in telerehabilitation.

Hepatitis C testing practices and prevalence in a high-risk urban ambulatory care setting.

Approximately 3.2 million persons are chronically infected with the hepatitis C virus (HCV) in the U.S.; most are not aware of their infection. Our objectives were to examine HCV testing practices to determine which patient characteristics are associated with HCV testing and positivity, and to estimate the prevalence of HCV infection in a high-risk urban population. The study subjects were all patients included in the baseline phase of the Hepatitis C Assessment and Testing Project (HepCAT), a serial cross-sectional study of HCV screening strategies. We examined all patients with a clinic visit to Montefiore Medical Center from 1/1/08 to 2/29/08. Demographic information, laboratory data and ICD-9 diagnostic codes from 3/1/97-2/29/08 were extracted from the electronic medical record. Risk factors for HCV were defined based on birth date, ICD-9 codes and laboratory data. The prevalence of HCV infection was estimated assuming that untested subjects would test positive at the same rate as tested subjects, based on risk-factors. Of 9579 subjects examined, 3803 (39.7%) had been tested for HCV and 438 (11.5%) were positive. The overall prevalence of HCV infection was estimated to be 7.7%. Risk factors associated with being tested and anti-HCV positivity included: born in the high-prevalence birth-cohort (1945-64), substance abuse, HIV infection, alcohol abuse, diagnosis of cirrhosis, end-stage renal disease, and alanine transaminase elevation. In a high-risk urban population, a significant proportion of patients were tested for HCV and the prevalence of HCV infection was high. Physicians appear to use a risk-based screening strategy to identify HCV infection.

Trunk and pelvis movement compensation in people with multiple sclerosis: Relationships to muscle function and gait performance outcomes.

BACKGROUND: Problems with gait are common in people with multiple sclerosis (MS), but little is known about pelvis and trunk kinematics, especially in the frontal plane. RESEARCH QUESTION: Are pelvis and trunk kinematics in people with MS related to muscle function, spatiotemporal parameters, and gait performance? METHODS: In this cross-sectional study, 20 people with MS (Expanded Disability Status Scale 1.5-5.5) and 10 people with comparable age and sex (CTL) underwent threedimensional gait analysis, muscle function assessments (hip and trunk strength and endurance), and gait performance measures (Timed 25-Foot Walk - T25FW, 2-Minute Walk Test - 2MWT). Frontal and sagittal plane pelvis and trunk excursion during the stance period of walking were compared between groups; and in the MS group, associations were determined between kinematic variables, muscle function, spatiotemporal parameters, and gait performance. RESULTS: Compared to the CTL group, the MS group had significantly greater sagittal plane trunk and pelvis excursion for both the stronger (p = 0.031) and weaker (p = 0.042) sides; less frontal plane trunk and pelvis excursion for both the stronger (p = 0.008) and weaker (p = 0.024) sides; and more sagittal plane trunk excursion for the stronger side (p = 0.047) during stance phase. There were low-to-moderate correlations in the MS group for sagittal plane pelvis excursion with muscle function (p = 0.019 to 0.030), spatiotemporal parameters (p < 0.001 to 0.005), and gait performance (p = < 0.001 to 0.001). Using linear regression, frontal and sagittal plane pelvis excursion were significant predictors of both T25FW and 2MWT, explaining 34 % and 46 % of the variance of each gait performance measure, respectively. SIGNIFICANCE: Rehabilitation interventions may consider addressing pelvis movement compensations in order to improve spatiotemporal parameters and gait performance in people with MS.

Predicting the cumulative risk of false-positive mammograms.

BACKGROUND: The cumulative risk of a false-positive mammogram can be substantial. We studied which variables affect the chance of a false-positive mammogram and estimated cumulative risks over nine sequential mammograms. METHODS: We used medical records of 2227 randomly selected women who were 40-69 years of age on July 1, 1983, and had at least one screening mammogram. We used a Bayesian discrete hazard regression model developed for this study to test the effect of patient and radiologic variables on a first false-positive screening and to calculate cumulative risks of a false-positive mammogram. RESULTS: Of 9747 screening mammograms, 6. 5% were false-positive; 23.8% of women experienced at least one false-positive result. After nine mammograms, the risk of a false-positive mammogram was 43.1% (95% confidence interval [CI] = 36.6%-53.6%). Risk ratios decreased with increasing age and increased with number of breast biopsies, family history of breast cancer, estrogen use, time between screenings, no comparison with previous mammograms, and the radiologist's tendency to call mammograms abnormal. For a woman with highest-risk variables, the estimated risk for a false-positive mammogram at the first and by the ninth mammogram was 98.1% (95% CI = 69.3%-100%) and 100% (95% CI = 99.9%-100%), respectively. A woman with lowest-risk variables had estimated risks of 0.7% (95% CI = 0.2%-1.9%) and 4.6% (95% CI = 1. 1%-12.5%), respectively. CONCLUSIONS: The cumulative risk of a false-positive mammogram over time varies substantially, depending on a woman's own risk profile and on several factors related to radiologic screening. By the ninth mammogram, the risk can be as low as 5% for women with low-risk variables and as high as 100% for women with multiple high-risk factors.

