Search

Objective: Pharmacy-managed medication assistance programs (MAP) have the potential to recoup losses incurred by the pharmacy department, but whether this offsets the personnel cost of the program has not been well-established. The purpose of this study was to conduct a cost-benefit analysis of the pharmacy-managed MAP at an urban teaching clinic at Hartford Hospital in Hartford, Conn. Methods: Patients were enrolled into a MAP at Hartford Hospital, a large urban teaching hospital, based on referrals from social workers. Patients were assisted in identifying pharmaceutical manufacturers providing free drugs and completing applications. The program's benefit was defined as the value of the drugs procured using average wholesale price (AWP) in 2005 US dollars. The costs to the pharmacy consisted of personnel cost (time administering the program times a wage rate of $18.02/h). The net benefit was calculated as the value of the drugs procured minus personnel costs. Threshold sensitivity analysis and Monte Carlo simulation were performed by varying drug value, personnel time, and wage rate. Results: Over the 24-month period (May 2003 through April 2005), 143 patients were enrolled into the program, with 328 medication shipments received. The total benefit for all drugs was $83,504. An average of 4 h/wk were spent administering the program, resulting in personnel costs of $7,496. The program yielded a net benefit of 576,008. Upon sensitivity analysis, the break-even point was reached when the drug value was reduced to 57,496, personnel lime increased to 4,634 hours (44.5 h/wk), or the wage rate increased to $200/h. When the value of the drug procured, personnel time, and wage rate were simultaneously varied within plausible ranges ($68,175-$171,584, 2 h/wk-40 h/wk, and $13.65/h-$43.60/h, respectively), Monte Carlo simulation demonstrated there was a 96.1% chance of the program being cost-beneficial. Conclusion: This study demonstrated that Hartford Hospital's pharmacy-managed MAP for indigent inpatients was cost-beneficial. The conclusions of the study were found to be robust to changes in drug value, personnel time, and wage rate. [ABSTRACT FROM AUTHOR]

BACKGROUND: Prophylactic beta-blockade is the recommended strategy for suppressing atrial fibrillation after cardiothoracic surgery (CTS). However, beta-blockade's impact on the hospital length of stay (LOS) and other economic end points has not been adequately assessed. OBJECTIVE: The present evaluation sought to determine whether beta-blocker use after CTS is a cost-effective strategy for the prevention of postoperative atrial fibrillation (POAF). METHODS: This was a piggyback cost-effectiveness analysis of a prospective cohort evaluation comprising 1660 patients undergoing CTS at an urban academic hospital from October 1999 to October 2003. Patients receiving beta-blocker prophylaxis were matched 1:1 with control patients not receiving prophylaxis based on age >70 years, valvular surgery, history of atrial fibrillation, male sex, and use of preoperative digoxin or beta-blockers. The incidence of POAF, total hospital costs, and LOS were compared in each group. Nonparametric bootstrapping analysis was performed to examine the study results as part of a quadrant analysis and to calculate CIs for the incremental cost-effectiveness ratio. LOS and total costs were also compared in patients with and without POAF, regardless of beta-blocker use. RESULTS: Use of prophylactic beta-blockade was associated with a 17.3% reduction in the incidence of POAF (P = 0.02) and a 2.2-day reduction in LOS (P = 0.001) compared with nonuse. It also was associated with a 25.7% reduction in total hospital costs compared with nonuse (mean [SD], $30,978 [$33,108] vs $41,700 [$67,369], respectively; P < 0.001), possibly due to a 27.6% reduction in room and board costs ($11,144 [$15,398] vs $14,920 [$22,132]; P < 0.001). In the bootstrapping analysis, 99.0% of the time prophylactic beta-blockade fell into quadrant IV, which indicated superior effectiveness and lower total costs. Regardless of beta-blocker use, patients who developed POAF had a significantly longer LOS compared with those who did not develop POAF (14.7 [19.1] days vs 10.1 [11.1] days, respectively; P < 0.001) and higher total costs ($47,240 [$85,941] vs $32,516 [$34,644]; P < 0.001). CONCLUSIONS: At the institution studied, beta-blocker prophylaxis against POAF after CTS was associated with significantly reduced total costs compared with nonuse of beta-blocker prophylaxis. Patients who developed POAF had significantly increased LOS and total costs compared with those who did not develop POAE An adequately powered prospective, randomized, placebo-controlled trial is necessary to confirm the results of this evaluation. [ABSTRACT FROM AUTHOR]

The purpose of this essay is to explore the implications of #metoo and #aidtoo for understanding nonprofit/nongovernmental organization (NPO/NGO) theory and practice. We provide an overview of how women have experienced sexual violence in the context of NPOs/NGOs and draw on an intersectional feminist theory lens to highlight the context that enables violence to persist, and which requires more than implementing bureaucratic accountability reforms. We end by discussing potential avenues for creating change to end such violence.

