Objective Estimates Improve Risk Stratification for Primary Graft Dysfunction after Lung Transplantation.

Primary graft dysfunction (PGD) is a major cause of early mortality after lung transplant. We aimed to define objective estimates of PGD risk based on readily available clinical variables, using a prospective study of 11 centers in the Lung Transplant Outcomes Group (LTOG). Derivation included 1255 subjects from 2002 to 2010; with separate validation in 382 subjects accrued from 2011 to 2012. We used logistic regression to identify predictors of grade 3 PGD at 48/72 h, and decision curve methods to assess impact on clinical decisions. 211/1255 subjects in the derivation and 56/382 subjects in the validation developed PGD. We developed three prediction models, where low-risk recipients had a normal BMI (18.5-25 kg/m(2) ), chronic obstructive pulmonary disease/cystic fibrosis, and absent or mild pulmonary hypertension (mPAP<40 mmHg). All others were considered higher-risk. Low-risk recipients had a predicted PGD risk of 4-7%, and high-risk a predicted PGD risk of 15-18%. Adding a donor-smoking lung to a higher-risk recipient significantly increased PGD risk, although risk did not change in low-risk recipients. Validation demonstrated that probability estimates were generally accurate and that models worked best at baseline PGD incidences between 5% and 25%. We conclude that valid estimates of PGD risk can be produced using readily available clinical variables.

Increased risk of hip fracture associated with dually treated HIV/hepatitis B virus coinfection.

HIV and hepatitis B virus (HBV) infections are each associated with reduced bone mineral density, but it is unclear whether HIV/HBV coinfection is associated with an increased risk of fracture. We determined whether dually treated HIV/HBV patients had a higher incidence of hip fracture compared to treated HBV-monoinfected, antiretroviral therapy (ART)-treated HIV-monoinfected and HIV/HBV-uninfected patients. We conducted a cohort study among 4156 dually treated HIV/HBV-coinfected, 2053 treated HBV-monoinfected, 96,253 ART-treated HIV-monoinfected, and 746,794 randomly sampled uninfected persons within the US Medicaid populations of California, Florida, New York, Ohio and Pennsylvania (1999-2007). Coinfected patients were matched on propensity score to persons in each comparator cohort. Weighted survival models accounting for competing risks were used to estimate cumulative incidences and hazard ratios (HRs) with 95% confidence intervals (CIs) of incident hip fracture for dually treated coinfected patients compared to (i) HBV-monoinfected receiving nucleos(t)ide analogue or interferon alfa therapy, (ii) HIV-monoinfected on ART and (iii) uninfected persons. Dually treated coinfected patients had a higher cumulative incidence of hip fracture compared to ART-treated HIV-monoinfected (at 5 years: 1.70% vs 1.24%; adjusted HR, 1.37 [95% CI, 1.03-1.83]) and uninfected (at 5 years: 1.64% vs 1.22%; adjusted HR, 1.35 [95% CI, 1.03-1.84]) persons. The cumulative incidence of hip fracture was higher among coinfected than treated HBV-monoinfected patients (at 5 years: 0.70% vs 0.27%), but this difference was not statistically significant in competing risk analysis (adjusted HR, 2.62 [95% CI, 0.92-7.51]). Among Medicaid enrollees, the risk of hip fracture was higher among dually treated HIV/HBV-coinfected patients than ART-treated HIV-monoinfected and uninfected persons.

Incidence and risk factors for incomplete HBV DNA suppression in HIV/HBV-co-infected patients initiating tenofovir-based therapy.

