Hospital Volume and Operative Mortality for General Surgery Operations Performed Emergently in Adults.

OBJECTIVE: This study aimed to answer 2 questions: first, to what degree does hospital operative volume affect mortality for adult patients undergoing 1 of 10 common emergency general surgery (EGS) operations? Second, at what hospital operative volume threshold will nearly all patients undergoing an emergency operation realize the average mortality risk? BACKGROUND: Nontrauma surgical emergencies are an underappreciated public health crisis in the United States; redefining where such emergencies are managed may improve outcomes. The field of trauma surgery established regionalized systems of care in part because studies demonstrated a clear relationship between hospital volume and survival for traumatic emergencies. Such a relationship has not been well-studied for nontrauma surgical emergencies. METHODS: Retrospective cohort study of all acute care hospitals in California performing nontrauma surgical emergencies. We employed a novel use of an ecological analysis with beta regression to investigate the relationship between hospital operative volume and mortality. RESULTS: A total of 425 acute care hospitals in California performed 165,123 EGS operations. Risk-adjusted mortality significantly decreased as volume increased for all 10 EGS operations (P < 0.001 for each); the relative magnitude of this inverse relationship differed substantially by procedure. Hospital operative volume thresholds were defined and varied by operation: from 75 cases over 2 years for cholecystectomy to 7 cases for umbilical hernia repair. CONCLUSIONS: Survival rates for nontrauma surgical emergencies were improved when operations were performed at higher-volume hospitals. The use of ecological analysis is widely applicable to the field of surgical outcomes research.

Impact of Cost Display on Ordering Patterns for Hospital Laboratory and Imaging Services.

BACKGROUND: Physicians "purchase" many health care services on behalf of patients yet remain largely unaware of the costs of these services. Electronic health record (EHR) cost displays may facilitate cost-conscious ordering of health services. OBJECTIVE: To determine whether displaying hospital lab and imaging order costs is associated with changes in the number and costs of orders placed. DESIGN: Quasi-experimental study. PARTICIPANTS: All patients with inpatient or observation encounters across a multi-site health system from April 2013 to October 2015. INTERVENTION: Display of order costs, based on Medicare fee schedules, in the EHR for 1032 lab tests and 1329 imaging tests. MAIN MEASURES: Outcomes for both lab and imaging orders were (1) whether an order was placed during a hospital encounter, (2) whether an order was placed on a given patient-day, (3) number of orders placed per patient-day, and (4) cost of orders placed per patient-day. KEY RESULTS: During the lab and imaging study periods, there were 248,214 and 258,267 encounters, respectively. Cost display implementation was associated with a decreased odds of any lab or imaging being ordered during the encounter (lab adjusted odds ratio [AOR] = 0.97, p = .01; imaging AOR = 0.97, p < .001), a decreased odds of any lab or imaging being ordered on a given patient-day (lab AOR = 0.95, p < .001; imaging AOR = 0.97, p < .001), a decreased number of lab or imaging orders on patient-days with orders (lab adjusted count ratio = 0.93, p < .001; imaging adjusted count ratio = 0.98, p < .001), and a decreased cost of lab orders and increased cost of imaging orders on patient-days with orders (lab adjusted cost ratio = 0.93, p < .001; imaging adjusted cost ratio = 1.02, p = .003). Overall, the intervention was associated with an 8.5 and 1.7% reduction in lab and imaging costs per patient-day, respectively. CONCLUSIONS: Displaying costs within EHR ordering screens was associated with decreases in the number and costs of lab and imaging orders.

Identification of metastatic cancer in claims data.

