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Background: Perioperative hypothermia is still very common and associated with numerous adverse effects. The effects of benzodiazepines, administered as premedication, on thermoregulation have been studied with conflicting results. We investigated the hypotheses that premedication with flunitrazepam would lower the preoperative core temperature and that prewarming could attenuate this effect., Methods: After approval by the local research ethics committee 50 adult cardiac surgical patients were included in this prospective, randomized, controlled, single-centre study with two parallel groups in a university hospital setting. Core temperature was measured using a continuous, non-invasive zero-heat flux thermometer from 30 min before administration of the oral premedication until beginning of surgery. An equal number of patients was randomly allocated via a computer-generated list assigning them to either prewarming or control group using the sealed envelope method for blinding. The intervention itself could not be blinded. In the prewarming group patients received active prewarming using an underbody forced-air warming blanket. The data were analysed using Student's t-test, Mann-Whitney U-test and Fisher's exact test., Results: Of the randomized 25 patients per group 24 patients per group could be analysed. Initial core temperature was 36.7 ± 0.2 °C and dropped significantly after oral premedication to 36.5 ± 0.3 °C when the patients were leaving the ward and to 36.4 ± 0.3 °C before induction of anaesthesia. The patients of the prewarming group had a significantly higher core temperature at the beginning of surgery (35.8 ± 0.4 °C vs. 35.5 ± 0.5 °C, p = 0.027), although core temperature at induction of anaesthesia was comparable. Despite prewarming, core temperature did not reach baseline level prior to premedication (36.7 ± 0.2 °C)., Conclusions: Oral premedication with benzodiazepines on the ward lowered core temperature significantly at arrival in the operating room. This drop in core temperature cannot be offset by a short period of active prewarming., Trial Registration: This trial was prospectively registered with the German registry of clinical trials under the trial number DRKS00005790 on 20th February 2014.

Despite advantages of low molecular weight heparin (LMWH), enoxaparin over heparin (UFH) for venous thromboembolism (VTE), a hospital's prescribing trends analysis showed use of each was about equal. In an attempt to increase LMWH over UFH use, electronic medical record (EMR) changes for medical service patients and education via multidisciplinary grand rounds was provided to all services. This was a unique opportunity to study LMWH and UFH use pre and post interventions at our institution. Citrix Pharmacy data was extracted for 3 months pre and post intervention (August 2016-February 2017). Inclusion criteria were age > 18 and LMWH or UFH VTE prophylaxis. Exclusion criteria were one time or duplicate orders and VTE treatment doses. Primary endpoint was hospital services VTE use with focus on medicine service which had both interventions compared to single intervention among all other services. LMWH use increased from 51 to 57.3% (p < 0.001) and UFH use decreased from 49 to 42.7% (p < 0.001) for all services. For medicine service, LMWH use increased 52.5-59.6% (p < 0.001) and UFH use decreased 47.5-40.4% (p < 0.001). For other services, LMWH use increased 48.8-53.6% (p = 0.005) and UFH use decreased 51.2-46.4% (p = 0.005). EMR changes and prescribers' grand rounds education resulted in 7.1% increase of LMWH use for medicine and 4.8% increase for all other services. The net increase (95% CI) in LMWH use in medicine service is 2.3% (- 1.91%, 6.56%) compared to the other services p = 0.281. Future studies are needed to reassess the effects of continued education and outcome of interventions.

We present a case of a severe reaction after anti-thymocyte administration despite premedication and strict adherence to administration guidelines during the conditioning regimen. Due to the severity of the adverse drug reaction, we believe that this case should be reported.

Local drug application to the inner ear offers a number of advantages over systemic delivery. Local drug therapy currently encompasses extracochlear administration (i. e., through intratympanic injection), intracochlear administration (particularly for gene and stem cell therapy), as well as various combinations with auditory neurosensory prostheses, either evaluated in preclinical or clinical studies, or off-label. To improve rehabilitation with cochlear implants (CI), one focus is the development of drug-releasing electrode carriers, e. g., for delivery of glucocorticosteroids, antiapoptotic substances, or neurotrophins to the inner ear. The performance of cochlear implants may thus be improved by protecting neuronal structures from insertion trauma, reducing fibrosis in the inner ear, and by stimulating growth of neuronal structures in the direction of the electrodes. Controlled drug release after extracochlear or intracochlear application in conjunction with a CI can also be achieved by use of a biocompatible, resorbable controlled-release drug-delivery system. Two case reports for intracochlear controlled release drug delivery in combination with cochlear implants are presented. In order to treat progressive reduction in speech discrimination and increased impedance, two cochlear implant patients successfully underwent intracochlear placement of a biocompatible, resorbable drug-delivery system for controlled release of dexamethasone. The drug levels reached in inner ear fluids after different types of local drug application strategies can be calculated using a computer model. The intracochlear drug concentrations calculated in this way were compared for different dexamethasone application strategies., Competing Interests: Compliance with ethical guidelinesConflict of interestS.K. Plontke, G. Götze, T. Rahne, and A. Liebau declare that they have no competing interests.All patients were informed about the off-label use of the controlled-release drug-delivery system and signed an informed consent form.