Premise: With digitization and data sharing initiatives underway over the last 15 years, an important need has been prioritizing specimens to digitize. Because duplicate specimens are shared among herbaria in exchange and gift programs, we investigated the extent to which unique biogeographic data are held in small herbaria vs. these data being redundant with those held by larger institutions. We evaluated the unique specimen contributions that small herbaria make to biogeographic understanding at county, locality, and temporal scales., Methods: We sampled herbarium specimens of 40 plant taxa from each of eight states of the United States of America in four broad status categories: extremely rare, very rare, common native, and introduced. We gathered geographic information from specimens held by large (≥100,000 specimens) and small (<100,000 specimens) herbaria. We built generalized linear mixed models to assess which features of the collections may best predict unique contributions of herbaria and used an Akaike information criterion-based information-theoretic approach for our model selection to choose the best model for each scale., Results: Small herbaria contributed unique specimens at all scales in proportion with their contribution of specimens to our data set. The best models for all scales were the full models that included the factors of species status and herbarium size when accounting for state as a random variable., Conclusions: We demonstrated that small herbaria contribute unique information for research. It is clear that unique contributions cannot be predicted based on herbarium size alone. We must prioritize digitization and data sharing from herbaria of all sizes., (© 2020 The Authors. American Journal of Botany published by Wiley Periodicals LLC on behalf of Botanical Society of America.)

Microsatellite markers have become a popular and useful tool for investigating evolutionary processes at shallow taxonomic scales such as within a species or between extremely closely related species. Rhododendron sect. Pentanthera is a closely related group of deciduous azaleas that demonstrate both naturally occurring and horticulturally derived hybridization. Two species, flame azalea and Cumberland azalea, represent a particularly recalcitrant evolutionary problem, which will benefit from the development of rapidly evolving molecular markers. Microsatellite markers were specifically developed for Rhododendron calendulaceum, the flame azalea, for use in studies of genetic structure and potential hybridization with its close relative Rhododendron cumberlandense, the Cumberland azalea. Forty-eight primer pairs designed from paired-end Illumina MiSeq data were screened for robust amplification. Sixteen of these pairs were PCR-amplified in the presence of fluorescently labeled primers and genotyped in 66 flame azalea individuals from three geographically dispersed populations. Fifteen primer pairs were both reliable and polymorphic and exhibit ample variability for use in downstream population-level investigations. Cross-amplification in all other members of Rhododendron sect. Pentanthera was highly successful, suggesting broad utility across the entire clade. The novel microsatellite markers presented here functioned well within the target species and amplified with high success in the remaining members of the clade. They represent a significant improvement to the genetic toolkit available for Rhododendron sect. Pentanthera, and particularly for the flame/Cumberland azalea evolutionary problem.

Premise: Microsatellite markers were developed for Labrador tea ( Rhododendron groenlandicum , Ericaceae) to facilitate downstream genetic investigation of this species and the extremely closely related, circumboreal Rhododendron subsect. Ledum ., Methods and Results: Forty-eight primer pairs were designed using Illumina data and screened for excellent amplification. Sixteen successful pairs were developed as microsatellite markers using fluorescently labeled amplification to generate chromatogram data. These data were evaluated for intrapopulation and interpopulation variability in three populations from Alaska and Maine, USA, and the Northwest Territories, Canada. Fourteen polymorphic markers genotyped reliably, each with one to eight alleles. Cluster analysis indicates that across the range, populations can be easily discriminated. Cross-amplification in other Rhododendron subsect. Ledum species shows broad application of the developed markers within this small, well-supported clade., Conclusions: These microsatellite markers exhibit significant variability and will be useful in population genetics within R. groenlandicum and for investigation of species boundaries across Rhododendron subsect. Ledum ., (© 2019 Sheik et al. Applications in Plant Sciences is published by Wiley Periodicals, Inc. on behalf of the Botanical Society of America.)

Premise: Microsatellite markers were developed for sandmyrtle, Kalmia buxifolia (Ericaceae), to facilitate phylogeographic studies in this taxon and possibly many of its close relatives., Methods and Results: Forty-eight primer pairs designed from paired-end Illumina MiSeq data were screened for robust amplification. Sixteen pairs were amplified again, but with fluorescently labeled primers to facilitate genotyping. Resulting chromatograms were evaluated for variability using three populations from Tennessee, North Carolina, and New Jersey, USA. Eleven primer pairs were reliable and polymorphic (mean 3.92 alleles), one was reliable but monomorphic, and four were not reliable. The markers exhibited lower heterozygosity (mean 0.246) than expected (mean 0.464). Cross-amplification in the remaining nine Kalmia species exhibited a phylogenetic pattern, suggesting broad applicability of the markers across the genus., Conclusions: These microsatellite markers will be useful in population genetics and species boundaries studies of K. buxifolia , K. procumbens , and likely all other Kalmia species.

