A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators.

PURPOSE: To determine whether early goal-directed therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the emergency department (ED) with septic shock. METHODS: Using a search strategy of PubMed, EmBase and CENTRAL, we selected all relevant randomised clinical trials published from January 2000 to January 2015. We translated non-English papers and contacted authors as necessary. Our primary analysis generated a pooled odds ratio (OR) from a fixed-effect model. Sensitivity analyses explored the effect of including non-ED studies, adjusting for study quality, and conducting a random-effects model. Secondary outcomes included organ support and hospital and ICU length of stay. RESULTS: From 2395 initially eligible abstracts, five randomised clinical trials (n = 4735 patients) met all criteria and generally scored high for quality except for lack of blinding. There was no effect on the primary mortality outcome (EGDT: 23.2% [495/2134] versus control: 22.4% [582/2601]; pooled OR 1.01 [95% CI 0.88-1.16], P = 0.9, with heterogeneity [I(2) = 57%; P = 0.055]). The pooled estimate of 90-day mortality from the three recent multicentre studies (n = 4063) also showed no difference [pooled OR 0.99 (95% CI 0.86-1.15), P = 0.93] with no heterogeneity (I(2) = 0.0%; P = 0.97). EGDT increased vasopressor use (OR 1.25 [95% CI 1.10-1.41]; P < 0.001) and ICU admission [OR 2.19 (95% CI 1.82-2.65); P < 0.001]. Including six non-ED randomised trials increased heterogeneity (I(2) = 71%; P < 0.001) but did not change overall results [pooled OR 0.94 (95% CI 0.82 to 1.07); P = 0.33]. CONCLUSION: EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.

Parental perception of children's weight in a paediatric primary care setting.

OBJECTIVE: To determine how parents of overweight children perceived their children's weight status compared with actual body mass index (BMI). METHODS: This descriptive, cross-sectional study assessed parental perception of and concern about weight, diet and physical activity of 3-12-year-olds. BMI values >or=85th and <95th percentile and >or=95th percentile were considered at risk for overweight and overweight respectively. Differences between groups were tested with chi-squared analyses or Fishers exact test as appropriate and further explored using logistic regression analysis. RESULTS: Questionnaires were completed at 612 health maintenance visits (278 girls). Overall, 15% of both boys and girls were at risk for overweight and 22% of boys and 24% of girls were overweight. Forty-nine per cent of parents recognized their overweight children as overweight. Perceptions were more often correct for parents of girls than boys (63% versus 36%, P < 0.001) and for older compared with younger children (61.7% versus 17.5%, P < 0.001). CONCLUSIONS: Parents of overweight children frequently did not perceive their children as exceeding healthy weight standards. Targeting parental perception as a point of intervention is necessary.

Selective overexpression of the hypoxia-inducible transcription factor, HIF-2alpha, in placentas from women with preeclampsia.

Transcription factors orchestrate the development of extraembryonic tissues. Because placental hypoxia likely plays an important role in both normal and abnormal placentation, we have been investigating the hypoxia-inducible transcription factors (HIFs) in the human placenta. In this report, we focus on the placentas from women with preeclampsia. Because the placenta is a large, heterogeneous organ, we employed a systematic and unbiased approach to placental sampling, and our results are based on the analyses of eight biopsy sites per placenta. We observed no significant differences in HIF-1alpha or -2alpha mRNA expression between normal term and preeclamptic placentas. Nor was HIF protein expression significantly different, with the notable exception of HIF-2alpha, which, on average, was increased by 1.7-fold in the preeclamptic placentas (P: < 0.03 vs. normal term placentas). Considering all 48 paired placental biopsy sites (eight sites each for six normal term and six preeclamptic placentas), HIF-2alpha protein levels in the preeclamptic placentas exceeded those in the normal term placentas in 39, or 81%, of the paired sites (P: < 0.0013). The HIF-2alpha immunoreactivity was mainly located in the nuclei of the syncytiotrophoblast and fetoplacental vascular endothelium in the preeclamptic villous placenta. To control for the earlier gestational age of the preeclamptic placentas, an additional group of placentas from preterm deliveries without preeclampsia were also evaluated. The HIF protein expression was comparable in these preterm specimens and the normal term placentas. We conclude that protein expression of HIF-2alpha, but not of HIF-1alpha or -1beta, is selectively increased in the preeclamptic placenta. The molecular mechanism(s) of this abnormality as well as the genes affected downstream are currently under investigation. To our knowledge, this is the first report of abnormal HIF-2alpha expression in human disease other than cancer.

