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1.
J Mater Chem B ; 5(41): 8183-8192, 2017.
Article in English | MEDLINE | ID: mdl-29354263

ABSTRACT

CD44 is a widely-distributed type I transmembrane glycoprotein that binds hyaluronic acid (HA) in most cell types, including primary tumor cells and cancer-initiating cells and has roles in cell migration, cell-cell, and cell-matrix adhesion. HA-derived conjugates and nanoparticles that target the CD44 receptor on cells have been reported for targeted delivery of therapeutics and imaging agents. Altering crucial interactions of HA with CD44 active sites holds significant importance in modulating targeting ability of hyaluronic acid to other cancer types that do not express the CD44 receptor or minimizing the interaction with CD44+ cells that are not target cells. The approach adopted here was deacetylation of the N-acetyl group and selective sulfation on the C6-OH on the HA polymer, which form critical interactions with the CD44 active site. Major interactions identified by molecular modeling were confirmed to be hydrogen bonding of the C6-OH with Tyr109 and hydrophobic interaction of the N-acetyl group with Tyr46, 83 and Ile 92. Modified HA was synthesized and characterized and its interactions were assessed by in vitro and molecular modeling approaches. In vitro techniques included flow cytometry and fluorescence polarization, while in silico approaches included docking and binding calculations by a MM-PBSA approach. These studies indicated that while both deacetylation and sulfation of HA individually decrease CD44 interaction, both chemical modifications are required to minimize interaction with CD44+ cells. The results of this study represent the first step to effective retargeting of HA-derived NPs for imaging and drug delivery.

2.
Br J Cancer ; 111(6): 1139-49, 2014 Sep 09.
Article in English | MEDLINE | ID: mdl-25025965

ABSTRACT

BACKGROUND: Despite its promise as a highly useful therapy for pancreatic cancer (PC), the addition of external beam radiation therapy to PC treatment has shown varying success in clinical trials. Understanding PC radioresistance and discovery of methods to sensitise PC to radiation will increase patient survival and improve quality of life. In this study, we identified PC radioresistance-associated pathways using global, unbiased techniques. METHODS: Radioresistant cells were generated by sequential irradiation and recovery, and global genome cDNA microarray analysis was performed to identify differentially expressed genes in radiosensitive and radioresistant cells. Ingenuity pathway analysis was performed to discover cellular pathways and functions associated with differential radioresponse and identify potential small-molecule inhibitors for radiosensitisation. The expression of FDPS, one of the most differentially expressed genes, was determined in human PC tissues by IHC and the impact of its pharmacological inhibition with zoledronic acid (ZOL, Zometa) on radiosensitivity was determined by colony-forming assays. The radiosensitising effect of Zol in vivo was determined using allograft transplantation mouse model. RESULTS: Microarray analysis indicated that 11 genes (FDPS, ACAT2, AG2, CLDN7, DHCR7, ELFN2, FASN, SC4MOL, SIX6, SLC12A2, and SQLE) were consistently associated with radioresistance in the cell lines, a majority of which are involved in cholesterol biosynthesis. We demonstrated that knockdown of farnesyl diphosphate synthase (FDPS), a branchpoint enzyme of the cholesterol synthesis pathway, radiosensitised PC cells. FDPS was significantly overexpressed in human PC tumour tissues compared with healthy pancreas samples. Also, pharmacologic inhibition of FDPS by ZOL radiosensitised PC cell lines, with a radiation enhancement ratio between 1.26 and 1.5. Further, ZOL treatment resulted in radiosensitisation of PC tumours in an allograft mouse model. CONCLUSIONS: Unbiased pathway analysis of radioresistance allowed for the discovery of novel pathways associated with resistance to ionising radiation in PC. Specifically, our analysis indicates the importance of the cholesterol synthesis pathway in PC radioresistance. Further, a novel radiosensitiser, ZOL, showed promising results and warrants further study into the universality of these findings in PC, as well as the true potential of this drug as a clinical radiosensitiser.