This comprehensive systematic review and meta-analysis aims to quantify the association between different types of childhood maltreatment and suicidality. We searched five bibliographic databases, including Medline, PsychINFO, Embase, Web of Science and CINAHL, until January 2018. Random-effects meta-analysis was employed followed by univariable and multivariable meta-regressions. Heterogeneity was quantified using the I2 statistic and formal publication bias tests were undertaken. The methodological quality of the studies was critically appraised and accounted in the meta-regression analyses. Data from 68 studies based on n = 261.660 adults were pooled. All different types of childhood maltreatment including sexual abuse [odds ratio (OR) 3.17, 95% confidence interval (CI) 2.76-3.64], physical abuse (OR 2.52, 95% CI 2.09-3.04) and emotional abuse (OR 2.49, 95% CI 1.64-3.77) were associated with two- to three-fold increased risk for suicide attempts. Similar results were found for the association between childhood maltreatment and suicidal ideation. Complex childhood abuse was associated with a particularly high risk for suicide attempts in adults (OR 5.18, 95% CI 2.52-10.63). Variations across the studies in terms of demographic and clinical characteristics of the participants and other core methodological factors did not affect the findings of the main analyses. We conclude that there is solid evidence that childhood maltreatment is associated with increased odds for suicidality in adults. The main outstanding challenge is to better understand the mechanisms which underpin the development of suicidality in people exposed to childhood maltreatment because current evidence is scarce.

Premise of the Study: Microsatellite markers were developed for Polypodium appalachianum (Polypodiaceae) to facilitate investigation of species boundaries between P. appalachianum and its putative hybrid, P. virginianum , and potentially among other members of the Miocene-age P. vulgare species complex., Methods and Results: Forty-eight primer pairs were designed from Illumina data and screened for successful amplification. Sixteen pairs were genotyped and evaluated for variability within and among three populations in North Carolina, Vermont, and New Hampshire. Twelve of these primer pairs were reliable and polymorphic, exhibiting one to 10 alleles per locus. Cross-species amplification experiments were conducted for P. virginianum and four additional close relatives from the P. vulgare complex in order to maximize information about likely utility within a phylogenetic context., Conclusions: These microsatellite markers will be useful in population genetics and species boundaries studies of P. appalachianum and P. virginianum , and likely in other species within the P. vulgare complex.

Premise of the Study: Microsatellite primers were developed for a widespread limestone endemic sedge, Carex eburnea , to facilitate investigation of the genetic diversity and phylogeography of this taxon and its closest relative, C. mckittrickensis ., Methods and Results: Forty-eight primer pairs were designed from Illumina sequence data and screened for suitability. Fourteen of these primer pairs were polymorphic and generated one to seven alleles per locus. Cross-species amplifications were conducted for all four members of Carex sect. Albae ., Conclusions: These primer pairs can be used to assess the genetic diversity and population structure in future studies of C. eburnea and C. mckittrickensis , and likely in other members of Carex sect. Albae .

Background: Recently, various evolution-related journals adopted policies to encourage or require archiving of phylogenetic trees and associated data. Such attention to practices that promote sharing of data reflects rapidly improving information technology, and rapidly expanding potential to use this technology to aggregate and link data from previously published research. Nevertheless, little is known about current practices, or best practices, for publishing trees and associated data so as to promote re-use., Findings: Here we summarize results of an ongoing analysis of current practices for archiving phylogenetic trees and associated data, current practices of re-use, and current barriers to re-use. We find that the technical infrastructure is available to support rudimentary archiving, but the frequency of archiving is low. Currently, most phylogenetic knowledge is not easily re-used due to a lack of archiving, lack of awareness of best practices, and lack of community-wide standards for formatting data, naming entities, and annotating data. Most attempts at data re-use seem to end in disappointment. Nevertheless, we find many positive examples of data re-use, particularly those that involve customized species trees generated by grafting to, and pruning from, a much larger tree., Conclusions: The technologies and practices that facilitate data re-use can catalyze synthetic and integrative research. However, success will require engagement from various stakeholders including individual scientists who produce or consume shareable data, publishers, policy-makers, technology developers and resource-providers. The critical challenges for facilitating re-use of phylogenetic trees and associated data, we suggest, include: a broader commitment to public archiving; more extensive use of globally meaningful identifiers; development of user-friendly technology for annotating, submitting, searching, and retrieving data and their metadata; and development of a minimum reporting standard (MIAPA) indicating which kinds of data and metadata are most important for a re-useable phylogenetic record.

