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In this paper results obtained from the parallelisation of existing 3D electromagnetic Finite Element codes within the ESPRIT HPCN project PARTEL are presented. The parallelisation procedure, based on the Bulk Synchronous Parallel approach, is outlined and the encouraging results obtained in terms of speed-up on some industrially significant test cases are described and discussed. Index terms - finite element methods, electromagnetic simulation software, parallel algorithms, high performance computing

Purpose: To explore adult community members' perspectives concerning barriers to mental health care that confront rural-dwelling youth., Methods: Group concept mapping, a participatory community-engaged research method, was used. Adult community members brainstormed and sorted statements describing barriers rural youth encounter in accessing mental health services. Point and cluster maps were created to visualize conceptual similarities between statements. Statements were rated according to their commonness and importance (1: low commonness/importance, 5: high commonness/importance)., Findings: Thirty-five adults sorted and/or rated 71 barriers facing rural youth in accessing mental health services. Seven conceptual clusters were identified: system-level barriers, knowledge and communication, youth concerns, parent/guardian concerns, parent/guardian barriers, costs and convenience, and school-level barriers. Within youth concerns, community members also identified a subcluster focused on stigma. Common and important statements related to limited after-school programs and community mental health support initiatives., Conclusions: Group concept mapping methodology provides structure for conceptualizing challenges facing rural youth in accessing mental health services. Policies should be informed by rural community concerns and priorities. After-school and support programs may align with mental health needs identified by rural communities., (© 2024 National Rural Health Association.)