Suppression of hepatitis B virus (HBV)-DNA to undetectable levels is an important goal for HIV/HBV-co-infected patients receiving anti-HBV-active antiretroviral therapy (ART), and current guidelines recommend that this outcome should be reached by 1 year of treatment. However, the proportion of patients that fail to achieve an undetectable HBV DNA at this time point and its determinants remain unknown in clinical practice. The objective of this study was to determine the incidence and risk factors for incomplete HBV suppression following 1 year of tenofovir-based ART. We performed a cohort study among tenofovir-treated HIV/HBV-co-infected patients. Patients had HBV viraemia, initiated tenofovir-based ART and had HBV DNA measured at 1 year of therapy. The primary outcome was incomplete HBV suppression (HBV DNA ≥2.6 log IU/mL) at 1 year. Logistic regression determined odds ratio (ORs) of incomplete HBV suppression for risk factors of interest. Among 133 patients, 54% (95% CI, 46-63%) had incomplete HBV suppression at 1 year. Incomplete suppression was associated with higher baseline HBV DNA (OR, 1.46 per log IU/mL increase; 95% CI, 1.1-1.94) and detectable HIV viraemia at 1 year (OR, 2.52; 95% CI, 1.19-5.32). Among 66 patients with suppressed HIV RNA at 1 year, 28 (42%) failed to achieve an undetectable HBV DNA. Failure to suppress HBV DNA by 1 year occurred in a sizeable proportion of tenofovir-treated HIV/HBV-co-infected patients. Higher HBV DNA and detectable HIV viraemia were risk factors for incomplete HBV suppression.

Risk of invasive pneumococcal disease varies by neighbourhood characteristics: implications for prevention policies.

This study investigates neighbourhood variation in rates of pneumococcal bacteraemia and community-level factors associated with neighbourhood heterogeneity in disease risk. We analysed data from 1416 adult and paediatric cases of pneumococcal bacteraemia collected during 2005-2008 from a population-based hospital surveillance network in metropolitan Philadelphia. Cases were geocoded using residential address to measure disease incidence by neighbourhood and identify potential neighbourhood-level risk factors. Overall incidence of pneumococcal bacteraemia was 36∙8 cases/100,000 population and varied significantly (0-67∙8 cases/100,000 population) in 281 neighbourhoods. Increased disease incidence was associated with higher population density [incidence rate ratio (IRR) 1∙10/10,000 people per mile², 95% confidence interval (CI) 1∙0-1∙19], higher percent black population (per 10% increase) (IRR 1∙07, 95% CI 1∙04-1∙09), population aged ≤5 years (IRR 3∙49, CI 1∙8-5∙18) and population aged ≥65 years (IRR 1∙19, CI 1∙00-1∙38). After adjusting for these characteristics, there was no significant difference in neighbourhood disease rates. This study demonstrates substantial small-area variation in pneumococcal bacteraemia risk that appears to be explained by neighbourhood sociodemographic characteristics. Identifying neighbourhoods with increased disease risk may provide valuable information to optimize implementation of prevention strategies.

Prescriber adherence to pharmacokinetic monitoring service recommendations for aminoglycoside dosing and the risk of acute kidney injury.

OBJECTIVE: The importance of adherence to aminoglycoside dosing recommendations by a pharmacokinetic monitoring service for preventing acute kidney injury (AKI) is unknown. We aimed to examine the association between AKI and discordance in aminoglycoside dosing between physician orders and recommendations by a pharmacokinetic monitoring service. MATERIALS: We utilized 2000 - 2003 data from a large quaternary care academic medical center, including: hand-written pharmacokinetic monitoring service recommendations; computerized physician order entry inpatient medication orders; and electronic inpatient laboratory orders and results. METHODS: We conducted a case-control study, nested within users of intravenous aminoglycosides. Outcomes of interest were cases of AKI, as determined by changes in serum creatinine. Exposures of interest were discordances between pharmacokinetic monitoring service recommendations and physician orders in the past 2 days with regard to total daily aminoglycoside dose. RESULTS: Most patients received once-daily or less frequent aminoglycoside dosing. In 1,414 evaluable aminoglycoside courses, 220 patients developed AKI, for a cumulative incidence of 15.6%. We identified 690 controls, matched these to 220 cases, and found adjusted odds ratios of 0.72 (95% CI: 0.37 - 1.39) for overdose discordance and of 0.83 (0.51 - 1.34) for underdose discordance, suggesting that discordance in dosing is not associated with AKI. CONCLUSION: Non-adherence to dosing recommendations for aminoglycosides was not associated with risk of AKI in a setting primarily of once-daily aminoglycoside administration.