Adipokinetic hormone (AKH) is the equivalent of mammalian glucagon, as it is the primary insect hormone that causes energy mobilization. In Drosophila, current knowledge of the mechanisms regulating AKH signaling is limited. Here, we report that AMP-activated protein kinase (AMPK) is critical for normal AKH secretion during periods of metabolic challenges. Reduction of AMPK in AKH cells causes a suite of behavioral and physiological phenotypes resembling AKH cell ablations. Specifically, reduced AMPK function increases life span during starvation and delays starvation-induced hyperactivity. Neither AKH cell survival nor gene expression is significantly impacted by reduced AMPK function. AKH immunolabeling was significantly higher in animals with reduced AMPK function; this result is paralleled by genetic inhibition of synaptic release, suggesting that AMPK promotes AKH secretion. We observed reduced secretion in AKH cells bearing AMPK mutations employing a specific secretion reporter, confirming that AMPK functions in AKH secretion. Live-cell imaging of wild-type AKH neuroendocrine cells shows heightened excitability under reduced sugar levels, and this response was delayed and reduced in AMPK-deficient backgrounds. Furthermore, AMPK activation in AKH cells increases intracellular calcium levels in constant high sugar levels, suggesting that the underlying mechanism of AMPK action is modification of ionic currents. These results demonstrate that AMPK signaling is a critical feature that regulates AKH secretion, and, ultimately, metabolic homeostasis. The significance of these findings is that AMPK is important in the regulation of glucagon signaling, suggesting that the organization of metabolic networks is highly conserved and that AMPK plays a prominent role in these networks.

Objectives: We conducted a randomized, blinded, controlled study evaluating the impact of anterior fat pad (AFP) maintenance on postoperative atrial fibrillation (POAF) incidence., Background: Drugs with antiadrenergic effects reduce POAF. Because the epicardial AFP is parasympathetically innervated, its routine excision during coronary artery bypass grafting (CABG) might precipitate autonomic imbalance and induce POAF., Methods: Patients (n = 180, mean age = 66 +/- 10 years, 80% men, 5% with previous atrial fibrillation) undergoing CABG surgery were randomized to either AFP maintenance or AFP removal. Routine prophylaxis against POAF with beta-blockers (85%) and amiodarone (28%) was allowed on the basis of caregivers' discretion. The development of POAF, total hospital costs, and heart rate variability was compared between groups., Results: Anterior fat pad maintenance did not reduce POAF incidence (34.8% vs. 35.2%, p = 0.950) or total hospital costs (data as medians with 25%, 75% percentiles: 22,940 dollars [17,629 dollars, 29,274 dollars] vs. 23,866 dollars [18,602 dollars, 30,370 dollars], p = 0.647) but was associated with higher heart rate variability (SD of normal-to-normal RR intervals [SDNN]: 31.7 +/- 24.6 vs. 22.7 +/- 8.3, p = 0.05 and SD of all 5-min mean RR intervals [SDANN 5]: 17.1 +/- 11.9 vs. 10.1 +/- 5.5, p = 0.003) than AFP removal., Conclusions: Maintaining the AFP prevents attenuation of parasympathetic tone after CABG but does not reduce POAF or total hospital costs in any appreciable way.

Background: Implantable cardioverter defibrillators (ICDs) are a life-saving therapy for many patients with cardiovascular disease at increased risk of fatal dysrhythmias. As men comprise the majority of the study population (67-92%) in clinical trials, the benefit to women is unknown. We performed a meta-analysis of primary prevention trials to evaluate the impact of ICDs in men and women on death from any cause., Methods: Included trials met the following criteria: (i) randomized controlled trials versus standard of care, (ii) ICD used as primary prevention in a well-described protocol and (iii) data provided on risk of death from any cause for both male and female patients., Results: Five clinical trials were included in this meta-analysis. The risk of death from any cause was significantly reduced by 26% in male patients who received ICD therapy compared to control, hazard ratio (HR) 0.74 (95% CI 0.60-0.91) but not amongst female patients, HR 0.81 (95% CI 0.60-1.09). As the COMPANION trial evaluated the combination of biventricular pacemaker with ICD therapy we conducted a separate analysis without the inclusion of this study. Male patients receiving ICD therapy demonstrated a similar 24% reduction in risk of death from any cause, HR 0.76 (95% CI 0.58-0.99) whilst female patients demonstrated a reduction of only 12%, HR 0.88 (95% CI 0.63-1.22)., Conclusions: Unlike their male counterparts, females did not significantly benefit from ICD therapy and without concurrent biventricular pacing, appear only to achieve a nonsignificant 12% reduction in risk of death.

Purpose: A meta-analysis was conducted to assess the safety of amiodarone in the prevention of postoperative atrial fibrillation., Methods: A search of the medical literature was conducted to identify randomized controlled trials of prophylactic amiodarone use in cardiothoracic surgery. Studies were independently reviewed by three investigators and selected for inclusion if they met the following three criteria: (1) randomized controlled trial of amiodarone versus placebo or routine treatment, (2) patients underwent coronary artery bypass graft or valvular surgery, and (3) reported data on the frequency of at least one of the following safety endpoints: bradycardia, hypotension, heart block, nausea, cerebral vascular accident, myocardial infarction, and death. Both random- and fixed-effects models were used to determine any significant associations between amiodarone and safety endpoints., Results: Eighteen trials were analyzed. A total of 3408 patients were enrolled in these trials (1736 received amiodarone and 1672 received placebo). Amiodarone increased the odds of developing bradycardia (odds ratio [OR], 1.70; 95% confidence interval [CI], 1.05-2.74) and hypotension (OR, 1.62; 95% CI, 1.04-2.54). The administration of i.v. amiodarone, an average daily dose exceeding 1 g, and postoperative amiodarone administration were each associated with a greater likelihood of hemodynamic adverse effects. Amiodarone did not appear to affect other safety endpoints., Conclusion: Meta-analysis showed amiodarone to be associated with an increased risk of developing bradycardia and hypotension when used for the prophylaxis of postoperative atrial fibrillation. The greatest risk in the occurrence of these adverse events arose when using regimens containing i.v. amiodarone, initiating prophylaxis during the postoperative period, and using regimens with average daily doses exceeding 1 g.

