Search

Most cases of small cell lung cancer (SCLC) are diagnosed at an advanced stage. The objective of this study was to investigate patient characteristics, survival, chemotherapy treatments, and health care use after a diagnosis of advanced SCLC in subjects enrolled in a health system network. This was a retrospective cohort study of patients aged ≥ 18 years who either were diagnosed with stage III/IV SCLC or who progressed to advanced SCLC during the study period (2005–2015). Patients identified from the Indiana State Cancer Registry and the Indiana Network for Patient Care were followed from their advanced diagnosis index date until the earliest date of the last visit, death, or the end of the study period. Patient characteristics, survival, chemotherapy regimens, associated health care visits, and durations of treatment were reported. Time-to-event analyses were performed using the Kaplan-Meier method. A total of 498 patients with advanced SCLC were identified, of whom 429 were newly diagnosed with advanced disease and 69 progressed to advanced disease during the study period. Median survival from the index diagnosis date was 13.2 months. First-line (1L) chemotherapy was received by 464 (93.2%) patients, most commonly carboplatin/etoposide, received by 213 (45.9%) patients, followed by cisplatin/etoposide (20.7%). Ninety-five (20.5%) patients progressed to second-line (2L) chemotherapy, where topotecan monotherapy (20.0%) was the most common regimen, followed by carboplatin/etoposide (14.7%). Median survival was 10.1 months from 1L initiation and 7.7 months from 2L initiation. Patients in a regional health system network diagnosed with advanced SCLC were treated with chemotherapy regimens similar to those in earlier reports based on SEER-Medicare data. Survival of patients with advanced SCLC was poor, illustrating the lack of progress over several decades in the treatment of this lethal disease and highlighting the need for improved treatments.

Background Many patients with atrial fibrillation (AF) remain undiagnosed despite availability of interventions to reduce stroke risk. Predictive models to date are limited by data requirements and theoretical usage. We aimed to develop a model for predicting the 2-year probability of AF diagnosis and implement it as proof-of-concept (POC) in a production electronic health record (EHR). Methods We used a nested case–control design using data from the Indiana Network for Patient Care. The development cohort came from 2016 to 2017 (outcome period) and 2014 to 2015 (baseline). A separate validation cohort used outcome and baseline periods shifted 2 years before respective development cohort times. Machine learning approaches were used to build predictive model. Patients ≥ 18 years, later restricted to age ≥ 40 years, with at least two encounters and no AF during baseline, were included. In the 6-week EHR prospective pilot, the model was silently implemented in the production system at a large safety-net urban hospital. Three new and two previous logistic regression models were evaluated using receiver-operating characteristics. Number, characteristics, and CHA2DS2-VASc scores of patients identified by the model in the pilot are presented. Results After restricting age to ≥ 40 years, 31,474 AF cases (mean age, 71.5 years; female 49%) and 22,078 controls (mean age, 59.5 years; female 61%) comprised the development cohort. A 10-variable model using age, acute heart disease, albumin, body mass index, chronic obstructive pulmonary disease, gender, heart failure, insurance, kidney disease, and shock yielded the best performance (C-statistic, 0.80 [95% CI 0.79–0.80]). The model performed well in the validation cohort (C-statistic, 0.81 [95% CI 0.8–0.81]). In the EHR pilot, 7916/22,272 (35.5%; mean age, 66 years; female 50%) were identified as higher risk for AF; 5582 (70%) had CHA2DS2-VASc score ≥ 2. Conclusions Using variables commonly available in the EHR, we created a predictive model to identify 2-year risk of developing AF in those previously without diagnosed AF. Successful POC implementation of the model in an EHR provided a practical strategy to identify patients who may benefit from interventions to reduce their stroke risk.

Rapid response teams (RRTs) improve mortality by intervening in the hours preceding arrest. Implementation of these teams varies across institutions.Our health-care system has two different RRT models at two hospitals: Hospital A does not utilize a proactive rounder while Hospital B does. We studied the patterns of RRT calls at each hospital focusing on the differences between night and day and during nursing shift transitions.The presence of proactive surveillance appeared to be associated with an increased total number of RRT calls with more than twice as many calls made at the smaller Hospital B than Hospital A. Hospital B had more calls in the daytime compared to the nighttime. Both hospitals showed a surge in the night-to-day shift transition (7-8am) compared to the preceding nighttime. Hospital A additionally showed a surge in calls during the day-to-night shift transition (7-8pm) compared to the preceding daytime.Differences in the diurnal patterns of RRT activation exist between hospitals even within the same system. As a continuously learning system, each hospital should consider tracking these patterns to identify their unique vulnerabilities. More calls are noted between 7-8am compared to the overnight hours. This may represent the reestablishment of the 'afferent' arm of the RRT as the hospital returns to daytime staffing and activity. Factors that influence the impact of proactive rounding on RRT performance may deserve further study.

Background Intrauterine devices are effective and safe, long-acting reversible contraceptives, but the risk of uterine perforation occurs with an estimated incidence of 1 to 2 per 1000 insertions. The European Active Surveillance Study for Intrauterine Devices, a European prospective observational study that enrolled 61,448 participants (2006–2012), found that women breastfeeding at the time of device insertion or with the device inserted at ≤36 weeks after delivery had a higher risk of uterine perforation. The Association of Uterine Perforation and Expulsion of Intrauterine Device (APEX-IUD) study was a Food and Drug Administration–mandated study designed to reflect current United States clinical practice. The aims of the APEX-IUD study were to evaluate the risk of intrauterine device–related uterine perforation and device expulsion among women who were breastfeeding or within 12 months after delivery at insertion. Objective We aimed to describe the APEX-IUD study design, methodology, and analytical plan and present population characteristics, size of risk factor groups, and duration of follow-up. Study Design APEX-IUD study was a retrospective cohort study conducted in 4 organizations with access to electronic health records: Kaiser Permanente Northern California, Kaiser Permanente Southern California, Kaiser Permanente Washington, and Regenstrief Institute in Indiana. Variables were identified through structured data (eg, diagnostic, procedural, medication codes) and unstructured data (eg, clinical notes) via natural language processing. Outcomes include uterine perforation and device expulsion; potential risk factors were breastfeeding at insertion, postpartum timing of insertion, device type, and menorrhagia diagnosis in the year before insertion. Covariates include demographic characteristics, clinical characteristics, and procedure-related variables, such as difficult insertion. The first potential date of inclusion for eligible women varies by research site (from January 1, 2001 to January 1, 2010). Follow-up begins at insertion and ends at first occurrence of an outcome of interest, a censoring event (device removal or reinsertion, pregnancy, hysterectomy, sterilization, device expiration, death, disenrollment, last clinical encounter), or end of the study period (June 30, 2018). Comparisons of levels of exposure variables were made using Cox regression models with confounding adjusted by propensity score weighting using overlap weights. Results The study population includes 326,658 women with at least 1 device insertion during the study period (Kaiser Permanente Northern California, 161,442; Kaiser Permanente Southern California, 123,214; Kaiser Permanente Washington, 20,526; Regenstrief Institute, 21,476). The median duration of continuous enrollment was 90 (site medians 74–177) months. The mean age was 32 years, and the population was racially and ethnically diverse across the 4 sites. The mean body mass index was 28.5 kg/m2, and of the women included in the study, 10.0% had menorrhagia ≤12 months before insertion, 5.3% had uterine fibroids, and 10% were recent smokers; furthermore, among these women, 79.4% had levonorgestrel-releasing devices, and 19.5% had copper devices. Across sites, 97,824 women had an intrauterine device insertion at ≤52 weeks after delivery, of which 94,817 women (97%) had breastfeeding status at insertion determined; in addition, 228,834 women had intrauterine device insertion at >52 weeks after delivery or no evidence of a delivery in their health record. Conclusion Combining retrospective data from multiple sites allowed for a large and diverse study population. Collaboration with clinicians in the study design and validation of outcomes ensured that the APEX-IUD study results reflect current United States clinical practice. Results from this study will provide valuable information based on real-world evidence about risk factors for intrauterine devices perforation and expulsion for clinicians.