Prognostic stratification in critically ill patients with acute renal failure requiring dialysis.

BACKGROUND: Despite the widespread availability of dialytic and intensive care unit technology, the probability of early mortality in critically ill persons with acute renal failure is distressingly high. Previous efforts to predict outcome in this population have been limited by small sample size and the absence of uniform exclusion criteria. Additionally, data obtained decades ago may not apply today owing to changes in case mix. METHODS: The medical records of 132 consecutive patients in the intensive care unit with acute renal failure who required dialysis from 1991 through 1993 were evaluated by a blinded reviewer. RESULTS: The overall in-hospital mortality rate was 70%. Twelve readily available historical, clinical, and laboratory variables were significantly associated with in-hospital mortality. Multivariate logistic regression analysis showed that mechanical ventilation, malignancy, and nonrespiratory organ system failure were independently associated with in-hospital mortality. Using a 95% positivity criterion, this model identified 24% of high-risk patients who died, without misclassification of any survivors. Of those who survived to hospital discharge, 33% were dialysis dependent and 28% were institutionalized long-term. CONCLUSIONS: Among critically ill patients, acute renal failure requiring dialysis is an ominous condition with a high risk of in-hospital mortality. This risk appears to depend largely on comorbid conditions, such as the need for mechanical ventilation and underlying malignancy. While this prognostic model requires prospective validation, it appears to identify a substantial fraction of patients for whom dialysis may be of limited or no benefit.

Timeliness and quality of care for elderly patients with acute myocardial infarction under health maintenance organization vs fee-for-service insurance.

BACKGROUND: A commonly voiced concern is that health maintenance organizations (HMOs) may withhold or delay the provision of urgent, essential care, especially for vulnerable patients like the elderly. OBJECTIVE: To compare the quality of emergency care provided in Minnesota to elderly patients with acute myocardial infarction (AMI) who are covered by HMO vs fee-for-service (FFS) insurance. METHODS: We reviewed the medical records of 2304 elderly Medicare patients who were admitted with AMI to 20 urban community hospitals in Minnesota (representing 91% of beds in areas served by HMOs) from October 1992 through July 1993 and from July 1995 through April 1996. MAIN OUTCOME MEASURES: Use of emergency transportation and treatment delay (>6 hours from symptom onset); time to electrocardiogram; use of aspirin, thrombolytics, and beta-blockers among eligible patients; and time from hospital arrival to thrombolytic administration (door-to-needle time). RESULTS: Demographic characteristics, severity of symptoms, and comorbidity characteristics were almost identical among HMO (n = 612) and FFS (n = 1692) patients. A cardiologist was involved as a consultant or the attending physician in the care of 80% of HMO patients and 82% of FFS patients (P = .12). The treatment delay, time to electrocardiogram, use of thrombolytic agents, and door-to-needle times were almost identical. However, 56% of HMO patients and 51% of FFS patients used emergency transportation (P = .02); most of this difference was observed for patients with AMIs that occurred at night (60% vs 52%; P = .02). Health maintenance organization patients were somewhat more likely than FFS patients to receive aspirin therapy (88% vs 83%; P = .03) and beta-blocker therapy (73% vs 62%; P = .04); these differences were partly explained by a significantly larger proportion of younger physicians in HMOs who were more likely to order these drug therapies. All differences were consistent across the 3 largest HMOs (1 staff-group model and 2 network model HMOs). Logistic regression analyses controlling for demographic and clinical variables produced similar results, except that the differences in the use of beta-blockers became insignificant. CONCLUSIONS: No indicators of timeliness and quality of care for elderly patients with AMIs were lower under HMO vs FFS insurance coverage in Minnesota. However, two indicators of quality care were slightly but significantly higher in the HMO setting (use of emergency transportation and aspirin therapy). Further research is needed in other states, in different populations, and for different medical conditions.

MR relaxometry for the facial ageing assessment: the preliminary study of the age dependency in the MR relaxometry parameters within the facial soft tissue.

