T. McGuire

Minimal interventions to decrease long-term use of benzodiazepines in primary care: a systematic review and meta-analysis

BACKGROUND Long-term use of benzodiazepines (BZDs) is common. Not only is such use ineffective, but it also has several risks in addition to dependence, and remains a significant problem among the older population. AIM To systematically review randomised controlled trials that evaluate the effectiveness of minimal interventions to reduce the long-term use of BZDs in primary care. DESIGN AND SETTING Systematic review and meta-analysis of randomised controlled trials in UK general practices. METHOD Cochrane Central, MEDLINE, and Embase (1967-2010) were searched for trials of minimal interventions (such as a single letter or one consultation from a GP) for patients in primary care with long-term (>3 months) BZD use. Pooled risk differences were calculated with 95% confidence intervals. RESULTS From 646 potentially relevant abstracts, three studies (615 patients) met all the inclusion criteria. The pooled risk ratio showed a significant reduction/cessation in BZD consumption in the minimal intervention groups compared to usual care (risk ratio [RR] = 2.04, 95% confidence interval [CI] = 1.5 to 2.8, [corrected] P<0.001; RR = 2.4, 95% CI = 1.3 to 4.3, P = 0.008) respectively. Two studies also reported a significant proportional reduction in consumption of BZD from baseline to 6 months in intervention groups compared to the control group. The secondary outcome of general health status was measured in two studies; both showed a significant improvement in the intervention group. CONCLUSION A brief intervention in the form of either a letter or a single consultation by GPs, for long-term users of BZD, is an effective and efficient strategy to decrease or stop their medication, without causing adverse consequences.

Common harms from amoxicillin: a systematic review and meta-analysis of randomized placebo-controlled trials for any indication

Background: When prescribing antibiotics for common indications, clinicians need information about both harms and benefits, information that is currently available only from observational studies. We quantified the common harms of the most frequently prescribed antibiotic, amoxicillin, from randomized placebo-controlled trials. Methods: For this systematic review, we searched MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, without language restriction, for any randomized, participant-blinded, placebo-controlled trials of amoxicillin or amoxicillin–clavulanic acid for any indication, in any setting. Our main outcome was any reported adverse event. Results: Of 730 studies identified, we included 45 trials: 27 involving amoxicillin, 17 involving amoxicillin–clavulanic acid and 1 involving both. The indications for antibiotic therapy were variable. The risk of bias was low, although only 25 trials provided data suitable for assessment of harms, which suggested under-reporting. Diarrhea was attributed to amoxicillin only in the form of amoxicillin–clavulanic acid (Peto odds ratio [OR] 3.30, 95% confidence interval [CI] 2.23–4.87). The OR for candidiasis (3 trials) was significantly higher (OR 7.77, 95% CI 2.23–27.11). Rashes, nausea, itching, vomiting and abnormal results on liver function tests were not significantly increased. The results were not altered by sensitivity analyses, nor did funnel plots suggest publication bias. The number of courses of antibiotics needed to harm was 10 (95% CI 6–17) for diarrhea with amoxicillin–clavulanic acid and 27 (95% CI 24–42) for candidiasis with amoxicillin (with or without clavulanic acid). Interpretation: Diarrhea was caused by use of amoxicillin–clavulanic acid, and candidiasis was caused by both amoxicillin and amoxicillin–clavulanic acid. Harms were poorly reported in most trials, and their true incidence may have been higher than reported. Nevertheless, these rates of common harms associated with amoxicillin therapy may inform decisions by helping clinicians to balance harms against benefits.

The emerging role of metformin in gestational diabetes mellitus.

Metformin use during pregnancy is controversial and there is disparity in the acceptance of metformin treatment in women with gestational diabetes mellitus (GDM) in Australia. Despite short term maternal and neonatal safety measures, the placental transfer of metformin during GDM treatment and the absence of long‐term safety data in offspring has regulators and prescribers cautious about its use. To determine the current role in GDM management, this literature review describes the physiological changes that occur in GDM and other forms of diabetes in pregnancy (DIP) and international changes in guidelines for GDM diagnosis. Management options are considered, with a focus on the evolving evidence for metformin, its mechanism of action, the maternal, foetal and neonatal outcomes associated with its use and benefit vs risk when compared with the current gold standard, insulin. Investigation reveals a favourable balance of evidence to support the safety and long‐term benefits, to mother and child, of using metformin as an alternate to insulin for treatment of GDM. Recent findings of the gastrointestinal‐directed action of metformin are at least as important as the hepatic effect and the availability of a novel delayed‐release metformin dose form to exploit this new information provides a product and therapeutic strategy ideally suited to the use of metformin in GDM.