PURPOSE: To develop algorithms to identify metastatic cancer in claims data, using tumor stage from an oncology electronic medical record (EMR) data warehouse as the gold standard. METHODS: Data from an outpatient oncology EMR database were linked to medical and pharmacy claims data. Patients diagnosed with breast, lung, colorectal, or prostate cancer with a stage recorded in the EMR between 2004 and 2010 and with medical claims available were eligible for the study. Separate algorithms were developed for each tumor type using variables from the claims, including diagnoses, procedures, drugs, and oncologist visits. Candidate variables were reviewed by two oncologists. For each tumor type, the selected variables were entered into a classification and regression tree model to determine the algorithm with the best combination of positive predictive value (PPV), sensitivity, and specificity. RESULTS: A total of 1385 breast cancer, 1036 lung, 727 colorectal, and 267 prostate cancer patients qualified for the analysis. The algorithms varied by tumor type but typically included International Classification of Diseases-Ninth Revision codes for secondary neoplasms and use of chemotherapy and other agents typically given for metastatic disease. The final models had PPV ranging from 0.75 to 0.86, specificity 0.75-0.97, and sensitivity 0.60-0.81. CONCLUSIONS: While most of these algorithms for metastatic cancer had good specificity and acceptable PPV, a tradeoff with sensitivity prevented any model from having good predictive ability on all measures. Results suggest that accurate ascertainment of metastatic status may require access to medical records or other confirmatory data sources.

Palliative care outcomes in surgical oncology patients with advanced malignancies: a mixed methods approach.

PURPOSE: To prospectively compare outcomes and processes of hospital-based early palliative care with standard care in surgical oncology patients (N = 152). METHODS: A randomized, mixed methods, longitudinal study evaluated the effectiveness of a hospital-based Pain and Palliative Care Service (PPCS). Interviews were conducted presurgically and at follow-up visits up to 1 year. Primary outcome measures included the Gracely Pain Intensity and Unpleasantness Scales and the Symptom Distress Scale. Qualitative interviews assessed social support, satisfaction with care, and communication with providers. Survival analysis methods explored factors related to treatment crossover and study discontinuation. Models for repeated measures within subjects over time explored treatment and covariate effects on patient-reported pain and symptom distress. RESULTS: None of the estimated differences achieved statistical significance; however, for those who remained on study for 12 months, the PPCS group performed better than their standard of care counterparts. Patients identified consistent communication, emotional support, and pain and symptom management as positive contributions delivered by the PPCS. CONCLUSIONS: It is unclear whether lower pain perceptions despite greater symptom distress were clinically meaningful; however, when coupled with the patients' perceptions of their increased resources and alternatives for pain control, one begins to see the value of an integrated PPCS.

Accounting for the relationship between per diem cost and LOS when estimating hospitalization costs.

BACKGROUND: Hospitalization costs in clinical trials are typically derived by multiplying the length of stay (LOS) by an average per-diem (PD) cost from external sources. This assumes that PD costs are independent of LOS. Resource utilization in early days of the stay is usually more intense, however, and thus, the PD cost for a short hospitalization may be higher than for longer stays. The shape of this relationship is unlikely to be linear, as PD costs would be expected to gradually plateau. This paper describes how to model the relationship between PD cost and LOS using flexible statistical modelling techniques. METHODS: An example based on a clinical study of clevidipine for the treatment of peri-operative hypertension during hospitalizations for cardiac surgery is used to illustrate how inferences about cost-savings associated with good blood pressure (BP) control during the stay can be affected by the approach used to derive hospitalization costs.Data on the cost and LOS of hospitalizations for coronary artery bypass grafting (CABG) from the Massachusetts Acute Hospital Case Mix Database (the MA Case Mix Database) were analyzed to link LOS to PD cost, factoring in complications that may have occurred during the hospitalization or post-discharge. The shape of the relationship between LOS and PD costs in the MA Case Mix was explored graphically in a regression framework. A series of statistical models including those based on simple logarithmic transformation of LOS to more flexible models using LOcally wEighted Scatterplot Smoothing (LOESS) techniques were considered. A final model was selected, using simplicity and parsimony as guiding principles in addition traditional fit statistics (like Akaike's Information Criterion, or AIC). This mapping was applied in ECLIPSE to predict an LOS-specific PD cost, and then a total cost of hospitalization. These were then compared for patients who had good vs. poor peri-operative blood-pressure control. RESULTS: The MA Case Mix dataset included data from over 10,000 patients. Visual inspection of PD vs. LOS revealed a non-linear relationship. A logarithmic model and a series of LOESS and piecewise-linear models with varying connection points were tested. The logarithmic model was ultimately favoured for its fit and simplicity. Using this mapping in the ECLIPSE trials, we found that good peri-operative BP control was associated with a cost savings of $5,366 when costs were derived using the mapping, compared with savings of $7,666 obtained using the traditional approach of calculating the cost. CONCLUSIONS: PD costs vary systematically with LOS, with short stays being associated with high PD costs that drop gradually and level off. The shape of the relationship may differ in other settings. It is important to assess this and model the observed pattern, as this may have an impact on conclusions based on derived hospitalization costs.