Aims: Cardioversion is a very commonly performed procedure for persistent atrial fibrillation (AF). However, there is no well-defined protocol to address failed external electrical direct current cardioversion. The aim of the study is to test the efficacy of a pre-defined stepwise cardioversion protocol for patients with persistent AF of ≤12 months. Success was the achievement of sinus rhythm., Methods and Results: The study population included patients with persistent AF of ≤12 months duration requiring rhythm management. Patients were offered cardioversion using a pre-defined stepwise protocol using different electrode placement locations, applying compression at end of expiration, and higher energy delivered simultaneously through two defibrillators. : A total of 414 patients were included in the study, of which 362 (87.4%) required a single successful cardioversion. The remaining 52 (12.5%) patients required additional cardioversion attempts using the stepwise cardioversion protocol with an overall success rate of 99.3%. Two simultaneous defibrillators were required in 14 patients (3.4%). Patients with multiple cardioversions (13.5%) experienced more local skin irritation and pain compared with patients with single cardioversion (13.5% vs. 3.5%, P = 0.004). The predictor for the need for multiple cardioversion attempts is high body mass index, while high transthoracic impedance is associated with failed cardioversion. No major complications were observed during the study., Conclusion: The stepwise cardioversion protocol has a high success rate of >99% and can be safely performed in outpatient or inpatient settings., Competing Interests: Conflict of interest: All authors declare that they have no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: The benefits of unsupervised exercise programmes in obstructive lung disease are unclear. The aim of this systematic review was to synthesise evidence regarding the efficacy of unsupervised exercise versus non-exercise-based usual care in patients with obstructive lung disease., Methods: Electronic databases (MEDLINE, CINAHL, Embase, Allied and Complementary Medicine Database, Web of Science, Cochrane Central Register of Controlled Trials and Physiotherapy Evidence Database) and trial registers (ClinicalTrials.gov, Current Controlled Trials, UK Clinical Trials Gateway and WHO International Clinical Trials Registry Platform) were searched from inception to April 2020 for randomised trials comparing unsupervised exercise programmes with non-exercise-based usual care in adults with chronic obstructive pulmonary disease (COPD), non-cystic fibrosis bronchiectasis or asthma. Primary outcomes were exercise capacity, quality of life, mortality, exacerbations and respiratory cause hospitalisations., Results: Sixteen trials (13 COPD, 2 asthma, 1 chronic bronchitis: 1184 patients) met the inclusion criteria. Only data on COPD populations were available for meta-analysis. Unsupervised exercise resulted in a statistically but not clinically significant improvement in the 6-Minute Walk Test (n=5, MD=22.0 m, 95% CI 4.4 to 39.6 m, p=0.01). However, unsupervised exercise did lead to statistically significant and clinically meaningful improvements in St. George's Respiratory Questionnaire (n=4, MD=-11.8 points, 95% CI -21.2 to -2.3 points, p=0.01) and Chronic Respiratory Disease Questionnaire domains (dyspnoea: n=4, MD=0.5 points, 95% CI 0.1 to 0.8 points, p<0.01; fatigue: n=4, MD=0.7 points, 95% CI 0.4 to 1.0 points, p<0.01; emotion: n=4, MD=0.5 points, 95% CI 0.2 to 0.7 points, p<0.01; mastery: unable to perform meta-analysis) compared with non-exercise-based usual care., Discussion: This review demonstrates clinical benefits of unsupervised exercise interventions on health-related quality of life in patients with COPD. High-quality randomised trials are needed to examine the effectiveness of prescription methods., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: When patients with implantable cardioverter defibrillators (ICD) develop symptomatic atrial fibrillation (AF), external direct current cardioversion (EDCCV), as well as internal cardioversion using their ICD, are the options available. It is currently unknown which of these two methods are more effective. We compared the effectiveness of EDCCV versus internal cardioversion to terminate AF in patients with a single-coil ICD., Methods: This randomized controlled trial (clinicaltrial.gov NCT03164395) enrolled consecutive patients with a single-coil ICD that presented with symptomatic AF of less than 1-year duration. They received either the maximum energy internal shock through the ICD or an EDCCV using transcutaneous pads of 200 J. The primary endpoint was a successful conversion to sinus rhythm after one shock. Crossover was permitted if the first shock was unsuccessful., Results: Thirty-one patients were enrolled in the study, including 16 in the internal ICD cardioversion group. The study included patients with a mean age of 59.5 ± 16.0 years, 41.9% females, median AF duration 1 month (interquartile range 1-3), 45.2% non-ischemic cardiomyopathies, mean EF 28.6 ± 16.0%, and 45.2% biventricular ICD. There were no significant differences in baseline clinical characteristics between the two groups. In the internal cardioversion group, 5/16 patients (31.3%) met the primary endpoint versus 14/15 (93.3%) in the EDCCV group, p < 0.001. All patients that failed the first shock were subsequently cardioverted externally., Conclusion: Among patients with a single-coil ICD and symptomatic AF of less than 1 year, external direct current cardioversion is much more effective than internal shock through the ICD.

Purpose: Catheter ablation (CA) is an effective treatment for atrial fibrillation (AF). The differences in complication rates and outcomes between women and men remain poorly studied. We aimed to study the sex differences in morbidity and mortality associated with CA in AF., Methods: Using weighted sampling from the National Inpatient Sample database, women and men with a primary diagnosis of AF and a primary procedure of CA (2004-2013) were identified. We compared the following outcomes based on the sex: (1) major complications [post-procedure transfusion, cardiac drain or surgery, pulmonary embolism, cerebrovascular accident, major cardiac events, kidney failure requiring dialysis, and sepsis], (2) overall complications (minor and/or major complications), and (3) in-hospital mortality., Results: Among 85,977 patients who underwent CA for AF, 27821 (32.4%) were women. Overall complications were more frequent among women versus among men (12.4% versus 9.0%; p < 0.001), as well as major complications (4.7% versus 2.7%; p < 0.001). However, there was no difference in mortality (0.3% versus 0.2%; p = 0.22). After adjusting for other factors, women were more likely than men to have major complication (odds ratio 1.48, 95% CI 1.21-1.82; p < 0.001). Prior CABG was associated with lower risk of major complications in both sexes (odds ratio in the overall cohort 0.27, 95% CI 0.12-0.61; p = 0.002), mostly driven by the reduction in tamponade and pericardial drain., Conclusions: Among patients who underwent catheter ablation for AF, the female sex was associated with higher rate of complications compared to male but no difference in mortality. Prior CABG was associated with a significant reduction of major complications in both sexes.

