Environmentally sustainable emergency medicine.

Emergency clinicians worldwide are demonstrating increasing concern about the effect of climate change on the health of the populations they serve. The movement for sustainable healthcare is being driven by the need to address the climate emergency. Globally, healthcare contributes significantly to carbon emissions, and the healthcare sector has an important role to play in contributing to decarbonisation of the global economy. In this article, we consider the implications for emergency medicine of climate change, and suggest ways to improve environmental sustainability within emergency departments. We identify examples of sustainable clinical practice, as well as outlining research proposals to address the knowledge gap that currently exists in the area of provision of environmentally sustainable emergency care.

Associations among integrated psychoneuroimmunological factors and metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) has been reported to cause considerable psychoneuroimmunology (PNI) disturbances such as, psychological distress, autonomic nervous imbalance, and impaired immune function. Associations among these psychoneuroimmunology (PNI) factors and their integrated effects with MetS and risk components of MetS necessitate further exploration. OBJECTIVE: This study investigated associations among psychoneuroimmunological factors, their integrated effects with MetS and risk components of MetS. METHODS: This was a cross-sectional study. Participants were recruited from two health management centers at a medical center in Northern Taiwan. Demographics and data on psychological distress (e.g., perceived stress and depression) were collected using self-reported questionnaires. Heart rate variability (HRV) and C-reactive protein values (CRP) were measured to evaluate participants' autonomic nervous function and immune reaction. The risk components of MetS (e.g., elevated blood pressure, impaired fasting glucose, dyslipidemia, and abdominal obesity) were identified according to the Taiwan-specific definition of MetS and were determined based on participants' health examination profiles. RESULTS: A total of 345 participants with complete data were included for data analysis. Compared with healthy controls, participants with MetS exhibited higher depression scores (11.2±8.5 vs. 8.7±7.0), higher CRP values (2.1±2.5 vs. 0.7±1.0), and lower HRV (total power: 758.7±774.9 vs. 1064.4±1075.0). However, perceived stress in participants with MetS did not significantly differ from that of their healthy counterparts (p>0.05). Univariate analyses indicated that associations among psychoneuroimmunological factors and MetS risk components were statistically heterogeneous: a) perceived stress and depression were significantly associated only with high blood glucose (p<0.05); b) CRP was significantly associated with all MetS risk components (p<0.05); and c) HRV was significantly associated with high triglycerides and high fasting blood glucose (p<0.05). Multivariate analysis indicated that the integrated effects of depression, CRP, and HRV were significantly associated with MetS (p<0.01) after controlling for age and education level. CONCLUSIONS: Higher depression scores, higher CRP values, and lower HRV are independently and additively associated with MetS and risk components of MetS. Accordingly, a multidisciplinary approach to alleviating psychological distress, immune dysfunction, and autonomic nervous imbalance is recommended for promoting well-being in people with subclinical metabolic abnormalities or MetS to minimize downstream health consequences.

Impact of a pharmacy benefit change on new use of mail order pharmacy among diabetes patients: the Diabetes Study of Northern California (DISTANCE).

OBJECTIVE: To assess the impact of a pharmacy benefit change on mail order pharmacy (MOP) uptake. DATA SOURCES/STUDY SETTING: Race-stratified, random sample of diabetes patients in an integrated health care delivery system. STUDY DESIGN: In this natural experiment, we studied the impact of a pharmacy benefit change that conditionally discounted medications if patients used MOP and prepaid two copayments. We compared MOP uptake among those exposed to the benefit change (n = 2,442) and the reference group with no benefit change (n = 8,148), and estimated differential MOP uptake across social strata using a difference-in-differences framework. DATA COLLECTION/EXTRACTION METHODS: Ascertained MOP uptake (initiation among previous nonusers). PRINCIPAL FINDINGS: Thirty percent of patients started using MOP after receiving the benefit change versus 9 percent uptake among the reference group (p < .0001). After adjustment, there was a 26 percentage point greater MOP uptake (benefit change effect). This benefit change effect was significantly smaller among patients with inadequate health literacy (15 percent less), limited English proficiency (14 percent less), and among Latinos and Asians (24 and 16 percent less compared to Caucasians). CONCLUSIONS: Conditionally discounting medications delivered by MOP effectively stimulated MOP uptake overall, but it unintentionally widened previously existing social gaps in MOP use because it stimulated less MOP uptake in vulnerable populations.