Dyslipoproteinaemia in postmenopausal women with a history of eclampsia.

OBJECTIVE: To test the hypothesis that postmenopausal women with a history of eclampsia manifest a more high risk lipid profile than postmenopausal women with a history of normal pregnancy. SETTING: The Department of Obstetrics and Gynaecology, National University Hospital, Reykjavik, Iceland, and the Magee-Womens Research Institute, Pittsburgh, Pennsylvania, USA. PARTICIPANTS: Thirty Icelandic women with a history of eclampsia, aged between 50 and 67 years at the time of re-examination (cases) were individually matched for current age, and for age and parity at index pregnancy, to 30 unrelated Icelandic women with a history of normal pregnancy (controls). METHODS: The participating women completed a health and family history questionnaire and underwent a physical examination. Fasting plasma low density lipoprotein diameter, serum lipids, insulin, and glucose were measured. RESULTS: Mean low density lipoprotein size was significantly smaller and apolipoprotein B concentration was higher in women with prior eclampsia. The percentage of cases receiving blood pressure medication (33%) was significantly greater than controls (6.7%). Thirteen cases had had hypertensive complications in at least one other pregnancy (recurrent subgroup); postmenopausally, these women displayed significantly increased diastolic blood pressures, smaller-sized low density lipoprotein, increased apolipoprotein B, decreased high density lipoprotein2 (HDL2) cholesterol, and increased total cholesterol: HDL cholesterol ratio compared with their controls. Fourteen cases were normotensive in all other pregnancies (nonrecurrent); these showed no differences from their controls. CONCLUSIONS: Dyslipoproteinaemia is more prevalent among postmenopausal women with prior eclampsia, especially with recurrent hypertension in pregnancy, than in postmenopausal women with prior normal pregnancies.

Effect of primary congenital hypothyroidism upon expression of genes mediating murine brain glucose uptake.

Using hyt/hyt mice that exhibit naturally occurring primary hypothyroidism (n = 72) and Balb/c controls (n = 66), we examined the mRNA, protein, and activity of brain glucose transporters (Glut 1 and Glut 3) and hexokinase I enzyme at various postnatal ages (d 1, 7, 14, 21, 35, and 60). The hyt/hyt mice showed an age-dependent decline in body weight (p < 0.04) and an increase in serum TSH levels (p < 0.001) at all ages. An age-dependent translational/posttranslational 40% decline in Glut 1 (p = 0.02) with no change in Glut 3 levels was observed. These changes were predominant during the immediate neonatal period (d 1). A posttranslational 70% increase in hexokinase enzyme activity was noted at d 1 alone (p < 0.05) with no concomitant change in brain 2-deoxy-glucose uptake. This was despite a decline in the hyt/hyt glucose production rate. We conclude that primary hypothyroidism causes a decline in brain Glut 1 associated with no change in Glut 3 levels and a compensatory increase in hexokinase enzyme activity. These changes are pronounced only during the immediate neonatal period and disappear in the postweaned stages of development. These hypothyroid-induced compensatory changes in gene products mediating glucose transport and phosphorylation ensure an adequate supply of glucose to the developing brain during transition from fetal to neonatal life.

Normal approximation diagnostics for the Cox model.

We discuss two diagnostic methods for assessing the accuracy of the normal approximated confidence region to the likelihood-based confidence region for the Cox proportional hazards model with censored data. The proposed diagnostic methods are extensions of the contour measures of Hodges (1987, Journal of the American Statistical Association 82, 149-154) and Cook and Tsai (1990, Journal of the American Statistical Association 85, 770-777) and the curvature measures of Jennings (1986, Journal of the American Statistical Association 81, 471-476) and Cook and Tsai (1990). These methods are also illustrated in a study of hepatocyte growth factor in patients with lung cancer and a Mayo Clinic randomized study of participants with primary biliary cirrhosis.