Background: Subcutaneous implantable cardioverter defibrillators (S-ICDs) have gained increasing popularity because of certain advantages over transvenous ICDs. However, while conventional ICDs require a single surgical incision to implant, S-ICDS need two or three incisions, making them less appealing., Objective: This study sought out to investigate the feasibility of using a single-incision technique to implant S-ICDs., Methods: Patients qualifying for S-ICDs were considered for a single incision. A single incision is performed by making a left inframammary incision and then the subcutaneous tissue is dissected medially toward the lower sternum. Two sutures are placed in the fascia in the xiphoid area to anchor the lead and a tunneling tool is used to dissect the tissue to place the lead parallel to the sternum. Then subcutaneous tissues are dissected down the lateral chest wall over the muscle fascia to create the pulse generator pocket in the vicinity of the fifth and sixth intercostal spaces and near the mid-axillary line., Results: Eleven patients (six males and five females) successfully underwent S-ICD implantation with a single incision without acute complications (64% for primary prevention). The mean age is 47.4 ± 15.8 years. There were no lead dislodgements, inappropriate shocks, or any other issues during a median follow-up of 10 months (interquartile range 5-17). One patient had a successful appropriate shock for ventricular fibrillation about one year after device implant., Conclusions: A single incision for subcutaneous ICDs is feasible and safe in our early experience., (© 2018 Wiley Periodicals, Inc.)

Catheter ablation (CA) is an effective treatment for ventricular arrhythmias (VA), with a potential for complications. The presence of structural heart disease (SHD) is associated with a higher complication rate although there is no data comparing CA of VA between patients with SHD and those without. We aimed to compare trends, morbidity, and mortality associated with real world practice of CA for VA (ventricular tachycardia and premature ventricular contraction) based on the presence of SHD. Using weighted sampling in the National Inpatient Sample database, we collected and compared characteristics and outcomes of patients with or without SHD that underwent CA of VA. Among 34,907 patients that underwent CA for VA (1999-2013), 18,014 (51.6%) had SHD. Major and all complications occurred among 1,135/18,014 (6.3%) and 2139/18,014 (11.9%) patients with SHD respectively compared with 355/16,893 (2.1%) and 739/16,893 (4.4%) for patients without SHD, p < 0.001 for both comparisons. Furthermore, 452/18,014 (2.51%) with SHD died versus 20/16,893 (0.12%) without SHD, p < 0.001. Heart failure was associated with an odds ratio (OR) of 3.09 for major complications (95%CI: 1.53-6.27, p = 0.002) for patients with SHD while coronary artery disease OR for major complications was 2.47 (95%CI: 1.44-4.23, p = 0.001) for patients without SHD. There was a significant increase in major complications over the 15-year study period in patients with SHD, p < 0.001. In conclusion, the presence of SHD during CA for VA increased the complication rate of major and any complications by approximately threefold for both and the hospital mortality by >20-fold compared with patients without SHD., (Copyright © 2018. Published by Elsevier Inc.)

Background: Ablation is an effective treatment for atrioventricular nodal reentrant tachycardia (AVNRT). The occurrence of junctional ectopic rhythm (JER), including junctional ectopic tachycardia, following AVNRT ablation has been described as an extremely rare phenomenon, but may be underestimated. We aimed to determine the incidence of JER following AVNRT ablation within our institution, as well as that reported in the literature via an extensive review., Methods: We reviewed our adult ablation institutional experience for the occurrence of JER after AVNRT ablation from 2009 to 2016. Additionally, we conducted an extensive literature search using different databases looking for AVNRT ablation case series. The individually reported complications of these studies were reviewed, with a primary endpoint defined as the occurrence of JER shortly after AVNRT ablation. The study was approved by our institutional review board., Results: Our institutional data revealed 6/126 patients (prevalence 4.8%) developed non-preexisting JER post-AVNRT ablation. Four patients were asymptomatic. Two patients had persistent symptoms lasting over a year, with one patient requiring repeat ablation. The literature review included 149 adult and pediatric studies. There were three cases of reported JER, out of a total of 37,541 patients (31,768 adults and 5,773 pediatric; prevalence 0.008%). The three JER patients were pediatric, and all required further therapeutic intervention., Conclusion: JER might be an underreported complication of AVNRT ablation. It seems most often to be transient and self-limited, occurring days to weeks after ablation, but may also be debilitating, requiring more aggressive management., (© 2017 Wiley Periodicals, Inc.)

