Miracle-dz/UniFAR-FTUs huggingface dataset:
Sex Differences in Inappropriate Drug Use: a Register-Based Study of Over 600,000 Older People

Background: Several studies have observed a higher rate of inappropriate drug use in elderly women than in elderly men, although few have focused explicitly on sex differences. Also, educational level (a measure of socioeconomic status) has been associated with both polypharmacy and inappropriate drug use in the elderly population, which could explain sex differences in inappropriate drug use. Objective: To investigate whether sex is associated with inappropriate drug use in a large general population of older people, after adjustment for age, socioeconomic status (ie, educational level), and comorbidity (ie, number of drugs). Methods: We conducted an analysis of data on sex, age, dispensed drugs, and education for people aged 75–89 years who were registered in the Swedish Prescribed Drug Register between July and October 2005 (N = 645,429). The main outcome measures were the filling of prescriptions for anticholinergic drugs or long-acting benzodiazepines, concurrent use of 3 or more psychotropic drugs, and potentially serious drug–drug interactions. Results: Potentially inappropriate drug use was more common in women (24.6%) than in men (19.3%). More women than men were exposed to all types of inappropriate drug use, except for potentially serious drug–drug interactions. Logistic regression analysis showed that women were more likely to be exposed to potentially inappropriate drug use than were men (OR 1.24; 95% CI 1.23 to 1.26) after adjustment for age, education, and number of drugs (used as a proxy for comorbidity). In particular, female sex was highly associated with Inappropriate psychotropic use (eg, long-acting benzodiazepines: adjusted OR [ORadjusted] 1.45; 95% CI 1.42 to 1.49; >3 psychotropic drugs: QRadjusted 1.50; 95% CI 1.47 to 1.53). In contrast, women had a lower probability of potentially serious drug-drug interactions than did men (ORadjusted 0.81; 95% CI 0.80 to 0.83). Conclusions: Inappropriate drug use in the elderly should be monitored separately for women and men. Our results suggest that neither socioeconomic status nor comorbidity seem to explain sex differences in inappropriate drug use. Future research in other large study populations is needed for investigation of other explanations behind these sex differences.
Echinocandins: The Newest Class of Antifungals

Objective: To review the mechanism of action, antifungal spectrum of activity, pharmacodynamics, pharmacokinetics, clinical efficacy, and safety of the echinocandins. Data Sources: A MEDLINE search (1982–May 2009) was conducted for articles published in the English language using the key words caspofungin, micafungin, anidulafungin, and echinocandins. Study Selection and Data Extraction: Medicinal chemistry, in vitro, and animal studies, as well as human trials were reviewed for information on the pharmacodynamics, pharmacokinetics, efficacy, and safety of each echinocandin. Clinical trials were reviewed and included to compare and contrast the available echinocandins. Data Synthesis: Three echinocandin antifungal agents are currently approved for use in the US: caspofungin, micafungin, and anidulafungin. The echinocandins have a unique mechanism of action, inhibiting β-(1,3)-d-glucan synthase, an enzyme that is necessary for the synthesis of an essential component of the cell wall of several fungi. The echinocandins display fungistatic activity against Aspergillus spp. and fungicidal activity against most Candida spp. , including strains that are fluconazole-resistant. The echinocandins have been shown to be efficacious for the treatment of esophageal candidiasis, candidemia, and invasive candidiasis. In addition, caspofungin has demonstrated efficacy as empiric treatment of febrile neutropenia and salvage therapy for the treatment of invasive aspergillosis, and it is the only echinocandin approved for use in pediatric patients. Micafungin is the only echinocandin approved for use as prophylaxis against Candida infections in patients undergoing hematopoietic stem cell transplantation. Overall, resistance to echinocandins is still rare, and all agents are well tolerated, with similar adverse effect profiles and few drug–drug interactions. Conclusions: Echinocandins, the newest addition to the arsenal of antifungals, offer potential advantages over other classes of agents. Clinicians should assess their distinguishing characteristics, including route of metabolism, drug interaction profile, and approved indications for use, when determining which agent to include on a formulary.
Increasing off-time improves sleep-disordered breathing induced by vagal nerve stimulation