Subject(s)
Adenocarcinoma/radiotherapy , Cholesterol/biosynthesis , Diphosphonates/pharmacology , Geranyltranstransferase/genetics , Imidazoles/pharmacology , Pancreatic Neoplasms/radiotherapy , Radiation Tolerance/drug effects , Radiation-Sensitizing Agents/pharmacology , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Animals , Cell Line, Tumor , DNA, Complementary/analysis , Diphosphonates/therapeutic use , Gene Expression Profiling , Gene Knockdown Techniques , Geranyltranstransferase/analysis , Humans , Imidazoles/therapeutic use , Immunohistochemistry , Mice , Mice, Inbred C57BL , Oligonucleotide Array Sequence Analysis , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Radiation Tolerance/genetics , Radiation-Sensitizing Agents/therapeutic use , Zoledronic Acid
3.
Psychol Med ; 38(3): 385-96, 2008 Mar.
Article in English | MEDLINE | ID: mdl-17922939

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) affects 14 to 20 million Americans and is associated with increased prevalence of affective disorders, contributing significantly to disability. This study compared cognitive behavioral therapy (CBT) group treatment for anxiety and depression with COPD education for COPD patients with moderate-to-severe anxiety and/or depressive symptoms. METHOD: A randomized controlled trial (RCT) was conducted between 11 July 2002 and 30 April 2005 at the Michael E. DeBakey VA Medical Center, Houston, TX. Participants were 238 patients treated for COPD the year before, with forced expiratory value in 1 second (FEV)1/forced vital capacity (FVC)<70% and FEV1<70% predicted, and symptoms of moderate anxiety and/or moderate depression, who were being treated by a primary care provider or pulmonologist. Participants attended eight sessions of CBT or COPD education. Assessments were at baseline, at 4 and 8 weeks, and 4, 8 and 12 months. Primary outcomes were disease-specific and generic quality of life (QoL) [Chronic Respiratory Questionnaire (CRQ) and Medical Outcomes Survey Short Form-36 (SF-36) respectively]. Secondary outcomes were anxiety [Beck Anxiety Inventory (BAI)], depressive symptoms [Beck Depression Inventory-II (BDI-II)], 6-minute walk distance (6MWD) and use of health services. RESULTS: Both treatments significantly improved QoL, anxiety and depression (p<0.005) over 8 weeks; the rate of change did not differ between groups. Improvements were maintained with no significant change during follow-up. Ratios of post- to pretreatment use of health services were equal to 1 for both groups. CONCLUSIONS: CBT group treatment and COPD education can achieve sustainable improvements in QoL for COPD patients experiencing moderate-to-severe symptoms of depression or anxiety.


Subject(s)
Anxiety Disorders/therapy , Cognitive Behavioral Therapy/methods , Depressive Disorder/therapy , Patient Education as Topic/methods , Pulmonary Disease, Chronic Obstructive/psychology , Aged , Anxiety Disorders/diagnosis , Anxiety Disorders/epidemiology , Comorbidity , Depressive Disorder/diagnosis , Depressive Disorder/epidemiology , Female , Follow-Up Studies , Health Services/statistics & numerical data , Health Status , Humans , Male , Personality Inventory , Psychotherapy, Group/methods , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/therapy , Quality of Life , Surveys and Questionnaires , Texas/epidemiology , Treatment Outcome
4.
Soc Sci Med ; 53(10): 1275-85, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11676400

ABSTRACT

A fundamental assumption of utility-based analyses is that patient utilities for health states can be measured on an equal-interval scale. This assumption, however, has not been widely examined. The objective of this study was to assess whether the rating scale (RS), standard gamble (SG), and time trade-off (TTO) utility elicitation methods function as equal-interval level scales. We wrote descriptions of eight prostate-cancer-related health states. In interviews with patients who had newly diagnosed, advanced prostate cancer, utilities for the health states were elicited using the RS, SG, and TTO methods. At the time of the study, 77 initial and 73 follow-up interviews had. been conducted with a consecutive sample of 77 participants. Using a Rasch model, the boundaries (Thurstone Thresholds) between four equal score sub-ranges of the raw utilities were mapped onto an equal-interval logit scale. The distance between adjacent thresholds in logit units was calculated to determine whether the raw utilities were equal-interval. None of the utility scales functioned as interval-level scales in our sample. Therefore, since interval-level estimates are assumed in utility-based analyses, doubt is raised regarding the validity of findings from previous analyses based on these scales. Our findings need to be replicated in other contexts, and the practical impact of non-interval measurement on utility-based analyses should be explored. If cost-effectiveness analyses are not found to be robust to violations of the assumption that utilities are interval, serious doubt will be cast upon findings from utility-based analyses and upon the wisdom of expending millions in research dollars on utility-based studies.


