Effect of levofloxacin on lithium – a pharmacokinetic study in rabbits

The aim of this study was to evaluate potential drug–drug interaction between lithium and levofloxacin. The study was conducted on New Zealand white rabbits with three groups having two subgroups each (n = 12). The first group compared the pharmacokinetic (Pk) parameters of lithium when lithium was given as a single dose (56 mg/kg) and when lithium was co‐administered with levofloxacin (35 mg/kg). The second group compared the Pk parameters of lithium when lithium was given for 6 days alone and when levofloxacin was given on the sixth day after lithium steady‐state levels were achieved. The third group compared the Pk parameters of lithium when lithium was given alone for 8 days and levofloxacin was given on days 6, 7, and 8 along with lithium. Apart from this, creatinine levels were also measured to detect nephrotoxicity effects because of this co‐administration. It was found that there was increase in lithium levels in all three groups. The increase was significant when a single dose of levofloxacin was administered with steady‐state level of lithium (C_max of lithium: 2.54 ± 0.15 vs 2.79 ± 0.12 mm , P < 0.001 and AUC_0‐α of lithium: 24.36 ± 3.68 vs 31.88 ± 4.83 mmol/mL h, P < 0.001). The increase in lithium levels was also significant when levofloxacin was coprescribed for 3 days after lithium steady‐state levels were achieved (C_max increased from 2.72 ± 0.29 to 3.96 ± 0.29 mm , P < 0.001 and AUC_0‐α increased from 27.1 ± 4.96 to 42.64 ± 4.94 mmol/mL h). Levofloxacin increases lithium levels when they are co‐administered, and this interaction might be clinically significant as they may be coprescribed.     

Refractory Hypoglycemia from Ciprofloxacin and Glyburide Interaction

Patients taking multiple medications may suffer from unpredictable and complex drug–drug interactions resulting in significant morbidity and mortality. There are few reports in the literature of hypoglycemia with concurrent administration of an oral hyperglycemic agent and a fluoroquinolone antibiotic. We present a case of a diabetic patient taking glyburide who was prescribed ciprofloxacin and developed prolonged hypoglycemia, which persisted for over 24 hours. The mechanisms by which these agents interact to produce prolonged hypoglycemia are complex and probably multifactorial. Patients stabilized on glyburide who are started on a fluoroquinolone should have their glucose levels monitored closely.     

Palpation simulator with stable haptic feedback

Background: The main difficulty in constructing palpation simulators is to compute and to generate stable and realistic haptic feedback without vibration. When a user haptically interacts with highly non-homogeneous soft tissues through a palpation simulator, a sudden change of stiffness in target tissues causes unstable interaction with the object. Material and methods: We propose a model consisting of a virtual adjustable damper and an energy measuring element. The energy measuring element gauges energy which is stored in a palpation simulator and the virtual adjustable damper dissipates the energy to achieve stable haptic interaction. Results: To investigate the haptic behavior of the proposed method, impulse and continuous inputs are provided to target tissues. If a haptic interface point meets with the hardest portion in the target tissues modeled with a conventional method, we observe unstable motion and feedback force. However, when the target tissues are modeled with the proposed method, a palpation simulator provides stable interaction without vibration. Conclusion: The proposed method overcomes a problem in conventional haptic palpation simulators where unstable force or vibration can be generated if there is a big discrepancy in material property between an element and its neighboring elements in target tissues.     

Miconazole and nystatin used as topical antifungal drugs interact equally strongly with warfarin