Left ventricular thrombus (LVT) formation usually necessitates short term anticoagulation for thrombus resolution and to prevent embolic events. Historically, vitamin K antagonist therapy has been the treatment of choice. However, with the advent of direct acting anticoagulants, their role in the management of LVT is not clear. Patients were included if they had received rivaroxaban or apixaban for more than 1 day for LVT documented on imaging. The primary objective was resolution of LVT at 3 months based on assessment by an independent cardiologist review of initial and subsequent imaging results. The principle safety objective was to assess major or clinically relevant non-major bleeding using GUSTO, TIMI, and BARC bleeding criteria. During the 2-year study period seven patients were treated with rivaroxaban and three with apixaban. Two patients who had received apixaban and one on rivaroxaban were lost to follow up. In those with an initial and follow-up ECHO (n = 6) the median time to follow up imaging was 214 (IQR 33-414) days and complete LVT resolution was observed in 83% of patients. One patient on rivaroxaban had a bleeding events that was minimal (TIMI), Type 2 (BARC), or classified as mild (GUSTO) due to pulmonary hemorrhage. In those deemed not to be a candidate for vitamin K antagonist the use of rivaroxaban or apixaban may be a considered in the treatment of LVT. Further research in this area is needed to assess the efficacy and safety of using FXAI for treatment of LVT.

Objectives: We evaluated an intervention combining policy training and technical assistance for childcare teachers with a nutrition education curriculum to improve (1) the knowledge and self-efficacy of childcare teachers in implementing obesity prevention policies and practices, (2) the quantity and quality of nutrition and physical activity education, and (3) the childcare wellness environment., Methods: Thirteen teachers and 8 administrators (2 of whom were also teachers) from 8 childcare programs in Clarke County, Georgia, participated in the Healthy Child Care Georgia intervention during June-October 2015. The intervention included (1) training and technical assistance on obesity prevention policies, systems, and practices and (2) direct education by teachers using the Eat Healthy, Be Active curriculum. We assessed changes in program wellness policy adoption and teacher knowledge and self-efficacy from pre- to post-intervention through self-report questionnaires, interviews, and focus groups., Results: Teachers' knowledge scores (maximum score = 100) rose significantly from a mean (SD) pre-intervention of 67.1 (14.6) to post-intervention of 83.2 (14.3) ( P < .001). The mean score for "teaching nutrition and activity to children" (maximum score = 105) rose significantly from 86.9 (8.2) to 93.5 (5.2) ( P = .011) and for "modeling and supporting children" (maximum score = 63) from 55.8 (5.1) to 59.5 (4.5) ( P = .015). The mean (SD) scores for breastfeeding and infant feeding policy/practice adoption (maximum score = 6) increased significantly from 2.5 (1.8) to 3.7 (1.9) ( P = .043) and for nutrition education policy/practice adoption (maximum score = 4) from 2.0 (1.3) to 3.3 (1.4) ( P = .019). The combined approach enhanced classroom nutrition education and improved the adoption of best practices., Conclusion: Future studies should examine the effects of using a combined approach to promote nutrition and physical activity policies and practices in the early care and education setting.