Subject(s)
Health Status , Patient Satisfaction/statistics & numerical data , Prostatic Neoplasms/psychology , Prostatic Neoplasms/therapy , Psychometrics/methods , Quality-Adjusted Life Years , Value of Life/economics , Cost-Benefit Analysis , Focus Groups , Humans , Interviews as Topic , Logistic Models , Male , Probability , Prostatic Neoplasms/economics , Psychometrics/economics , Psychometrics/statistics & numerical data , Risk Assessment , Risk-Taking
5.
J Clin Epidemiol ; 54(8): 755-65, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11470383

ABSTRACT

The aim of this research was to develop and evaluate an instrument for measuring dyspepsia-related health to serve as the primary outcome measure for randomized clinical trials. Building on our previous work we developed SODA (Severity of Dyspepsia Assessment), a multidimensional dyspepsia measure. We evaluated SODA by administering it at enrollment and seven follow-up visits to 98 patients with dyspepsia who were randomized to a 6-week course of omeprazole versus placebo and followed over 1 year. The mean age was 53 years, and six patients (6%) were women. Median Cronbach's alpha reliability estimates over the eight visits for the SODA Pain Intensity, Non-Pain Symptoms, and Satisfaction scales were 0.97, 0.90, and 0.92, respectively. The mean change scores for all three scales discriminated between patients who reported they were improved versus those who were unchanged, providing evidence of validity. The effect sizes for the Pain Intensity (.98) and Satisfaction (.87) scales were large, providing evidence for responsiveness. The effect size for the Non-Pain Symptoms scale was small (.24), indicating lower responsiveness in this study sample. SODA is a new, effective instrument for measuring dyspepsia-related health. SODA is multidimensional and responsive to clinically meaningful change with demonstrated reliability and validity.


Subject(s)
Anti-Ulcer Agents/therapeutic use , Dyspepsia/classification , Dyspepsia/drug therapy , Health Status , Omeprazole/therapeutic use , Adult , Aged , Double-Blind Method , Female , Humans , Male , Middle Aged , Patient Satisfaction , Quality of Life , Reproducibility of Results , Severity of Illness Index
6.
Med Care ; 38(10): 1040-50, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11021677

ABSTRACT

OBJECTIVE: The objective of this study was to evaluate the convergent validity of 3 types of utility measures: standard gamble, time tradeoff, and rating scale. RESEARCH DESIGN: A prospective cohort of 120 men with advanced prostate cancer were first asked to rank order 8 health states, and then utility values were obtained from each participant for each of the 8 health states through 2 of the 3 techniques evaluated (standard gamble, time tradeoff and rating scale). Participants were randomly assigned to 1 of 3 possible pairs of techniques. The validity of the 3 methods, as measured by the convergence and raw score differences of the techniques, was assessed with ANOVA. The ability of the techniques to differentiate health states was determined. The inconsistencies between rankings and utility values were also measured. Proportions of illogical utility responses were assessed as the percent of times when states with more symptoms were given higher or equal utility values than states with fewer symptoms. RESULTS: There were significant differences in raw scores between techniques, but the values were correlated across health states. Utility values were often inconsistent with the rank order of health states. In addition, utility assessment did not differentiate the health states as well as the rank order. Furthermore, utility values were often illogical in that states with more symptoms received equal or higher utility values than states with fewer symptoms. CONCLUSIONS: Use of the utility techniques in cost-effectiveness analysis and decision making has been widely recommended. The results of this study raise serious questions as to the validity and usefulness of the measures.


Subject(s)
Attitude to Health , Decision Making , Patient Participation , Prostatic Neoplasms/therapy , Psychometrics/methods , Aged , Aged, 80 and over , Analysis of Variance , Cost-Benefit Analysis , Humans , Male , Middle Aged , Prostatic Neoplasms/economics , Reproducibility of Results , United States
7.
Am J Med Qual ; 14(1): 55-63, 1999.
Article in English | MEDLINE | ID: mdl-10446664

ABSTRACT

The objective of this study was to describe patterns of hospital and clinic use and survival for a large nationwide cohort of patients with heart failure. A retrospective cohort study of patients treated in the Veterans Affairs medical care system was conducted using linked administrative databases as data sources. In 1996, the average heart failure cohort member had 1-2 hospitalizations, 14 inpatient days, 6-7 visits with the primary physician, 15 other visits for consultations or tests, and 1-2 urgent care visits per 12 months. The overall risk-adjusted 5-year survival rate was 36%. Hospital use rates in the cohort fell dramatically between 1992 and 1996. One-year survival rates increased slightly over the period. Patients with heart failure are heavy users of services and have a very poor prognosis. Utilization and outcome data indicate the need for major efforts to assure quality of care and to devise innovative ways of delivering comprehensive services.