Vagal nerve stimulation (VNS) has been reported to adversely impact breathing in sleep. While continuous positive airway pressure is often employed to treat these patients, little data exist on the effects of adjusting various settings on VNS-induced sleep-disordered breathing. We describe a patient in whom increasing off-time caused resolution of VNSinduced arterial oxygen desaturations in sleep, which we believe is a novel observation.
Effect of a Pharmacy-Based Health Literacy Intervention and Patient Characteristics on Medication Refill Adherence in an Urban Health System

BACKGROUND Limited health literacy is associated with poor understanding of medication instructions and may be related to medication adherence. OBJECTIVE To evaluate a 3-part intervention (automated telephone reminder calls to refill prescriptions, picture prescription card, and clear health communication training for pharmacists) intended to increase refill adherence through attention to health literacy. METHODS Three pharmacies that serve a primarily indigent, minority population served as the intervention sites, and one pharmacy served as the control site. To evaluate the impact of the 6-month intervention on medication adherence, pharmacy refill data were used to calculate the cumulative medication gap (CMG), in which values close to zero indicate better adherence. The primary measure of treatment effect was a comparison of the change in refill adherence within each group, from baseline to follow-up. RESULTS A total of 173 patients were enrolled in the intervention group and 102 patients in the control group. Medication adherence was significantly different between intervention (CMG = 0.25) and control (CMG = 0.18) groups at baseline (p = 0.004). Refill adherence in the intervention group improved slightly during follow-up (CMG = 0.23), while it worsened slightly in the control group (CMG = 0.21), but the change in adherence between intervention and control groups was not significantly different (p = 0.4). Between 80% and 90% of intervention participants indicated that receiving the picture prescription and phone call interventions helped them remember when and how to take their medications and refill their prescriptions. No patient characteristics, including health literacy, were consistently associated with adherence. CONCLUSIONS Implementation of a 3-part intervention—automated telephone reminders, picture prescription card, and pharmacist communication skills training—did not significantly improve refill adherence among inner-city patients. Further study should explore whether other aspects of medication management, such as dosing or adverse events, can be improved through these types of interventions, implemented either alone or in combination.
SISCOM and FDG-PET in patients with non-lesional extratemporal epilepsy: correlation with intracranial EEG, histology, and seizure outcome

AimsTo assess the practical localising value of subtraction ictal single-photon emission computed tomography (SISCOM) coregistered with MRI and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with extratemporal epilepsy and normal MRI.MethodsWe retrospectively studied a group of 14 patients who received surgery due to intractable epilepsy and who were shown to have focal cortical dysplasia, undetected by MRI, based on histological investigation. We coregistered preoperative SISCOM and PET images with postoperative MRI and visually determined whether the SISCOM focus, PET hypometabolic area, and cerebral cortex, exhibiting prominent abnormalities on intracranial EEG, were removed completely, incompletely, or not at all. These results and histopathological findings were compared with postoperative seizure outcome.ResultsTwo patients underwent one-stage multimodal imageguided surgery and the remaining 12 underwent long-term invasive EEG. SISCOM findings were localised for all but 1 patient. FDG-PET was normal in 3 subjects, 2 of whom had favourable postsurgical outcome (Engel class I and II). Complete resection of the SISCOM focus (n=3), the area of PET hypometabolism (n=2), or the cortical regions with intracranial EEG abnormalities (n=7) were predictive of favourable postsurgical outcome. Favourable outcome was also encountered in: 4 of 8 patients with incomplete resection and 1 of 2 with no resection of the SISCOM focus; 4 of 7 patients with incomplete resection and 1 of 2 with no resection of the PET hypometabolic area; and 2 of 7 patients with incomplete resection of the area corresponding to intracranial EEG abnormality. Nocorrelation between histopathological FCD subtype and seizure outcome was observed.ConclusionComplete resection of the dysplastic cortex localised by SISCOM, FDG-PET or intracranial EEG is a reliable predictor of favourable postoperative seizure outcome in patients with non-lesional extratemporal epilepsy.
Outcome after epilepsy surgery in children with MRI-negative non-idiopathic focal epilepsies