Metabolic modeling using statistical and spreadsheet software: Application to the glucose minimal model.

Kinetic non-linear metabolic models are used extensively in medical research and increasingly for clinical diagnostic purposes. An example of such a model is the Glucose Minimal Model by Bergman and colleagues [1]. This model is similar to pharmacokinetic/pharmacodynamic models in that like pharmacokinetic/pharmacodynamic models, it is based on a small number of fairly simple ordinary differential equations and it aims to determine how the changing concentration of one blood constituent influences the concentration of another constituent. Although such models may appear prima facie, to be relatively simple, they have gained a reputation of being difficult to fit to data, especially in a consistent and repeatable fashion. Consequently, researchers and clinicians have generally relied on dedicated software packages to do this type of modeling. This article describes the use of statistical and spreadsheet software for fitting the Glucose Minimal Model to data from an insulin modified intravenous glucose tolerance test (IM-IVGTT). A novel aspect of the modeling is that the differential equations that are normally used to describe insulin action and the disposition of plasma glucose are first solved and expressed in their explicit forms so as to facilitate the estimation of Glucose Minimal Model parameters using the nonlinear (nl) optimization procedure within statistical and spreadsheet software. The most important clinical parameter obtained from the Glucose Minimal Model is insulin sensitivity (SI). Using IM-IVGTT data from 42 horses in one experiment and 48 horses in a second experiment, we demonstrate that estimates of SI derived from the Glucose Minimal Model fitted to data using STATA and Excel, are highly concordant with SI estimates obtained using the industry standard software, MinMod Millennium. This work demonstrates that there is potential for statistical and spreadsheet software to be applied to a wide range of kinetic non-linear modeling problems.

The impact of development of acute lung injury on hospital mortality in critically ill trauma patients.

OBJECTIVE: The additional impact of development of acute lung injury on mortality in severely-injured trauma patients beyond baseline severity of illness has been questioned. We assessed the contribution of acute lung injury to in-hospital mortality in critically ill trauma patients. DESIGN: Prospective cohort study. The contribution of acute lung injury to in-hospital mortality was evaluated in two ways. First, multivariable logistic regression models were used to test the independent association of acute lung injury with in-hospital mortality while adjusting for baseline confounding variables. Second, causal pathway models were used to estimate the amount of the overall association of baseline severity of illness with in-hospital mortality that is attributable to the interval development of acute lung injury. SETTING: Academic level 1 trauma center. PATIENTS: Two hundred eighty-three critically ill trauma patients without isolated head injury and with an Injury Severity Score > or = 16 were evaluated for development of acute lung injury in the first 5 days after trauma. MEASUREMENTS AND MAIN RESULTS: Of the 283 patients, 38 (13.4%) died. The unadjusted mortality rate was nearly three-fold greater in the acute lung injury group (23.9% vs. 8.4%; odds ratio = 3.36; 95% confidence interval 1.67-6.77; p = 0.001). Acute lung injury remained an independent risk factor for death after adjustment for age, baseline Acute Physiologic and Chronic Health Evaluation III score, Injury Severity Score, and blunt mechanism of injury (odds ratio = 2.87; 95% confidence interval 1.29-6.37; p = 0.010). Forty percent of the total association of the baseline Acute Physiologic and Chronic Health Evaluation III score with mortality occurred via an indirect association through acute lung injury, and the remaining 60% via a direct effect. CONCLUSIONS: Development of acute lung injury in critically ill trauma patients without isolated head injury contributes independently to in-hospital mortality beyond baseline severity of illness measures. In addition, a significant portion of the association between baseline illness severity and risk of death in these patients might be explained by the interval development of acute lung injury.

Defining optic nerve tortuosity.