Hospital Variation in Geriatric Surgical Safety for Emergency Operation.

BACKGROUND: The American College of Surgeons maintains that surgical care in the US has not reached optimal safety and quality. This can be driven partially by higher-risk, emergency operations in geriatric patients. We therefore sought to answer 2 questions: First, to what degree does standardized postoperative mortality vary in hospitals performing nonelective operations in geriatric patients? Second, can the differences in hospital-based mortality be explained by patient-, operative-, and hospital-level characteristics among outlier institutions? STUDY DESIGN: Patients 65 years and older who underwent 1 of 8 common emergency general surgery operations were identified using the California State Inpatient Database (2010 to 2011). Expected mortality was obtained from hierarchical, Bayesian mixed-effects logistic regression models. A risk-adjusted hospital-level standardized mortality ratio (SMR) was calculated from observed-to-expected in-hospital deaths. "Outlier" hospitals had an SMR 80% CI that did not cross the mean SMR of 1.0. High-mortality (SMR >1.0) and low-mortality (SMR <1.0) outliers were compared. RESULTS: We included 24,207 patients from 107 hospitals. SMRs varied widely, from 2.3 (highest) to 0.3 (lowest). Eleven hospitals (10.3%) were poor-performing high-SMR outliers, and 10 hospitals (9.3%) were exceptional-performing low-SMR outliers. SMR was 3 times worse in the high-SMR compared with the low-SMR group (1.7 vs 0.6; p < 0.001). Patient-, operation-, and hospital-level characteristics were equivalent among outlier-hospitals. CONCLUSIONS: Significant hospital variation exists in standardized mortality after common general surgery operations done emergently in older patients. More than 10% of institutions have substantial excess mortality. These findings confirm that the safety of emergency operation in geriatric patients can be significantly improved by decreasing the wide variability in mortality outcomes.

Regionalization of emergency general surgery operations: A simulation study.

BACKGROUND: It has been theorized that a tiered, regionalized system of care for emergency general surgery (EGS) patients-akin to regional trauma systems-would translate into significant survival benefits. Yet data to support this supposition are lacking. The aim of this study was to determine the potential number of lives that could be saved by regionalizing EGS care to higher-volume, lower-mortality EGS institutions. METHODS: Adult patients who underwent one of 10 common EGS operations were identified in the California Inpatient Database (2010-2011). An algorithm was constructed that "closed" lower-volume, higher-mortality hospitals and referred those patients to higher-volume, lower-mortality institutions ("closure" based on hospital EGS volume-threshold that optimized to 95% probability of survival). Primary outcome was the number of lives saved. Fifty thousand regionalization simulations were completed (5,000 for each operation) employing a bootstrap resampling method to proportionally redistribute patients. Estimates of expected deaths at the higher-volume hospitals were recalculated for every bootstrapped sample. RESULTS: Of the 165,123 patients who underwent EGS operations over the 2-year period, 17,655 (10.7%) were regionalized to a higher-volume hospital. On average, 128 (48.8%) of lower-volume hospitals were "closed," ranging from 68 (22.0%) hospital closures for appendectomy to 205 (73.2%) for small bowel resection. The simulations demonstrated that EGS regionalization would prevent 9.7% of risk-adjusted EGS deaths, significantly saving lives for every EGS operation: from 30.8 (6.5%) deaths prevented for appendectomy to 122.8 (7.9%) for colectomy. Regionalization prevented 4.6 deaths per 100 EGS patient-transfers, ranging from 1.3 for appendectomy to 8.0 for umbilical hernia repair. CONCLUSION: This simulation study provides important new insight into the concept of EGS regionalization, suggesting that 1 in 10 risk-adjusted deaths could be prevented by a structured system of EGS care. Future work should expand upon these findings using more complex discrete-event simulation models. LEVEL OF EVIDENCE: Therapeutic/Care Management, level IV.