Subject(s)
Heart Failure/mortality , Hospitals, Veterans/statistics & numerical data , Outpatient Clinics, Hospital/statistics & numerical data , United States Department of Veterans Affairs/statistics & numerical data , Adult , Aged , Analysis of Variance , Cohort Studies , Female , Humans , Male , Middle Aged , Survival Rate , United States/epidemiology
8.
Health Serv Res ; 34(3): 777-90, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10445902

ABSTRACT

OBJECTIVES: To evaluate the hospital multistay rate to determine if it has the attributes necessary for a performance indicator that can be applied to administrative databases. DATA SOURCES/STUDY SETTING: The fiscal year 1994 Veterans Affairs Patient Treatment File (PTF), which contains discharge data on all VA inpatients. STUDY DESIGN: Using a retrospective study design, we assessed cross-hospital variation in (a) the multistay rate and (b) the standardized multistay ratio. A hospital's multistay rate is the observed average number of hospitalizations for patients with one or more hospital stays. A hospital's standardized multistay ratio is the ratio of the geometric mean of the observed number of hospitalizations per patient to the geometric mean of the expected number of hospitalizations per patient, conditional on the types of patients admitted to that hospital. DATA COLLECTION/EXTRACTION METHODS: Discharge data were extracted for the 135,434 VA patients who had one or more admissions in one of seven disease groups. PRINCIPAL FINDINGS: We found that 17.3 percent (28,300) of the admissions in the seven disease categories were readmissions. The average number of stays per person (multistay rate) for an average of seven months of follow-up ranged from 1.15 to 1.45 across the disease categories. The maximum standardized multistay ratio ranged from 1.12 to 1.39. CONCLUSIONS: This study has shown that the hospital multistay rate offers sufficient ease of measurement, frequency, and variation to potentially serve as a performance indicator.


Subject(s)
Hospitals, Veterans/standards , Patient Readmission/statistics & numerical data , Quality Indicators, Health Care , Algorithms , Analysis of Variance , Cohort Studies , Diagnosis-Related Groups/statistics & numerical data , Hospitals, Veterans/statistics & numerical data , Humans , Linear Models , Patient Discharge/statistics & numerical data , Risk Adjustment/statistics & numerical data , Severity of Illness Index , United States , United States Department of Veterans Affairs
9.
Med Care ; 37(6): 580-8, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10386570

ABSTRACT

BACKGROUND: Utility techniques are the most commonly used means to assess patient preferences for health outcomes. However, whether utility techniques produce valid measures of preference has been difficult to determine in the absence of a gold standard. OBJECTIVE: To introduce and demonstrate two methods that can be used to evaluate how well utility techniques measure patients' preferences. SUBJECTS AND DESIGN: Patients treated for advanced prostate cancer (n = 57) first ranked eight health states in order of preference. Four utility techniques were then used to elicit patients' utilities for each health state. MEASURES: The rating scale, standard gamble, time trade-off, and a modified version of willingness-to-pay techniques were used to elicit patients' utilities. Technique performance was assessed by computing a differentiation and inconsistency score for each technique. RESULTS: Differentiation scores indicated the rating scale permitted respondents to assign unique utility values to about 70% of the health states that should have received unique values. When the other techniques were used, about 40% or less of the health states that should have received unique utility scores actually did receive unique utility scores. Inconsistency scores, which indicate how often participants assign utility scores that contradict how they value health states, indicated that the willingness-to-pay technique produced the lowest rate of inconsistency (10%). However, this technique did not differ significantly from the rating scale or standard gamble on this dimension. CONCLUSIONS: Differentiation and inconsistency offer a means to evaluate the performance of utility techniques, thereby allowing investigators to determine the extent to which utilities they have elicited for a given decision problem are valid. In the current investigation, the differentiation and inconsistency methods indicated that all four techniques performed at sub-optimal levels, though the rating scale out-performed the standard gamble, time trade-off, and willingness-to-pay techniques.