Small low-density lipoproteins and vascular cell adhesion molecule-1 are increased in association with hyperlipidemia in preeclampsia.

The pregnancy disorder preeclampsia is characterized by endothelial cell dysfunction that may be promoted by abnormal increases in circulating lipids, particularly triglycerides and free fatty acids. Serum triglyceride concentration is a major regulatory determinant of low-density lipoprotein (LDL) size and density distribution. Smaller, denser LDL particles have several intrinsic properties capable of inducing endothelial dysfunction. The present nested, case-control study of gestationally matched preeclamptic and normal pregnant women tested the hypothesis that hypertriglyceridemia in preeclampsia is accompanied by decreases in LDL peak particle diameter (predominant LDL size). Plasma LDL peak particle diameter was determined by nondenaturing 2% to 16% polyacrylamide gel electrophoresis. Correlations of LDL diameter with the concentration of serum triglycerides, free fatty acids, total cholesterol, LDL-cholesterol, and apolipoprotein B (apo B) were determined. In the same individuals, we measured serum concentrations of a marker of vascular dysfunction previously reported to be increased in preeclampsia, soluble vascular cell adhesion molecule-1 (VCAM-1), and examined the association of VCAM-1 with LDL diameter and serum lipids. LDL peak particle diameter was decreased in preeclampsia relative to normal pregnancy (P < .01). The LDL-cholesterol:apo B ratio, which frequently decreases with decreasing LDL diameter, was also decreased (P < .04). Triglyceride concentrations were increased in preeclampsia (P < .0002), and there was a significant inverse relationship between LDL peak particle diameter and triglycerides (r = -.55, P < .02). Serum soluble VCAM-1 concentrations were markedly increased in preeclampsia (P < .0003). Apo B (P < .004), free fatty acids (P < .01), total cholesterol (P < .01), and LDL-cholesterol (P < .02) were also increased. VCAM-1 correlated with apo B (r = .50, P < .03) and LDL-cholesterol (r = .50, P < .03), but showed no relationship with the LDL diameter, LDL-cholesterol:apo B ratio, or other lipids. We conclude that the predominance of smaller, denser LDL, a potential contributor to endothelial cell dysfunction, is a feature of preeclampsia. However, the serum VCAM-1 level, one indicator of endothelial involvement, may be influenced more by quantitative lipoprotein changes (serum apo B or LDL-cholesterol) than by LDL particle size.

Assessment of covariate effects in Aalen's additive hazard model.

We study the properties of test statistics for a covariate effect in Aalen's additive hazard model and propose several new test statistics. The proposed statistics are derived by using the weights from linear rank statistics for comparing two survival curves. We compare these statistics with the two statistics proposed by Aalen using Monte Carlo simulations. Several different survival configurations are considered in the simulation study: proportional hazards; crossing hazards; hazard differences early in time, and hazard differences for large survival times. Of the proposed test statistics, one is superior for detecting hazard differences for large survival times and another is superior for detecting early hazard differences and crossing hazards.

The clinical significance of hepatocyte growth factor for non-small cell lung cancer.

BACKGROUND: Hepatocyte growth factor (HGF) is a cytokine that is released after injury. It is a paracrine factor that is produced by mesenchymal cells; epithelial and endothelial cells respond to HGF through its receptor, the c-met protein. Hepatocyte growth factor induces cell growth and cell movement and is also highly angiogenic. Evidence from breast cancer patients suggests that HGF is a negative prognostic indicator for breast cancer and is associated with invasive disease. METHODS: We measured the HGF content in tumor tissue from 56 non-small cell lung cancer patients using the Western blot technique. The amount of HGF in tumor extracts was quantitated by densitometry after transfer of proteins to nitrocellulose and exposure to antibodies. Survival curves were generated based on clinical information obtained for each patient. RESULTS: Our data indicate that HGF is also a negative prognostic indicator in lung cancer. As in the study of breast cancer patients, HGF was associated with recurrence and poor survival; the relative risk was seen to increase with increasing HGF tumor content. At levels of HGF greater than 100 units, the relative risk was 10, compared with that in patients with an HGF level of 1 unit. Node-negative patients with an elevated HGF tumor content had a significantly poorer outcome than node-positive patients with a low HGF tumor content. The same relationship was observed if the patients were stratified by stage: elevated HGF was associated with stage I patients whose disease recurred and who died of their disease, and stage I patients with elevated HGF had a worse survival than higher stage patients with a low level of HGF. CONCLUSIONS: These results suggest that elevated HGF may predict a more aggressive biology in non-small cell lung cancer patients. The level of HGF may be useful as an indicator of high risk in early stage lung cancer patients.