BACKGROUND AND PURPOSE: Optic nerve tortuosity is one of several nonmalignant abnormalities documented on MR imaging in patients with neurofibromatosis type 1 and may be related to the development of optic pathway gliomas. This study seeks an operational definition for optic nerve tortuosity. MATERIALS AND METHODS: A focus group of 3 pediatric neuroradiologists reviewed 20 MR images of the brain and orbits of patients suspected to have optic nerve tortuosity in the absence of optic pathway glioma and found 6 radiographic factors that occurred frequently. Subsequently, 28 MR images were assessed for the presence of optic nerve tortuosity, using a global assessment question that reflects a neuroradiologist's confidence in the presence of optic nerve tortuosity, and for the presence of the 6 radiographic factors, to identify a combination of these factors that best predicted a diagnosis of optic nerve tortuosity. RESULTS: We found perfect inter-rater agreement between 3 readers on the presence/absence of tortuosity in 75% of cases. Lack of congruity of the optic nerves, in more than 1 coronal section and dilation of the subarachnoid space surrounding the optic nerves, when found together are sensitive (89%) and specific (93%) for a diagnosis of tortuosity on the global scale. The absence of these 2 factors, along with absence of deviation of the optic nerve within the axial plane, provides a reliable test to exclude tortuosity. CONCLUSION: Lack of congruity of the optic nerves in more than 1 coronal section and dilation of the subarachnoid space surrounding the optic nerves together provide an operational radiographic definition of optic nerve tortuosity.

The effects of contemporary use of coronary stents on in-hospital mortality. Registry Committee of the Society for Cardiac Angiography and Interventions.

OBJECTIVES: This study was designed to determine the effect of coronary stents on in-hospital mortality. BACKGROUND: Despite extensive use of stents for percutaneous coronary interventions (PCIs), their effect on serious in-hospital events, especially mortality, is not well defined. METHODS: A cohort study was performed using 16,811 consecutive native-vessel PCI procedures performed on patients in the Society for Cardiac Angiography & Interventions Registry from July 1, 1996, through December 31, 1998. Patients undergoing balloon-only angioplasty were compared with those receiving a planned or unplanned stent. Procedures with other devices were excluded. Multivariable analyses adjusted for detailed clinical characteristics and for individual laboratory. RESULTS: Stents were associated with a significant reduction in in-hospital mortality (0.3%) compared with balloon procedures (0.6%; multivariable odds ratio [OR] 0.55; 95% confidence interval [CI] 0.34, 0.89; p = 0.014). The risk of emergency coronary bypass also was reduced by stenting (0.3% vs. 0.7%; multivariable OR 0.47; 95% CI: 0.29, 0.76; p = 0.002). Adjustment for the use of glycoprotein IIb/IIIa inhibitors did not change the results, and the effects of stenting relative to balloon procedures were similar in those procedures with and without glycoprotein IIb/IIIa blockade (p = 0.94). CONCLUSIONS: This study suggests that coronary stenting, compared with balloon procedures, reduces in-hospital mortality, independent of the clinical setting.

Effects of coronary stents on cardiovascular outcomes in broad-based clinical practice.

BACKGROUND: Although stents have been shown to reduce the need for repeated percutaneous coronary intervention (PCI) in randomized trials, the effects of stents in broad-based, diverse clinical practice have not been well studied, nor has their effect on subsequent myocardial infarction or cardiac death. METHODS: A retrospective cohort study was performed that included all 43 hospitals performing PCI in Pennsylvania in the last quarter of 1995, with the use of the Pennsylvania Health Care Cost Containment Council database. All 5258 patients who underwent PCI, excluding those with previous PCI within the preceding 6 months, were included. The primary outcomes were in-hospital events (death or coronary bypass), 6-month revascularization rates, and 6-month rates of cardiac death or myocardial infarction. RESULTS: A total of 1240 patients (24%) had a stent procedure. Compared with nonstent procedures, stents reduced the risk of in-hospital events (multivariable odds ratio adjusted for patient and hospital level differences, 0.63; 95% confidence interval, 0.41-0.97), primarily because of a 52% reduction in the need for coronary bypass. Stents also reduced the need for follow-up revascularization procedures (multivariable hazard ratio, 0.72; 95% confidence interval, 0.59-0. 87), primarily because of a 31% reduction in repeated PCI. However, stents had no effect on 6-month rate of myocardial infarction or cardiac death (multivariable hazard ratio, 0.97; 95% confidence interval, 0.71-1.33). CONCLUSIONS: Using stents decreases the need for repeated PCI in broad-based clinical practice, confirming results from randomized trials. However, this study did not detect any effect on subsequent myocardial infarction or cardiac death.