Subject(s)
Choice Behavior , Health Status , Patient Satisfaction/statistics & numerical data , Prostatic Neoplasms/psychology , Prostatic Neoplasms/therapy , Surveys and Questionnaires/standards , Treatment Outcome , Aged , Bias , Financing, Personal , Humans , Male , Prostatic Neoplasms/economics , Reproducibility of Results , Risk-Taking , Texas , Time Factors
10.
Med Care ; 37(2): 140-8, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10024118

ABSTRACT

BACKGROUND: Little data exist supporting the association of quality of care and nonfatal adverse outcomes in hospitalized patients, yet those outcomes are routinely scrutinized in quality assessment efforts. OBJECTIVE: To determine whether measurable differences in quality of care are associated with the occurrence of non-fatal, in-hospital, and treatment-related complications. DESIGN: Retrospective cohort study. SUBJECTS: A total of 2,268 patients who were discharged alive from 9 Southwestern Veterans Affairs Medical Centers with congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) or diabetes mellitus. MEASURES: Retrospective chart review was performed to collect information on patient severity of illness, in-hospital complication occurrence, and process quality of care. Process quality was assessed as the adherence scores for admission work-up and for treatment during the hospital stay. Process quality represents the proportion of applicable admission or treatment criteria that were met by that patient's care providers. Once severity of illness was taken into account Cox proportional hazards regression was used to assess the independent contribution of process quality of care to complication occurrence. RESULTS: Higher admission work-up adherence scores for COPD patients and higher treatment adherence scores for COPD and diabetes patients were associated with a lower risk of complication occurrence. The adjusted risk ratios of complications for higher versus lower adherence scores (with 95% CI) were 0.64 (0.43, 0.97) and 0.52 (0.33, 0.80) for admission and treatment, respectively, in COPD patients, and 0.51 (0.31, 0.83) for treatment in diabetics. No significant association was found in CHF patients. CONCLUSION: Better admission work-up and treatment quality in COPD patients, as well as treatment quality in diabetic patients, are associated with lower risk of nonfatal treatment-related complications in the study population.


Subject(s)
Diabetes Complications , Heart Failure/complications , Hospitals, Veterans/standards , Iatrogenic Disease/epidemiology , Lung Diseases, Obstructive/complications , Quality of Health Care , APACHE , Adult , Aged , Aged, 80 and over , Cohort Studies , Diabetes Mellitus/therapy , Female , Heart Failure/therapy , Humans , Incidence , Lung Diseases, Obstructive/therapy , Male , Medical History Taking , Middle Aged , Outcome and Process Assessment, Health Care , Patient Discharge , Retrospective Studies , Risk Factors , Southwestern United States/epidemiology
11.
N Engl J Med ; 340(1): 32-9, 1999 Jan 07.
Article in English | MEDLINE | ID: mdl-9878643

ABSTRACT

BACKGROUND: In the United States, geographic variation in hospital use is common. It is uncertain whether there are similar geographic variations in the health care system of the Department of Veterans Affairs (VA), which differs from the private sector because it predominantly serves men with annual incomes below $20,000, has a central system of administration, and uses salaried physicians. Thus, it might be less likely to have geographic variations. METHODS: We used VA data bases to obtain information on patients treated for eight diseases (chronic obstructive pulmonary disease, pneumonia, congestive heart failure, angina, diabetes, chronic renal failure, bipolar disorder, and major depression). We analyzed their use of hospital and outpatient services by assessing the risk-adjusted numbers of hospital days (the average number of days a patient spent in the hospital per 12 months of follow-up, regardless of the number of hospital stays), hospital-discharge rates, and clinic-visit rates from 1991 through 1995 for the entire system and within the 22 geographically based health care networks. RESULTS: We found substantial geographic variation in hospital use for all eight cohorts of patients and all the years studied. Variations in the numbers of hospital days per person-year among the networks were greatest among patients with chronic obstructive pulmonary disease (ranging from a factor of 2.7 to a factor of 3.1) during a given year and smallest among patients with angina (ranging from a factor of 1.5 to a factor of 2.1). Levels of hospital use were highest in the Northeast and lowest in the West. The variation in the rates of clinic visits for principal medical care among the networks ranged from a factor of approximately 1.6 to a factor of 4.0; variations in the rates were greatest among patients with chronic renal failure and smallest among patients with chronic obstructive pulmonary disease. There was no clear geographic pattern in the rates of outpatient-clinic use. CONCLUSIONS: There are significant geographic variations in the use of hospital and outpatient services in the VA health care system. Because VA physicians are unable to increase their income by changing their patterns of practice, our findings suggest that their practice styles are similar to those of other physicians in their geographic regions.