Study Objective: To determine whether prophylactic amiodarone, dosed according to Atrial Fibrillation Suppression Trial (AFIST) I and II regimens, is a cost-effective strategy for prevention of postoperative atrial fibrillation., Design: Cost-effectiveness analysis of retrospective cohort study., Setting: Urban, academic hospital., Patients: A total of 2046 patients who underwent cardiothoracic surgery between February 1, 1998, and October 31, 2003. Of these patients, 186 received amiodarone and 1860 served as controls., Measurements and Main Results: Each patient who received prophylactic amiodarone using the AFIST I or II dosing strategies was matched for age, sex, history of valvular surgery, history of atrial fibrillation, beta-blocker intolerance, and receipt of preoperative digoxin therapy with 10 patients who did not receive prophylactic amiodarone. Occurrence of postoperative atrial fibrillation, total hospital costs, and both intensive care unit (ICU) and total hospital length of stay (LOS) were compared between groups. Nonparametric bootstrapping was conducted to examine study results as part of a quadrant analysis and to calculate confidence intervals for the incremental cost-effectiveness ratio. The ICU and total hospital LOS, and total costs for patients with and without postoperative atrial fibrillation were also compared. Fewer patients receiving prophylactic amiodarone developed postoperative atrial fibrillation compared with controls (23.1% vs 29.9%, p=0.05). Total hospital costs for the amiodarone group were 28% less than those for the control group (24,131 US dollars +/- 26,539 vs 33,518 US dollars +/- 40,892, p=0.002). Approximately 98% of the time, patients receiving amiodarone prophylaxis fell into the quadrant that showed superior efficacy and lower total costs. Patients who developed postoperative atrial fibrillation, compared with those who did not, regardless of amiodarone prophylaxis, had a longer mean +/- SD stay in the ICU (6.9 +/- 17.1 vs 3.7 +/- 7.9 days, p<0.001), a longer mean total hospital LOS (14.8 +/- 18.8 vs 10.2 +/- 10.4 days, p+/-0.001), and higher mean total hospital costs (41,574 US dollars +/- 54,721 vs 28,968 US dollars +/- 31,046, p<0.001)., Conclusion: Prophylactic amiodarone was shown to reduce the occurrence of postoperative atrial fibrillation as well as total hospital costs in patients undergoing cardiothoracic surgery. In patients who developed postoperative atrial fibrillation, both ICU and total hospital LOS as well as total hospital costs were increased.

We reviewed the current body of evidence supporting the use of Echinacea to reduce URI symptoms and improve QoL. Different Echinacea species have been administered either alone or in combination with other herbals and in various doses and dosage forms. Studies depicting Echinacea's effect on URI symptoms and QoL are contradictory. Despite some positive effects on symptom severity and QoL, given the current data available it would be inappropriate to attribute QoL benefit to Echinacea. The possibility that various facets of QoL may be improved with Echinacea cannot be ruled out. Further research into this compound is warranted.

Background: A recent multicenter observational study of 4,657 patients reported a 52% lower risk of postcardiothoracic surgery (CTS) atrial fibrillation (AF) among South American vs United States patients. This study did not evaluate whether the decreased incidence in AF was attributable to differing ethnicity (Hispanic vs Caucasian) or to another cause., Methods: A cohort study of CTS patients at Hartford Hospital was undertaken to evaluate whether Hispanic patients had a lower incidence of post-CTS AF than Caucasians. First, Hispanic patients were compared to the total Caucasian population. Then differences in important baseline predictors of AF were probed between groups. Finally, Hispanic patients undergoing CTS were matched (1:4 matching) with Caucasian patients based upon known predictors of post-CTS AF including age >70 years, valvular surgery, AF history, previous CTS, peripheral vascular disease, gender, pre-CTS digoxin and beta-blocker intolerance., Results: In the total population [n = 2,739, with 97 (3.5%) Hispanics, 66.6 +/- 11.6 years, 70.9% male, 66.9% valve surgery], Hispanics were 38% less likely to develop AF (15.5% vs 24.8%, P = 0.035). However, the Hispanic patients were 11.9 years younger (P< 0.001) with 14.7% more women (P = 0.002) which reduces the risk of post-CTS AF; they also had a 12.8% higher risk of valvular surgery (P = 0.009) which is known to enhance the risk. When these factors and other important variables were matched for, a total of 485 patients (n = 97 Hispanics, 388 Caucasian) were evaluated (55.8 +/- 13.1 years, 57.3% male, 45.4% valvular surgery). Hispanic and Caucasian patients had a similar incidence of post-CTS AF (15.5% vs 18.3%, P = 0.513)., Conclusion: Hispanic patients do not have an innately lower risk of post-CTS AF than Caucasians.