Association of immunoreactive hepatocyte growth factor with poor survival in resectable non-small cell lung cancer.

We have shown previously that hepatocyte growth factor (HGF), which is produced by lung fibroblasts, is a potent mitogen and motogen for both normal and neoplastic bronchial epithelium, and that expression of the HGF receptor, the c-met proto-oncogene protein, is uniformly found in the human bronchial epithelium and in non-small cell lung carcinomas (NSCLCs; P. Singh-Kaw et al., Am. J. Physiol., 268: L1012-L1020, 1995). Yamashita et al. have reported an association of HGF with poor survival in invasive ductal carcinoma of the breast (Cancer Res., 54: 1630-1633, 1994). There are few prognostic markers for lung cancer, and the high recurrence rate for stage I lung cancer suggests the frequent presence of undetectable tumor burden in such patients. Criteria are needed to evaluate these patients for risk of recurrence. We have now evaluated whether HGF present in resectable lung tumors has prognostic significance. In this study, 56 primary NSCLCs, mainly adenocarcinomas, were examined for presence of HGF by quantitative Western blot. These tumors consisted of tissue from 34 stage I patients, 9 stage II patients, and 13 stage IIIa patients who underwent curative resection for primary NSCLC. Extracts of whole tumor tissue were analyzed after separation of proteins by electrophoresis and transfer of proteins to nitrocellulose membranes. Immunoreactive (ir)-HGF was visualized by reaction with a polyclonal anti-HGF antiserum and quantitated by densitometry. Lung tumor content of ir-HGF varied widely among individuals. Median ir-HGF content in tumor extracts was 15.3 ng/40 microg of tumor protein; mean ir-HGF was 27.2 ng/40 microg of tumor protein. The median and mean ir-HGF were both significantly higher in tumor tissue from patients who suffered a recurrence during the follow-up period compared with those with no evidence or residual disease; this was true of all patients (P = 0.0001) and stage I patients analyzed separately (P = 0.002). Analysis of survival curves indicated that ir-HGF levels higher than the median were associated with poor overall survival (P < 0.03). Univariate analysis showed three factors related to poor overall survival in this set of patients: ir-HGF, tumor (T) status (a measure of primary tumor size and extent), and age. Nodal (N) status and stage were only marginally related to overall survival, most likely because the majority of the patients in the study were stage I. N status, stage, and T status were related to disease-free survival, however. Multivariate Cox analysis showed that ir-HGF, T status, and age independently had a negative impact on overall survival. ir-HGF was a strong independent negative prognostic indicator (P = 0.0001) with a relative risk of 1.022 per unit of ir-HGF (ng/40 microg of protein). This demonstrates that, in this group of patients, the relative risk of ir-HGF content increased continuously as ir-HGF increased, and exceeded 10 at units of ir-HGF of 100 or more. In comparison, in this group of patients, the relative risk of a T status greater than 1 was 4.75 and that of age greater than 65 was 3.95. The combined negative effect of a T status greater than 1 and elevated ir-HGF on survival was also highly pronounced (P < 0.005). In addition, elevated ir-HGF had a negative impact on survival when patients were stratified by stage or N status. Stage I patients with high ir-HGF values had a worse outcome than stage II or stage IIIa patients with low ir-HGF values. Elevated ir-HGF was strongly associated with poor outcome for resectable NSCLC patients as a group, and also identified stage I patients with poor outcome, indicating that it could be a useful indicator of risk of relapse and death in patients who have early lung cancer. The impact of elevated ir-HGF was especially prominent in patients whose T status was greater than 1, suggesting that patients with both risk factors who are stag

A prediction rule to identify low-risk patients with community-acquired pneumonia.