Subject(s)
Chronic Disease/therapy , Hospitals, Veterans/statistics & numerical data , Outpatient Clinics, Hospital/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Cohort Studies , Hospital Bed Capacity , Humans , Length of Stay/statistics & numerical data , Male , Multivariate Analysis , Patient Discharge/statistics & numerical data , Risk Adjustment , Statistics, Nonparametric , United States , Utilization Review
12.
J Clin Epidemiol ; 50(11): 1231-40, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9393379

ABSTRACT

This article and the following article (Parts I and II) report the development of two clinical staging systems for HIV-infected individuals. The objective of the research reported here (Part I) was to construct a clinical staging system to predict progression to AIDS. We analyzed data from VA Cooperative Study Number 298, a multicenter, double-blind, randomized trial that compared immediate versus deferred zidovudine therapy in 338 HIV-infected individuals who did not have AIDS at enrollment. Baseline variables were tested in univariate Cox regression for their relationship to progression to AIDS, and those that appeared predictive were examined in multivariable analysis. Based on these analyses, we constructed a new clinical staging system based on CD4+ cell count, age, hemoglobin, oral hairy leukoplakia or oral thrush, and fever. The stages of the system were significant predictors of progression to AIDS (p = 0.0001, log-rank test). In conclusion, simple, valid, clinical staging systems for HIV-infected patients can be constructed using information that is readily available in clinical practice settings. Such systems provide better prognostic distinction than CD4+ cell count alone by taking into account the known prognostic effects of other variables.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/classification , Veterans , Zidovudine/therapeutic use , Acquired Immunodeficiency Syndrome/diagnosis , Adult , CD4 Lymphocyte Count , Cohort Studies , Disease Progression , Double-Blind Method , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Male , Markov Chains , Predictive Value of Tests , Severity of Illness Index , Treatment Outcome
13.
J Clin Epidemiol ; 50(11): 1241-8, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9393380

ABSTRACT

This article (Part II) and the preceding article (Part I) report the development of two clinical staging systems for HIV-infected individuals. The objective of the research reported here (Part II) was to construct a clinical staging system to predict survival in patients with AIDS. We analyzed data from VA Cooperative Study Number 298, a multicenter, double-blind, randomized trial that compared immediate versus deferred zidovudine therapy in HIV-infected individuals. Baseline variables obtained at the onset of AIDS in 204 individuals were tested in univariate Cox regression for their relationship to survival, and those that appeared predictive were examined in multivariable analysis. Based on these analyses, we constructed a new AIDS Clinical Staging System. The system is based on age, CD4+ cell count, type of first AIDS-defining condition, and functional status. The stages of the system were significant predictors of survival (p = 0.0001, log-rank test). In conclusion, valid, simple clinical staging systems for patients with AIDS can be developed based on a few variables that are readily available in clinical settings.


Subject(s)
Acquired Immunodeficiency Syndrome/mortality , Veterans , Acquired Immunodeficiency Syndrome/classification , Acquired Immunodeficiency Syndrome/drug therapy , Adult , Anti-HIV Agents/therapeutic use , Double-Blind Method , Female , Humans , Male , Markov Chains , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Severity of Illness Index , Survival Rate , Treatment Outcome , Zidovudine/therapeutic use
14.
Med Care ; 35(10): 1044-59, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9338530

ABSTRACT

OBJECTIVES: To help resolve the current controversy over the validity of early readmission as an indicator of the quality of care, the authors critically reviewed the literature using meta-analysis to derive summary estimates of effect and evaluate inter-study heterogeneity. METHODS: The authors selected reports meeting five criteria: (1) presentation of new data on medical-surgical hospitalization of adults; (2) measurement of outcome as a person-specific readmission; (3) readmission within < or = 31 days; (4) examination of some aspect of the process of inpatient care; (5) inclusion of a comparison group. One meta-analysis examined 13 comparisons of readmission rates after substandard versus normative care, another examined 9 comparisons of readmission rates after normative versus exceptional care, and the third examined all 22 comparisons together. Two authors applied inclusion criteria and extracted data on methods and findings. Two others classified studies on 11 methodological variables for the heterogeneity evaluation. RESULTS: The summary odds ratio for readmission after substandard care was 1.24 (0.99-1.57) relative to normative care; for readmission after normative care the summary odds ratio was 1.45 (0.90-2.33) relative to exceptional care. The individual odds ratios varied significantly (chi2, 21 df = 50.34, P = 0.0003). Most of the variance in study odds ratios could be explained by whether the study focused on the quality of patient care or the qualifications of patient care providers. The summary odds ratio for the 16 homogeneous comparisons focusing on the quality of patient care was 1.55 (1.25-1.92). CONCLUSIONS: Early readmission is significantly associated with the process of inpatient care. The risk of early readmission is increased by 55% when care is of relatively low quality, that is, substandard or normative instead of normative or exceptional.