Postoperative atrial fibrillation can occur in 25% to 40% of patients undergoing cardiothoracic surgery. Although the majority of postoperative atrial fibrillation is benign, it has been associated with prolonged hospital length of stay. Magnesium prophylaxis against postoperative atrial fibrillation has been evaluated in several clinical trials; however these trials were small in size and therefore conveyed mixed or inconclusive results. In an attempt to better understand magnesium's role in this setting, we conducted a meta-analysis. A systematic literature search was conducted from January 1999 through August 2004 to identify trials of prophylactic magnesium in the setting of cardiothoracic surgery. The primary outcome measure was the incidence of postoperative atrial fibrillation. Trials were further analyzed based on cumulative doses of magnesium and perioperative time of initiation of prophylaxis, as well as length of stay. Seven randomized trials were identified. Upon meta-analysis, magnesium was found to prevent postoperative atrial fibrillation with an odds ratio of 0.66 and 95% confidence interval of 0.51 to 0.87. The incidence of postoperative atrial fibrillation was also significantly reduced in the low dose with an odds ratio of 0.36 and 95% confidence interval of 0.23 to 0.56, and in the preoperative groups with an odds ratio of 0.46 and 95% confidence interval of 0.31 to 0.67. Prophylactic magnesium reduced length of stay (n = 6 studies) by a weighted mean difference of 0.29 days, with a 95% confidence interval 0.54 to 0.05. Prophylactic magnesium reduced cardiothoracic surgery patients' risk of postoperative atrial fibrillation and length of stay. Administering lower doses and initiating prophylaxis in the preoperative period achieved the greatest reduction in postoperative atrial fibrillation.

As bacterial resistance continues to increase, optimising the potential for successful clinical outcomes with antimicrobial therapy requires consideration of pharmacodynamic concepts in order to maximise bacterial eradication and minimise the potential for further resistance. Based on the pharmacodynamic characteristics of specific antibiotics, dosage modifications can be implemented to improve the likelihood of bactericidal exposure. Considering their concentration-dependent bactericidal activity, aminoglycosides benefit from increased dosages and infrequent administration, so as to achieve a maximum concentration/minimum inhibitory concentration (MIC) of 10-12. In contrast, beta-lactams are concentration-independent killers and benefit greatest by increasing the time above the MIC (T > MIC). This can be accomplished with the use of prolonged or continuous infusion. By optimising pharmacodynamic parameters with these methodologies, successful treatment of pathogens may be possible in patient populations for whom standard dosing regimens are not effective.

Background: Two previous meta-analyses of amiodarone for prevention of postoperative atrial fibrillation (POAF) after cardiothoracic surgery did not evaluate total hospital cost, concluded that data on stroke are incomplete, and did not evaluate the effect of clinical heterogeneity between trials., Objective: To conduct a meta-analysis examining amiodarone's prophylactic impact on cardiothoracic surgery POAF, length of stay (LOS), stroke, and total costs., Methods: Three reviewers conducted a systematic literature search of MEDLINE, EMBASE, CINAHL, and the Cochrane Library (1966-SEPTEMBER 2004). Studies were included if they met the following criteria: (1) randomized controlled trial versus placebo/routine treatment, (2) coronary artery bypass graft and/or valvular surgery, (3) Jadad score > or = 3, (4) reported data on incidence of POAF or stroke, LOS, or total costs, (5) used electrocardiographic/Holter monitoring, and (6) monitored subjects for > or = 2 days. A random-effects model was utilized. Subgroup and sensitivity analyses were conducted., Results: Fifteen trials were identified, including 1512 and 1429 patients in the amiodarone and control groups, respectively. Amiodarone reduced POAF (OR 0.50; 95% CI 0.42 to 0.60) and decreased stroke (n = 8 studies), LOS (n = 10), and total costs (n = 6) (OR 0.47; 95% CI 0.23 to 0.96; -0.73 days, 95% CI -0.95 to -0.51; and -dollar 1619, 95% CI -3395 to 156, respectively). Surgery type, beta-blocker use, route of administration, use of a fixed-effects model, or exclusion of unblinded/unpublished studies did not affect the overall results. No statistical heterogeneity was observed for any endpoint evaluated (p > 0.22 for all comparisons)., Conclusions: Prophylactic treatment with amiodarone decreases patients' risk of POAF and stroke while reducing LOS.