Impact of a Medicare MTM program: evaluating clinical and economic outcomes.

OBJECTIVES: To assess the impact of a Medicare Medication Therapy Management (MTM) program in a large integrated health plan on patient mortality, hospitalization and emergency department (ED) utilization, and daily prescription costs. STUDY DESIGN: Retrospective matched cohort study. METHODS: Patients who received MTM services between 2006 and 2010 were matched to control patients who were enrolled in Medicare but did not receive MTM services. They were matched in a 1:4 ratio based on age, gender, geographic location, and prospective diagnostic-cost-group (DxCG) risk score. Multivariate regressions were used to analyze the outcomes. Subgroup analyses were conducted for patients enrolled in 2010 because the Centers for Medicare & Medicaid Services lowered the drug-cost threshold for MTM eligibility and changed from opt-in to optout participation. RESULTS: We identified 34,532 members who received MTM services and 138,128 control members. The MTM group was found to have a significantly reduced mortality (hazard ratio 0.86, 95% confidence interval [CI], 0.84-0.88; P <.001), lower odds for hospitalization (odds ratio [OR] = 0.97, 95% CI, 0.94-0.99; P = .018), higher odds for emergency department visits (OR = 1.17, 95% CI, 1.14-1.20; P <.001), and no differences in change in daily medication costs when compared to the matched group. The subgroup analysis of the 2010 cohort found similar results with better outcomes than the overall cohort. CONCLUSIONS: Medicare MTM services resulted in lower mortality and odds for hospitalization for enrolled patients compared with matched controls. This study observed an increase in ED visits and no differences in change in daily medication costs in MTM services.

Evaluation of clinical and safety outcomes associated with conversion from brand-name to generic tacrolimus in transplant recipients enrolled in an integrated health care system.

STUDY OBJECTIVE: To evaluate clinical and safety outcomes among transplant recipients whose tacrolimus was converted from the brand-name formulation to a generic formulation. DESIGN: Retrospective analysis. DATA SOURCE: Clinical databases and electronic records from a large, integrated health care system in California. PATIENTS: A total of 234 clinically stable, adult transplant recipients (renal, liver, and heart) whose tacrolimus was converted from the brand-name formulation to a generic formulation between October 1, 2010, and December 31, 2010, according to a physician-approved protocol. MEASUREMENTS AND MAIN RESULTS: For each patient, pre- and postconversion tacrolimus trough concentrations and serum creatinine concentrations were analyzed. Data were also collected on the percentage of patients who required dosage titration, drug cost savings, and rates of reversion to brand-name tacrolimus, biopsy-proved acute allograft rejections, and mortality. No significant differences were noted in mean ± SD pre- and postconversion tacrolimus trough levels (6.74 ± 1.61 vs 6.96 ± 2.31 ng/ml, p=0.137) or serum creatinine concentrations (1.33 ± 0.48 vs 1.36 ± 0.82 mg/dl, p=0.302). The mean ± SD percent change in tacrolimus trough concentration was 5.63 ± 32.95%. Thirty-six patients (15.4%) required dosage titration. Six patients (2.6%) reverted back to brand-name tacrolimus. No deaths or acute rejections occurred. Use of the generic product saved each patient an average of $45/month in drug acquisition cost and $26/prescription copayment. CONCLUSION: Clinical experience as well as research data show that use of generic tacrolimus results in trough concentrations that are comparable to the brand-name drug. Given the lack of adverse events reported and the cost savings recognized, conversion from brand-name tacrolimus to generic tacrolimus should be encouraged. Since dosage titration may be required, close therapeutic drug monitoring is recommended.

Association between exposure to topical tacrolimus or pimecrolimus and cancers.