Top-tier emergency general surgery hospitals: Good at one operation, good at them all.

BACKGROUND: There is a longstanding interest in the field of management science to study high performance organizations. Applied to medicine, research on hospital performance indicates that some hospitals are high performing, while others are not. The objective of this study was to identify a cluster of high-performing emergency general surgery (EGS) hospitals and assess whether high performance at one EGS operation was associated with high performance on all EGS operations. METHODS: Adult patients who underwent one of eight EGS operations were identified in the California State Inpatient Database (2010-2011), which we linked to the American Hospital Association database. Beta regression was used to estimate a hospital's risk-adjusted mortality, accounting for patient- and hospital-level factors. Centroid cluster analysis grouped hospitals by patterns of mortality rates across the eight EGS operations using z scores. Multinomial logistic regression compared hospital characteristics by cluster. RESULTS: A total of 220 acute care hospitals were included. Three distinct clusters of hospitals were defined based on assessment of mortality for each operation type: high-performing hospitals (n = 66), average performing (n = 99), and low performing (n = 55). The mortality by individual operation type at the high-performing cluster was consistently at least 1.5 standard deviations better than the low-performing cluster (p < 0.001). Within-cluster variation was minimal at high-performing hospitals compared with wide variation at low-performing hospitals. A hospital's high performance in one EGS operation type predicted high performance on all EGS operation types. CONCLUSION: High-performing EGS hospitals attain excellence across all types of EGS operations, with minimal variability in mortality. Poor-performing hospitals are persistently below average, even for low-risk operations. These findings suggest that top-performing EGS hospitals are highly reliable, with systems of care in place to achieve consistently superior results. Further investigation and collaboration are needed to identify the factors associated with high performance. LEVEL OF EVIDENCE: Prognostic, level III.

Hospital Operative Volume as a Quality Indicator for General Surgery Operations Performed Emergently in Geriatric Patients

BACKGROUND: Within the growing geriatric population, there is an increasing need for emergency operations. Optimizing outcomes can require a structured system of surgical care based on key quality indicators. To investigate this, the current study sought to answer 2 questions. First, to what degree does hospital emergency operative volume impact mortality for geriatric patients undergoing emergency general surgery (EGS) operations? Second, at what procedure-specific hospital volume will geriatric patients undergoing an emergency operation achieve at or better than average mortality risk? STUDY DESIGN: Retrospective cohort study of geriatric patients (aged 65 years and older) who underwent 1 of 10 EGS operations identified from the California State Inpatient Database (2010 to 2011). ß-Logistic generalized linear regression was used, with the hospital as the unit of analysis, to investigate the relationship between hospital operative volume and in-hospital riskv-adjusted mortality. Hospital operative volume thresholds to optimize probability of survival were defined. RESULTS: There were 41,860 operations evaluated at 299 hospitals. For each operation, mortality decreased as hospital emergency operative volume increased (p < 0.001 for each operation); for every standardized increase in volume (meaning +1 natural logarithm of volume), the reduction in mortality ranged from 14% for colectomy to 61% for appendectomy. Hospital volume thresholds, which optimize to 95% probability of survival, varied by procedure, with a mean of 14 operations over 2 years. More than 50% of hospitals did not meet the threshold benchmarks, representing 22% of patients. CONCLUSIONS: Survival rates for geriatric patients were improved substantially when emergency operations were performed at hospitals with higher operative volumes. Consistent with all active Quality Programs of the American College of Surgeons, hospital operative volume appears to be an important metric of surgical quality for older patients undergoing emergency operations.

Evaluating mortality outlier hospitals to improve the quality of care in emergency general surgery.