Objective: Angiotensin II has been shown to increase hepatic glucose production and decrease insulin sensitivity. Patients who utilize either an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) may experience a decreased incidence of new-onset type 2 diabetes., Research Design and Methods: Three reviewers conducted a systematic literature search of Medline, EMBASE, CINAHL, and the Cochrane Library (1966 to present) to extract a consensus of trial data involving an ACEI or ARB with an end point of new-onset type 2 diabetes. Studies were included if they were randomized controlled trials verses placebo/routine therapy. A random-effects model was utilized. Subgroup and sensitivity analyses were conducted., Results: Eleven trials were identified, including 66,608 patients. An ACEI or ARB prevented new-onset type 2 diabetes (odds ratio 0.78 [95% CI 0.73-0.83]). The influence of either an ACEI (six trials) or an ARB (five trials) alone on new-onset type 2 diabetes was similar (0.79 [0.71-0.89] and 0.76 [0.70-0.82], respectively). Regardless of indication for use, hypertension (seven trials), coronary artery disease (two trials), or heart failure (two trials), reductions in new-onset type 2 diabetes were maintained (0.79 [0.72-0.85], 0.76 [0.60-0.95], and 0.70 [0.50-0.96], respectively). No statistical heterogeneity was observed for any evaluation (P > 0.1 for all comparisons). ACEIs and ARBs did not reduce the odds of mortality, cardiovascular, or cerebrovascular events versus control therapy among all of these studies combined or the hypertension trials. ACEIs and ARBs did reduce the odds of these outcomes among the coronary artery disease studies versus control therapy., Conclusions: ACEIs or ARBs may decrease patients' odds of developing new-onset type 2 diabetes but does not reduce the odds of mortality, cardiovascular, or cerebrovascular outcomes over the study follow-up periods among patients with hypertension.

Purpose: The relationship between adding aprotinin to standard care and the frequency of postoperative atrial fibrillation or flutter (POAF) in patients undergoing cardiothoracic surgery (CTS) with cardiopulmonary bypass (CPB) was studied., Methods: This was a retrospective cohort evaluation. All patients at a hospital who underwent CTS with CPB between October 1999 and October 2003 and who received aprotinin during surgery were included in the treatment group. Control patients were those who did not receive aprotinin; they were matched with treatment group patients for age, valvular surgery, history of atrial fibrillation or flutter, renal dysfunction, peripheral artery disease, smoking, angina, diabetes mellitus, congestive heart failure, previous CTS, sex, beta-blocker intolerance, and use of preoperative digoxin. The primary endpoint was POAF; secondary endpoints were perioperative transfusion use, length of stay (LOS), stroke, myocardial infarction, renal failure, graft occlusion, and death., Results: A total of 438 patients (219 per group) were evaluated. The patients' mean age was 68 years, 67% were men, and 74% had had valvular surgery. Patients who received aprotinin (mean +/- S.D. dose, 2.75 million +/- 1.24 million kallikrein-inhibiting units) did not have a significantly lower frequency of POAF than control patients (28% versus 27%, respectively [p = 0.92]), nor was there a significant difference in secondary endpoints., Conclusion: Aprotinin therapy was not associated with a significant reduction in POAF in patients undergoing CTS with CPB. Perioperative transfusion use, LOS, stroke, myocardial infarction, renal failure, graft occlusion, and mortality also did not differ significantly between aprotinin and control groups.

Antimicrobial resistance among bacterial pathogens continues to challenge clinicians. It is the main reason for antibiotic therapy to be deemed inappropriate and leads to unfavorable outcomes and increased costs. Knowledge of local susceptibility patterns can help clinicians empirically choose the appropriate antibiotic. In addition, the proper dosage regimen, based on pharmacodynamics, is essential to maximize the likelihood of achieving optimal therapy. Pharmacodynamic surveillance studies have demonstrated that percent susceptibility provides an accurate estimate of bactericidal exposure at standard dosage regimens for carbapenems, ceftazidime, and cefepime, whereas percent susceptibility overestimates actual bactericidal exposure for piperacillin/tazobactam and ciprofloxacin. The empiric use of appropriate broad-spectrum antimicrobial therapy at the correct dosages for severe infections should improve clinical outcomes and result in economic benefit. Initial therapy should have a high likelihood of covering resistant pathogens.

Study Objective: To evaluate the effect of prophylactic amiodarone on length of stay (LOS), postoperative stroke, and postoperative atrial fibrillation (POAF)., Design: Retrospective cohort study., Setting: Hartford Hospital, Hartford, Connecticut., Patients: Two thousand forty-six patients who underwent cardiothoracic surgery from February 1998-October 2003 (186 received amiodarone, 1860 were controls)., Measurements and Main Results: Patients receiving any of the prophylactic amiodarone regimens used in the Atrial Fibrillation Suppression Trials (AFIST) I and II were matched (1:10 matching) for age, valvular surgery, history of atrial fibrillation, sex, beta-blocker intolerance, and preoperative digoxin therapy with patients not receiving amiodarone prophylaxis. The AFIST regimens consisted of oral amiodarone 6 g over 6 days and 7 g over 10 days, beginning on preoperative days 1 and 5, respectively, or a hybrid intravenous and oral loading regimen delivering amiodarone 7 g over 5 days. Mean+/-SD age of the patients was 68.9+/-9.8 years, 75% were men, and 21% had undergone valvular surgery. Patients receiving prophylactic amiodarone had a shorter LOS (8.6+/-6.0 days) than controls (11.6+/-14.0 days, p=0.003) and a reduced frequency of POAF (23.1% vs 29.9%, p=0.05). Frequency of stroke was not significantly affected (2.2% vs 2.7% in the amiodarone vs control groups, p=0.61)., Conclusion: Use of the prophylactic amiodarone regimens from the AFIST trials reduced LOS by 3.0 days and frequency of POAF by 22.7%.