Background: For older individuals with multimorbidity the appropriateness of prescribing preventive medicines remains a challenge., Objective: Investigate the prevalence and temporal trends in utilisation of preventive medicines in older New Zealanders from 2005 to 2013 stratified according to age, sex, ethnicity and district health board domicile., Methods: A repeated cross-sectional analysis was conducted on pharmaceutical dispensing data for all individuals' ≥ 65 years. Variable medication possession ratio (VMPR) was used to measure adherence. Prescribing of low-dose aspirin, clopidogrel, dipyridamole, warfarin, dabigatran, statins and bisphosphonates with a VMPR≥0.8 were examined., Results: Aspirin utilisation increased by 19.55% (95% CI: 19.39-19.70), clopidogrel by 2.93% (95% CI: 2.88-2.97) and dipyridamole decreased by 0.65% (95% CI: -0.70 to -0.59). Utilisation of aspirin with clopidogrel increased by 1.78% (95% CI: 1.74-1.81) and aspirin with dipyridamole increased by 0.54% (95% CI: 0.50-0.58%).Warfarin decreased by 0.87% (95% CI: -0.96 to -0.78) and dabigatran increased by 0.65% (95% CI: 0.60-0.70). Statins increased by 7.0% (95% CI: 6.82-7.18) and bisphosphonates decreased by 2.37% (95% CI: -2.44 to -2.30). Aspirin, clopidogrel, dabigatran and statins utilisation showed a greater increase in males. Interestingly, clopidogrel, warfarin and statins use increased in older adults aged 85+ compared to the younger age groups (65-84 years)., Conclusion: To our knowledge, this is the first study investigating the prevalence and trends of preventive medicines use in older people in New Zealand. This study may facilitate further research to examine the appropriateness of prescribing these medicines in older people with multimorbidity., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The international strategies in the treatment of rheumatic diseases have changed dramatically in the last 10 years. In addition to the prescription of a basic medication as soon as possible, biologics are increasingly being used for drug treatment of rheumatic diseases in Germany. The domains of orthopedic surgeons and orthopedic rheumatologists are still the extended conservative and surgical treatment of inflammatory systemic diseases, which continue to play an important role despite the improved drug therapy options. Orthopedic surgeons should principally be familiar with the use of antirheumatic drugs, especially with respect to the perioperative management. However, there is also a role for the orthopedic surgeon in the early detection of inflammatory systemic diseases and in cooperation with rheumatologists in the medicinal treatment of selected diseases. Because patients with initial stages of joint pain, e.g. from rheumatoid arthritis (RA), spondyloarthritis (SpA) or psoriatic arthropathy often present first to an orthopedic surgeon, recognition of the early stages by the primary treating physician, including the necessary rapid induction of drug therapy is especially important. In addition there is a shortage of internist rheumatologists in Germany so that selective referral and close cooperation between the two physicians become of great importance.

The recruitment and activation of blood platelets initiate ischemic events in patients with coronary artery diseases (myocardial infarction). Moreover, platelet activation and aggregation are key events triggering early and late thrombotic complications (stent thromboses) in patients successfully treated with coronary stent implantation. Hence, the inhibition of the thromboxane A2 synthesis by aspirin and the ADP-receptor pathway by clopidogrel have drastically reduced the risk of ischemic complications following coronary stenting. However, clopidogrel has several inherent limitations, including the high incidence of non- or low-responders and the increased risk of bleeding due to the prolonged persistence of its anti-platelet effect. The latter is of particular concern in patients who require non-deferrable surgery. In recent years, novel anti-platelet substances have been clinically evaluated and are now approved for use in patients. These substances offer several potential advantages over the previous strategies and could pave the way for more individualized anti-platelet regimens. In this review, we give an overview on the available clinical data evaluating the benefits of these novel anti-platelet substances.

Behind the multiple arguments for and against the use of premedication, sedative drugs in children is a noble principle that of minimizing psychological trauma related to anesthesia and surgery. However, several confounding factors make it very difficult to reach didactic evidence-based conclusions. One of the key confounding issues is that the nature of expectations and responses for both parent and child vary greatly in different environments around the world. Studies applicable to one culture and to one hospital system (albeit multicultural) may not apply elsewhere. Moreover, the study of hospital-related distress begins at the start of the patient's journey and ends long after hospital discharge; it cannot be focused completely on just the moment of anesthetic induction. Taking an example from actual practice experience, the trauma caused by the actual giving of a premedication to a child who absolutely does not want it and may struggle may not be recorded in a study but could form a significant component of overall effect and later psychological pathology. Clearly, attitudes by health professionals and parents to the practice of routine pediatric premedication, vary considerably, often provoking strong opinions. In this pro-con article we highlight two very different approaches to premedication. It is hoped that this helps the reader to critically re-evaluate a practice, which was universal historically and now in many centers is more selective.