Clinical Decision Support and Palivizumab: A Means to Protect from Respiratory Syncytial Virus.

BACKGROUND AND OBJECTIVES: Palivizumab can reduce hospitalizations due to respiratory syncytial virus (RSV), but many eligible infants fail to receive the full 5-dose series. The efficacy of clinical decision support (CDS) in fostering palivizumab receipt has not been studied. We sought a comprehensive solution for identifying eligible patients and addressing barriers to palivizumab administration. METHODS: We developed workflow and CDS tools targeting patient identification and palivizumab administration. We randomized 10 practices to receive palivizumab-focused CDS and 10 to receive comprehensive CDS for premature infants in a 3-year longitudinal cluster-randomized trial with 2 baseline and 1 intervention RSV seasons. RESULTS: There were 356 children eligible to receive palivizumab, with 194 in the palivizumab-focused group and 162 in the comprehensive CDS group. The proportion of doses administered to children in the palivizumab-focused intervention group increased from 68.4% and 65.5% in the two baseline seasons to 84.7% in the intervention season. In the comprehensive intervention group, proportions of doses administered declined during the baseline seasons (from 71.9% to 62.4%) with partial recovery to 67.9% during the intervention season. The palivizumab-focused group improved by 19.2 percentage points in the intervention season compared to the prior baseline season (p < 0.001), while the comprehensive intervention group only improved 5.5 percentage points (p = 0.288). The difference in change between study groups was significant (p = 0.05). CONCLUSIONS: Workflow and CDS tools integrated in an EHR may increase the administration of palivizumab. The support focused on palivizumab, rather than comprehensive intervention, was more effective at improving palivizumab administration.

A predictive risk index for nosocomial pneumonia in the intensive care unit.

PURPOSE: To develop a scoring system for stratifying patients in intensive care units (ICUs) by risk of developing nosocomial pneumonia (NP) and to identify the time period associated with the highest risk. PATIENTS AND METHODS: Two hundred and three patients 18 years of age or older and residing in the ICU for 72 hours or more were followed until development of NP or death or for 48 hours after discharge from the ICU. After the identification of independent risk factors for NP, a scoring system was developed to arrive at a predictive risk index for NP. RESULTS: Twenty-six (12.8%) patients developed NP. The presence of a nasogastric (NG) tube [odds ratio (OR) = 6.48, 95% confidence intervals (CI) = 2.11 to 19.82], upper abdominal/thoracic surgery (OR = 4.34, 95% CI = 1.43 to 13.14), and bronchoscopy (OR = 2.95, 95% CI = 1.02 to 8.52), most commonly performed for respiratory toilet, were identified as independent risk factors on multivariate analysis. The risks associated with endotracheal intubation and altered consciousness, although not independently significant, were highest when these factors were present for 1 to 4 days after the 72 hours required for study entry (endotracheal intubation, OR = 2.2 to 2.5; altered consciousness, OR = 1.4 to 2.0). The risk then declined; ORs of less than 1 were observed at 7 days. The risk associated with the NG tube was highest during the first 6 days (OR = 6.0 to 19.5). Although a subsequent decrease in risk was observed, the OR was still greater than 2 at 7 days. To obtain a predictive risk index for NP, a scoring system was developed using a multivariate model. This system has a sensitivity of 85% and a specificity of 66% in predicting NP in this ICU population. CONCLUSION: ICU patients can be stratified into high- and low-risk groups for NP using a bedside scoring system. Endotracheal intubation, altered mental status, and NG tube are associated with the highest risk of NP during the first 1 to 6 days of their presence after 72 hours of stay in the ICU. After this time period, the risk associated with these factors decreases. Bronchoscopy may be an independent risk factor for NP that has not been previously recognized. This procedure, often done in the ICU for respiratory toilet, may be an avoidable risk in this group of patients.