What is known and Objective: Medline search disclosed 10 case reports of interactions between oral anticoagulants and miconazole oral gel, but none so far between nystatin solution and anticoagulants. We report on change in anticoagulant activity with use of different topical antifungal drugs, miconazole oral gel and vaginal suppositories, and nystatin solution. Methods: We conducted a retrospective study that included 43 patients on stable anticoagulation before the introduction of topical antifungal drugs. Miconazole oral gel was prescribed for 32 patients, nystatin solution for eight patients and miconazole vaginal suppositories for three patients. Results and Discussion: Nineteen (44·2%) of the patients reported bleeding complications and some of these were severe. Fifteen of 32 who used miconazole oral gel and four of 8 of those who used nystatin solution were affected. Before use of the antifungal drugs, the mean weekly warfarin dose in the nystatin group was 14·5 mg, and after antifungal drugs, 9 mg, P = 0·038, while the mean international normalized ratio (INR) before antifungal drugs was 2·5 (range 1·9–3·5) and afterwards it was 10·6 (range 4·5–19·3), P = 0·0001. In the miconazole oral gel group the mean weekly warfarin dose was 15·7 mg, and after 10·8 mg, P = 0·008, while the mean INR before antifungal drugs was 2·44 (range 1·92–3·18) and afterwards it was 8·8 (range 4·9–16·9), P < 0·0001. What is new and Conclusion: Miconazole oral gel and topically applied nystatin solution have equally strong effects on warfarin activity and can provoke major bleeding. Prospective evaluation of this effect is called for. However, based on our results the warfarin dose adjustment appears necessary when the anticoagulant is used concomitantly with those topical antifungals.     

Aphasia and stroke therapeutic alliance measure (A-STAM): Development and preliminary psychometric evaluation

Abstract

Purpose: The therapeutic alliance, also known as the therapeutic relationship, may influence treatment process and outcome in aphasia rehabilitation; however, we currently lack a reliable tool to measure this relationship. This study aimed to develop a novel measure of the therapeutic alliance applicable to this population and provide preliminary evidence of the measure’s psychometric properties.

Method: Statements were generated from the: (1) therapeutic alliance literature, (2) qualitative interviews with stakeholders, and (3) Q methodological insights with people with aphasia (PWA) (n?=?455). A representative sample of statements was identified from the data set (n?=?57) and reviewed by expert panels (professionals and PWA), culminating in a 42-item clinician and patient version of the aphasia and stroke therapeutic alliance measure (A-STAM). Reliability and validity of both the clinician and patient versions of A-STAM were investigated with 34 Clinician-patient dyads engaging in therapy.

Result: Internal consistency and test–retest reliability were excellent for both clinician (α?=?92; ICC = 0.93) and patient versions of A-STAM (α?=?0.92; ICC = 0.97). In both versions, scores correlated highly with psychotherapeutic measures of therapeutic alliance, indicative of good construct validity (r_s = 0.75; r_s = 0.77).

Conclusion: The findings establish the preliminary reliability and validity of A-STAM and support further investigation into the measure’s psychometric properties in larger samples.     

Theory or theories? A commentary on ‘initial steps towards a theory and praxis of person–environment interaction in disability’

Purpose.?This article comments on the paper by Rene Jahiel and Marcia Joslyn Scherer elsewhere in this issue.

Methods.?This article adds theoretical constructs.

Results.?In commenting on their paper, this article makes four broad points. First, the sub-components identified by Drs. Jahiel and Scherer comprise critical factors of disability and the environment that must be taken into account when examining personal interactions with the environment. Second, as important as these factors are, operationalization of the model is hindered by a lack of mutual exclusivity between the sub-components both within and between the disability and environmental components. Third, power can be assessed in terms of the relative strength of individual functioning versus environmental functioning via a systematic appraisal of those elements essential to understanding the concept of accessibility. Finally, the demographic distinction between cohort and period trend analysis is an important consideration to take into account when assessing the time dimension, as the authors urge.     

Do all health and social care professionals interact equally: a study of interactions in multidisciplinary teams in the United Kingdom

Problems around deficits in interprofessional collaboration have been identified since the National Health Service (NHS) was introduced. It is within the context of the current policy focus on improving collaborative working that this study was undertaken. A direct observational study using the Bales' Interaction Process Analysis tool was carried out in two older persons teams to explore patterns of interaction in the multidisciplinary team meetings. Analysis revealed some key differences in the way in which different professions interacted. Occupational therapists, physiotherapists, social workers (SW) and nurses rarely asked for opinions and for orientation. The consultant (the individual in charge of the medical team) tended to have high rates for asking for orientation, giving opinions and giving orientation. Although some nurses did have high individual rates for the giving of orientation. The data from the research has highlighted that therapists, SWs and nurses are reluctance to voice their opinions in multidisciplinary teams and thus conformity may dominate its culture. It is suggested that therapists, SWs and nurses need to cite their opinions in teams more effectively if they are to be competent and committed patient-centred practitioners.     