Objective: We assessed the role of DHEA supplementation on pregnancy rates in women with diminished ovarian function., Design: This is a case control study of 190 women with diminished ovarian function. The study group includes 89 patients who used supplementation with 75 mg daily of oral, micronized DHEA for up to 4 months prior to entry into in vitro fertilization (IVF). The control group is composed of 101 couples who received infertility treatment, but did not use DHEA. The primary outcome was clinical pregnancy after the patient's initial visit. We developed a Cox proportional hazards model to compare the proportional hazards of pregnancy among women using DHEA with the controls group., Results: Cumulative clinical pregnancy rates were significantly higher in the study group (25 pregnancies; 28.4% vs. 11 pregnancies; 11.9%; relative hazard of pregnancy in study group (HR 3.8; 95% CI 1.2-11.8; p < 0.05)., Conclusions: DHEA treatment resulted in significantly higher cumulative pregnancy rates. These data support a beneficial effect of DHEA supplementation among women with diminished ovarian function.

Objective: To determine the prevalence of substandard antiemetic therapy among recently published trials conducted in patients with cancer who received emetogenic chemotherapy., Data Sources: A MEDLINE search was conducted (2000-July 2004) using the key words 5-HT(3) antagonists, ondansetron, granisetron, dolasetron, tropisetron, ramosetron, palonosetron, NK-1 antagonists, and aprepitant., Study Selection and Data Extraction: All antiemetic trials in patients receiving chemotherapy that were published from January 2000 to July 2004 were evaluated. Standard prophylactic antiemetic therapy was derived from contemporary antiemetic guidelines published by oncology professional organizations and expert panels. The number of patients and studies in which patients received standard and substandard antiemetic therapy was determined for both the acute and delayed phases of chemotherapy-induced nausea and vomiting (CINV). Separate determinations were made for severely and moderately emetogenic chemotherapy. The annual percentage of studies in which substandard antiemetic prophylaxis was given and the percentage of patients who received substandard prophylaxis also were determined., Data Synthesis: Fifty-six studies were reviewed, which included a total of 10 274 patients and 125 study arms. The percentage of patients who received substandard antiemetic prophylaxis was 30% (n = 3063) for acute CINV and 33% (n = 3413) for delayed CINV. The average annual percentage of studies that employed substandard prophylaxis during this time period was 54%., Conclusions: In recent antiemetic trials for CINV, the employment of substandard antiemetic therapy is common. These results raise important ethical questions regarding contemporary antiemetic trial design.

Antimicrobial agents are commonly used after hematopoietic stem cell transplant (HSCT) to prevent bacterial, viral and fungal infections. A pharmacy practice survey was undertaken to evaluate prevailing practices. The 31 centers evaluated transplanted over 3400 patients in 2001. Over half used bacterial prophylaxis; all with fluoroquinolones. A significantly higher proportion (90-100%) used fungal and viral prophylaxis. Most centers used fluconazole for fungal prophylaxis, but the dose used varied from 400 mg (the recommended dose) to 100 mg. Itraconazole and amphotericin preparations were used by some centers for allograft recipients because of their activity against aspergillosis. Most centers used brief viral prophylaxis for autograft recipients aimed at preventing HSV reactivation. Viral prophylaxis for allograft recipients was usually much more prolonged, reflecting concern over cytomegalovirus infections. Overall, there was significant deviation from recommended guidelines in many of the practices. Our survey suggests that substantial variation exists among transplant centers in their approach to antimicrobial prophylaxis after HSCT. This probably stems from the lack of definitive studies and strong recommendations in several areas, availability of newer agents that have not been adequately studied in the HSCT setting, and a desire to improve outcome before definitive studies are available for newer agents, a process that could take several years.

Predicting which patients will experience postoperative nausea and vomiting is difficult. Prophylactic antiemetic administration has been shown to reduce unplanned admission after day case surgery. In published comparative studies of antiemetic efficacy, droperidol has been considered to be the 'gold standard' against which other agents are measured. The recent withdrawal of droperidol due to reports of cardiac arrhythmias and the potential for sudden death has left a vacancy for a safe and effective antiemetic. This article explores the published literature for alternatives to droperidol as a single dose or prophylaxis in patient controlled analgesia devices.