BACKGROUND Annual computed tomography (CT) scans are a component of the current standard of care for the posttreatment surveillance of survivors of colorectal cancer (CRC) after curative-intent resection. The authors conducted a retrospective study with the primary aim of assessing patient, physician, and organizational characteristics associated with the receipt of CT surveillance among veterans. METHODS The Department of Veterans Affairs Central Cancer Registry was used to identify patients diagnosed with AJCC collaborative stage I to III CRC between 2001 and 2009. Patient sociodemographic and clinical (ie, CRC stage and comorbidity) characteristics, provider specialty, and organizational characteristics were measured. Hierarchical multivariable logistic regression models were used to assess the association between patient, provider, and organizational characteristics on receipt of 1) consistently guideline-concordant care (at least 1 CT every 12 months for both of the first 2 years of CRC surveillance) versus no CT receipt and 2) potential overuse (>1 CT every 12 months during the first 2 years of CRC surveillance) of CRC surveillance using CT. The authors also analyzed the impact of the 2005 American Society of Clinical Oncology update in CRC surveillance guidelines on care received over time. RESULTS For 2263 survivors of stage II/III CRC who were diagnosed after 2005, 19.4% of patients received no surveillance CT, whereas potential overuse occurred in both surveillance years for 14.9% of patients. Guideline-concordant care was associated with younger age, higher stage of disease (stage III vs stage II), and geographic region. In adjusted analyses, younger age and higher stage of disease (stage III vs stage II) were found to be associated with overuse. There was no significant difference in the annual rate of CT scanning noted across time periods (year ≤ 2005 vs year > 2005). CONCLUSIONS Among a minority of veteran survivors of CRC, both underuse and potential overuse of CT surveillance were present. Patient factors, but no provider or organizational characteristics, were found to be significantly associated with patterns of care. The 2005 change in American Society of Clinical Oncology guidelines did not appear to have an impact on rates of surveillance CT. Cancer 2017;123:2338-2351. © 2017 American Cancer Society.

Objectives: Delirium is a highly prevalent syndrome of acute brain dysfunction among critically ill patients that has been linked to multiple risk factors, such as age, preexisting cognitive impairment, and use of sedatives; but to date, the relationship between race and delirium is unclear. We conducted this study to identify whether African-American race is a risk factor for developing ICU delirium. Design: A prospective cohort study. Setting: Medical and surgical ICUs of a university-affiliated, safety net hospital in Indianapolis, IN. Patients: A total of 2,087 consecutive admissions with 1,008 African Americans admitted to the ICU services from May 2009 to August 2012. Interventions: None. Measurements and Main Results: Incident delirium was defined as first positive Confusion Assessment Method for the ICU result after an initial negative Confusion Assessment Method for the ICU; and prevalent delirium was defined as positive Confusion Assessment Method for the ICU on first Confusion Assessment Method for the ICU assessment. The overall incident delirium rate in African Americans was 8.7% compared with 10.4% in Caucasians (p = 0.26). The prevalent delirium rate was 14% in both African Americans and Caucasians (p = 0.95). Significant age and race interactions were detected for incident delirium (p = 0.02) but not for prevalent delirium (p = 0.3). The hazard ratio for incident delirium for African Americans in the 18–49 years age group compared with Caucasians of similar age was 0.4 (0.1–0.9). The hazard and odds ratios for incident and prevalent delirium in other groups were not different. Conclusions: African-American race does not confer any additional risk for developing incident or prevalent delirium in the ICU. Instead, younger African Americans tend to have lower rates of incident delirium compared with Caucasians of similar age.

BackgroundData on initiation and utilization of direct-acting antiviral therapies for hepatitis C virus infection in the United States are limited. This study evaluated treatment initiation, time to treatment, and real-world effectiveness of direct-acting antiviral therapy in individuals with hepatitis C virus infection treated during the first 2 years of availability of all-oral direct-acting antiviral therapies.MethodsA retrospective cohort analysis was undertaken using electronic medical records and chart review abstraction of hepatitis C virus-infected individuals aged >18 years diagnosed with chronic hepatitis C virus infection between January 1, 2014, and December 31, 2015 from the Indiana University Health database.ResultsEight hundred thirty people initiated direct-acting antiviral therapy during the 2-year observation window. The estimated incidence of treatment initiation was 8.8%±0.34% at the end of year 1 and 15.0%±0.5% at the end of year 2. Median time to initiating therapy was 300 days. Using a Cox regression analysis, positive predictors of treatment initiation included age (hazard ratio, 1.008), prior hepatitis C virus treatment (1.74), cirrhosis (2.64), and history of liver transplant (1.5). History of drug abuse (0.43), high baseline alanine aminotransferase levels (0.79), hepatitis B virus infection (0.41), and self-pay (0.39) were negatively associated with treatment initiation. In the evaluable population (n = 423), 83.9% (95% confidence interval, 80.1-87.3%) of people achieved sustained virologic response.ConclusionIn the early years of the direct-acting antiviral era

Anticossos; Immunoteràpia; Càncer de cap i coll Anticuerpos; Inmunoterapia; Cáncer de cabeza y cuello Antibodies; Immunotherapy; Head and neck cancer Background Patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) progressing on platinum-based chemotherapy have poor prognoses and limited therapeutic options. Programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) are frequently upregulated in HNSCC. The international, multi-institutional, single-arm, phase II HAWK study ( NCT02207530 ) evaluated durvalumab monotherapy, an anti-PD-L1 monoclonal antibody, in PD-L1-high patients with platinum-refractory R/M HNSCC. Patients and methods Immunotherapy-naïve patients with confirmed PD-L1-high tumour cell expression (defined as patients with ≥25% of tumour cells expressing PD-L1 [TC ≥ 25%] using the VENTANA PD-L1 [SP263] Assay) received durvalumab 10 mg/kg intravenously every 2 weeks for up to 12 months. The primary end-point was objective response rate; secondary end-points included progression-free survival (PFS) and overall survival (OS). Results Among evaluable patients (n = 111), objective response rate was 16.2% (95% confidence interval [CI], 9.9–24.4); 29.4% (95% CI, 15.1–47.5) for human papillomavirus (HPV)-positive patients and 10.9% (95% CI, 4.5–21.3) for HPV-negative patients. Median PFS and OS for treated patients (n = 112) was 2.1 months (95% CI, 1.9–3.7) and 7.1 months (95% CI, 4.9–9.9); PFS and OS at 12 months were 14.6% (95% CI, 8.5–22.1) and 33.6% (95% CI, 24.8–42.7). Treatment-related adverse events were 57.1% (any grade) and 8.0% (grade ≥3); none led to death. At data cut-off, 24.1% of patients remained on treatment or in follow-up. Conclusion Durvalumab demonstrated antitumour activity with acceptable safety in PD-L1-high patients with R/M HNSCC, supporting its ongoing evaluation in phase III trials in first- and second-line settings. In an ad hoc analysis, HPV-positive patients had a numerically higher response rate and survival than HPV-negative patients. This study was supported by AstraZeneca.

BACKGROUND US healthcare underperforms on quality and safety metrics. Inpatient care constitutes an immense opportunity to intervene to improve care. OBJECTIVE Describe a model of inpatient care and measure its impact. DESIGN A quantitative assessment of the implementation of a new model of care. The graded implementation of the model allowed us to follow outcomes and measure their association with the dose of the implementation. SETTING AND PATIENTS Inpatient medical and surgical units in a large academic health center. INTERVENTION Eight interventions rooted in improving interprofessional collaboration (IPC), enabling data-driven decisions, and providing leadership were implemented. MEASUREMENTS Outcome data from August 2012 to December 2013 were analyzed using generalized linear mixed models for associations with the implementation of the model. Length of stay (LOS) index, case-mix index–adjusted variable direct costs (CMI-adjusted VDC), 30-day readmission rates, overall patient satisfaction scores, and provider satisfaction with the model were measured. RESULTS The implementation of the model was associated with decreases in LOS index (P < 0.0001) and CMI-adjusted VDC (P = 0.0006). We did not detect improvements in readmission rates or patient satisfaction scores. Most providers (95.8%, n = 92) agreed that the model had improved the quality and safety of the care delivered. CONCLUSIONS Creating an environment and framework in which IPC is fostered, performance data are transparently available, and leadership is provided may improve value on both medical and surgical units. These interventions appear to be well accepted by front-line staff. Readmission rates and patient satisfaction remain challenging. Journal of Hospital Medicine 2015;10:773–779. © 2015 Society of Hospital Medicine