BACKGROUND: Expected performance rates for various outcome metrics are a hallmark of hospital quality indicators used by Agency of Healthcare Research and Quality, Center for Medicare and Medicaid Services, and National Quality Forum. The identification of outlier hospitals with above- and below-expected mortality for emergency general surgery (EGS) operations is therefore of great value for EGS quality improvement initiatives. The aim of this study was to determine hospital variation in mortality after EGS operations, and compare characteristics between outlier hospitals. METHODS: Using data from the California State Inpatient Database (2010-2011), we identified patients who underwent one of eight common EGS operations. Expected mortality was obtained from a Bayesian model, adjusting for both patient- and hospital-level variables. A hospital-level standardized mortality ratio (SMR) was constructed (ratio of observed to expected deaths). Only hospitals performing three or more of each operation were included. An "outlier" hospital was defined as having an SMR with 80% confidence interval that did not cross 1.0. High- and low-mortality SMR outliers were compared. RESULTS: There were 140,333 patients included from 220 hospitals. Standardized mortality ratio varied from a high of 2.6 (mortality, 160% higher than expected) to a low of 0.2 (mortality, 80% lower than expected); 12 hospitals were high SMR outliers, and 28 were low SMR outliers. Standardized mortality was over three times worse in the high SMR outliers compared with the low SMR outliers (1.7 vs. 0.5; p < 0.001). Hospital-, patient-, and operative-level characteristics were equivalent in each outlier group. CONCLUSION: There exists significant hospital variation in standardized mortality after EGS operations. High SMR outliers have significant excess mortality, while low SMR outliers have superior EGS survival. Common hospital-level characteristics do not explain the wide gap between underperforming and overperforming outlier institutions. These findings suggest that SMR can help guide assessment of EGS performance across hospitals; further research is essential to identify and define the hospital processes of care which translate into optimal EGS outcomes. LEVEL OF EVIDENCE: Epidemiologic Study, level III.

High-performance acute care hospitals: Excelling across multiple emergency general surgery operations in the geriatric patient.

BACKGROUND: As the geriatric population grows, the need for hospitals performing high quality emergency general surgery (EGS) on older patients will increase. Identifying clusters of high-performing geriatric emergency general surgery hospitals would substantiate the need for in-depth analyses of hospital-specific structures and practices that benefit older EGS patients. The objectives of this study were therefore to identify clusters of hospitals based on mortality performance for geriatric patients undergoing common EGS operations and to determine if hospital performance was similar for all operation types. METHODS: Hospitals in the California State Inpatient Database were included if they performed a range of eight common EGS operations in patients 65 years or older, with a minimum requirement of three of each operation performed over 2 years. Multivariable beta regression models were created to define hospital-level risk-adjusted mortality. Centroid cluster analysis was used to identify groups of hospitals based on mortality and to determine if mortality-performance differed by operation. RESULTS: One hundred seven hospitals were included, performing a total of 24,279 operations in older patients. Hospitals separated into three distinct clusters: high, average, and low performers. The high-performing hospitals had survival rates 1 to 2 standard deviations better than the low-performers (p < 0.001). For each cluster, high performance in any one EGS operation consistently translated into high performance across all EGS operations. CONCLUSION: Hospitals conducting EGS operations in the geriatric patient population cluster into three distinct groups based on their survival performance. High-performing hospitals significantly outperform the average and low performers across every operation. The high-performers achieve reliable, high-quality results regardless of operation type. Further qualitative research is needed to investigate the perioperative drivers of hospital performance in the geriatric EGS population. LEVEL OF EVIDENCE: Study Type Prognostic, level III.