Is an anticholinergic agent superior to a beta 2-agonist in improving dyspnea and exercise limitation in COPD?

STUDY OBJECTIVE: To evaluate the impact of a week-long course of inhaled albuterol compared with ipratropium on expiratory peak flow, exercise performance, and dyspnea in patients with stable COPD. DESIGN AND INTERVENTIONS: A double-blind, two-period, crossover evaluation, wherein the subjects inhaled albuterol, two puffs four times a day (qid) for 7 days, or ipratropium, two puffs quid for 7 days, in random sequence. SETTING: Outpatients of the Pennsylvania State University Hospital, Lebanon VA Medical Center, and local private office practices. PARTICIPANTS: A sample of 15 subjects with stable COPD with FEV1 < 55% predicted. MEASUREMENTS AND RESULTS: Variables measured at baseline (no inhaled bronchodilator) and/or on day 7 of each arm included FEV1 (liters), 12-min walk test distance (meters), "rescue" puffs of metaproterenol needed each week, and dyspnea scoring after walking, on the Borg Category Scale (0 to 10 = maximal). There was no significant difference in distance walked in 12 min (mean of 751.0 +/- 55.5 [+/- SE]) vs 755.7 +/- 61.3 m) or perceived dyspnea (mean 2.7 +/- 0.4 vs 3.3 +/- 0.4) during albuterol or ipratropium use. Seven patients preferred ipratropium, seven preferred albuterol, and one had no preference. CONCLUSION: We conclude that the effects of 1 week of albuterol or ipratropium have similar effects on exercise performance and subjective dyspnea in patients with stable COPD.

In vivo accuracy of two radiographic systems in the detection of Björk-Shiley convexo-concave heart valve outlet strut single leg separations.

OBJECTIVE: Modified cineradiographic systems have been used clinically to detect partially broken outlet struts in normally functioning Björk-Shiley convexo-concave heart valves. Almost all such valves were explanted, presuming that full failure would likely follow. Inasmuch as the clinical setting only rarely permits examination of normally rated valves, the accuracy of radiographic detection cannot be clinically defined. This study uses the clinical radiographic technique in sheep implanted with known-status convexo-concave valves, comparing its accuracy and that of a newly developed, geometric image magnification radiography system. METHODS: Twenty-one sheep with mitral convexo-concave valves were studied on both systems. Five were used for extensive training. When operators were expert with both systems, images of four intact valves and 12 valves with outlet strut single leg separations, along with a seventeenth single leg separation valve used for calibration, were integrated into 112 image sets organized into a balanced incomplete block design for evaluation by eight trained, blinded reviewers. RESULTS: Cineradiography sensitivity was 24% versus 31% for direct image magnification. The odds ratio for detection of single leg separation by direct image magnification versus cineradiography was 2.0 (95% confidence interval, 0.76 to 5.9; p = 0.13). Cineradiography specificity was 93% versus 90% for direct image magnification. Sensitivity and specificity varied markedly by reviewer, with sensitivity ranging from 8% to 55% and specificity from 51% to 100% for the combined technologies. CONCLUSIONS: The data support the need for more intensive training for convexo-concave valve imaging and further investigation of unconventional radiographic technologies. Clinical cineradiography of convexo-concave valves may detect as little as 25% of valves having a single leg separation, underestimating the prevalence of single leg separations and thereby implying more rapid progression to full fracture than is actually the case.

Determining the time before birth when ischemia and hypoxemia initiated cerebral palsy.