Background: Heat-shock protein 990 (HSP990) is a potent and selective synthetic small-molecule HSP90 inhibitor. The primary objectives of this phase I first-in-human study were to determine dose-limiting toxicities (DLTs), maximum-tolerated dose (MTD) and recommended phase II dose (RP2D). Secondary objectives included characterisation of the safety profile, pharmacokinetics (PKs) and pharmacodynamics (PDs). Methods: Heat-shock protein 990 was administered orally once or two times weekly on a 28-day cycle schedule in patients with advanced solid tumours. Dose escalation was guided by a Bayesian logistic regression model with overdose control. Results: A total of 64 patients were enrolled. Fifty-three patients received HSP990 once weekly at 2.5, 5, 10, 20, 30, 50 or 60 mg, whereas 11 patients received HSP990 two times weekly at 25 mg. Median duration of exposure was 8 weeks (range 1–116 weeks) and 12 patients remained on treatment for >16 weeks. Dose-limiting toxicities occurred in seven patients and included diarrhoea, QTc prolongation, ALT/AST elevations and central neurological toxicities. The most common drug-related adverse events were diarrhoea, fatigue and decreased appetite. Further dose escalation beyond 60 mg once weekly was not possible owing to neurological toxicity. Rapid absorption, no drug accumulation and large interpatient variability in PK exposures were observed. No objective responses were seen; 25 patients had a best overall response of stable disease. Conclusions: Heat-shock protein 990 is relatively well tolerated, with neurological toxicity being the most relevant DLT. The single agent MTD/RP2D of HSP990 was declared at 50 mg once weekly.

Members of the Society of Hospital Medicine were surveyed about geographic cohorting (GCh); 369 responses were analyzed, two thirds of which were from GCh participants. Improved collaboration with the bedside nurse, increased nonclinical interactions, decreased paging interruptions, and improved efficiency were perceived by >50%. Narrowed clinical expertise, increased fragmentation, increased face-to-face interruptions, and an adverse impact on camaraderie within the hospitalist group were reported by 25% to 50%. Academic practices were associated with positive perceptions while higher patient loads were associated with negative perceptions. Comments on GCh benefits invoked improvements in (1) interprofessional collaboration, (2) efficiency, (3) patient-centeredness, (4) nursing satisfaction, and (5) GCh mediated facilitation of other interventions. GCh downsides included (1) professional and personal dissatisfaction, (2) concerns about providing suboptimal care, and (3) implementation barriers. GCh is receiving attention. Although it facilitates important benefits, it is perceived to mediate unintended consequences, which should be addressed in redesign efforts.

Heme oxygenase-1 (HO-1) exerts vasoprotective effects. Such benefit in diabetic vasculopathy, however, remains unclear. We hypothesize that bilirubin mediates HO-1–induced vascular benefits in diabetes. Diabetic db/db mice were treated with hemin (HO-1 inducer) for 2 weeks, and aortas were isolated for functional and molecular assays. Nitric oxide (NO) production was measured in cultured endothelial cells. Hemin treatment augmented endothelium-dependent relaxations (EDRs) and elevated Akt and endothelial NO synthase (eNOS) phosphorylation in db/db mouse aortas, which were reversed by the HO-1 inhibitor SnMP or HO-1 silencing virus. Hemin treatment increased serum bilirubin, and ex vivo bilirubin treatment improved relaxations in diabetic mouse aortas, which was reversed by the Akt inhibitor. Biliverdin reductase silencing virus attenuated the effect of hemin. Chronic bilirubin treatment improved EDRs in db/db mouse aortas. Hemin and bilirubin reversed high glucose–induced reductions in Akt and eNOS phosphorylation and NO production. The effect of hemin but not bilirubin was inhibited by biliverdin reductase silencing virus. Furthermore, bilirubin augmented EDRs in renal arteries from diabetic patients. In summary, HO-1–induced restoration of endothelial function in diabetic mice is most likely mediated by bilirubin, which preserves NO bioavailability through the Akt/eNOS/NO cascade, suggesting bilirubin as a potential therapeutic target for clinical intervention of diabetic vasculopathy.

Background and objective Electronic health records databases are increasingly used for identifying cohort populations, covariates, or outcomes, but discerning such clinical ‘phenotypes’ accurately is an ongoing challenge. We developed a flexible method using overlapping (Venn diagram) queries. Here we describe this approach to find patients hospitalized with acute congestive heart failure (CHF), a sampling strategy for one-by-one ‘gold standard’ chart review, and calculation of positive predictive value (PPV) and sensitivities, with SEs, across different definitions. Materials and methods We used retrospective queries of hospitalizations (2002–2011) in the Indiana Network for Patient Care with any CHF ICD-9 diagnoses, a primary diagnosis, an echocardiogram performed, a B-natriuretic peptide (BNP) drawn, or BNP >500 pg/mL. We used a hybrid between proportional sampling by Venn zone and over-sampling non-overlapping zones. The acute CHF (presence/absence) outcome was based on expert chart review using a priori criteria. Results Among 79 091 hospitalizations, we reviewed 908. A query for any ICD-9 code for CHF had PPV 42.8% (SE 1.5%) for acute CHF and sensitivity 94.3% (1.3%). Primary diagnosis of 428 and BNP >500 pg/mL had PPV 90.4% (SE 2.4%) and sensitivity 28.8% (1.1%). PPV was

Objectives: To evaluate whether race influences agreement between screening results and documentation of cognitive impairment and delirium. Design: Secondary data analysis. Setting: An urban, public hospital and healthcare system. Participants: Hospitalized older adults aged 65 and older admitted to general inpatient medical services evaluated for cognitive impairment (n = 851) and evaluated for delirium (n = 424). Measurements: Cognitive impairment and delirium were measured in each participant using the Short Portable Mental Status Questionnaire (SPMSQ) and the Confusion Assessment Method (CAM), respectively, as the reference identification method. Clinical documentation of cognitive impairment and delirium was defined according to the presence of International Classification of Diseases, Ninth Revision (ICD-9), codes from within 1 year before hospitalization through discharge for cognitive impairment or from hospital admission through discharge for delirium. Results: Two hundred ninety-four participants (34%) had cognitive impairment based on SPMSQ performance, and 163 (38%) had delirium based on CAM results. One hundred seventy-one (20%) of those with cognitive impairment had an ICD-9 code for cognitive impairment, whereas 92 (22%) of those with delirium had an ICD-9 code for delirium. After considering age, sex, education, socioeconomic status, chronic comorbidity, and severity of acute illness, of those who screened positive on the SPMSQ, African Americans had a higher adjusted odds ratio (AOR) than non-African Americans for clinical documentation of cognitive impairment (AOR = 1.66, 95% confidence interval (CI) = 0.95�2.89), and of those who screened negative on the SPMSQ, African Americans had higher odds of clinical documentation of cognitive impairment (AOR = 2.10, 95% CI = 1.17�3.78) than non-African Americans. There were no differences in clinical documentation rates of delirium between African Americans and non-African Americans. Conclusion: Racial differences in coding for cognitive impairment may exist, resulting in higher documentation of cognitive impairment in African Americans screening positive or negative for cognitive impairment.

Background Delirium evaluation in patients in the ICU requires the use of an arousal/sedation assessment tool prior to assessing consciousness. The Richmond Agitation-Sedation Scale (RASS) and the Riker Sedation-Agitation Scale (SAS) are well-validated arousal/sedation tools. We sought to assess the concordance of RASS and SAS assessments in determining eligibility of patients in the ICU for delirium screening using the confusion assessment method for the ICU (CAM-ICU). Methods We performed a prospective cohort study in the adult medical, surgical, and progressive (step-down) ICUs of a tertiary care, university-affiliated, urban hospital in Indianapolis, Indiana. The cohort included 975 admissions to the ICU between January and October 2009. Results The outcome measures of interest were the correlation and agreement between RASS and SAS measurements. In 2,469 RASS and SAS paired screens, the rank correlation using the Spearman correlation coefficient was 0.91, and the agreement between the two screening tools for assessing CAM-ICU eligibility as estimated by the κ coefficient was 0.93. Analysis showed that 70.1% of screens were eligible for CAM-ICU assessment using RASS (7.1% sedated [RASS −3 to −1]; 62.6% calm [0]; and 0.4% restless, agitated [+1 to +3]), compared with 72.1% using SAS (5% sedated [SAS 3]; 66.5% calm [4]; and 0.6% anxious, agitated [5, 6]). In the mechanically ventilated subgroup, RASS identified 19.1% CAM-ICU eligible patients compared with 24.6% by SAS. The correlation coefficient in this subgroup was 0.70 and the agreement was 0.81. Conclusion Both SAS and RASS led to similar rates of delirium assessment using the CAM-ICU.