Acute passive cigarette smoke exposure and inhaled human insulin (Exubera) pharmacokinetics.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Active cigarette smoking is associated with increased permeability of the pulmonary alveolar epithelium, resulting in faster absorption of inhaled drugs such as Exubera (EXU). Absorption of EXU is increased approximately twice to four times as much in chronic smokers compared with nonsmokers. The rate of clearance of radioaerosols such as technetium-labelled diethylenetriamine penta-acetic acid is decreased in response to passive smoke exposure. WHAT THIS STUDY ADDS: Passive smoke exposure causes a decrease in lung permeability, an effect opposite to that of active smoking. Acute passive smoke exposure results in a decrease in EXU bioavailability and does not create a risk of hypoglycaemia. These results are consistent with previous studies of radioaerosol lung clearance. AIMS Relative to nonsmokers, the bioavailability of inhaled human insulin (Exubera(R); EXU) is markedly increased in chronic smokers. The pharmacokinetics of EXU following passive cigarette smoke exposure is unknown. METHODS In an open-label, crossover study, healthy nonsmoking volunteers received two treatments in randomized sequence separated by a 2-week wash-out: (i) EXU 3 mg with no passive smoke exposure and (ii) EXU 3 mg after passive smoke exposure (atmospheric nicotine levels 75-125 mug m(-3)) for 2 h. Blood samples were obtained at prespecified times up to 6 h after EXU administration. RESULTS: Twenty-seven subjects completed both study periods. Mean plasma insulin AUC(0-360) decreased by 17% [ratio 83%, 95% confidence interval (CI) 68.8, 99.5] and mean C(max) by 29% (ratio 71%, 95% CI 59.8, 83.1) after passive cigarette smoke exposure. The median (range) t(max) was 60 min (20-120 min) and 75 min (20-360 min) in the EXU with no exposure and EXU passive exposure groups, respectively. EXU was well tolerated. CONCLUSIONS: Unlike active chronic smoking, acute passive cigarette smoke exposure modestly decreases EXU bioavailability and thus should not increase hypoglycaemia risk. These results are consistent with those from published literature involving technetium-labelled diethylenetriamine penta-acetic acid and suggest that passive cigarette smoke exposure causes an acute decrease in lung permeability vs. active smoking, which causes an increase in permeability.

The prevention of chemotherapy induced peripheral neuropathy by concurrent treatment with drugs used for bipolar disease: a retrospective chart analysis in human cancer patients.

Peripheral neuropathy is a major adverse effect in the use of chemotherapeutic drugs. In nearly 50% of patients, chemotherapy induced peripheral neuropathy (CIPN) has been reported as irreversible. With increasing numbers of patients surviving treatment as well as increasing duration of survival after treatment, reducing the side effects of chemotherapy and improving the quality of life has become a major focus of cancer survivorship. Multiple classes of chemotherapeutic drugs including taxanes, platinum agents and vinka alkaloids list peripheral neuropathy as the main dose-limiting side effect of treatment. We previously found that drugs that interfere with the microtubule function, including taxanes and vinca alkaloids, bind to neuronal calcium sensor 1 (NCS1), leading to aberrant calcium signaling. The altered calcium signaling can be mitigated by application of drugs used to treat bipolar disease (e.g., lithium and valproic acid) prior to initiation of chemotherapy. Because pre-treatment with these drugs prevented CIPN in mice treated with taxanes, we sought clinical evidence by performing a retrospective chart review study of the VA electronic health record to see whether or not there would be evidence to support our scientific belief that patients treated with lithium or valproic acid while receiving chemotherapy have a lower risk for development of CIPN than patients who received chemotherapy alone. Our data did provide evidence supporting the belief that treatment with lithium or valproic acid concurrently with chemotherapy was associated with a decreased incidence of developing CIPN.

Variability in Affect and Willingness to Take Medication.

OBJECTIVE: To determine if 1) patients have distinct affective reaction patterns to medication information, and 2) whether there is an association between affective reaction patterns and willingness to take medication. METHODS: We measured affect in real time as subjects listened to a description of benefits and side effects for a hypothetical new medication. Subjects moved a dial on a handheld response system to indicate how they were feeling from "Very Good" to "Very Bad". Patterns of reactions were identified using a cluster-analytic statistical approach for multiple time series. Subjects subsequently rated their willingness to take the medication on a 7-point Likert scale. Associations between subjects' willingness ratings and affect patterns were analyzed. Additional analyses were performed to explore the role of race/ethnicity regarding these associations. RESULTS: Clusters of affective reactions emerged that could be classified into 4 patterns: "Moderate" positive reactions to benefits and negative reactions to side effects ( n = 186), "Pronounced" positive reactions to benefits and negative reactions to side effects ( n = 110), feeling consistently "Good" ( n = 58), and feeling consistently close to "Neutral" ( n = 33). Mean (standard error) willingness to take the medication was greater among subjects feeling consistently Good 4.72 (0.20) compared with those in the Moderate 3.76 (0.11), Pronounced 3.68 (0.14), and Neutral 3.62 (0.26) groups. Black subjects with a Pronounced pattern were less willing to take the medication compared with both Hispanic ( P = 0.0270) and White subjects ( P = 0.0001) with a Pronounced pattern. CONCLUSION: Patients' affective reactions to information were clustered into specific patterns. Reactions varied by race/ethnicity and were associated with treatment willingness. Ultimately, a better understanding of how patients react to information may help providers develop improved methods of communication.