The last decade has witnessed substantial progress in the prevention and treatment of venous thromboembolism. However, the risk of deep vein thrombosis remains high in trauma patients and those undergoing orthopaedic surgery despite use of the best available prophylaxis. Existing antithrombotics also carry a significant risk of bleeding and other adverse effects, including heparin-induced thrombocytopenia (HIT). More effective and safer anticoagulants are therefore needed. Current approaches for improving the benefit:risk ratio of antithrombotic therapy include the development of indirect thrombin inhibitors with a high anti-Xa:anti-IIa activity ratio, and the use of direct thrombin inhibitors. Novel indirect thrombin inhibitors under investigation include pentasaccharide and the heparinoid danaparoid. These agents may offer reduced bleeding risk compared with conventional therapies, but there is no evidence of greater antithrombotic efficacy. However, due to low cross-reactivity with anti-heparin-platelet factor 4 antibodies, danaparoid and pentasaccharide may prove valuable in the management of HIT. Theoretically, the antithrombotic effect of direct thrombin inhibitors may be greater than that of indirect inhibitors because direct inhibitors are not dependent on endogenous cofactors and are able to inhibit both free and clot-bound thrombin. Direct inhibitors of the active site of thrombin and recombinant variants of hirudin, originally derived from the medicinal leech, are currently under investigation. Early data on lepirudin and desirudin suggest that recombinant hirudins may have clinical applications in thromboprophylaxis for high-risk patients, acute cardiology indications and HIT.

Aims: Cardioverter-defibrillators are conventionally implanted under general anaesthesia. However, implantation under conscious sedation is being increasingly used. It has been shown that cardioverter-defibrillators can be implanted in a more pacemaker-like approach: under local anaesthesia for the surgical procedure, and with mild sedation for defibrillation threshold testing only. The aim of the present study was to compare local and general anaesthesia in defibrillation threshold testing and implantation of cardioverter-defibrillators., Methods and Results: Forty patients were assigned to two groups: in the first 20 consecutive patients the cardioverter-defibrillator was implanted under general anaesthesia (GA), and in the subsequent 20 patients under local anaesthesia (LA). There was no significant difference between the two groups in regard of age, body weight, underlying disease, left ventricular ejection fraction, and NYHA classification. The defibrillation threshold was 13.7 +/- 5.5 J under local anaesthesia versus 10.7 +/- 4.7 J under general anaesthesia (n.s.). For defibrillation threshold testing 7.9 +/- 3.6 shocks had to be applied in patients under general anaesthesia versus 6.2 +/- 1.3 shocks under local anaesthesia (n.s.). Mean heart rate, arterial oxygen saturation and mean arterial blood pressure remained stable throughout defibrillation threshold testing, irrespective of the type of anaesthesia used. The duration of the surgical procedure was 62 +/- 16 min under GA and 60 +/- 14 min under LA (n.s.), however, the entire implantation procedure was significantly longer in patients under general anaesthesia than in those under local anaesthesia (124 +/- 24 min and 97 +/- 22 min, respectively, p < 0.005). There were no complications in either group and the procedure was well tolerated. With the use of local anaesthesia the cost of anaesthesia were reduced by 72%., Conclusion: Local anaesthesia in combination with mild sedation is as safe and well tolerated as general anaesthesia in cardioverter-defibrillator implantation. Lidocaine used for local anaesthesia does not adversely affect the defibrillation threshold. Device implantation in a pacemaker-like approach results in a significant reduction in total procedure time and costs, and facilitates scheduling of the procedure.

This article describes the global results of the evaluation of a concerted action programme on quality assurance in hospitals that was executed between 1990 and 1993 in a total of 262 hospitals in 15 European countries. The programme aimed to introduce quality assurance notions into European hospitals and focused on four specific topics; record keeping, prophylactic antibiotic use in surgery, preoperative assessment and the prevention of bedsores. Evaluation took place on a national level (descriptive country reports), hospital level (questionnaire) and topic level (questionnaire and results of QA studies performed in the participating hospitals). Different situational and operational factors on national, hospital and topic level, that seem to influence the effectiveness of strategies for the implementation of quality assurance, are identified. The relative importance of these factors is discussed and supported with empirical evidence. Part of the analysis is based on quantitative data based on comparing the situation in 113 hospitals in 1990 and 1993, before and after the intervention.

Developments in anaesthesia for intracranial surgery over the past 35 years are illustrated by a comparison of personal practice in 1943-45 and in 1977-79, with some reference to techniques developed during the intervening years.

The results of a 5-year follow-up survey of the use of prophylactic antibiotics in gastrointestinal surgery in Scotland are reported. There have been significant increases in the routine use of prophylactic antibiotics during elective cholecystectomy (21% to 53% of surgeons; P less than 0.001) and appendicectomy (49% to 79% of surgeons; P less than 0.001). In addition a substantial number of surgeons used prophylactic antibiotics in selected high risk patients undergoing biliary tract surgery and gastroduodenal surgery.