Transmission of infectious microbes via health care workers has been associated with increasing morbidity and mortality of hospitalized patients, but years after publication of guidelines on the subject, the incidence of health care–associated infections remains high,1 contributing to morbidity, mortality, increased hospital stay,2 and inflated health care costs. The majority of nosocomial infections are due to transmission of bacteria by direct or indirect contact between health care workers and patients,3 making proper hand hygiene one of the most effective ways to decrease transmission of infective organisms.4 However, simple hand washing is a difficult intervention to implement, especially in intensive care units (ICUs), where acuity is high and time is precious. Traditionally, ICUs in the United States have been open units with teams of primary care physicians providing care for patients and intensivists acting as consultants. Recently, the trend has been to close the ICU and have a dedicated ICU team provide patient care. To date, no direct observations have been published on the practice patterns of health care workers regarding the number of contacts with patients and the workers’ hand-washing habits in an open ICU vs a closed ICU. We performed a time-motion analysis of patient contacts and hand washing among health care personnel in a medical ICU at Wishard Memorial Hospital, a 460-bed county teaching hospital affiliated with Indiana University School of Medicine in Indianapolis. The aim of the study was to determine prospectively the number of contacts that health care workers have with patients and the percentage of hand washing among health care workers in an open ICU and then to compare that information with similar observations collected in the same ICU after the unit was closed. We hypothesized that closing the ICU would decrease the number of health care workers’ contacts with patients while increasing the workers’ hand-washing frequency.

The relative efficacy of natural language processing (NLP) of text reports compared to structured data queries for identifying patients from electronic health records (EHRs) with metastatic cancer remains unclear. Such identification is critical for identifying and recruiting potential study candidates for cancer trials, particularly trials of cancer chemotherapy. For such purposes, we performed a direct comparison between NLP and structured data query methods for identifying patients with metastatic melanoma. Using EHR data from two large institutions, we found that NLP of text reports identified close to three times as many patients with metastatic melanoma compared to a structured data query algorithm (1,727 vs. 607 patients). Using an external tumour registry, we also found NLP had much higher sensitivity than structured query for identifying such patients (67% vs. 35%). Our results emphasise the importance of employing NLP criteria when identifying potential cancer study candidates with metastatic disease.

A roundtable to discuss monitoring of serum 25-hydroxyvitamin D [25(OH)D] in the NHANES was held in late July 2009. Topics included the following: 1) options for dealing with assay fluctuations in serum 25(OH)D in the NHANES conducted between 1988 and 2006; 2) approaches for transitioning between the RIA used in the NHANES between 1988 and 2006 to the liquid chromatography tandem MS (LC-MS/MS) measurement procedure to be used in NHANES 2007 and later; 3) approaches for integrating the recently available standard reference material for vitamin D in human serum (SRM 972) from the National Institute of Standards and Technology (NIST) into the NHANES; 4) questions regarding whether the C-3 epimer of 25-hydroxyvitamin D3 [3-epi-25(OH)D3] should be measured in NHANES 2007 and later; and 5) identification of research and educational needs. The roundtable experts agreed that the NHANES data needed to be adjusted to control for assay fluctuations and offered several options for addressing this issue. The experts suggested that the LC-MS/MS measurement procedure developed by NIST could serve as a higher order reference measurement procedure. They noted the need for a commutability study for the recently released NIST SRM 972 across a range of measurement procedures. They suggested that federal agencies and professional organizations work with manufacturers to improve the quality and comparability of measurement procedures across all laboratories. The experts noted the preliminary nature of the evidence of the 3-epi-25(OH)D3 but felt that it should be measured in 2007 NHANES and later.

Context: Several genome-wide association studies (GWAS) have been performed to identify genes contributing to bone mineral density (BMD), typically in samples of elderly women and men. Objective: The objective of the study was to identify genes contributing to BMD in premenopausal women. Design: GWAS using the Illumina 610Quad array in premenopausal European-American (EA) women and replication of the top 50 single-nucleotide polymorphisms (SNPs) for two BMD measures in African-American (AA) women. Subjects: Subjects included 1524 premenopausal EA women aged 20–45 yr from 762 sibships and 669 AA premenopausal women aged 20–44 yr from 383 sibships. Interventions: There were no interventions. Main Outcome Measures: BMD was measured at the lumbar spine and femoral neck by dual-energy x-ray absorptiometry. Age- and weight-adjusted BMD values were tested for association with each SNP, with P values determined by permutation. Results: SNPs in CATSPERB on chromosome 14 provided evidence of association with femoral neck BMD (rs1298989, P = 2.7 × 10−5; rs1285635, P = 3.0 × 10−5) in the EA women, and some supporting evidence was also observed with these SNPs in the AA women (rs1285635, P = 0.003). Genes identified in other BMD GWAS studies, including IBSP and ADAMTS18, were also among the most significant findings in our GWAS. Conclusions: Evidence of association to several novel loci was detected in a GWAS of premenopausal EA women, and SNPs in one of these loci also provided supporting evidence in a sample of AA women.

Bone mineral density (BMD) achieved during young adulthood (peak BMD) is one of the major determinants of osteoporotic fracture in later life. Genetic variants associated with BMD have been identified by three recent genome-wide association studies. The most significant single-nucleotide polymorphisms (SNPs) from these studies were genotyped to test whether they were associated with peak BMD in premenopausal American women. Femoral neck and lumbar spine BMD were determined by dual-energy X-ray absorptiometry in two groups of premenopausal women: 1524 white women and 512 black women. In premenopausal white women, two SNPs in the C6orf97/ESR1 region were significantly associated with BMD (p < 4.8 × 10−4), with suggestive evidence for CTNNBL1 and LRP5 (p < .01). Evidence of association with one of the two SNPs in the C6orf97/ESR1 region also was observed in premenopausal black women. Furthermore, SNPs in SP7 and a chromosome 4 intergenic region showed suggestive association with BMD in black women. Detailed analyses of additional SNPs in the C6orf97/ESR1 region revealed multiple genomic blocks independently associated with femoral neck and lumbar spine BMD. Findings in the three published genome-wide association studies were replicated in independent samples of premenopausal American women, suggesting that genetic variants in these genes or regions contribute to peak BMD in healthy women in various populations. © 2010 American Society for Bone and Mineral Research.