Subjective Numeracy and the Influence of Order and Amount of Audible Information on Perceived Medication Value.

BACKGROUND: Order and amount of information influence patients' risk perceptions, but most studies have evaluated patients' reactions to written materials. The objective of this study was to examine the effect of 4 communication strategies, varying in their order and/or amount of information, on judgments related to an audible description of a new medication and among patients who varied in subjective numeracy. METHODS: We created 5 versions of a hypothetical scenario describing a new medication. The versions were composed to elucidate whether order and/or amount of the information describing benefits and adverse events influenced how subjects valued a new medication. After listening to a randomly assigned version, perceived medication value was measured by asking subjects to choose one of the following statements: the risks outweigh the benefits, the risks and benefits are equally balanced, or the benefits outweigh the risks. RESULTS: Of the 432 patients contacted, 389 participated in the study. Listening to a brief description of benefits followed by an extended description of adverse events resulted in a greater likelihood of perceiving that the medication's benefits outweighed the risks compared with 1) presenting the extended adverse events description before the benefits, 2) giving a greater amount of information related to benefits, and 3) sandwiching the adverse events between benefits. These associations were only observed among subjects with average or higher subjective numeracy. CONCLUSION: If confirmed in future studies, our results suggest that, for patients with average or better subjective numeracy, perceived medication value is highest when a brief presentation of benefits is followed by an extended description of adverse events.

Multiple-dose pharmacokinetics of the selective nicotinic receptor partial agonist, varenicline, in healthy smokers.

Varenicline is a novel and selective alpha4beta2 nicotinic acetylcholine receptor partial agonist developed for smoking cessation. The primary objectives of this double-blind, placebo-controlled, dose-escalation study were to determine the pharmacokinetics, safety, and tolerability of multiple oral doses of varenicline given as tablets once (1 mg, 2 mg, and 3 mg) or twice (1 mg) daily to healthy adult smokers. Within each dose level, 8 subjects were randomized to varenicline and 4 subjects to placebo. Varenicline was well tolerated at doses up to and including 2 mg daily. Dose-proportional increases in maximum observed plasma concentrations and area under the plasma concentration-time curve from time zero to the end of the dosing interval values were observed between the 1-mg and 2-mg daily doses of varenicline. Once- and twice-daily dosing resulted, on average, in an approximate 2- and 3-fold increase in varenicline systemic exposure, respectively, compared with single dose. There was no evidence of concentration- or time-dependent changes in the pharmacokinetics of varenicline upon repeat dosing.

The proximal association between smoking and alcohol use among first year college students.

OBJECTIVE: This study was undertaken to evaluate the association between patterns of day-to-day smoking and drinking among first year college students. METHOD: Using 210 days of weekly time-line follow-back diary data, the authors examined the within-person relationships between smoking and drinking. Bivariate time series procedures were utilized. RESULTS: Findings revealed a high degree of significant cross-correlations between smoking and drinking in which the amount of use of one substance could be predicted by current, as well as past and future use of the other. For the majority of participants, smoking and drinking were positively associated with the alternate behavior. The most common pattern of prediction for individuals was within day (i.e. synchronous correlations). When examining rates of individuals showing significant cross-correlations according to their level of either smoking or drinking, those smoking less than one cigarette on average per day were found to be less likely to demonstrate a synchronous cross-correlation between the two behaviors than those smoking at higher rates. No significant association was found between level of drinking and the rate of significant synchronous cross-correlations between smoking and drinking. CONCLUSIONS: Reports of daily behavior over long periods of time have the potential to provide insight into the more proximal influences of smoking and alcohol use on one another. Future research is needed to establish the specific factors (i.e. third variables) and related mechanisms that may drive both behaviors.