BACKGROUND: The Food and Drug Administration has issued a public health advisory regarding cancer risk from topical calcineurin inhibitors. OBJECTIVE: To compare the rates of cancer among patients with common dermatologic conditions who were exposed or not exposed to topical calcineurin inhibitors. METHODS: A retrospective cohort observational study used data from an integrated healthcare delivery system on 953,064 subjects with diagnoses of atopic dermatitis or eczema between 2001 and December 2004. The main endpoint was initial cancer diagnosis. Chart review was performed to confirm cancer diagnosis in the subjects exposed to topical calcineurin inhibitors when any particular cancer rate was at least 3 times higher than that in unexposed subjects. Data were analyzed using the Cox proportional hazards model. RESULTS: Age- and sex-adjusted hazard ratios for all cancers were 0.93 (95% CI 0.81 to 1.07; p = 0.306) for tacrolimus-exposed versus -unexposed subjects and 1.15 (95% CI 0.99 to 1.31; p = 0.054) for pimecrolimus-exposed versus -unexposed subjects. T-cell lymphoma was the only cancer associated with a significantly increased risk among subjects exposed to tacrolimus (HR = 5.04, 95% CI 2.39 to 10.63; p < 0.001) or pimecrolimus (HR = 3.76, 95% CI 1.71 to 8.28; p = 0.010). Subsequent chart review of subjects in the exposed group with T-cell lymphoma found that 4 of 16 had skin lesions that were suspected to be the early lesions of T-cell lymphoma prior to exposure to tacrolimus or pimecrolimus. After these 4 cases were excluded, the age and sex hazard ratio for T-cell lymphoma was 5.44 (95% CI 2.51 to 11.79; p < 0.001) for tacrolimus and 2.32 (95% CI 0.89 to 6.07; p = 0.086) for pimecrolimus. There was no statistically significantly increased risk for other subgroups of cancer, including melanoma. CONCLUSIONS: Exposure to topical tacrolimus or pimecrolimus was not associated with an increase in the overall cancer rate. Use of topical tacrolimus may be associated with an increased risk of T-cell lymphoma.

Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously screened.

OBJECTIVE: To screen commonly used prescription drugs for possible carcinogenic effects. METHODS: In a large health care program we identified 105 commonly used drugs, not previously screened. Recipients were followed for up to 12½ years for incident cancer. Nested case-control analyses of 55 cancer sites and all combined included up to ten matched controls per case, with lag of at least 2 years between drug dispensing and cancer. Positive associations entailed a relative risk of 1.50, with p ≤ 0.01 and higher risk for three or more, than for one prescription. Evaluation included further analyses, searches of the literature, and clinical judgment. RESULTS: There were 101 associations of interest for 61 drugs. Sixty-six associations were judged to have involved substantial confounding. We found evidence that of the remaining 35, the following associations may not be due to chance: sulindac with gallbladder cancer and leukemia, hyoscyamine with nonHodgkin lymphoma, nortriptyline with esophageal and hepatic cancer, oxazepam with lung cancer, both fluoxetine and paroxetine with testicular cancer, hydrochlorothiazide with renal and lip cancer, and nifedipine with lip cancer. CONCLUSIONS: These preliminary findings suggest that further studies are indicated regarding sulindac, hyoscyamine, nortriptyline, oxazepam, fluoxetine, paroxetine, hydrochlorothiazide, and nifedipine.

Screening statins for possible carcinogenic risk: up to 9 years of follow-up of 361,859 recipients.

PURPOSE: Determine the risk of cancer in statin users. METHODS: Risk of cancer in up to 9.4 years after first recorded receipt of statins was evaluated in subscribers of an integrated health care program in northern California. Statin use and cancer development were ascertained from the program's pharmacy records and cancer registry from August 1994 to December 2003. RESULTS: Most of the 361,859 statin users received lovastatin, simvastatin or both. Results are presented from analyses with 2-year lag and use for over 5 years. Most of the observed associations were likely due to chance or confounding. The few associations that seemed less readily explainable were increased risk of cancers of the thyroid, esophagus and urinary tract and decreased risk of colon cancer in men. Increased risk of lung cancer was the only nominally statistically significant positive association in women and could be partially attributable to their smoking habits. CONCLUSIONS: Overall this study provided no strong evidence of either causation or prevention of cancer by statins.

Vitamin E in renal therapeutic regiments.