Background: Dormant conduction unmasked by adenosine predicts clinical recurrences of cavotricuspid isthmus (CTI) dependent atrial flutter following catheter ablation. Conventional practice involves a waiting period of 20 to 30 minutes after achievement of a bidirectional line of block (BDB) to monitor for recovery of conduction., Objective: Assess whether abolition of dormant conduction with adenosine immediately after CTI ablation and BDB can predict the lack of CTI conduction recovery during the following 30 minutes., Methods: Consecutive patients undergoing catheter ablation for CTI-dependent atrial flutter were studied. Following the completion of CTI ablation and documentation of BDB, adenosine (≥12 mg IV) was administered immediately. In cases of dormant conduction, the CTI was ablated again until its abolition. After the achievement of BDB without dormant conduction, spontaneous CTI reconnection during the following 30 minutes and dormant conduction with adenosine at 30 minutes were evaluated., Results: A CTI block was achieved in 171 patients. Nine patients (5.3%) had dormant conduction across the CTI immediately after ablation and BDB, and required further ablation. Two patients (1.2%) had subsequent spontaneous time-dependent reconnection within 30 minutes. Two other patients (1.2%) developed late dormant conduction with adenosine at 30 minutes. All 4 patients underwent further ablation., Conclusion: A negative adenosine challenge immediately after CTI ablation with bidirectional block, or after abolition of dormant conduction with further ablation, strongly predicted the absence of subsequent spontaneous reconnection within 30 minutes. Based on these results, the conventional waiting period is unnecessary in 97.6% patients without dormant conduction after CTI-dependent flutter ablation., (© 2017 Wiley Periodicals, Inc.)

Background: Implantable cardioverter-defibrillator (ICD) shocks are potentially associated with myocardial injury, altered hemodynamics, apoptosis, and inflammatory signaling. Their precise cellular impact can be explored after defibrillation testing (DFT) via biomarkers. We evaluated changes in biomarkers after ICD shocks during DFT., Methods: We prospectively enrolled outpatients presenting for first implantation of a cardiac device. Biomarkers indicative of myocardial injury, inflammation, and apoptosis were measured before and after implantation, and compared between patients receiving DFT (DFT+) to those not (DFT-)., Results: Sixty-three patients were enrolled, 40 in the DFT+ group and 23 in the DFT- group. Average levels of troponin I, hsCRP, Calprotectin, N-terminal pro B-type natriuretic peptide (NTproBNP), and sFas increased by >50% after cardiac device implantation compared to baseline. Increase in troponin never exceeded the 50-fold upper limit of normal (2 ng/mL). Troponin trended higher in the DFT+ group at 8 hours (median 0.18 ng/mL, interquartile range [IQR] 0.11-0.48) versus the DFT- group (0.10 ng/mL, IQR 0.06-0.28, P = 0.0501); NTproBNP had a similar trend (P = 0.0581). sFas significantly increased in the DFT+ group from baseline (median 4663 pg/mL, IQR 2908-5679) to 24 hours (5039 pg/mL, IQR 3274-6261; P = 0.0338) but not in the DFT- group (P = 0.4705)., Conclusion: DFT testing is associated with acutely increased plasma levels of troponin and sFas, a biomarker of apoptosis, along with a trend toward higher NTproBNP., (© 2017 Wiley Periodicals, Inc.)

Percutaneous drainage of the peritoneal cavity has been recently evaluated for the treatment of perforated viscous in the very low birth weight (VLBW) neonate and percutaneous decompression for abdominal compartment syndrome (ACS) has been studied in older patient populations. This is the first reported case of using this technique to treat ACS in a VLBW neonate.

Developing temperature fields in frozen cheese sauce undergoing microwave heating were simulated and measured. Two scenarios were investigated: a centric and offset placement on the rotating turntable. Numerical modeling was performed using a dedicated electromagnetic Finite Difference Time Domain (FDTD) module that was two-way coupled to the PHYSICA multiphysics package. Two meshes were used: the food material and container were meshed for the heat transfer and the microwave oven cavity and waveguide were meshed for the microwave field. Power densities obtained on the structured FDTD mesh were mapped onto the unstructured finite volume method mesh for each time-step/turntable position. On heating for each specified time-step the temperature field was mapped back onto the FDTD mesh and the electromagnetic properties were updated accordingly. Changes in thermal/electric properties associated with the phase transition were fully accounted for as well as heat losses from product to cavity. Detailed comparisons were carried out for the centric and offset placements, comparing experimental temperature profiles during microwave thawing with those obtained by numerical simulation.