BACKGROUND: There is considerable variability in rates of hospitalization of patients with community-acquired pneumonia, in part because of physicians' uncertainty in assessing the severity of illness at presentation. METHODS: From our analysis of data on 14,199 adult inpatients with community-acquired pneumonia, we derived a prediction rule that stratifies patients into five classes with respect to the risk of death within 30 days. The rule was validated with 1991 data on 38,039 inpatients and with data on 2287 inpatients and outpatients in the Pneumonia Patient Outcomes Research Team (PORT) cohort study. The prediction rule assigns points based on age and the presence of coexisting disease, abnormal physical findings (such as a respiratory rate of > or = 30 or a temperature of > or = 40 degrees C), and abnormal laboratory findings (such as a pH <7.35, a blood urea nitrogen concentration > or = 30 mg per deciliter [11 mmol per liter] or a sodium concentration <130 mmol per liter) at presentation. RESULTS: There were no significant differences in mortality in each of the five risk classes among the three cohorts. Mortality ranged from 0.1 to 0.4 percent for class I patients (P=0.22), from 0.6 to 0.7 percent for class II (P=0.67), and from 0.9 to 2.8 percent for class III (P=0.12). Among the 1575 patients in the three lowest risk classes in the Pneumonia PORT cohort, there were only seven deaths, of which only four were pneumonia-related. The risk class was significantly associated with the risk of subsequent hospitalization among those treated as outpatients and with the use of intensive care and the number of days in the hospital among inpatients. CONCLUSIONS: The prediction rule we describe accurately identifies the patients with community-acquired pneumonia who are at low risk for death and other adverse outcomes. This prediction rule may help physicians make more rational decisions about hospitalization for patients with pneumonia.

Hospitalized pneumonia. Outcomes, treatment patterns, and costs in urban and rural areas.

OBJECTIVES: To describe discharge rates, geographic and patient characteristics, treatment patterns, costs, and outcomes of patients hospitalized with community-acquired pneumonia (CAP) in Pennsylvania hospitals and compare these patients from rural and urban counties. DESIGN: A retrospective database study. PATIENTS: Adult patients (age > or = 18) with an ICD-9-CM diagnosis of pneumonia discharged from 193 Pennsylvania hospitals (n = 36,222) in 1991 from the MediQual Systems Pennsylvania database. MEASUREMENTS: Patient characteristics included a pneumonia-specific severity index, microbiologic etiology, and a number of comorbid conditions. Treatment indicators included the specialty of the admitting physician, length of stay, admittance to an intensive care unit, and mechanical ventilation. Cost indicators included charges and estimated costs. Outcomes measured were inpatient mortality and discharge disposition. Counties in Pennsylvania were classified into seven urban or rural groups, and patients were classified by the county of residence. RESULTS: The discharge rate for CAP was 4.0 per 1,000 and did not vary systematically across urban or rural counties. Most patients were treated in local hospitals. The average distance between residence and hospital was 5.4 miles and varied with urban or rural classification (range 2.5-9.3 miles). Among CAP patients, 37.8% were at low risk of mortality, with no systematic differences across rural or urban patients with respect to pneumonia severity. Rural patients were more likely to be treated by a family physician and somewhat less likely to be admitted to an intensive care unit or to be mechanically ventilated. Costs of treating rural patients were lower. In-hospital mortality rates, with controls for admission severity, were comparable or better for rural patients than for urban patients. CONCLUSIONS: Patients with CAP are treated in hospitals located in counties similar to ones in which they reside. The cost of treatment was lower for rural patients than for urban patients, but outcomes were not different.

Prognosis and outcomes of patients with community-acquired pneumonia. A meta-analysis.