A 28-year-old Caucasian man who applied topical 5% permethrin cream once for the treatment of scabies infestation experienced a severe dystonic reaction on the left side of his neck. Assessment of causality using the Naranjo algorithm revealed a probable relationship between this adverse drug event and application of topical permethrin. Dystonic or musculoskeletal adverse reactions, including muscle spasms, have been reported with pyrethroid insecticides only after inappropriate occupational dermal exposure. These reported reactions occurred 4-48 hours after exposure and lasted from a few days to a few weeks. The mechanism behind these adverse effects may be related to permethrin's ability to delay sodium channel closure within nerve cells. This may result in a lowered threshold of nerve fibers to activation of further action potentials, leading to repetitive firing and hyperexcitation of the nervous system. Clinicians should be aware of this rare but potential adverse effect of permethrin.

Background: Previous studies have shown that post-cardiothoracic surgery atrial fibrillation (AF) increases the risk of hospital length of stay (LOS), overall mortality, pulmonary edema, and need for a balloon pump. A meta-analysis of 2 previous trials showed a nonsignificant reduction in LOS with postoperative beta-blockers but only encompassed 1200 patients, with few valve surgery patients, and neither study used a hospital within the US., Objective: To evaluate the impact of postoperative beta-blockers on LOS and AF. Secondary endpoints of overall mortality, pulmonary edema, and need for an intra-aortic balloon pump (IABP) were also evaluated between groups., Methods: This was a prospective cohort evaluation of all patients undergoing cardiothoracic surgery at our institution between October 1999 and October 2003. Patients receiving prophylactic postoperative beta-blockers were matched (1:1) with patients not receiving prophylaxis for age >70 years, valvular surgery, history of AF, gender, and use of preoperative digoxin and beta-blockers., Results: Patients (n = 1660) receiving postoperative beta-blockade had a reduction in LOS (mean +/- SD 10.22 +/- 11.38 vs 12.40 +/- 15.67; p = 0.001) and AF (23.5% vs 28.4%; p = 0.02). Mortality, pulmonary edema, and need for IABP were reduced by >50% (p < 0.001; p = 0.001; p < 0.001, respectively), while myocardial infarction and stroke were not significantly impacted., Conclusions: In this observational cohort study, prophylactic postoperative beta-blocker use was associated with shorter hospital LOS by an average of 2.2 days and a 17.3% lower incidence of AF. It may also be associated with reductions in overall mortality, pulmonary edema, and need for an IABP.

No significant differences could be found in the HLA-DR antigen frequency of two groups of patients with insulin dependent diabetes mellitus (IDDM). One group consisted of 49 patients with proliferative diabetic retinopathy and the other group of 31 patients with no ophthalmoscopic evidence of diabetic retinopathy.

HLA-DR matching has been shown in a retrospective study of 72 renal transplant patients to significantly enhance graft survival at 12 months. HLA-A and -B antigen matching also increased the graft survival rate significantly. Analysis of combined HLA-A, -B and -DR matching suggested an improvement in graft survival rate with better matching, but this did not attain statistical significance. It is now our policy to use HLA-DR matching prospectively and to ensure that all recipients receive a kidney with a maximum of 1 HLA-DR incompatibility and a minimum of 2 HLA-A and -B antigens shared.

Eighty-eight (43 per cent) of 204 patients with insulin-dependent diabetes had limited joint mobility affecting mainly the small joints of the hands. The presence of limited joint mobility correlated with duration of diabetes and with the presence of retinopathy. Patients with longstanding diabetes were approximately 2.5 times more likely to have proliferative retinopathy if limited joint mobility was present than if it was absent, although the risk for non-proliferative or background retinopathy was not increased. In patients with longstanding diabetes and limited joint mobility nerve conduction velocity and vibration perception threshold were significantly reduced compared with patients having similar duration of diabetes but normal joints. The association between insulin-dependent diabetes and HLA-DR3 and HLA-DR4 was confirmed, but there was no difference, between patients with and without limited joint mobility, in the frequency of the various HLA types. Limitation of joint mobility appears to be another "chronic complication' of diabetes, developing in parallel with retinopathy and deteriorating peripheral nerve function, and possibly of similar aetiology.