Delirium has been associated with a high risk of mortality in medical patients. Despite the high incidence of delirium in patients who undergo hemapoietic stem cell transplantation (HSCT), delirium as a risk factor for death has not been examined in this population. Thirty adult patients undergoing HSCT who were admitted to the University of Iowa Blood and Marrow Transplantation Program inpatient unit were assessed prospectively from 1 to 2 weeks before transplantation, throughout their inpatient stay, and at 100 days after transplantation. The Delirium Rating Scale and Memorial Delirium Assessment Scale were used twice weekly during the inpatient period to assess delirium severity and occurence. Patients' self-reports of medical history, computerized medical records, and neuropsychological and psychiatric assessments were used to identify pretransplantation risk factors. The incidence of delirium (Delirium Rating Scale score >12 or Memorial Delirium Assessment Scale score >or=8) was 43% and occurred with highest frequency in the first 2 weeks after transplantion. The presence of delirium at any point during hospitalization after transplantation and transplant type (allogeneic) were highly predictive of mortality (p < .0005; odds ratios, 14.0 and 14.4). In conclusion, this study highlights the importance of monitoring for delirium during the acute recovery period after transplantation and suggests that early or even prophylactic treatment for delirium should be studied. Studies to determine the factors that connect delerium soon after transplantation to mortality are highly warranted.

Percutaneous absorption and model membrane variations of melatonin (MT) in aqueous-based propylene glycol and 2-hydroxypropyl-beta-cyclodextrin vehicles were investigated. The excised hairless mouse skin (HMS) and two synthetic ethylene vinyl acetate (EVA) and microporous polyethylene (MPE) were selected as a model membrane. The solubility of MT was determined by phase equilibrium study. The vertical Franz type cell was used for diffusion study. The concentration of MT was determined using reverse phase HPLC system. The MT solubility was the highest in a mixture of PG and 2-HP beta CD. The percutaneous absorption of MT through excised HMS increased as the solubility increased. However, the permeability coefficient decreased and then slightly increased in a mixture of PG and 2-HP beta CD. On the other hand, both flux and permeability coefficient through EVA membrane decreased as the solubility increased. No MT was detected over 12 h after starting diffusion through MPE membrane. The flux of MT was dependent on the type of membrane selected. Flux of MT was greatest in excised HMS followed by EVA and MPE membrane. Flux of MT through EVA membrane was 5-20 times lower when compared to excised HMS. Interestingly, volumes of donor phase when MPE membrane was used, significantly increased during the study period. The HMS might be applicable to expect plasma concentration of MT in human subjects based on flux and pharmacokinetic parameters as studied previously. The current studies may be applied to deliver MT transdermally using aqueous-based vehicles and to fabricate MT dosage forms.

The physicochemical properties of melatonin (MT) in propylene glycol (PG) and 2-hydroxypropyl-beta-cyclodextrin (2-HPbetaCD) vehicles were characterized. MT was endothermally decomposed as determined by differential scanning calorimetry (DSC). Melting point and heat of fusion obtained were 116.9+/-0.24 degrees C and 7249+/-217 cal/mol, respectively. MT as received from a manufacture was very pure, at least 99.9%. The solubility of MT in PG solution increased slowly until reaching 40% PG and then steeply increased. Solubility of MT increased linearly as concentration of 2-HPbetaCD without PG increased (R(2)=0.993). MT solubility in the mixtures of PG and 2-HPbetaCD also increased linearly but was less than the sum of its solubility in 2-HPbetaCD and PG individually. The MT solubility was low in water, simulated gastric or intestinal fluid but the highest in the mixture of PG (40 v/v%) and 2-HPbetaCD (30 w/v%) although efficiency of MT solubilization in 2-HPbetaCD decreased as the concentration of PG increased. MT was degraded in a fashion of the first order kinetics (r(2)>0.90). MT was unstable in strong acidic solution (HCl-NaCl buffer, pH 1.4) but relatively stable in other pH values of 4 approximately 10 at 70 degrees C. In HCl-NaCl buffer, MT in 10% PG was more quickly degraded and then slowed down at a higher concentration. However, the degradation rate constant of MT in 2-HPbetaCD was not changed significantly when compared to the water. The current studies can be applied to the dosage formulations for the purpose of enhancing percutaneous absorption or bioavailability of MT.