OBJECTIVES: To investigate the location-specific tissue properties and age-related changes of the facial fat and facial muscles using quantitative MRI (qMRI) analysis of longitudinal magnetization (T1) and transverse magnetization (T2) values. METHODS: 38 subjects (20 males and 18 females, 0.5-87 years old) were imaged with a mixed turbo-spin echo sequence at 1.5 T. T1 and T2 measurements were obtained within regions of interest in six facial fat regions including the buccal fat and subcutaneous cheek fat, four eyelid fat regions (lateral upper, medial upper, lateral lower and medial lower) and five facial muscles including the orbicularis oculi, orbicularis oris, buccinator, zygomaticus major and masseter muscles bilaterally. RESULTS: Within the zygomaticus major muscle, age-associated T1 decreases in females and T1 increases in males were observed in later life with an increase in T2 values with age. The orbicularis oculi muscles showed lower T1 and higher T2 values compared to the masseter, orbicularis oris and buccinator muscles, which demonstrated small age-related changes. The dramatic age-related changes were also observed in the eyelid fat regions, particularly within the lower eyelid fat; negative correlations with age in T1 values (p<0.0001 for age) and prominent positive correlation in T2 values in male subjects (p<0.0001 for male×age). Age-related changes were not observed in T2 values within the subcutaneous cheek fat. CONCLUSIONS: This study demonstrates proof of concept using T1 and T2 values to assess age-related changes of the facial soft tissues, demonstrating tissue-specific qMRI measurements and non-uniform ageing patterns within different regions of facial soft tissues.

The accuracy of symptom reporting by patients complaining of palpitations.

PURPOSE: To examine the relationship between patients' reports of palpitations and documented arrhythmias. PATIENTS AND METHODS: Consecutive patients complaining of palpitations and referred for 24-hour ambulatory electrocardiographic monitoring were studied using self-report questionnaires and a structured diagnostic interview. Electrocardiographic results were subsequently analyzed in conjunction with symptom diaries. Positive predictive value was used to estimate the likelihood that a reported symptom coincided with a documented arrhythmia. Sensitivity was calculated as a measure of the likelihood that an arrhythmia would be detected and reported as a symptom. RESULTS: Positive predictive value was inversely related to somatization, hypochondriacal attitudes, and psychiatric symptoms. It was not related to chronicity of palpitations, previously diagnosed heart disease, more extensive medical care utilization, or clinically significant arrhythmias. Patients were generally insensitive to their arrhythmias, failing to note the vast majority. CONCLUSIONS: Somatizing and hypochondriacal patients are not more sensitive to or accurately aware of subtle changes in cardiac activity, but rather may be expressing a response bias toward reporting somatic and psychologic distress in general. Apparently, patients do not learn to discriminate and detect cardiac activity more accurately as a result of having more medical care or suffering longer with their symptoms.

Screening for colorectal cancer with flexible sigmoidoscopy by nonphysician endoscopists.

PURPOSE: Screening with sigmoidoscopy reduces the risk of death from colorectal cancer. Only 30% of eligible patients have undergone sigmoidoscopy, in part because of a limited supply of endoscopists. We evaluated the performance and safety of screening sigmoidoscopic examinations by trained nonphysician endoscopists in comparison with board-certified gastroenterologists. SUBJECTS AND METHODS: Asymptomatic patients 50 years or older without evidence of fecal occult blood and no personal history or family history of a first-degree relative with colorectal cancer under age 55 years were offered sigmoidoscopy. All examinations were performed either by a gastroenterologist or a trained nonphysician endoscopist at a staff model health maintenance organization. Outcomes included the depth of examination, number and histology of polyps, and complications. RESULTS: Nonphysicians performed 2,323 sigmoidoscopic examinations, and physicians performed 1,378 examinations. The mean (+/-SD) depth of sigmoidoscopy examinations performed by nonphysicians was 52 +/- 10 cm compared with 55 +/- 9 cm (P <0.001) in physicians. Nonphysicians detected neoplastic polyps in a greater proportion of patients (7.8%) than physicians (5.8%), but this difference was not significant after adjusting for differences in the age, sex, and family history of the patients (P = 0.35). No major complications occurred. The cost per examination, including the nonphysician training cost, was lower for nonphysicians ($186 per examination) than for physicians ($283 per examination). CONCLUSIONS: Appropriately trained nonphysicians may be capable of performing safe and effective screening for colorectal cancer with flexible sigmoidoscopy. An increased use of nonphysicians to perform sigmoidoscopy may increase the availability and reduce the cost of the procedure.