Are pregnancy planning and timing associated with preterm or small for gestational age births?

OBJECTIVE: To investigate whether unplanned or poorly timed pregnancies (self-reported at enrollment) are associated with preterm or small for gestational age births. DESIGN: Prospective cohort study. SETTING: Not applicable. PATIENT(S): Two thousand six hundred fifty-four pregnant women <18 weeks estimated gestational age with a singleton pregnancy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Preterm and small for gestational age births. RESULT(S): In adjusted analyses, pregnancy planning was not statistically significantly associated with preterm (odds ratio [OR] 1.18; 95% confidence interval [CI], 0.85-1.65) or small for gestational age birth (OR 1.17; 95% CI, 0.69-1.97). Similarly, poorly timed pregnancies were not statistically significantly associated with preterm (OR 0.85; 95% CI, 0.53-1.38) or small for gestational age birth (OR 0.92; 95% CI, 0.65-1.29). Combining pregnancy planning (yes/no) and timing (yes/no) into a 4-level category showed no statistically significant association with preterm birth or small for gestational age. CONCLUSION(S): In a large cohort with antenatally assessed pregnancy planning and timing, outcome data collected from medical record abstraction, and robust analysis adjusting for multiple confounding factors including maternal demographics, medical conditions, and other risk factors, neither pregnancy planning nor pregnancy timing showed a statistically significant association with preterm or small for gestational age infants. This study improves upon previous analyses that lacked adjustment for confounding and used retrospective self-reporting to assess pregnancy planning and timing, and preterm and small for gestational age births. Findings may differ in higher risk populations with higher prevalence of preterm or small for gestational age births.

Smoking and depression: an examination of mechanisms of comorbidity.

OBJECTIVE: Although the association between depression and smoking has been consistently established, little evidence regarding the mechanisms that influence this association is currently available. The present study evaluates alternate familial mechanisms of comorbidity between depression and smoking. METHOD: Probands from a case-control family study were selected from outpatient specialty clinics or through a random-digit dialing procedure. A total of 133 probands and 273 directly interviewed, first-degree relatives of the probands were included in the present analyses. RESULTS: The pattern of cross-aggregation of heavy smoking and depression differed according to the subtype of depressive disorder. There was evidence of a shared etiology between dysthymia and heavy smoking, whereas major and double depression did not demonstrate a shared vulnerability with heavy smoking. CONCLUSIONS: This report contributes to the present sparse evidence regarding the mechanisms involved in the etiology of smoking and depressive disorders and highlights the need for greater attention to this issue through genetic epidemiological study methods.

A prospective study of perceived susceptibility to breast cancer and nonadherence to mammography screening guidelines in African American and White women ages 40 to 79 years.

This prospective study examined the influence of perceived susceptibility to breast cancer on nonadherence to recommended mammography screening guidelines. The study population included 1,229 African American and White women ages 40 to 79 years who obtained an index mammography screening examination at one of five urban hospitals in Connecticut between October 1996 and January 1998. Information on perceived susceptibility to breast cancer and on multiple covariates was obtained by telephone interview on average 1.5 months after the index screening. Subsequent adherence to mammography screening guidelines was ascertained by follow-up interview on average 29 months after the index exam. Across race, age, and family breast cancer history, women who believed that their susceptibility was high (i.e., "very likely" to develop breast cancer) were less likely to adhere to screening guidelines than women who believed that their susceptibility was moderate [adjusted odds ratio (OR), 2.83; 95% confidence interval (CI), 1.51-5.30], but the effect was stronger in older women. Women ages 40 to 49 years (but not ages 50-79 years) who believed that their susceptibility was low (i.e., "not likely" or "a little likely" to develop breast cancer) were also less likely to adhere to guidelines than those who reported moderate susceptibility (adjusted OR, 3.07; 95% CI, 1.66-5.68, and adjusted OR, 2.78; 95% CI, 1.63-4.73). In contrast to most previous studies that found a positive linear relationship between perceived susceptibility to breast cancer and mammography screening, these findings suggest a more complex relationship that should be considered when developing interventions to improve adherence to mammography screening guidelines.