Subject(s)
Hospitals/standards , Outcome and Process Assessment, Health Care , Patient Readmission/statistics & numerical data , Quality of Health Care , Adult , Analysis of Variance , Confounding Factors, Epidemiologic , Hospitals/statistics & numerical data , Humans , Odds Ratio , Patient-Centered Care/standards , Regression Analysis , Reproducibility of Results , Research Design , Time Factors
15.
Med Care ; 35(8): 768-81, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9268250

ABSTRACT

OBJECTIVES: Adverse outcome rates are increasingly used as yardsticks for the quality of hospital care. However, the validity of many outcome studies has been undermined by the application of one outcome to all patients in large, diagnostically diverse populations, many of which lack evidence of a link between antecedent process of care and the rate of the outcome, the underlying assumption of the analysis. METHODS: To address this analytic problem, the authors developed a model that improves the ability to identify quality problems because it selects diseases for which there are processes of care known to affect the outcome of interest. Thus, for these diseases, the outcome is most likely to be causally related to the antecedent care. In this study of hospital readmissions, risk-adjusted models were created for 17 disease categories with strong links between process and outcome. Using these models, we identified outlier hospitals. RESULTS: The authors hypothesized that if the model improved on identifying hospitals with quality of care problems, then outlier status would not be random. That is, hospitals found to have extreme rates in one year would be more likely to have extreme rates in subsequent years, and hospitals with extreme rates in one condition would be more likely to have extreme rates in related disease categories. It was hypothesized further that the correlation of outlier status across time and across diseases would be stronger in the 17 disease categories selected by the model than in 10 comparison disease categories with weak links between process and outcome. CONCLUSIONS: The findings support all these hypotheses. Although the present study shows that the model selects disease-outcome pairs where hospital outlier status is not random, the causal factors leading to outlier status could include (1) systematic unmeasured patient variation, (2) practice pattern variation that, although stable with time, is not indicative of substandard care, or (3) true quality-of-care problems. Primary data collection must be done to determine which of these three factors is most causally related to hospital outlier status.


Subject(s)
Hospitals, Veterans/statistics & numerical data , Logistic Models , Outcome and Process Assessment, Health Care/organization & administration , Outliers, DRG , Patient Readmission/statistics & numerical data , Health Services Research , Humans , Practice Patterns, Physicians' , Predictive Value of Tests , Reproducibility of Results , Time Factors , United States , United States Department of Veterans Affairs
16.
J Gen Intern Med ; 11(10): 622-4, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8945694

ABSTRACT

This study evaluated the predictive validity of two clinical staging systems for HIV infection (the Rabeneck and Royce systems) using data obtained from the Department of Veterans Affairs Cooperative Study Number 298, a randomized clinical trial involving 335 symptomatic patients with CD4 counts of 200 to 500/mm3. The relation between the HIV clinical stages and progression to AIDS was examined using Kaplan-Meier estimates, and Cox models were used to determine if the stages remained predictive after controlling for CD4 count. Both systems were significant independent predictors of progression to AIDS. This work demonstrates that simple, valid staging systems for HIV infection can be developed that provide greater prognostic distinction than the CD4 count alone.


Subject(s)
Acquired Immunodeficiency Syndrome/immunology , CD4 Lymphocyte Count , Acquired Immunodeficiency Syndrome/diagnosis , Acquired Immunodeficiency Syndrome/drug therapy , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/therapeutic use , Double-Blind Method , Evaluation Studies as Topic , Female , HIV Infections/diagnosis , HIV Infections/drug therapy , HIV Infections/immunology , Humans , Male , Predictive Value of Tests , Prognosis , Sensitivity and Specificity , Zidovudine/administration & dosage , Zidovudine/therapeutic use
17.
J Am Optom Assoc ; 66(10): 603-7, 1995 Oct.
Article in English | MEDLINE | ID: mdl-7499713