In 2001, approximately 12.6 million individuals aged 65 and older were discharged from American hospitals with an average length of stay of 5.8 days1 and up to 66% of them suffered from cognitive impairment (CI)2–20. CI in hospitalized older adults includes a variety of disorders ranging from mild cognitive deficit, delirium, to full-blown dementia. Dementia is a syndrome of decline in memory plus at least one other cognitive domain, such as language, visuo-spatial, or executive function sufficient to interfere with social or occupational functioning in an alert person21. Delirium is a disturbance of consciousness with reduced ability to focus, sustain, or shift attention that occurs over a short period of time and tends to fluctuate over the course of the day22. Mild cognitive impairment without dementia is defined as the presence of a cognitive deficit in the absence of delirium that does not affect functional performance23. Hospitalized older adults with CI are vulnerable to hospital complications including delirium, physical restraints, urinary catheters, and tethers2,3,24–35. The management of their medical or surgical illnesses requires avoiding certain medications with anticholinergic activities that might worsen cognition36. Furthermore, CI may delay diagnostic and therapeutic procedures, demand more time for informed-consent related issues, and result in difficulty in adherence to medical recommendations37,38. The special needs of hospitalized older adults with delirium and dementia has been shown to increase demands on nursing staff, risk of post-discharge institutionalization, length of stay and health care costs3–10,27,39–48. We wanted to look specifically at CI because it often goes undetected49–51 and can have a great impact on the hospital course of elders. Screening for CI among hospitalized older adults has been considered to have potential benefit in hospital care of older adults52. Screening may lead to early detection by uncovering subtle symptoms not yet apparent to families or other caregivers who know the patient well but do not notice small declines or changes in day-to-day functioning. Early recognition of CI may lead to early treatment and subsequently may delay progression of cognitive decline improve health outcomes. Screening may enhance physician’s prescribing practices and reduce exposure to harmful medications among these vulnerable patients. Finally, delirium is an important prognostic indicator and screening patients could provide invaluable information towards the overall clinical picture. Despite all of this, the current literature does not provide sufficient information to support the use of routine screening on admission2–20,41,52–54. Most of the published studies were conducted among elders who stayed in the hospital for more than 48 hours, missing data on the crucial first 48 hours of the hospital course2–20,41,52–54. These studies did not evaluate the impact of unrecognized CI on the hospital course and the majority of these studies were not conducted in the urban and lower socioeconomic status populations of elders that are the most vulnerable for bad health outcomes2–20,41,52–54. Finally, few studies evaluated the impact of delirium superimposed on cognitive impairment on the hospital course and mortality of elders2–20,41,52–54. With these details in mind we wanted to explore the impact of cognitive impairment recognition among patients aged 65 and older admitted to the medical services of an urban, public hospital in Indianapolis to determine the prevalence and the impact of recognized and unrecognized CI on the hospital course of these elders. Furthermore, we examined the role of delirium superimposed on these hospitalized elders with CI.

In today's environment, providers are extremely time-constrained. Assembling relevant contextual data to make decisions on laboratory results can take a significant amount of time from the day. The Regenstrief Institute has created a system which leverages data within Indiana Health Information Exchange's (IHIE's) repository, the Indiana Network for Patient Care (INPC), to provide well-organized and contextual information on returning laboratory results to outpatient providers. The system described here uses data extracted from INPC to add historical test results, medication-dispensing events, visit information, and clinical reminders to traditional laboratory result reports. These "Enhanced Laboratory Reports" (ELRs) are seamlessly delivered to outpatient practices connected through IHIE via the DOCS4DOCS clinical messaging service. All practices, including those without electronic medical record systems, can receive ELRs. In this paper, the design and implementation issues in creating this system are discussed, and generally favorable preliminary results of attitudes by providers towards ELRs are reported.

The effectiveness of parathyroidectomy (PTHX) for the control of secondary hyperparathyroidism was assessed in 46 adult end-stage renal disease (ESRD) patients whose bone mineral content at the midshaft and distal radius was measured using single-photon absorptiometry (SPA) every 6 months before and after the surgery. They were compared to 46 age-, race-, and sex-matched ESRD patient controls who had not undergone surgery but who had had at least five SPA studies at similar intervals. Presurgery midradius bone mass was significantly lower for PTHX patients compared to controls. Comparing changes in bone mass of PTHX patients across surgery to controls in comparable time periods showed that PTHX patients lost significantly less bone mass after surgery. Similar results were obtained when rates of change in bone mass were evaluated. When patient characteristics were examined, the effect of surgery was found to be diminished in elderly patients and in oophorectomized patients. It is concluded that PTHX can have a salutary effect on renal osteodystrophy in the appendicular skeleton, but factors other than bone mass also need to be considered in identifying those patients who will benefit from surgery.

The identification of those at highest risk of osteoporotic fractures is a clinical goal that requires appropriate statistical comparisons of potential predictors of fractures. This article provides a formal approach for comparing individual predictors (e.g., bone mass at one site vs bone mass at another), or sets of predictors (e.g., bone mass vs other risk factors), and contrasts newer methods, such as bootstrapping, to receiver-operating-characteristics (ROC) curves, which have been previously used. The advantages of the bootstrapping approach are illustrated using time-to-fracture data from a published study demonstrating the use of baseline bone mass measurements in the prediction of fractures in 521 subjects with variable lengths of follow-up, extending to 12.5 years. Bone mineral density (BMD) was shown to be significantly better than bone mineral content (BMC) in predicting fractures in free-living subjects, but not in retirement-community subjects. Bone mineral apparent density (BMAD) was also compared with BMC and BMD and shown not to improve fracture prediction in these subjects.

A group of 118 children, aged 5.3-14 years, were enrolled in a prospective study of calcium supplementation and bone mass. At entry to the study, questionnaires regarding the child's usual physical activity were administered to the children and their mothers. Repeated activity assessments at 6 month intervals indicated good within-person agreement for total activity and for most individual activities. Consistent positive associations were observed between bone mineral densities (BMD) in the radius, spine, and hip and most activities. A summary measure (total hours of weight-bearing activity) was significantly related to BMD in the radius and hip, independently of age or gender effects. Self-reported sports and play activities were associated with BMD, but neither time spent watching television nor hours of physical education classes were associated either positively or negatively with skeletal mass. These data suggest that important increments in skeletal mass may result from physical activity during childhood.

OBJECTIVES: To evaluate the effectiveness of computer-assisted decision support in reducing potentially inappropriate prescribing to older adults. DESIGN: Randomized, controlled trial. SETTING: An academic emergency department (ED) in Indianapolis, Indiana, where computerized physican order entry was used to write all medication prescriptions. PARTICIPANTS: Sixty-three emergency physicians were randomized to the intervention (32 physicians) or control (31 physicians) group. INTERVENTION: Decision support that advised against use of nine potentially inappropriate medications and recommended safer substitute therapies. MEASUREMENTS: The primary outcome was the proportion of ED visits by seniors that resulted in one or more prescriptions for an inappropriate medication. The main secondary outcomes were the proportions of medications prescribed that were inappropriate and intervention physicians' reasons for rejecting the decision support. RESULTS: The average age of the patients was 74, two-thirds were female, and just over half were African American. Decision support was provided 114 times to intervention physicians, who accepted 49 (43%) of the recommendations. Intervention physicians prescribed one or more inappropriate medications during 2.6% of ED visits by seniors, compared with 3.9% of visits managed by control physicians (P=.02; odds ratio=0.55, 95% confidence interval=0.34–0.89). The proportion of all prescribed medications that were inappropriate significantly decreased from 5.4% to 3.4%. The most common reason for rejecting decision support was that the patient had no prior problems with the medication. CONCLUSION: Computerized physican order entry with decision support significantly reduced prescribing of potentially inappropriate medications for seniors. This approach might be used in other efforts to improve ED care.Trial Registration: Clinical trials.gov Identifier: NCT00297869.

Differences in osteoporotic hip fracture incidence between American whites and blacks and between women and men are considered to result, in part, from differences in bone mineral density and geometry at the femur. The aim of this study was to quantify differences in femoral bone density and geometry between a large sample of healthy American white and black women and men.Healthy American white (n=612) and black (n=164) premenopausal women, aged 23 to 57 years, and healthy American white (n=492) and black (n=169) men, aged 20 to 63 years, had volumetric bone mineral density (vBMD) and geometry variables measured at the femur by computerized tomography (CT), and areal bone mineral density (aBMD) at femoral neck measured by dual X-ray absorptiometry (DXA).American blacks had higher vBMD at the femoral neck and femoral shaft cortex than American whites whereas femoral axis length and femoral neck area were not different. Men had lower vBMD at the femoral neck and femoral cortex than women but had greater femoral axis length and femoral neck area than women. The higher aBMD in American blacks than whites persisted after correction for measured area whereas the higher aBMD in men than women disappeared.At the femoral neck, American whites have lower bone density than American blacks but similar geometry. Women have higher bone density than men in both races but have smaller geometry variables. The differences in bone density may account in part for the differences in hip fracture incidence between American blacks and whites, whereas the differences in femur size may account for the differences in hip fracture rates between men and women.