OBJECTIVE: To systematically review the medical literature on the prognosis and outcomes of patients with community-acquired pneumonia (CAP). DATA SOURCES: A MEDLINE literature search of English-language articles involving human subjects and manual reviews of article bibliographies were used to identify studies of prognosis in CAP. STUDY SELECTION: Review of 4573 citations revealed 122 articles (127 unique study cohorts) that reported medical outcomes in adults with CAP. DATA EXTRACTION: Qualitative assessments of studies' patient populations, designs, and patient outcomes were performed. Summary univariate odds ratios (ORs) and rate differences (RDs) and their associated 95% confidence intervals (CIs) were computed to estimate a summary effect size for the association of prognostic factors and mortality. DATA SYNTHESIS: The overall mortality for the 33,148 patients in all 127 study cohorts was 13.7%, ranging from 5.1% for the 2097 hospitalized and ambulatory patients (in six study cohorts) to 36.5% for the 788 intensive care unit patients (in 13 cohorts). Mortality varied by pneumonia etiology, ranging from less than 2% to greater than 30%. Eleven prognostic factors were significantly associated with mortality using both summary ORs and RDs: male sex (OR = 1.3; 95% CI, 1.2 to 1.4), pleuritic chest pain (OR = 0.5; 95% CI, 0.3 to 0.8), hypothermia (OR = 5.0; 95% CI, 2.4 to 10.4), systolic hypotension (OR = 4.8; 95% CI, 2.8 to 8.3), tachypnea (OR = 2.9; 95% CI, 1.7 to 4.9), diabetes mellitus (OR = 1.3; 95% CI, 1.1 to 1.5), neoplastic disease (OR = 2.8; 95% CI, 2.4 to 3.1), neurologic disease (OR = 4.6; 95% CI, 2.3 to 8.9), bacteremia (OR = 2.8; 95% CI, 2.3 to 3.6), leukopenia (OR = 2.5, 95% CI, 1.6 to 3.7), and multilobar radiographic pulmonary infiltrate (OR = 3.1; 95% CI, 1.9 to 5.1). Assessments of other clinically relevant medical outcomes such as morbid complications (41 cohorts), symptoms resolution (seven cohorts), return to work or usual activities (five cohorts), or functional status (one cohort) were infrequently performed. CONCLUSIONS: Mortality for patients hospitalized with CAP was high and was associated with characteristics of the study cohort, pneumonia etiology, and a variety of prognostic factors. Generalization of these findings to all patients with CAP should be made with caution because of insufficient published information on medical outcomes other than mortality in ambulatory patients.

Methods for bounding the marginal survival distribution.

For time to event data with many potential failure types, one cannot uniquely determine the distribution of time to a specific event type, or marginal survival distribution, in the case where event types are mutually exclusive. In this paper we discuss several methods for estimating functions that bound the non-identifiable marginal survival distribution in the competing risks problem. We compute and compare bounds for data simulated from two bivariate survival distributions. Results show that the methods provide a suitable estimate of the marginal survival probability when one has specified dependence correctly. Data from a large clinical trial for breast cancer illustrate the methods.

Comparison of a disease-specific and a generic severity of illness measure for patients with community-acquired pneumonia.

OBJECTIVE: To compare the performances of a disease-specific severity of illness index and a prototypical generic severity of illness measure, MedisGroups Admission Severity Groups (ASGs), for patients with community-acquired pneumonia. DESIGN: A retrospective database study. PATIENTS: Adult patients (aged > or = 18 years) with an ICD-9-CM principal diagnosis of pneumonia in 78 MedisGroups Comparative Database hospitals. METHODS: The pneumonia severity of illness index (PSI) was developed to predict hospital mortality using logistic regression analyses in a 70% random sample of study patients. The performances of the PSI and the generic severity measure were assessed among the remaining 30% of patients by comparing observed mortalities within the five PSI and ASG severity classes, and areas under their receiver operating characteristic (ROC) curves. Both the PSI and the generic severity measure were used to estimate the 95% confidence interval of the expected number of deaths in each of the 78 study hospitals. Hospitals with an observed number of deaths outside these limits were identified as outliers. RESULTS: There were 14,199 study patients who had community-acquired pneumonia, and 1,542 (10.9%) died during hospitalization. In comparison with the generic severity measure, the PSI more accurately identified patients at extremely low risk of death, and had a larger area under its ROC curve (0.84 vs 0.79; p < 0.0001). Of the 78 study hospitals, 17 (21.8%) were classified as outliers for mortality by at least one severity adjustment system. Among the 11 low-outlier hospitals, six were classified by the generic severity measure alone, two by the PSI alone, and three by both systems; among the six high-outlier hospitals, one was classified by the generic measure alone, three by the PSI alone, and two by both systems. CONCLUSIONS: The PSI provided more accurate estimates of hospital mortality and classified different hospital outliers for mortality than did the generic severity of illness measure for patients with community-acquired pneumonia.