Predictors of Safety-Related Enquiries about Psychotropic Medication in Young People and Families Accessing a Medicines Information Service

BACKGROUND Many consumers express concerns about the safety of psychotropic medication for young people. Despite the increased use of psychotropic medication in children and adolescents, few studies have examined information needs of this group and predictors of safety-related concerns. METHODS This study was conducted within a national, consumer-based medicines information service. Between September, 2002, and December, 2005, all calls relating to use of psychotropic medications in children and adolescents were identified and reviewed. Information extracted included call characteristics, reason for calling, prior information, and medication details. Calls related to safety were compared to calls about non-safety-related issues. RESULTS A total of 286 calls related to psychotropic medication in young people were reviewed. The majority of callers were adults calling on behalf of either a child (73.4%) or client (12.9%). Stimulants were the most common medication enquired about (44.0% of calls), followed by antidepressants (40.2%), and antipsychotics (18.9%). More than half of all calls were for medicines not registered for pediatric use. Almost two thirds of calls related to safety issues (61.9%; 177/286). Safety-related calls were not related to specific medication groups (e.g., stimulants or antidepressants). Significant and independent predictors of safety-related concerns were medication not registered for pediatric use (p < 0.05), receipt of lay information (p < 0.05), concomitant enquiry about nonpsychotropic medication (p < 0.01), and a potential medication problem (p < 0.05). CONCLUSIONS Safety is one of the key areas of concern in young people and families accessing a medicines information service with questions about psychotropic medication. Off-label use of medication was common and may contribute to safety concerns. Provision of information that is tailored for young people has the potential to improve outcomes in this group.

Monitoring salivary melatonin concentrations in children with sleep disorders using liquid chromatography-tandem mass spectrometry

Background: Melatonin is synthesized in the pineal gland and is an important circadian phase marker, especially in the determination of sleep patterns. Both temporary and permanent abnormal sleep patterns occur in children; therefore, it is desirable to have methods for monitoring melatonin in biological fluids in the diagnosis and treatment of such disorders. Objective: The objective of the study is to develop a liquid chromatography–tandem mass spectrometry method for the determination of melatonin in saliva and to apply it to monitoring salivary concentrations in children with sleep disorders. Methods: A deuterated internal standard (d7-melatonin) was added to a diluted saliva sample (20 µL) in an autosampler vial insert, and 50 µL were injected. Plasticware was strictly avoided, and all glassware was scrupulously cleaned and then baked at 120°C for at least 48 hours to obtain satisfactory performance. Reverse-phase chromatography was performed on a C8 column using a linear gradient elution profile comprising mobile phases A (0.1% aqueous formic acid) and B (15% methanol in acetonitrile containing 0.1% formic acid), pumped at a total flow rate of 0.8 mL/min. The run time was 8 minutes. After atmospheric pressure chemical ionization, mass spectrometric detection was in positive ion mode. Mass detection was by selected reaction monitoring mode with the following mass transitions used for quantification: melatonin, m/z 233.0 → 173.8 and d7-melatonin, m/z 240.0 → 178.3. Results: Linearity (r > 0.999) was established from 3.9 to 1000 pg/mL. Imprecision (coefficient of variation percent) was less than 11%, and accuracy was 100–105% (7.0–900 pg/mL). The method was selective, and the mean (range) ratio of the slopes of calibrations in water to those in daytime saliva samples collected from 10 healthy adult subjects was 0.989 (0.982–0.997), indicating negligible matrix effects. The application of the assay was demonstrated in healthy adults and in children being clinically investigated for sleep disturbances. Conclusions: A validated liquid chromatography–tandem mass spectrometry method suitable for monitoring salivary melatonin in children with circadian rhythm sleep disorders is reported. The method also has potential application to pediatric population pharmacokinetic studies using sparse sampling of saliva as the biological sample matrix.