MRI is one of the most important diagnostic tools in the presurgical evaluation of patients suffering from pharmaco-refractory focal epilepsies. Presence of a lesion on MRI influences both diagnostic classification as well as selection for surgery; however, the implications for MRI-negative cases are far from well defined for such patients. Detection of potentially epileptogenic lesions depends on the techniques applied (high-field MRI, post-processing, etc.) and the experience of the neuroradiologist. The proportion of MRI-negative patients in reported epilepsy surgery cohorts ranges from 16 to 47%. Most MRI-negative patients undergo invasive long-term EEG recordings before a final decision regarding resection is possible. Post-operative seizure freedom rates, with few exceptions, range from 40 to 50%. Selection of surgical candidates and post-operative outcomes may be improved by recent developments in structural and functional imaging techniques and multimodal approaches. This report gives an overview of outcomes after epilepsy surgery in MR-negative patients with a focus on children. Issues regarding definitions, the role of established and recently introduced diagnostic tools, and the question of how outcome might be improved in the future are discussed.
Contraceptive knowledge and practice among HIV-positive women receiving antiretroviral therapy at a district hospital in KwaZulu-Natal

Abstract Objectives: To determine the knowledge and use of contraceptives by HIV-positive women attending an ART clinic. Design: Observational descriptive cross-sectional study. Setting and subjects: Many human immunodeficiency virus (HIV)-positive South African women fall pregnant each year while receiving antiretroviral therapy (ART). In 2010, 2 056 women of childbearing age attended the ART clinic at a district hospital south of Durban. Between October 2010 and June 2011, data were collected using a validated questionnaire from 400 women on their contraceptive knowledge and use. Women over 18 years of age who consented to participate, and who had been receiving ART for more than a month, were eligible for participation in the study. Outcome measures: Contraceptive knowledge and use. Results: All participants had received counselling on male condom use. The majority of HIV-positive women receiving ART preferred the male condom as their contraception of choice. Knowledge of male condoms was excellent, but only 66% of the study group used condoms, and just over 50% used a dual method of contraception (male condoms plus another contraceptive method). While 97% of participants were knowledgeable about injectable contraception, only 40% used the latter as a form of contraception. Ninety-two per cent of the participants reported recent sexual activity, 14% had fallen pregnant while receiving ART, and 64% planned on having a child in the future. Conclusion: The low use of dual contraception was a cause for concern. Recommendations include the integration of family planning services into HIV care at all ART sites. This should promote proper fertility management for women receiving ART.
Adherence to treatment and influencing factors in a sample of Chinese epilepsy patients

AimTo assess adherence to antiepileptic drugs (AEDs) and factors associated with non-adherence in a sample of Chinese patients with epilepsy.MethodsA cross-sectional descriptive study was carried out on patients who had no change in treatment regimen over the last six months. Data on adherence to medication and related factors for each patient were gathered using a questionnaire.ResultsOf a total of 368 patients studied, 48.1% of patients were non-adherent with regards to AEDs. There were no demographic differences (based on gender, age, seizure type, and rural or urban location) between adherent and non-adherent patients. Adherence was positively and significantly correlated with duration of illness (p=0.007). The primary reason for non-adherence was forgetfulness or not having medication on hand (69.6%), followed by a negative attitude (12.8%), a bad patient-prescriber relationship (9.5%), side effects (5.4%), inability to buy drugs (1.9%), and other reasons (0.8%). ConclusionThe non-adherence of epilepsy patients is common in China. Targeted management programs and communication strategies are necessary to improve adherence to AED treatments in patients with epilepsy and avoid the clinical consequences of poor adherence.
Cognitive screening instrument use in primary care: is it changing?

Aim: To measure the frequency of cognitive screening instrument (CSI) use in referrals from primary care to a dedicated secondary care cognitive function clinic. Methods: Over a 6-month period (July–December 2013), referral letters for consecutive patients referred from primary care (n = 140) were examined for mention of CSI use. Results: Although the total number of referrals from primary care increased compared with previous cohorts, there was no significant increase in the proportion (31.4%) administered a CSI before referral. However, newer CSIs specifically designed for use in primary care were used more frequently than previously. Conclusion: There is no evidence from this study that national dementia directives are reducing the observed versus expected dementia diagnosis gap.
Early add-on treatment vs alternative monotherapy in patients with partial epilepsy.