Fever in pediatric primary care: occurrence, management, and outcomes.

OBJECTIVE: To describe the epidemiology, management, and outcomes of children with fever in pediatric primary care practice. PATIENTS: A cohort of 20 585 children 3 to 36 months of age cared for in 11 pediatric offices of a health maintenance organization between 1991 and 1994. METHODS: Using automated medical records we identified all office visits with temperatures >/=38 degrees C for a random sample of 5000 children, and analyzed diagnoses conferred, laboratory tests performed, and antibiotics prescribed. We also determined the frequency of in-person and telephone follow-up after initial visits for fever. Finally, we reviewed hospital claims data for the entire cohort of 20 585 to identify cases of meningitis, meningococcal sepsis, and death from infection. RESULTS: Among 3819 initial visits of an illness episode, 41% of children had no diagnosed bacterial or specific viral source. Of these, 13% with a temperature of 38 degrees C to 39 degrees C and 36% with a temperature of >/=39 degrees C received laboratory testing. Almost half (43%) received some documented follow-up care in the subsequent 7 days. Among the 26 970 child-years of observation in the entire cohort, 15 children (56 per 100 000 child-years) were treated for bacterial meningitis or meningococcal sepsis. Five had an office visit for fever in the week before hospitalization, but only 1 had documented fever >/=39 degrees C and received neither laboratory testing for occult bacteremia nor treatment with an antibiotic. CONCLUSION: The majority of febrile children in ambulatory settings were diagnosed with a bacterial infection and treated with an antibiotic. Of highly febrile children without a source, 36% received laboratory testing consistent with published expert recommendations, and short-term follow-up was common. Meningitis or death after an office visit for fever without a source was predictably rare. These data suggest that increased testing and/or treatment of febrile children beyond the rates observed here are unlikely to affect population rates of meningitis substantially.

Medical profiling: improving standards and risk adjustments using hierarchical models.

The conclusions from a profile analysis to identify performance extremes can be affected substantially by the standards and statistical methods used and by the adequacy of risk adjustment. Medically meaningful standards are proposed to replace common statistical standards. Hierarchical regression methods can handle several levels of random variation, make risk adjustments for the providers' case-mix differences, and address the proposed standards. These methods determine probabilities needed to make meaningful profiles of medical units based on standards set by all appropriate parties.

Enrollees' perceptions of participating in the education of medical students at an academically affiliated HMO.

PURPOSE: Little is known about how enrollees in health maintenance organizations (HMOs) perceive the benefits and risks of participating in the education of medical students. This case study elicited the views of enrollees of one academically affiliated HMO about the education of medical students. METHOD: Data from focus groups were used to design two questionnaires that were mailed to 488 adult patients and 298 parents or guardians of pediatric patients. A sample of non-respondents was followed up by telephone. Descriptive analyses were performed on the responses to the questionnaires. RESULTS: Response rates were 46% (adult) and 43% (parent or guardian). More than 75% of the respondents thought the HMO should be involved in teaching, most because teaching contributes to the training of better doctors and increases the skills of teacher-clinicians. Of those who responded, 28% of adults were concerned about risks to confidentiality and 18% were concerned about increased costs for enrollees. Nearly 50% of adults would be uncomfortable with students participating in visits involving "internal" examinations or emotional problems. Of those who responded, 56% of adults and 33% of parents or guardians were uncomfortable about a student's conducting an unsupervised history and physical examination. A total of 52% of adults preferred that the preceptor and student discuss their case in their presence. Respondents who had seen students previously were more comfortable with student activities associated with their care. CONCLUSIONS: The respondents thought the HMO should be involved in teaching, but they had specific concerns about the effects of student participation. Educators in other settings may wish to explore these concerns among their patient populations and develop policies to maximize the "enrollee-friendliness" of medical education in HMOs. While the study provides a first look at how enrollees at one HMO viewed participation in medical students' education, further research is needed at HMOs elsewhere to determine the representativeness of the study's findings.

Trimethoprim-sulfamethoxazole and hypouricemia.