Discharge planning from home health care and patient status post-discharge.

An exploratory study of 57 elderly patients discharged from home health agencies sought to identify how they and their caregivers were prepared for discharge and how they were managing. Data were collected from the home care records and post-discharge interviews with patients and caregivers. Results indicate little evidence of formal discharge planning. However, home care records appear to underreport what home care staff do. On follow-up, over half of the patients had improvement in their health, two-thirds were independent in activities of daily living, and few patients had need of formal services.

Efficacy of pneumococcal vaccination in adults. A meta-analysis of randomized controlled trials.

BACKGROUND: Because of the prevalence of pneumococcal pneumonia, the substantial morbidity and mortality associated with many pneumococcal infections, and an increase in the incidence of antibiotic resistance among pneumococcal isolates, considerable efforts for disease prevention have been made using a polyvalent polysaccharide pneumococcal vaccine. Despite numerous clinical trials of the vaccine, its efficacy in the prevention of pneumococcal infections and other clinically relevant medical outcomes in adults remains uncertain. METHODS: To assess quantitatively the efficacy of pneumococcal vaccination, a MEDLINE literature search, manual reviews of article bibliographies, and communications with pneumococcal vaccine investigators were used to identify randomized controlled trials of the pneumococcal vaccine. Independent review of 594 articles revealed nine randomized trials with 12 vaccine and control study groups that evaluated clinically relevant outcomes in adults. To estimate a summary effect size for all outcomes, Mantel-Haenszel odds ratios (ORs) and Dersimonian and Laird rate differences (RDs) and their associated 95% confidence intervals (CIs) were computed. RESULTS: Summary ORs demonstrated a statistically significant protective effect of the vaccine for four pneumococcal infection-related outcomes: definitive pneumococcal pneumonia (OR = 0.34; 95% CI = 0.24 to 0.48), definitive pneumococcal pneumonia for vaccine-containing pneumococcal antigen types only (vaccine types only) (OR = 0.17; 95% CI = 0.09 to 0.33), presumptive pneumococcal pneumonia (OR = 0.47; 95% CI = 0.35 to 0.63), and presumptive pneumococcal pneumonia (vaccine types only) (OR = 0.39; 95% CI = 0.26 to 0.59). The summary RDs, which account for heterogeneity among studies, confirmed a statistically significant protective effect for two of these same outcomes: definitive pneumococcal pneumonia (RD = 4/1000; 95% CI = 0/1000 to 7/1000) and definitive pneumococcal pneumonia (vaccine types only) (RD = 8/1000; 95% CI = 1/1000 to 16/1000). Summary ORs and RDs failed to demonstrate a protective effect for pneumonia (all causes), bronchitis, and mortality (all causes) or mortality due to pneumonia or pneumococcal infection. Subgroup analyses showed that for all four pneumococcal infection-related outcomes, vaccine efficacy differed for high- and low-risk subjects, demonstrating efficacy for low-risk subjects and lack of efficacy for high-risk subjects. CONCLUSIONS: Pneumococcal vaccination appears efficacious in reducing bacteremic pneumococcal pneumonia in low-risk adults. However, evidence from randomized controlled trials fails to demonstrate vaccine efficacy for pneumococcal infection-related or other medical outcomes in the heterogeneous group of subjects currently labeled as high risk.