OBJECTIVE: To test the hypothesis that lymphocyte and normoblast counts in neonatal blood can be used to identify the time that ischemia and hypoxemia produced cerebral palsy. METHODS: Blood lymphocyte and normoblast counts were analyzed at intervals after birth in 16 neonates for whom we knew the time when antenatal ischemic and hypoxemic brain damage began. These counts were compared with counts from normal newborns, infants with low Apgar scores and no cerebral palsy, and infants with cerebral palsy caused by developmental and other early gestational disorders. RESULTS: Lymphocyte counts increased to more than 10,000/mm3 and normoblast counts to 2000/mm3 or more within 2 hours after the brain-damaging ischemia and hypoxemia began. Lymphocyte counts returned to normal levels 24 hours after the damaging event took place, and normoblast counts in 24-36 hours. Normal neonates had a mean +/- one standard deviation lymphocyte count of 4430 +/- 1418/mm3 and a normoblast count of 560 +/- 771/mm3. CONCLUSION: Following the changing counts of lymphocytes and normoblasts in neonates' blood may accurately identify the time before birth when brain-damaging ischemia and hypoxemia began.

Contraceptive requirements for clinical research.

OBJECTIVE: To survey the type and frequency of use of contraceptive requirements for entry into clinical trials. METHODS: We reviewed 410 protocols submitted between January 1994 and January 1997 to one Institutional Review Board. RESULTS: Contraception or sterility for women was required in 171 (41.7%) protocols without explanation and 146 (35.6%) based on study drug. Eight and one half percent hd no exclusions. Signature certification of contraceptive use was required in 138 protocols; 230 required certification of understanding requirements; and 101 required two signatures. Signature certification documenting no pregnancy at enrollment was required in 234 protocols. There were no requirements for signatures from male subjects. Celibacy or sexual orientation were not recognized as reasons for waiver from signature requirements. CONCLUSION: The broad application of contraceptive requirements potentially creates disproportionate burdens and access by gender to participation in clinical research. Careful elucidation of methods, timing, and the consent process in order to avoid potential fetal risk and encourage inclusion of hormonally intact women will improve research and access.

Incidence of adverse events and negligence in hospitalized patients: results of the Harvard Medical Practice Study I. 1991.

BACKGROUND: As part of an interdisciplinary study of medical injury and malpractice litigation, we estimated the incidence of adverse events, defined as injuries caused by medical management, and of the subgroup of such injuries that resulted from negligent or substandard care. METHODS: We reviewed 30121 randomly selected records from 51 randomly selected acute care, non-psychiatric hospitals in New York State in 1984. We then developed population estimates of injuries and computed rates according to the age and sex of the patients as well as the specialties of the physicians. RESULTS: Adverse events occurred in 3.7% of the hospitalizations (95% confidence interval 3.2 to 4.2), and 27.6% of the adverse events were due to negligence (95% confidence interval 22.5 to 32.6). Although 70.5% of the adverse events gave rise to disability lasting less than 6 months, 2.6% caused permanently disabling injuries and 13.6% led to death. The percentage of adverse events attributable to negligence increased in the categories of more severe injuries (Wald test chi(2) = 21.04, p<0.0001). Using weighted totals we estimated that among the 2671863 patients discharged from New York hospitals in 1984 there were 98609 adverse events and 27179 adverse events involving negligence. Rates of adverse events rose with age (p<0.0001). The percentage of adverse events due to negligence was markedly higher among the elderly (p<0.01). There were significant differences in rates of adverse events among categories of clinical specialties (p<0.0001), but no differences in the percentage due to negligence. CONCLUSIONS: There is a substantial amount of injury to patients from medical management, and many injuries are the result of substandard care.

Minimal benefit of earlier-than-recommended repeat colonoscopy among US Medicare enrollees following a negative colonoscopy.