BACKGROUND: Hypouricemia has been reported in a substantial fraction of patients with AIDS and attributed to an HIV-related renal urate transport defect. We tested the alternative hypothesis that hypouricemia was associated with the administration of high-dose trimethoprim-sulfamethoxazole (TMP-SMX). METHODS: Sociodemographic, clinical, and repeated laboratory data on 45 hospitalized patients with Pneumocystis carinii pneumonia (PCP) with and without HIV infection, were abstracted by a blinded reviewer. The primary outcome of interest was the percent change in serum uric acid concentration from baseline to hospital day 5 +/- 1. RESULTS: Subjects who received TMP-SMX were older (mean age 44.8 vs. 37.0, p = 0.02), less likely to be HIV-seropositive (61% vs. 94%, p = 0.01), and more likely to have received glucocorticoid therapy (75% vs. 35%, p = 0.01) than those who received pentamidine, dapsone-trimethoprim, clindamycin-primaquine, sulfadiazine-pyramethamine, or a combination of these agents. The administration of TMP-SMX was associated with a 37% +/- 12% reduction in serum uric acid concentration, adjusting for the effects of age, sex, race, HIV antibody status, renal function, serum sodium, and the use of diuretics and glucocorticoids (p = 0.005). CONCLUSION: Among a diverse cohort of hospitalized patients with PCP, treatment with high-dose TMP-SMX was strongly associated with a reduction in serum uric acid concentration over time.

How low birthweight and gestational age contribute to increased inpatient costs for multiple births.

The dramatic rise in the number of multiple gestation births has led to concerns about heavy resource use by these newborns and the design of cost-effective interventions. This study uses medical records data to compare single and multiple births in terms of hospital charges by cost center, length of stay, neonatal intensive care unit (NICU) days, and discharge status. Potential mediators examined were gestational age and birthweight. These factors, respectively, accounted for 50% and 40% of the increase in total charges due to multiple gestation. The remaining "direct effect" was due primarily to longer hospital stays among twins and higher daily charges among higher-order multiples. Room and board charges were higher for multiples, while charges in other categories were actually lower, after controlling for birthweight and gestational age. Birthweight and gestational age accounted fully for the increased use of NICU services among multiples. These results show that while prevention of multiple gestation, where possible, is of paramount importance, strategies that decrease preterm delivery and/or increase birthweight should attenuate the adverse economic impact of multiple gestation pregnancies.

[Thromboendarterectomy of chronic thromboembolic pulmonary hypertension]. / Trombendarterektomi af kronisk tromboembolisk pulmonal hypertension.

Chronic thromboembolic pulmonary hypertension has a five year survival rate of less than 10% in patients with a systolic pulmonary artery pressure of 50 mmHg with no convincing effect of medical treatment. The operative mortality from pulmonary thrombendarterectomy in specialised centres has been reduced to 9%, suggesting this treatment as being an option. The results from thrombendarterectomy of two Danish patients are reported. The first patient, a 34 year-old woman was operated at the centre in San Diego with the assistance of a Danish thoracic surgeon. The second, a 60 year-old man was operated at our institution by this surgeon. Following removal of sufficient amount of embolic masses and intimal tissue, the patients were discharged from hospital with a substantial improvement in their clinical status and near normalisation of pulmonary artery pressure, which remained at the latest follow-up (3 to 22 months).

[Changes in PaO2, PaCO2 and pH during the apnea test]. / Aendringer i PaO2, PaCO2 og pH under apnøtest.

Changes in PaCO2, PaO2 and arterial pH were monitored during a 10 min apnoea test in nine clinically brain dead subjects. The patients were preoxygenated for 15 min with 100% O2. During the apnoea test they were oxygenated by tracheal cannulation with 5 l O2 per min. PaCO2 rose 1.3-2.1 kPa during the first two minutes of apnoea. Patients with PaCO2 greater than or equal to 5.5 kPa at the beginning of apnoea all had PaCO2 greater than 8 kPa after 5 min of apnoea for five minutes. With one exception, all of the patients were sufficient oxygenated during the apnoea test. If patients are ventilated to a PaCO2 greater than or equal to 5.5 kPa then 5 min of apnoea testing will increase PaCO2 above 8 kPa. As a few patients may develop hypoxemia, patients should be monitored with pulseoximetry.

[Perioperative treatment of diabetics]. / Perioperativ diabetesbehandling.

The metabolic changes in connection with fasting, anaesthesia and surgery in diabetic patients and non-diabetic patients are reviewed. Various perioperative forms of treatment are described. The forms of treatment most commonly employed are infusion of glucose-insulin-potassium (GIK) and subcutaneous administration of insulin followed by infusion of glucose (KON). The more intensive GIK regime provides the diabetic patient with a biochemical regulation which resembles that found in non-diabetics. It has not been proved whether this marginal regulation influences the well-being, morbidity or mortality of the patients. In critically ill patients or patients with concurrent diseases, the GIK regime is recommended as this provides optimal regulation of the diabetes. In the remaining patients, local conditions will influence the choice of form of treatment.