Administration of vitamin E in children with immunoglobulin A (IgA) nephropathy, focal segmental glomerulosclerosis (FSGS) and type I diabetes demonstrated potential towards ameliorating progression. Oral vitamin E therapy reduced endothelial dysfunction, lipid peroxidation and oxidative stress in patients with chronic kidney failure (CKF). Moreover, the use of vitamin E-bonded hemodialyzers reduced atherosclerotic changes, erythropoietin dosage and muscular cramps in patients on hemodialysis (HD). However, several controlled clinical trials failed to document beneficial effects on the study subjects' cardiovascular and renal outcomes. A recent report of increased all-cause mortality in adult patients receiving high dose vitamin E therapy has caused considerable concern and debate. These issues regarding the efficacy and safety of vitamin E in renal therapeutic regimens will be reviewed in this article.

Longitudinal study of new and prevalent use of self-monitoring of blood glucose.

OBJECTIVE: We sought to assess longitudinal association between self-monitoring of blood glucose (SMBG) and glycemic control in diabetic patients from an integrated health plan (Kaiser Permanente Northern California). RESEARCH DESIGN AND METHODS: Longitudinal analyses of glycemic control among 1) 16,091 patients initiating SMBG (new-user cohort) and 2) 15,347 ongoing users of SMBG (prevalent-user cohort). SMBG frequency was based on pharmacy use (number of blood glucose test strips dispensed), and glycemic control was based on HbA(1c) (A1C). In the new-user cohort, ANCOVA models (pre- and posttest design) were used to assess the effect of initiating SMBG. In the prevalent-user cohort, repeated-measure, mixed-effects models with random-intercept and time-dependent covariates were used to assess changes in SMBG and A1C. All models were stratified by therapy (no medications, oral agents only, or insulin) and adjusted for baseline A1C, sociodemographics, insulin injection frequency, comorbidity index, medication adherence, smoking status, health care use, and provider specialty. RESULTS: Greater SMBG practice frequency among new users was associated with a graded decrease in A1C (relative to nonusers) regardless of diabetes therapy (P < 0.0001). Changes in SMBG frequency among prevalent users were associated with an inverse graded change in A1C only among pharmacologically treated patients (P < 0.0001). CONCLUSIONS: These observational findings are consistent with short-term benefits of initiating SMBG practice for all patients but continuing benefits only for pharmacologically treated patients. Differences in effectiveness between new versus prevalent users of SMBG have implications for guideline development and interpretation of observational outcomes data.

A method for the analysis of ginsenosides, malonyl ginsenosides, and hydrolyzed ginsenosides using high-performance liquid chromatography with ultraviolet and positive mode electrospray ionization mass spectrometric detection.

A high-performance liquid chromatographic separation coupled to diode array absorbance and positive mode electrospray mass spectrometric detection has been developed for the analysis of ginsenosides, malonyl ginsenosides, and hydrolyzed ginsenosides in extracts of Asian ginseng (Panax ginseng) and American ginseng (P. quinquefolius). The method is capable of separating, identifying, and quantifying the predominant ginsenosides found in heated alcoholic extracts of Asian and American ginseng roots routinely sold as nutraceuticals. It also separates and identifies the malonyl ginsenosides often found in cold alcoholic extracts of ginseng root and has the potential to quantify these compounds if pure standards are available. Furthermore, it can separate and identify ginsenoside hydrolysis products such as those readily produced in situations mimicking gastric situations, including those used for dissolution studies (i.e., 0.1 N HCl, 37 degrees C).

Compound library management.

The increasing size of the collections used for drug-discovery purposes has demanded both hardware and software automation of compound management in order to cope with the increasing demands of HTS. Splitting the collection into a number of copies in different formats is a desirable approach to keep a balance between rapid response to the demands and best storage conditions. Flexibility to different assay configurations can be provided with the appropriate selection of liquid handlers, and the informatic management systems should be accessible to keep track of the samples and link them to a variety of information that can help interpret HTS data. In this respect, QC data on the compounds and quality checks of the equipment used are highly desirable. It is also prudent for a large organization with different research sites to have a unified database and compatible plate format and concentration in order to be able to exchange samples and share screening results. The accomplishment of all the previous requirements is the only way to ensure an efficient and effective compound library management.