Only half of consultants' medical recommendations are implemented. We created a tool that lets referring providers review and implement electronic recommendations made by consultants, with the hypothesis that facilitation with our tool could improve implementation.The tool was piloted among geriatrics consultants and hospitalists. Pre-post evaluation was done with control (before pilot; N=20) and intervention (after pilot; N=20) patients. Consultants wrote notes containing recommendations for all study patients, and entered electronic recommendations only for intervention patients. We analyzed all recommendations and surveyed hospitalists.A total of 249 recommendations were made for intervention patients versus 192 for controls (p0.05). Of all recommendations about intervention patients, 78% were implemented, compared to 59% for controls (p=0.01). Of the intervention recommendations, 77% were entered electronically using our tool; of these, 86% were implemented. All 24 survey respondents indicated that the system improved quality, saved time, and should be expanded.Consultant recommendations were implemented 30% more often when there was electronic facilitation of recommendations.

Phenotypic variation in bone mineral density (BMD) among healthy adults is influenced by both genetic and environmental factors. Genetic sequence variations in the adenylate cyclase 10 (ADCY10) gene, which is also called soluble adenylate cyclase, have previously been reported to be associated with low spinal BMD in hypercalciuric patients. Since ADCY10 is located in the region linked to spinal BMD in our previous linkage analysis, we tested whether polymorphisms in this gene are also associated with normal BMD variation in healthy adults. Sixteen single nucleotide polymorphisms (SNPs) distributed throughout ADCY10 were genotyped in two healthy groups of American whites: 1,692 premenopausal women and 715 men. Statistical analyses were performed in the two groups to test for association between these SNPs and femoral neck and lumbar spine areal BMD. We observed significant evidence of association (p

Low-intensity pulsed ultrasound (LIPUS) and nonsteroidal anti-inflammatory drugs (NSAIDs) were used to treat stress fracture. Bilateral stress fractures were induced in the ulnas of 48 adult rats. Animals were divided into two groups (NSAID and VEH), and treated 5 days per week with celecoxib (5 mg/kg) mixed in a vehicle solution of polyethylene glycol and saline (NSAID) or vehicle alone (VEH). One-to-three hours following drug administration, all animals were treated with unilateral active-LIPUS and contralateral inactive-LIPUS. Equal numbers of ulnas from each drug group were histologically evaluated at 2, 4, and 8 weeks following induction of stress fracture. Neither LIPUS nor NSAID influenced bone resorption, but each had significant and opposite effects on intracortical bone formation rate. These effects indicate that LIPUS may be used to facilitate stress fracture repair whereas NSAID may delay tissue level repair of stress fractures. There was no interaction between LIPUS and NSAID, indicating that the beneficial LIPUS effect was not mediated by the cyclooxygenase-2 pathway. LIPUS accelerated stress fracture healing, whereas the NSAID delayed repair. When used in combination, the beneficial LIPUS effect was not impaired by the detrimental NSAID effect.

Background There are 250,000 cases of central line-associated blood stream infections in the United States annually, some of which may be prevented by the removal of lines that are no longer needed. Objective To test the performance of criteria to identify an idle line as a guideline to facilitate its removal. Methods Patients with central lines on the wards were identified. Criteria for justified use were defined. If none were met, the line was considered "idle." We proposed the guideline that a line may be removed the day following the first idle day and compared actual practice with our proposed guideline. Results One hundred twenty-six lines in 126 patients were observed. Eighty-three (65.9%) were peripherally inserted central catheters. Twenty-seven percent (n= 34) were placed for antibiotics. Seventy-six patients had lines removed prior to discharge. In these patients, the line was in place for 522 days, of which 32.7% were idle. The most common reasons to justify the line included parenteral antibiotics and meeting systemic inflammatory response (SIRS) criteria. In 11 (14.5%) patients, the line was removed prior to the proposed guideline. Most (n = 36, 47.4%) line removals were observed to be in accordance with our guideline. In another 29 (38.2%), line removal was delayed compared to our guideline. Conclusions Idle days are common. Central line days may be reduced by the consistent daily reevaluation of a line's justification using defined criteria. The practice of routine central line placement for prolonged antibiotics and the inclusion of SIRS criteria to justify the line may need to be reevaluated. Journal of Hospital Medicine 2016;11:489-493. © 2016 Society of Hospital Medicine.

Osteoporosis treatment rates within 2 years following an index event (fragility fracture, osteoporotic bone mineral density (BMD) T-score, or osteoporosis ICD-9 codes) were determined from 2005 to 2011. Most patients were not treated. Fracture patients had the lowest treatment rate. Low treatment rates also occurred in patients that were male, black, or had non-commercial insurance. Clinical recognition of osteoporosis (osteoporotic BMD, assignment of an ICD-9 code, or the occurrence of fragility fractures) provides opportunities to treat patients at risk for future fracture. A cohort of 36,965 patients was identified from 2005 to 2011 in the Indiana Health Information Exchange, with index events after age 50 of either non-traumatic fractures, an osteoporosis ICD-9 code, or a BMD T-score ≤ −2.5. Patients with osteoporosis treatment in the preceding year were excluded. Medication records during the ensuing 2 years were extracted to identify osteoporosis treatments, demographics, comorbidities, and co-medications. Predictors of treatment were evaluated in a multivariable logistic regression model. The cohort was 78 % female, 11 % black, 91 % urban-dwelling, and 53 % commercially insured. The index events were as follows: osteoporosis diagnosis (47 % of patients), fragility fracture (44 %), and osteoporotic T-scores (9 %). Within 2 years after the index event, 23.3 % received osteoporosis medications (of which, 82.2 % were oral bisphosphonates). Treatment rates were higher after osteoporosis diagnosis codes (29.3 %) or osteoporotic T-score (53.9 %) than after fracture index events (10.5 %) (p

Objective: To evaluate quantitative measures of eye movements as possible biomarkers in prediagnostic and early stages of Huntington disease (HD). Methods: The study sample (n = 215) included individuals both at risk and recently diagnosed with HD. All participants completed a uniform clinical evaluation which included administration of the Unified Huntington’s Disease Rating Scale (UHDRS) by a movement disorder neurologist and molecular testing to determine HD gene status. A high resolution, video-based eye tracking system was employed to quantify measures of eye movement (error rates, latencies, SD of latencies, velocities, and accuracies) during a computerized battery of saccadic and steady fixation tasks. Results: Prediagnostic HD gene carriers and individuals with early HD demonstrated three types of significant abnormalities while performing memory guided and anti-saccade tasks: increased error rate, increased saccade latency, and increased variability of saccade latency. The eye movement abnormalities increased with advancing motor signs of HD. Conclusions: Abnormalities in eye movement measures are a sensitive biomarker in the prediagnostic and early stages of Huntington disease (HD). These measures may be more sensitive to prediagnostic changes in HD than the currently employed neurologic motor assessment.

The Alox15 gene was recently identified as a negative regulator of peak BMD in mice. Polymorphisms in human ALOX12, but not ALOX15, were significantly associated with spine BMD in white men and women, suggesting that ALOX12 may contribute to normal variation in BMD. Introduction: Osteoporosis is a complex disease with both genetic and environmental risk factors. A major determinant of osteoporosis is peak BMD, which is a highly heritable trait. Recently, the arachidonate 15-lipoxygenase (Alox15) gene was identified as a negative regulator of peak BMD in mice. Materials and Methods: To assess the contribution of lipoxygenase genes to normal BMD variation in healthy white men and women, we performed population- and family-based association studies of two arachidonate lipoxygenase genes: ALOX15, which is the human homolog of mouse Alox15, and ALOX12, which is functionally similar to Alox15. Single nucleotide polymorphisms (SNPs) distributed across the two genes were genotyped. BMD was measured at the femoral neck and lumbar spine in 411 men 18–61 years of age and 1291 premenopausal women 20–50 years of age. Results: Moderate evidence of association was found between spine BMD and six SNPs in the ALOX12 gene in both men and women (p = 0.0052–0.050). Furthermore, the most common SNP haplotype in ALOX12 showed evidence of significant association with high spine BMD in men (p = 0.0083), whereas the second most common haplotype was associated with high spine BMD in women (p = 0.0081). Conclusions: Polymorphisms in the ALOX12 gene may contribute to normal variation in spine BMD.