A case of sulphasalazine potentiating the hypoprothombinemic effect of warfarin resulting in bleeding

What is known and Objective: One case report demonstrated warfarin resistance associated with sulphasalazine therapy. Our objective is to report on a case of warfarin potentiation rather than resistance, associated with sulphasalazine therapy. Case summary: The patient was taking warfarin for two mechanical heart valves and was prescribed sulphasalazine for inflammatory bowel disease. He had stable international normalized ratios (INRs) before sulphasalazine administration. Approximately 3 weeks after starting sulphasalazine, he presented to the anticoagulation clinic with bruising and an INR of 6·1. The sulphasalazine was stopped, and the warfarin was held for 3 days; then the previous dose was resumed. Three weeks later, the INR returned to a therapeutic level. What is new and Conclusion: This is the first case of sulphasalazine potentiating the effect of warfarin. Sulphasalazine may potentiate the hypoprothombinemic effect of warfarin.     

Dual Device Therapy in the Setting of Changing ICD Technology: Device-Device Interaction Revisited

This case report concerns an adverse device-device interaction between a replacement ICD and a dual chamber rate responsive pacemaker. It was observed that subtle changes in the design of sensing circuits between an older first-generation ICD and the newer third-generation ICD device led to unexpected and dramatic changes in the interactive behavior of a dual device system. The new ICD was connected to chronically implanted hardware. The sensing behavior of the newer ICD included a shorter time constant in the decay of the automatic gain control function, resulting in triple sensing of both the atrial and ventricular paced stimuli and the evoked QRS complex. Physicians should be aware of new design changes in the future so as to anticipate such interactions. In the setting of rapidly changing technology, extra caution must be exercised when choosing to implant two devices in the same patient.     

Insight into the Genetic Epidemiology of Coronary Heart Disease

The associations between candidate gene polymorphisms and coronary heart disease (CHD) are complex as a consequence of pleiotropy, variation with age, selection due to the high lethality of the disease, and interactions with other genes and with environmental factors. Identification of the gene variants that contribute to CHD appears possible; this may considerably improve our understanding of the aetiology and mechanisms of this disease. Furthermore, simultaneous analysis of several predisposing alleles may help to identify high-risk individuals.     

Inappropriate Sensing of Atrial Stimuli in Patients with Third-Generation Defibrillators and DDD Pacemakers

Although the problem of ICD sensing of paced ventricular stimuli has been resolved by incorporation of VVI pacing into current ICDs, many patients require separate DDD pacemakers. We report a problematic PM-ICD interaction: the inability to prevent sensing of paced atrial stimuli (atrial sensing) leading to double-counting in DDD-PM-requiring patients with transvenous (TV) ICDs with aggressive autogain sensing (CPI Ventak® PRxII or III). Four of eight patients receiving both transvenous DDD PMs and ICDs (CPI Endotak® lead, at the RV apex), had atrial sensing, leading to double counting, despite intraoperative testing of multiple atrial locations with an active fixation lead. Five patients had a PRxlI/III ICD, four with atrial sensing (80%), and three a PRx without atrial sensing. Patients with atrial sensing were not distinguished by any clinical or device related variable. In patients with atrial sensing (all with heart block), the PM was programmed to VDD mode. No patient has received inappropriate therapy or failed to sense VP in follow-up. In many patients with TV ICDs who require DDD pacing, no atrial position can be found without ICD sensing of atrial stimuli. While in patients with heart block this problem can be circumvented by programming to the VDD mode, in patients with sinus incompetence it may only be resolved by the combination ICD-DDD PM, currently in development.     