Quality of published reports of the prognosis of community-acquired pneumonia.

OBJECTIVE: To systematically assess the quality of published reports of the prognosis of community-acquired pneumonia using a formal quality assessment instrument. DESIGN: Retrospective review of studies published during 1966-1991. ARTICLES: 108 articles related to the prognosis of community-acquired pneumonia retrieved by a computerized search. INTERVENTION: All articles, blinded to author(s), journal title, year of publication, and study institution(s), were independently reviewed by two investigators using a ten-item quality assessment instrument designed to evaluate: 1) identification of the inception cohort (4 items), 2) description of referral patterns (1 item), 3) subject follow-up (2 items), and 4) statistical methods (3 items). Adherence to each of the ten individual quality items and an overall quality score were calculated for all articles and across three time periods. MAIN RESULTS: Among all 108 articles that underwent quality assessment, 30 were published from 1966 to 1979, 61 from 1980 through 1989, and 17 from 1990 through 1991. The mean total quality score of all articles was 0.55 (range 0.22-0.90). There was a significant trend toward improvement in total quality scores over the three time periods (0.50 to 0.56 to 0.65; p < 0.001). However, several systematic errors in the study design or reporting of these studies were discovered throughout time: only 3.7% provided comparative information about nonenrolled patients, 28.7% determined whether the study institution was a referral center, 36.1% specified inclusion or exclusion criteria, and 45.5% used appropriate statistical analyses to adjust for more than one prognostic factor. CONCLUSIONS: Despite improvement in overall quality of published articles, systematic errors exist in the design and reporting of studies related to the prognosis of community-acquired pneumonia. The quality assessment tool employed in this study could be used to guide the development of high-quality outcomes research in the future.

Obesity as a risk factor for osteoarthritis of the hand and wrist: a prospective study.

The Tecumseh Community Health Study provides an opportunity to investigate the role of obesity in the etiology of osteoarthritis. This longitudinal study, conducted in Tecumseh, Michigan, began in 1962 with baseline examinations of clinical, biochemical, and radiologic characteristics. A 1985 reexamination of the cohort characterized osteoarthritis status in 1,276 participants, 588 males and 688 females, who were aged 50-74 years at this follow-up. Baseline obesity, as measured by an index of relative weight, was found to be significantly associated with the 23-year incidence of osteoarthritis of the hands among subjects disease free at baseline. Greater baseline relative weight was also associated with greater subsequent severity of osteoarthritis of the hands. The difference between baseline and follow-up weight values was not significantly associated with the incidence of osteoarthritis of the hands. Furthermore, there was no evidence that development of osteoarthritis subsequently led to increased incidence of obesity.

APACHE-L: a new severity of illness adjuster for inpatient medical care.

A principal concern regarding Medicare's diagnosis-related group (DRG)-based prospective payment system is whether hospitals caring for more severely ill patients may be undercompensated for the services they provide. Research on possible inequities in hospital payment has been hampered by the absence of an objective, easily obtained, and valid measure of patients' severity of illness. Because laboratory data are objective and computerized in most of our nation's hospitals, a system utilizing such data, if shown to discriminate between patients of differing expected resource use, could prove most helpful in examining possible inequities in prospective payment system hospital payment. At a major teaching hospital, data were used from length of stay inlier patients in the 10 most frequent medical DRGs in the U.S. to develop and evaluate a severity of illness system called APACHE-L. APACHE-L uses the laboratory component of the original APACHE score. Whereas DRGs explained 20% of the variation in length of stay for the top ten DRGs, APACHE-L explained up to an additional 14% of the variation. For ancillary resource use, DRGs explained 10% of the variance, and APACHE-L explained up to an additional 15%. Diagnosis-related group-specific analyses demonstrated that the amount of resource use variance explained by APACHE-L varied widely depending on the DRG (from R2 = .00 for DRG 410, chemotherapy; to R2 = .38 for DRG 320, kidney and urinary tract infections, age greater than 17 years with complications or comorbidities). The APACHE-L score, which is objective and readily available in our nation's hospitals, shows considerable promise as a severity of illness adjuster for a subset of DRGs.