The role of the LRP5 gene in rare BMD-related traits has recently been shown. We tested whether variation in this gene might play a role in normal variation in peak BMD. Association between SNPs in LRP5 and hip and spine BMD was measured in 1301 premenopausal women. Only a small proportion of the BMD variation was attributable to LRP5 in our sample. Introduction: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene have been implicated as the cause of multiple distinct BMD-related rare Mendelian phenotypes. We sought to examine whether the LRP5 gene contributes to the observed variation in peak BMD in the normal population. Materials and Methods: We genotyped 12 single nucleotide polymorphisms (SNPs) in LRP5 using allele-specific PCR and mass spectrometry methods. Linkage disequilibrium between the genotyped LRP5 SNPs was measured. We tested for association between these SNPs and both hip and spine BMD (adjusted for age and body weight) in 1301 healthy premenopausal women who took part in a sibling pair study aimed at identifying the genes underlying peak bone mass. Our study used both population-based (ANOVA) and family-based (quantitative transmission disequilibrium test) association methodology. Results and Conclusions: The linkage disequilibrium pattern and haplotype block structure within the LRP5 gene were consistent with that observed in other studies. Although significant evidence of association was found between LRP5 SNPs and both hip and spine BMD, only a small proportion of the total variation in these phenotypes was accounted for. The genotyped SNPs accounted for ∼0.8% of the variation in femoral neck BMD and 1.1% of the variation in spine BMD. Results from our sample suggest that natural variation in and around LRP5 is not a major contributor to the observed variability in peak BMD at either the femoral neck or lumbar spine in white women.

Although hypothyroidism is purportedly an important cause of depression, prior studies have involved small samples of young people and produced conflicting results. We examined the yield of thyroid-stimulating hormone (TSH) testing in a large group of elderly patients with major depression or dysthymic disorder. The study sample comprised 883 outpatients aged 60 years or older from 18 primary care sites enrolled in the intervention arm of a clinical trial of depression management. Thyroid function was assessed by a single TSH value. Depressive diagnoses were confirmed with the Structured Clinical Interview for DSM-IV (SCID) and depression severity was assessed with the HSCL-20, a modified depression scale of the Hopkins Symptom Checklist. TSH results were available for 725 (82.1%) participants. Although 32 (4.4%) of those tested had TSH>5 mIU/L, the vast majority (27/32) had marginally elevated results (5.1-9.4 mIU/L). Only five patients (0.7%) had TSH levels >10 mIU/L. Patients with elevated TSH did not differ from those with TSH < or = 5 mIU/L in the severity or symptom pattern of depression as measured by the baseline HSCL-20 score (P=.37) or SCID score (P=.44). These findings should caution physicians against acceptance of borderline TSH values as the primary cause of a patient's clinical depression.

Our goal was to review and extend statistical methods for discriminating between normal subjects and those with dementia or cognitive impairment. We compared six different methods to one constructed by expert opinion, in their brevity and predictive power. The methods include logistic regression and neural networks, with standard and least absolute shrinkage and selection operator (LASSO) variable selection, as well as decision trees with and without boosting. These methods were applied to the baseline data of a subgroup of subjects in a dementia study, using their screening interview items to predict their clinical diagnosis of normal or non-normal (cognitively impaired or demented). The derived models were then validated on a different subgroup of subjects in the same study who had the screening and clinical diagnosis two to five years later. Performance of different models was compared based on their sensitivity and specificity in the validation sample. Generally, the six statistical methods performed slightly to moderately better than the expert-opinion model. Neural networks generally performed better than the logistic and decision tree models. LASSO improved the performance of logistic and neural network models, but it eliminated few input variables in the neural network. The single decision tree performed at least as well as the standard logistic model, and with fewer items, making it an attractive pre-screening tool. Using the boosting option for decision trees did not substantially improve the performance. We recommend that for each situation, different methods of classification should be attempted to obtain optimal results for a given purpose.

BACKGROUND. It has not been demonstrated that the implementation of computerized quality improvement strategies can improve client-centered outcomes in public community based, long-term care (CBLTC) programs. OBJECTIVES. To test and evaluate 2 innovative computer-assisted, client-centered quality improvement strategies for public community-based, long-term care. The first strategy, the Normative Treatment Planning (NTP) program, assesses needs, prescribes services, and evaluates outcomes. The second strategy, the Client Feedback System (CFS) program, provides service vendors with feedback on client perceptions of services. RESEARCH DESIGN. A 2 x 2 factorial design with the 2 strategies using cluster randomization. SUBJECTS. A total of 2222 clients (86% of eligible program clients) enrolled in Indiana's state case management program and/or the Medicaid home and community-based services waiver program for the aged and disabled as of January 1, 1995. MEASURES. Outcomes of needs met and client satisfaction were measured through telephone surveys every 6 months for 2 years. RESULTS. A total of 1006 participants (45%) completed the 2-year evaluation study. For the group using only the NTP program, perception of needs met and client satisfaction were significantly better than the control group over the 2 years. During this period, the group using only the CFS program had significantly better client satisfaction than the control group. However, the effect sizes of the significant differences were small, and no statistically significant effects were found for the group using both programs. CONCLUSIONS. Client-centered quality improvement strategies can be implemented to enable public CBLTC programs to meet client needs better and increase client satisfaction.

The objective of this study was to determine if vasorelaxant responses to calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and acetylcholine are altered in aortic rings of mice lacking genetic expression of endothelial nitric oxide synthase (eNOS) or inducible nitric oxide synthase (iNOS) genes (i.e., eNOS- and iNOS-knockout mice) as compared with control (wild-type) mice. Aortic rings from eNOS-knockout (eNOS (-/-)) mice did not relax in response to acetylcholine, thereby confirming previous reports. Aortic rings from iNOS-knockout (iNOS (-/-)) mice relaxed in response to acetylcholine in an endothelium-dependent manner. However, maximum relaxations in endothelium-intact rings were significantly (p < 0.05) larger than in control mice (85.3 +/- 3.1% in iNOS (-/-) mice vs. 67.9 +/- 5.6% in controls). CGRP caused concentration-dependent relaxations in aortas of all three types of mice: control mice, iNOS (-/-) mice, and eNOS (-/-) mice. Vasorelaxant responses to CGRP in control and iNOS (-/-) mice had identical relationships; both were partially dependent on endothelium. In eNOS (-/-) mice, dose-response curves of CGRP in endothelium-intact and endothelium-denuded rings were not significantly different, indicating loss of the partial dependence on endothelium. The vasorelaxant responses to VIP were completely dependent on endothelium in control and iNOS (-/-) mice. Maximum relaxations to VIP in iNOS (-/-) mice (77.4 +/- 2.7%) were significantly greater than in control mice (64.0 +/- 5.5%). Vasorelaxant responses to VIP in eNOS (-/-) aortic rings were also endothelium-dependent, but responses were greatly attenuated compared with wild-type mice. Relaxations induced by VIP (1 x 10 ) in endothelium-intact aortic rings of eNOS (-/-) mice and control mice were 18.3 +/- 5.4% and 64.0 +/- 5.5%, respectively. These findings demonstrated that, in eNOS (-/-) mice, aortic vasorelaxant responses to CGRP were fully present but no longer dependent on the endothelium, and responses to VIP were greatly attenuated compared with control and responses to acetylcholine were abolished. In iNOS (-/-) mice, aortic vasorelaxant responses to VIP and acetylcholine were significantly greater than wild-type control, suggesting that induction of iNOS may have attenuated vascular responses to VIP and acetylcholine in wild-type controls.

A significant source of missing data in longitudinal epidemiological studies on elderly individuals is death. Subjects in large scale community-based longitudinal dementia studies are usually evaluated for disease status in study waves, not under continuous surveillance as in traditional cohort studies. Therefore, for the deceased subjects, disease status prior to death cannot be ascertained. Statistical methods assuming deceased subjects to be missing at random may not be realistic in dementia studies and may lead to biased results. We propose a stochastic model approach to simultaneously estimate disease incidence and mortality rates. We set up a Markov chain model consisting of three states, non-diseased, diseased and dead, and estimate the transition hazard parameters using the maximum likelihood approach. Simulation results are presented indicating adequate performance of the proposed approach.