Effect of concomitant administration of cimetidine hydrochloride on the pharmacokinetic and safety profile of tamsulosin hydrochloride 0.4 mg in healthy subjects

Background: Tamsulosin is an α₁-adrenergic receptor antagonist that is metabolized primarily via the cytochrome P450 (CYP450) enzymes. Cimetidine hydrochloride is a histamine H₂-receptor antagonist that is known to inhibit the activity of CYP enzymes.Objective: The purpose of this nonrandomized, sequential, drug-drug interaction study was to determine whether concomitant administration of cimetidine affects the pharmacokinetic and safety profile of tamsulosin 0.4 mg in healthy subjects.Methods: In this 11-day study, 10 healthy subjects aged 21 to 38 years received a single daily dose of placebo except on study days 2 and 8, when they received tamsulosin 0.4 mg. From day 5 through day 10, subjects also received a single oral tablet of cimetidine 400 mg every 6 hours. Safety monitoring was performed throughout the study. Plasma tamsulosin concentrations were determined at regular intervals after administration of the drug on days 2 and 8, and tamsulosin pharmacokinetic parameters were tested for equivalence on these 2 days.Results: Oral clearance of tamsulosin was significantly reduced (P < 0.004), and area under the plasma concentration—time curve extrapolated to infinity (AUC_0−∞) significantly increased (P < 0.004) during concomitant administration of cimetidine. However, the observed increase in AUC_0−∞ was not expected to be clinically important since tamsulosin is well tolerated at twice the dose used in this study. Some significant changes in vital signs (ie, diastolic blood pressure <60 mm Hg) and a number of mild adverse events such as headache were observed, but the overall safety profile of tamsulosin plus cimetidine was acceptable.Conclusions: The results of this pharmacokinetic study were likely due to inhibition by cimetidine of CYP450 isozymes that catalyze tamsulosin metabolism. Although this study was conducted in young, healthy volunteers, thereby limiting the conclusions that can be drawn, the results, taken in the context of similar studies conducted in the target population, do not suggest that dose adjustment of tamsulosin is necessary in patients concurrently receiving cimetidine therapy.     

儿童语言治疗中的"互动"作用

目的观察儿童语言治疗中“互动”的作用。方法采用中国康复研究中[S-S]法语言发育迟缓评价和构音障碍评价诊断和治疗儿童语言障碍患儿90例。结果本组患儿在其原有的基础上都有不同的进步，目前正在康复治疗中。结论语言治疗“互动”方法方便、经济，可激发患儿学习言语的乐趣，达到巩固训练的目的。     

PHARMACOKINETIC INTERACTION BETWEEN NIFEDIPINE AND PROPRANOLOL

In 8 healthy volunteers, single-dose nifedipine pharmacokinetics were compared with and without the coadministration of propranolol. An elevation of the mean Cmax was found, from 73.9 +/- 14.1 when nifedipine was taken alone, to 115.7 +/- 12.1 (SE) ng/ml (P less than 0.02) when the agent was combined with propranolol. The AUC0----infinity increased as well, from 287.1 +/- 33.5 to 363.0 +/- 54.3 (SE) (micrograms.hr)/l (P less than 0.01), indicating an increase in bioavailability. Propranolol treatment did not significantly affect the nifedipine half-life (alpha or beta phase) or the estimated volume of distribution, whereas systemic clearance tended to decrease in 6 of the subjects. The most likely explanation for increased bioavailability of nifedipine when coadministered with propranolol is by a reduction of the hepatic "first-pass" clearance, as a result of changes in hepatic blood flow.     

An unusual case of clarithromycin associated ergotism

A 41-year-old woman presented to the Emergency Department complaining of a 4-day history of worsening lower leg pain, pallor, and a sensation of coolness aggravated by exertion. Evaluation revealed severe lower extremity vasospasm. She recently had been prescribed clarithromycin for “flu-like” symptoms, and for many years had been taking a caffeine-ergotamine preparation for migraine headaches. Clarithromycin is known to interfere with ergotamine metabolism. This drug interaction is often not recognized. Ergot alkaloids are commonly used for migraine headaches and have vasoconstrictive properties. In a patient with ergotamine toxicity, these vasoconstrictive properties can lead to frank ischemia. We reviewed the literature for reports of ergotamine-associated ischemia and for reports of ergotamine toxicity caused by drug-drug interaction.