AIM The aim of this study was to evaluate the impact of two different therapeutic strategies in patients with partial seizures who were intractable to the first prescribed antiepileptic drug (AED); alternative monotherapy vs early add-on treatment. METHODS We conducted an open, cluster-randomised, prospective, controlled trial in patients with persistent partial seizures, despite treatment with one AED, who were never administered any other AEDs. Neurologists were randomised to two strategies: in group A, an alternative monotherapy with a second AED was employed; in group B, add-on treatment with a second AED was employed. The primary outcome was the percentage of seizure-free patients during a two-month period after six months of treatment. The secondary outcomes were: (i) the percentage of patients achieving a 50% reduction in the number of seizures at six months; (ii) the quality of life based on the Quality Of Life In Epilepsy scale; and (iii) tolerability. RESULTS A total of 143 neurologists were included and randomised, and 264 patients were evaluated. At six months, the primary outcome was 51% in group A and 45% in group B (p=0.34). The percentage of patients achieving a 50% reduction in the number of seizures at six months was 76% in group A and 84% in group B (p=0.53). The quality of life and the tolerability did not significantly differ between the two groups. CONCLUSIONS Alternative monotherapy or early treatment initiation with another AED drug resulted in similar efficacy, and the side effects associated with monotherapy and combined therapies were similar, which suggests that individual susceptibility is more important than the number and burden of AEDs used.
Raltegravir Plasma Concentrations in Treatment-Experienced Patients Receiving Salvage Regimens Based on Raltegravir with and without Maraviroc Coadministration

BACKGROUND: Raltegravir and maraviroc represent new, important resources for HIV-infected patients with intolerance or resistance to other antiretroviral agents. The safety and efficacy of both drugs have been investigated, but there is no information on possible pharmacokinetic interactions between these 2 drugs in clinical practice. OBJECTIVE: To evaluate raltegravir plasma concentrations in heavily treatment-experienced patients receiving salvage regimens and explore, in a preliminary assessment, the potential influence of maraviroc coadministration and other cofactors on raltegravir trough concentrations (Ctrough). METHODS: Fifty-four HIV-infected patients with triple class (nucleoside reverse transcriptase inhibitor, nonnucleoside reverse transcriptase inhibitor, protease inhibitor) treatment experience starting raltegravir 400 mg twice daily, with (n = 11) or without (n = 43) concomitant maraviroc 300 mg twice daily, were evaluated. All regimens included at least 3 drugs of at least 2 different classes. Raltegravir plasma Ctrough, after at least 1 month of treatment, were analyzed to compare groups of patients taking raltegravir only and raltegravir plus maraviroc. Immunovirological (CD4, HIV-RNA) and clinical data after 6 months of treatment were also collected and described. RESULTS: Raltegravir plasma Ctrough showed a large variability (range <0.020-2.47 μg/mL). Median levels were similar in the 2 groups (raltegravir + maraviroc 0.104 μg/mL, range 0.025−0.826; raltegravir 0.090 μg/mL, range <0.020-2.47, p = 0.400). Detectable (>0.02 μg/mL) raltegravir concentrations were observed in all patients receiving raltegravir + maraviroc and in 74% of patients receiving raltegravir alone (p = 0.060). After 6 months of treatment, the 2 groups had similar clinical, virologic, and immunologic conditions. CONCLUSIONS: Coadministration of maraviroc does not seem to have any relevant effects on raltegravir plasma Ctrough in heavily treatment-experienced patients receiving salvage regimens. Further studies should evaluate the potential additional benefits of maraviroc coadministration in terms of virologic and immunologic response.
Interpreting Poison Center Call Volume Associated with Tramadol