Background Adherence to oral bisphosphonates is often low, but even adherent patients may remain at elevated fracture risk. The goal of this study was to estimate the proportion of bisphosphonate-adherent women remaining at high risk of fracture. Methods A retrospective cohort of women aged 50 years and older, adherent to oral bisphosphonates for at least two years was identified, and data were extracted from a multi-system health information exchange. Adherence was defined as having a dispensed medication possession ratio ≥ 0.8. The primary outcome was clinical occurrence of: low trauma fracture (months 7–36), persistent T-score ≤ − 2.5 (months 13–36), decrease in bone mineral density (BMD) at any skeletal site ≥ 5%, or the composite of any one of these outcomes. Results Of 7435 adherent women, 3110 had either pre- or post-adherent DXA data. In the full cohort, 7% had an incident osteoporotic fracture. In 601 women having both pre- and post-adherent DXA to evaluate BMD change, 6% had fractures, 22% had a post-treatment T-score ≤ − 2.5, and 16% had BMD decrease by ≥ 5%. The composite outcomes occurred in 35%. Incident fracture was predicted by age, previous fracture, and a variety of co-morbidities, but not by race, glucocorticoid treatment or type of bisphosphonate. Conclusion Despite bisphosphonate adherence, 7% had incident osteoporotic fractures and 35% had either fracture, decreases in BMD, or persistent osteoporotic BMD, representing a substantial proportion of treated patients in clinical practices remaining at risk for future fractures. Further studies are required to determine the best achievable goals for osteoporosis therapy, and which patients would benefit from alternate therapies.

Objective The authors conducted a longitudinal, population-based survey of African Americans in Indianapolis, Indiana, and Yoruba in Ibadan, Nigeria, using the Community Screening Interview for Dementia to assess the predictive value of informant reports of changes in personality on incident dementia and Alzheimer disease. Methods In all, 3,021 subjects had informants' reports of changes in personality and dementia status (2,084 subjects residing in Ibadan and 937 subjects residing in Indianapolis). Results After adjusting for demographic, cognitive, and functional characteristics in two markedly different populations, socioeconomically and culturally, subjects with changes in personality had approximately twice the odds of having dementia as subjects with no change in personality Conclusions The finding that in two markedly different populations, personality change is a significant predictor of future dementia, independent of cognition and functional status, should make clinicians particularly sensitive to these reports when they occur in their elderly patients.

To design a brief cognitive screener with acceptable sensitivity and specificity for identifying subjects with cognitive impairment.Cohort one is assembled from a community-based survey coupled with a second-stage diagnostic evaluation using formal diagnostic criteria for dementia. Cohort two is assembled from referrals to a specialty clinic for dementing disorders that completed the same diagnostic evaluation.Urban neighborhoods in Indianapolis, Indiana and the Indiana Alzheimer Disease Center.Cohort one consists of 344 community-dwelling black persons identified from a random sample of 2212 black persons aged 65 and older residing in Indianapolis; cohort two consists of 651 subject referrals to the Alzheimer Disease Center.Formal diagnostic clinical assessments for dementia including scores on the Mini-mental state examination (MMSE), a six-item screener derived from the MMSE, the Blessed Dementia Rating Scale (BDRS), and the Word List Recall. Based on clinical evaluations, subjects were categorized as no cognitive impairment, cognitive impairment-not demented, or demented.The mean age of the community-based sample was 74.4 years, 59.4% of the sample were women, and the mean years of education was 10.1. The prevalence of dementia in this sample was 4.3% and the prevalence of cognitive impairment was 24.6%. Using a cut-off of three or more errors, the sensitivity and specificity of the six-item screener for a diagnosis of dementia was 88.7 and 88.0, respectively. In the same sample, the corresponding sensitivity and specificity for the MMSE using a cut-off score of 23 was 95.2 and 86.7. The performance of the two scales was comparable across the two populations studied and using either cognitive impairment or dementia as the gold standard. An increasing number of errors on the six-item screener is highly correlated with poorer scores on longer measures of cognitive impairment.The six-item screener is a brief and reliable instrument for identifying subjects with cognitive impairment and its diagnostic properties are comparable to the full MMSE. It can be administered by telephone or face-to-face interview and is easily scored by a simple summation of errors.

Purpose To report the successful long-term use of methadone and tramadol in treating low back pain in a marine police officer.

Autosomal dominant osteopetrosis type II (ADO2) is typically diagnosed from radiographs, which demonstrate the pathognomonic findings of osteosclerosis and endobone formation. Individuals with ADO2 also have elevated serum levels of tartrate-resistant acid phosphatase (TRAP) and the BB isoenzyme of creatine kinase (CK-BB). In the current study, we tested the utility of these enzymes in making or refuting a diagnosis of ADO2. Furthermore, because ADO2 has incomplete penetrance, we examined whether TRAP and CK-BB were helpful in identifying gene carriers. We studied eight families, measured serum levels of TRAP and CK-BB in 52 affected individuals and 12 obligate gene carriers, and compared their values with age-matched controls. Our results demonstrate that affected patients have significantly elevated levels of both TRAP and CK-BB. In contrast, gene carriers have values that are not different from controls. Furthermore, in our study population, TRAP and CK-BB have a high diagnostic sensitivity and specificity, particularly in children. From this large study of ADO2 patients and carriers, we conclude that: 1) TRAP and CK-BB are significantly elevated in patients with ADO2, 2) obligate carriers cannot be adequately identified by measurement of these analytes, and 3) TRAP and CK-BB are highly sensitive and specific diagnostic tests that can efficiently and effectively screen high-risk individuals who have not had previous radiographic assessment.

This study measured bone mineral content (BMC), bone mineral density (BMD), and bone area at the spine and hip to learn whether bone loss takes place premenopausally. Participants were 130 non-Hispanic white women 31 to 50 years of age who were in good general health and had taken no drugs that affect bone metabolism. Measurements were made by dual-energy x-ray absorptiometry at the L2-4 segment of the lumbar spine, in the femoral neck, and in the total hip. The studies were repeated at least twice over 1 to 9 years. Both BMC and bone area increased significantly over time in the spine, as did BMD. If, however, BMC was normalized by bone volume, there was no age-related change in volumetric density. Measurements of the total hip showed no significant change with age. BMD in the femoral neck declined at a rate of about 0.0036 g/cm2 per year. BMC was lost as well, so the drop in BMD was not an artifact of bone expansion. Changes in BMD correlated positively with weight change and estradiol levels and negatively with gonadotropin levels. Somewhat less bone loss was noted in subjects who gained more weight during the study. Higher levels of LH and FSH were documented in women who lost more than 1% of BMD per year. Estrogen levels were highest in women who manifested no bone loss. Declining BMD was more a result of a loss of BMC in women with high FSH levels, but due more to an expansion in bone area in those with relatively low FSH levels. The positive association between body weight change and BMD was not entirely mediated by higher estrogen. Premenopausal women more than 30 years of age in this study lost BMD at the femoral neck at an average annual rate of 0.4%. Bone loss was less in women who gained more weight but greater in those with reduced estrogen levels even in the absence of symptoms. Early bone loss might be preventable if premenopausal women with suboptimal sex hormone levels are detected at an early stage.

Background Limited data exist on the impact of dementia in developing nations, including its association with mortality. Objective The purpose of this paper is to assess the relationship between dementia and five-year mortality on a community dwelling elderly Yoruba population in the developing country of Nigeria and to compare those results with those from an elderly African–American community in Indianapolis. Methods A two-phase design was used to ascertain dementia status in two sites. In the first phase, the Community Screening Instrument for Dementia (CSI-D) was administered. In the second phase, subjects were sampled for the clinical assessment according to their CSI-D performance category. Proportional hazards regression was used to assess the relationship between mortality and cognitive status at both sites after adjusting for demographics and chronic disease conditions. Results For the entire screened population, poor and intermediate performance on the CSI-D is associated with increased mortality at both sites; however the effect of CSI-D performance did not significantly differ between the two sites. For the clinically assessed sample, dementia was significantly associated with increased mortality at both sites (Ibadan RR = 2.83, Indianapolis RR = 2.05), but the effect was not significantly different across the two sites. Conclusion Dementia resulted in an increased risk of mortality for Yoruba of a magnitude similar to African–Americans suggesting that the impact of dementia on mortality risk may be similar for developing and developed countries. Copyright © 2002 John Wiley & Sons, Ltd.