BACKGROUND: A large proportion of US Medicare beneficiaries undergo earlier-than-recommended follow-up colonoscopies after negative screening colonoscopy. Such practice entails substantial cost and added risk. AIMS: To compare the risk of colorectal cancer (CRC) associated with varying follow-up colonoscopy intervals following a negative colonoscopy, and to determine whether the potential benefit of a shorter colonoscopy follow-up interval would differ by gender. METHODS: We conducted a weighted cohort study using the Surveillance, Epidemiology and End Results-Medicare linked database (1991-2006) among 932,370 Medicare enrollees who are representative of the entire US elderly population. We compared the cumulative incidence of CRC among patients who underwent follow-up colonoscopies at different intervals following a negative colonoscopy. The primary outcome was incident CRC. RESULTS: The eligible study cohort (n = 480,864) included 106,924 patients who underwent ≥1 colonoscopy. Men were more likely to require polypectomy during their initial colonoscopy than women. Compared to the recommended 9-10 year follow-up colonoscopy interval, an interval of 5-6 years was associated with the largest CRC cumulative risk reduction [i.e. 0.17% (95% CI: 0.009-0.32%)]. The magnitude of risk reduction associated with shorter colonoscopy follow-up intervals was not significantly different between men and women. CONCLUSIONS: Among elderly individuals who undergo a negative colonoscopy, the magnitude of reduction in the cumulative CRC risk afforded by earlier-than-recommended follow-up colonoscopy is quite small, and probably cannot justify the risk and cost of increased colonoscopy frequency. In addition, there are insufficient differences between men and women to warrant gender-specific recommendations.

Anticoagulation therapy in patients with venous thromboembolic disease.

OBJECTIVE: To determine, in a representative sample of patients drawn from a variety of hospitals, the degree of adherence to consensus recommendations for anticoagulation among patients with deep vein thrombosis or pulmonary embolism. DESIGN: Cross-sectional review of a population-based random sample. SETTING: Twenty-one randomly selected Pennsylvania hospitals. PATIENTS: Of 357 randomly selected Medicare beneficiaries discharged from study hospitals with a diagnosis of deep venous thrombosis or pulmonary embolism during 1992, 43 charts were not reviewed for administrative reasons, 31 were miscoded or not treated with intravenous administration of heparin, and 13 were excluded for other reasons, leaving 270 in the final sample. MEASUREMENTS AND MAIN RESULTS: Overall, 179 patients (66%, 95% confidence interval [CI] 59%, 72%) received therapeutic anticoagulation (two consecutive partial thromboplastin times more than 1.5 times control) within 24 hours of starting heparin. Platelet counts were checked at least once during the first week of heparin therapy in 66% (95% CI 58%, 74%). At least 5 days of heparin therapy was given to 84% (95% CI 79%, 87%). Among 266 (99%) of the patients receiving warfarin, 193 (72%; 95% CI 63%, 80%) received heparin until the prothrombin time ratio or International Normalized Ratio was therapeutic. Patients who were started on warfarin therapy within 2 days of heparin had decreased length of stay (geometric mean 8.2 vs 9.7 days, p = .003). Compliance varied among hospitals. CONCLUSIONS: In a wide variety of hospitals, we found fair, but variable, compliance with consensus recommendations for anticoagulation of patients with venous thromboembolic disease. Simple interventions to improve compliance with these recommendations might improve quality of care and reduce costs.

Cost-effectiveness analysis of helicopter EMS for trauma patients.

STUDY OBJECTIVE: To evaluate the cost-effectiveness of helicopter EMS for trauma patients. METHODS: We applied a cost-effectiveness analysis from the service provider's perspective to cost and effectiveness estimates. The cost estimates comprise direct operating costs and additional survivors' hospital costs. The effectiveness estimates were calculated with the TRISS methodology from literature sources and data from a cohort of patients transported by helicopter during 1994 and 1995. Sensitivity analysis and discounting were used. Cost per life saved and discounted cost per year of life in 1995 US dollars were the main outcome measures. RESULTS: The reported literature survival benefit ranges from 1 to 12 additional survivors per 100 patients flown. Transport costs were $2,214 per patient, and each additional survivor's hospitalization averaged $15,883. For the base case (5 additional survivors per 100 patients flown), cost per life was $60,163 and discounted cost per year of life $2,454. Sensitivity analysis revealed that discounted cost per year of life could be as high as $9,677 or as low as $1,400 and that it was most dependent on the surviving benefit. These results are comparable to a reported median discounted cost per year of life of %19,000 for other commonly used lifesaving medical interventions. CONCLUSION: Assuming that helicopter air medical transport provides a substantial survival benefit for trauma patients, our findings suggest that this service is a cost-effective option for the treatment of trauma patients. The magnitude of the survival benefit is the most important factor determining cost-effectiveness.