Therapeutic Options in the Management of Sleep Disorders in Visually Impaired Children: A Systematic Review

BACKGROUND Treatment of sleep disorders in visually impaired children is complicated by a complex pathophysiology, a high incidence of sleep disorders in this population, and a dearth of management options. The significant impact on the health of these children and distress to their caregivers warrant a systematic assessment of the published literature on therapeutic approaches. OBJECTIVE This systematic review aims to assess the current therapeutic options in the management of sleep disorders in visually impaired children to identify knowledge gaps and guide future research. METHODS A search of primary literature was conducted using the bibliographic databases PubMed (1980-August 2010), EMBASE (1990-August 2010), Science Citation Index Expanded (1990-August 2010), and CINHAL (1992-August 2010) and the Cochrane Central Register of Controlled Trials (CENTRAL). Additional studies were identified through snowballing search techniques (manually by searching retrieved references and electronically by using citation-tracking software). Search terms included behavioral treatment, children, circadian rhythm, hypnosedatives, intellectual disability, light therapy, melatonin, phototherapy, random allocation, randomized controlled trial (RCT), sleep disorder, and visual impairment. Randomized and quasi-randomized clinical trials of therapeutic options (behavioral treatment, light therapy, melatonin, or hypnosedatives) used in participants aged 3 months to 18 years who had both a visual impairment and a sleep disorder were included. Independent extraction of articles was performed by 2 authors using predefined data fields, including quality of the therapeutic options, based on the Strength of Recommendation Taxonomy evidence-rating system. RESULTS Two RCTs were retrieved for melatonin, with improved effect on sleep latency (P = 0.019 and P < 0.05, respectively). However, separate analysis for visual impairment was not conducted. No RCTs were retrieved for behavioral intervention, light therapy, or hypnosedatives. Three studies using behavioral therapy (2 case reports and 1 case series) anecdotally showed improvement in sleep habit. No improvement in sleep rhythm was observed with a case series applying light therapy as an intervention. CONCLUSIONS Children with visual impairment and sleep disorders are a heterogeneous patient group, making diagnosis and treatment difficult. RCTs on treatment options remain in their infancy, with a lack of evidence for appropriate therapeutic strategies. Trials across a range of selected diagnoses need to be conducted with adequate sample populations to differentiate the efficacy of 4 different treatment modalities (behavioral therapy, light therapy, melatonin, and hypnosedatives) as agents for improving sleep.

The match between common antibiotics packaging and guidelines for their use in Australia

Objectives: To determine the potential for a source of surplus antibiotics in the community to come from the mismatch between the recommended duration of antibiotic treatment for common indications in primary care and that dictated by default pharmaceutical industry packaging.

Piloting an Objective Structured Clinical Examination to Evaluate the Clinical Competency of Pre‐Registration Pharmacists

Objectives: The primary aim of the study was to pilot the Objective Structured Clinical Examination (OSCE) as a method of evaluating the clinical competency of pre‐registration pharmacists trained in Brisbane and nearby hospitals. A secondary aim was to demonstrate that this model of assessment is transferable when used to evaluate preregistration pharmacists from the UK.

The bidirectional relationship between vasomotor symptoms and depression across the menopausal transition: a systematic review of longitudinal studies

Objective: To explore the nature of the bidirectional relationship between vasomotor symptoms (VMS) and depression, and to determine whether hot flashes and night sweats differentially affect the association between VMS and depression through their effect on sleep disruption. Methods: Multiple databases were searched from 1961 until July 31, 2016, and a manual search of reference lists of identified articles was conducted. Sixteen articles that involved 10,008 participants were identified and analyzed. Results: The methods of analyses and measurement of VMS and depression varied across the studies. Two studies explored the bidirectional association, but only one was significant in both directions (odds ratio [OR] depression to VMS 3.06, 95% confidence interval [CI] 1.43-6.58; OR VMS to depression 8.88, 95% CI 2.57-30.68). In both cases, the association between VMS leading to depressive symptoms was stronger than the opposite. Eleven studies examined VMS leading to depression, but only five showed a significant effect (OR 1.57-1.81, P ⩽ 0.02). Treating VMS and depressive symptoms as continuous variables (n = 3) diminished the relationship. Three studies showed a significant association of depression leading to VMS (OR 1.62-1.94, P ⩽ 0.01). We found little evidence for a specific effect of night sweats on the association between VMS and depressive symptoms. The effect might not be related to sleep disruption. Conclusions: There is a bidirectional association between VMS and depressive symptoms. The menopausal transition appears to increase the risk of recurrent episodes of depression that might not be explained only by VMS. Further investigation is needed to explain the differential effect of night sweats and hot flashes on depression.

What do health consumers want to know about childhood vaccination? An evaluation of data from an Australian medicines call centre

Objectives: Immunisation is crucial to population health. This study aimed to identify the information needs and concerns of health consumers regarding childhood vaccination.