ABSTRACT

BACKGROUND: Patients scheduled to undergo radial keratotomy in both eyes received redeepening incisions in one eye and single pass incisions in the other. Eye and order of surgery were assigned randomly and surgical parameters were otherwise identical in the two eyes. METHODS: This study was designed to measured the improvements in myopia obtained by radial keratotomy, with and without redeepening incisions. RESULTS: There was a greater decrease in spherical equivalent manifest refraction in the redeepening group than in the control group at 1 week (0.41 D) and 1 month (0.36 D) after surgery, as measured by keratometry. The difference in change between groups was 0.41 D at one week, 0.36 D at 1 month, and 0.26 D at 3 months. Change in spherical equivalent was significantly more in the redeepened group at 3 months after surgery (0.37 D); however, the improvement constituted only 8.8 percent of the decrease in myopia achieved by radial keratotomy without redeepening (3.87 D). CONCLUSIONS: Although redeepening yields an incremental effect in the correction of myopia, the technical difficulties of redeepening and the increased chance of perforation of the cornea with redeepening outweigh the benefits of the procedure.


Subject(s)
Cornea/surgery , Keratotomy, Radial , Myopia/surgery , Adult , Female , Humans , Male , Treatment Outcome
18.
Med Care ; 33(1): 75-89, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7823649

ABSTRACT

Health care payors and providers are increasingly monitoring hospital discharge data bases for adverse events as markers for quality of care. The principal criticisms of these analyses have focused on the impediments to risk adjustment posed by the incompleteness and inaccuracy of the data bases. However, efforts to address the inadequacies of the data bases will not correct deficiencies of the analytic process. These deficiencies arise from the application of one adverse outcome to all disease states. Instead, analysis should be restricted to comparisons of subgroups of patients in which a close fit exists between the quality of care for the disease state and the expected outcome. Furthermore, these disease-outcome pairs should be minimally subject to measurement error. The authors present a conceptual framework for developing such meaningful disease-outcome pairs, and using the hospital discharge data base of the Department of Veterans Affairs, show how the framework can be used to devise a monitoring strategy for re-admission.


Subject(s)
Diagnosis-Related Groups/standards , Health Services Research/methods , Outcome Assessment, Health Care/statistics & numerical data , Patient Readmission/statistics & numerical data , Data Collection/methods , Databases, Factual/standards , Diagnosis , Humans , Medical Records Systems, Computerized/statistics & numerical data , Models, Statistical , Patient Discharge , Prevalence , Professional Staff Committees , United States
19.
J Cataract Refract Surg ; 19(1): 52-5, 1993 Jan.
Article in English | MEDLINE | ID: mdl-8426323

ABSTRACT

Preoperative and postoperative anterior chamber reactions in a series of cataract surgery patients were measured with a Kowa FC-1000 laser flare/cell meter by two different technicians, and clinical assessments of inflammation were recorded. The average cell and flare readings by the two technicians were nearly identical at every time point, showing the laser flare/cell measurements to be highly reproducible. The correlations between laser flare/cell measurements and clinical assessments at postoperative time points were highly positive (P < .01), demonstrating the validity of the laser flare/cell measurements.


Subject(s)
Cataract Extraction/adverse effects , Inflammation/pathology , Lasers , Anterior Chamber/pathology , Cell Count , Female , Humans , Male , Middle Aged , Observer Variation , Ophthalmology/instrumentation , Reproducibility of Results
20.
J Cataract Refract Surg ; 19(1): 62-3, 1993 Jan.
Article in English | MEDLINE | ID: mdl-7864906

ABSTRACT

Twenty-eight patients who had an intraocular pressure greater than 30 mm Hg within 24 hours after cataract surgery were randomly assigned to be treated with medication or by paracentesis through a sideport incision. Paracentesis provided an immediate reduction in intraocular pressure, but within one hour pressures rebounded. Within two to three hours after treatment, the medication group had significantly greater mean reductions in intraocular pressure than the paracentesis group.


Subject(s)
Cataract Extraction/adverse effects , Drainage , Intraocular Pressure , Lenses, Intraocular , Ocular Hypertension/prevention & control , Acetazolamide/therapeutic use , Aged , Aqueous Humor , Female , Humans , Male , Ocular Hypertension/etiology , Pilocarpine/therapeutic use , Prospective Studies , Punctures , Treatment Outcome
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