The three different batches of an oral sustained release melatonin (MT) delivery system were prepared by aqueous-based fluid-bed coating of the sugar spheres for the evaluation ofin vitro release characteristics and plasma concentration profiles in human subjects. The MT contents in 20% coated sugar spheres of three batches (B1, B2 and B3) were 3.3+/-0.08, 2.4+/-0.1 and 2.5+/-0.13 mg per gram of coated sugar spheres, respectively. The release profiles of three different batches had a very similar fashion. However, the release half-lives (T(50%)) of MT from B1, B2 and B3 was 3.70+/-0.2, 5.2+/-0.2 and 4.9+/-0.07h, respectively. Plasma concentration profiles of sustained release 0.2mg melatonin-loaded sugar spheres containing 10% immediate release melatonin in gelatin capsules (B1 and B2) were then evaluated in human subjects. Thein vivo plasma concentration profiles of the two batches (B1 and B2) were very similar each other and located between the physiological endogenous ranges. The time to reach the peak concentration (T(max)) was more advanced in case of B1 when compared to B2. However, there was no statistically significant difference in the maximum concentration (C(max)) and the area under the curve (AUC) between B1 and B2. The AUC of melatonin-loaded sugar spheres containing 10% and 20% immediate release MT in human subjects had a good linearity between dose and AUC, regardless of the fraction of immediate release MT, indicating the first order elimination process of MT within these doses. The current oral sustained release MT delivery system may be utilized to treat circadian rhythm disorders if it is proven to be more clinically useful when compared to immediate release MT.

A transdermal delivery device (TDD)1 was applied to four human subjects to investigate whether melatonin (MT) could penetrate through human skin. The TDD (total surface area of 3.80 cm2) was applied to the forearm of each subject. Plasma MT concentrations increased above baseline in approximately 2-4 hours, although steady state was not achieved in the 8-hour study period. Intersubject variation of plasma MT among four subjects was noted. Urinary excretion of 6-sulphatoxymelatonin (6-STMT), a major metabolite of MT in humans, increased as plasma MT concentrations increased. Cumulative amounts of urinary 6-STMT increased over a 6-hour period when the TDD was applied and were three times greater than in controls. The urinary excretion rate of 6-STMT was statistically correlated with plasma MT concentration among subjects (r2 = 0.77). These data suggest that the urinary excretion rate of 6-STMT can be used as an index of MT plasma concentrations in human subjects. Although an intersubject variability in both plasma MT concentration and urinary excretion rate of 6-STMT was noted, it was evident that MT can be delivered transdermally in human subjects.

The incidence and cost of drug waste in a long-term care facility (LTCF) were compared for a unit dose and a traditional (30-day card) distribution system. Drug records for 74 LTCF patients were reviewed retrospectively to determine the number of drugs ordered and doses dispensed during a four-month period via a unit dose distribution system. Based on the same drug orders, the number of doses that would have been dispensed with a 30-day card system was projected. The drug costs and wastage costs for the two distribution systems were compared. The mean number of drugs ordered per patient was 5.86. differences between the two systems, mean number of doses dispensed per order, and their average cost per drug order were not statistically significant (p less than 0.05). Of the total number of doses that would have been dispensed via the 30-day card system, 12.98% would have been wasted, representing 13.07% of the total drug costs. Because the unit dose system eliminates the drug wastage associated with a 30-day card system, it has a positive impact on LTCF drug costs.