Letters aresubject to review priorto acceptance. They should address areas related to pharmacypractice. research, or education. or articles recently published. Corrections of previously published material alsoare accepted. Lettersare limitedto no more thanfiveauthors. In caseswhereadverse effects or druginteractions aredescribed, the Naranjo ADRprobability scale(ClinPharmacol Ther 1981 ;30:239.45) or DIPS scale(AnnPharmacother 2007;41 :674-80.001 10.1 345/aph.1H423). respectively. should be usedto determine ! he likelihood thatthe adverse effector interaction was drug-related. •• _ •• Ohio
Possible Increase in Liver Enzymes Secondary to Atorvastatin and Black Cohosh Administration

Introduction: Since the publication of the Women's Health Initiative (WHI) trials, there has been a decline in the use of hormonal replacement therapy (HRT). The risks outweighed the benefits in the WHI trials, and therefore women are seeking alternative treatments including herbal remedies to HRT for mitigation of postmenopausal conditions. The authors report a case of drug-herb interaction between black cohosh (Cimicifuga racemosa) and atorvastatin leading to elevation in liver enzymes. Case summary: A 53-year-old woman with a past medical history significant for atypical chest pain, family history of coronary artery disease, and menopause discontinued oral HRT and started black cohosh for treatment of her menopausal symptoms. The patient also reported taking atorvastatin, aspirin, glucosamine/chondroitin, and vaginal estradiol (Vagifem ® ). Routine lab results revealed an acute elevation of her liver enzymes. At this time, additional blood tests were performed to rule out other plausible causes of acute elevation in liver enzymes, which did not reveal other etiologies. It was recommended that she discontinue the black cohosh immediately due to a potential drug-herb interaction. Following the patient's discontinuation of black cohosh, her liver enzymes decreased within 1 week and completely returned to normal within 1 month. Discussion: Several case reports have associated black cohosh with hepatotoxicity. It was reported that a commercially available formulation of black cohosh may potently inhibit human cytochrome (CYP) 3A4. Inhibition of CYP3A4 by black cohosh could possibly elevate levels of atorvastatin, causing an elevation of liver enzymes. To the authors' knowledge, they report the first case report of drug-herb interaction with use of the black cohosh and atorvastatin. Conclusion: The use of black cohosh concomitantly with atorvastatin may potentially lead to a drug-herb interaction resulting in an elevation of liver enzymes. According to the Naranjo probability scale, there was a possible drug-induced adverse event. Black cohosh should not be routinely recommended for treatment of menopausal symptoms. However, if a patient chooses to use black cohosh against medical advice, particular attention should be given to the potential CYP3A4 drug interactions.
GPs’ perceptions of the management of ADHD in primary care: a study of Wandsworth GPs

Attention-deficit hyperactivity disorder (ADHD) is a growing diagnosis in child mental health in the UK and is increasingly being treated with methylphenidate (Ritalin, Equasym, Concerta). There are, however, clinical and public controversies over the diagnosis and ‘labelling’ of ADHD as a disorder, the use of drug treatments, and a relative paucity of guidance on the initial diagnosis and referral of the disorder. General practitioners (GPs) are involved in the assessment, diagnosis and treatment of children with ADHD and in liasing with the other parties involved, such as parents, teachers and specialists. Therefore their understanding of ADHD and its treatment is important. This study explores Wandsworth (South West London) GPs‘ understanding of ADHD as a disorder and their views of its management in order to provide more precise detail about the issues concerning the management of ADHD in primary care by GPs. Qualitative information was collected by semi-structured interviews (with 13 GPs) and quantitative information by means of questionnaires (93 completed by GPs) in Wandsworth. Whilst GPs had differing views of the aetiology of ADHD, there was a consensus view about the division of responsibility in the treatment of those diagnosed with ADHD. GPs felt uncomfortable initiating the prescribing of methylphenidate and stressed the importance of ongoing specialist involvement in the management of ADHD. There was also a feeling of inadequacy in terms of the training that GPs had received. It is suggested that guidance on the initial diagnosis of ADHD is drafted for GPs and that shared care protocols are agreed between primary care and secondary care so that the ongoing division of labour in the management of ADHD is made explicit, ensuring continuity of care.