Stability of oral liquid forms of cimetidine hydrochloride, furosemide, and theophylline repackaged in polypropylene oral syringes and glass vials was assessed. Commercial preparations of each product were used; 2-ml quantities were placed in both types of container and stored at 4, 25, 44, 60, and 76 degrees C. Six samples from each container type at each temperature were tested at various times. Stability was defined as no greater than 10% loss of labeled potency. Assay was by high-performance liquid chromatography. All three drugs retained more than 90% of label claim in both types of containers after 180 days at 4 degrees C and 25 degrees C. For cimetidine hydrochloride and furosemide at these temperatures, there was no significant difference in concentration by container type; at the higher storage temperatures, the degradation rate in polypropylene syringes was significantly faster. For theophylline, loss of volume of 10% or greater occurred after 60 days at temperatures greater than 25 degrees C for both container types. Drug loss at higher temperatures was attributed to precipitation of theophylline out of the elixir rather than chemical degradation. Oral liquid cimetidine hydrochloride, furosemide, and theophylline repackaged in either polypropylene oral syringes or glass vials can be stored at 4 degrees C and 25 degrees C for 180 days with less than 10% loss of potency.

Pharmacy services encompass more than dispensing medications. However, traditional pharmacy reimbursement methods are based heavily on the dispensing of medications--i.e., on selling a commodity rather than providing a service. The capitation reimbursement method described provides the pharmacist with a means of reimbursement for professional services independent of the number of medications consumed by the patient. The pharmacist is thus free to encourage reductions in the consumption of medications without incurring an economic penalty. Such reductions are not only of potential benefit to the patient but can also reduce the workload of the nursing home staff. The feasibility of this capitation system is demonstrated by the successful pharmacy practice described.

A rapid, sensitive method for the high-performance liquid chromatographic determination of propranolol in peritoneal dialysis fluid is described. An extraction step is replaced by the use of a C18 Sep-Pak cartridge for sample preparation. The procedure offers an acceptable alternative to sample extraction and will allow for pharmacokinetic studies of propranolol in patients undergoing peritoneal dialysis for chronic renal failure.

Ibuprofen is a non-steroidal anti-inflammatory agent which is extensively metabolized in both man and the rat. Cimetidine is a well known H2 antagonist which is known to inhibit microsomal enzyme drug metabolism. The influence of cimetidine on the disposition of ibuprofen was studied in Sprague-Dawley rats. Pretreatment with cimetidine was found to increase both the rate and extent of absorption of ibuprofen. Cimetidine treatment also inhibited acidification of gastric fluid. Pretreatment with SKF525A increased ibuprofen half-life but not absorption. Additional studies are necessary to determine the effect of cimetidine on the half-life and absorption of ibuprofen in man.

The stability of solutions of levodopa 1 mg/mL in 5% dextrose injection adjusted to pH 5 or 6 and stored at one of three temperatures was determined. Solutions were adjusted to pH 5 or 6 with sodium acetate injection or sodium phosphate injection, respectively. Three samples of solution adjusted to pH 5 were stored at each of three temperatures (4, 25, and 45 degrees C), and three samples of solution adjusted to pH 6 were stored at 25 degrees C. Samples were assayed for levodopa concentration by high-performance liquid chromatography at various times during the 21-day study period. All solutions maintained at least 90% of the initial concentration of levodopa for seven days. Discoloration of all solutions except those stored at 4 degrees C was noted at some point during the study period; solutions stored at 45 degrees C began to darken within 12 hours. The pH values of the solutions did not change during the study period. Under the conditions studied, solutions of levodopa 1 mg/mL in 5% dextrose injection adjusted to pH 5 or 6 are stable for seven days. Slight degradation of levodopa may cause a brownish-black discoloration of the admixtures.