Effect of percutaneous endoscopic gastrojejunostomy tube placement on levodopa pharmacokinetics

Authors’ response to letter to the editor: “Meta-analysis on vitamin C and the common cold in children may be misleading”

Vitamin D blood levels, unnecessary prescriptions, and retest in naïve patients

Meta-analysis on vitamin C and the common cold in children may be misleading

Systematic review of interventions to improve safety and quality of anticoagulant prescribing for therapeutic indications for hospital inpatients Abstract Purpose Anticoagulation-associated adverse drug events are common in hospitalised patients and result in morbidity, mortality, increased length of hospital stay and higher costs of care. Many are preventable. We reviewed the literature to identify and assess interventions intended to improve safety or quality anticoagulant prescribing. Methods A systematic search of EMBASE, MEDLINE, the Cochrane Library, Pretty Darn Quick-Evidence and Health Systems Evidence was undertaken to identify controlled studies assessing system-level interventions to improve prescribing of oral or parenteral therapeutic anticoagulation for any indication in hospitalised adults. Data were extracted for safety and quality outcomes, with studies grouped by intervention type for meta-analysis and narrative review. Results Of 10,640 records screened, 19 trials evaluating 12,742 participants were included for analysis. No study specifically evaluated prescribing of low molecular weight heparins (LMWHs) or direct acting oral anticoagulants (DOACs). Our findings suggest that physician-led anticoagulation consultation services may reduce bleeding rates in high-risk patients. On meta-analysis, decision supported warfarin dosing resulted in higher proportion of time with international normalised ratio in therapeutic range (p = 0.0007). Studies of other clinical decision support systems and heparin monitoring systems did not demonstrate improved safety, and quality findings were inconsistent. Systematic education and feedback programs were not efficacious. Conclusions There is currently insufficient high-quality evidence to recommend any reviewed intervention, though several warrant closer evaluation. Adequately powered controlled trials assessing safety outcomes and evidence-based quality markers in high-risk patient groups and studies of interventions to improve safety of LMWH and DOAC prescribing are needed.

Medication reconciliation: time to save? A cross-sectional study from one acute hospital Abstract Purpose Medication errors during transitional care are an important patient safety issue. Medication reconciliation is an established intervention to reduce such errors. Current evidence has not demonstrated an associated reduction in healthcare costs, however, with complexity and resource intensity being identified as issues. The aims of this study were to examine an existing process of medication reconciliation in terms of time taken, to identify factors associated with additional time, and to determine if additional time is associated with detecting errors of clinical significance. Methods A cross-sectional study was conducted. Issues arising during medication reconciliation incurring a time burden additional to the usual process were logged and quantified by pharmacists. Regression analyses investigated associations between patient characteristics and clinically significant errors and additional time. Cost for additional time in terms of hospital pharmacist salary was calculated. Results Eighty-nine patients were included. Having a personal record of medication at admission (OR 3.30, 95% CI: (1.05 to 10.42), p = 0.004) was a significant predictor of additional time. No significant associations were found between the occurrence of clinically significant error and additional time (p > 0.05). The most common reason for additional time was clarifying issues pertaining to primary care medication information. Projected annual 5-year costs for the mean additional time of 3.75 min were €1.8–1.9 million. Conclusions Spending additional time on medication reconciliation is associated with economic burden and may not yield benefit in terms of capturing clinically significant errors. There is a need to improve communication of medication information between primary and secondary care.

Drug-induced osteoporosis/osteomalacia: analysis in the French and Spanish pharmacovigilance databases Abstract Introduction Osteomalacia and osteoporosis are two metabolic bone disorders that increase the risk of fracture due to several causes. In terms of drugs, apart from corticosteroids, which are known to induce bone disorders, several other drugs used in chronic disease management have also been linked with an increased risk of osteoporosis and osteomalacia. Purpose The aim of this study was to describe spontaneous reports of drug-induced osteoporosis and osteomalacia in the French (FPVDB) and Spanish (SPVDB) pharmacovigilance databases. Methods Data were provided by the FPVDB and SPVDB. All reports of osteoporosis and osteomalacia recorded from 1985 up to 31 December 2015 inclusive were selected. Taking the time to onset of bone loss into account, all cases occurring in less than 1 month were excluded. Results A total of 369 reports (44 cases of osteomalacia, 325 cases of osteoporosis) were registered in the FPVDB and 64 (22 cases of osteomalacia, 42 cases of osteoporosis) in the SPVDB. In France, the top 5 drugs involved in the onset of osteoporosis were corticosteroids accounting for approximately half of the reports (n = 170) followed by systemic antiviral (n = 87), antacid (n = 29), antiepileptic (n = 27) and antithrombotic (n = 24) drugs. The 2 main classes of drugs implicated in osteomalacia were systemic antiretroviral drugs for half of the reports (n = 21) and antiepileptic drugs (n = 15). In Spain, corticosteroids were involved in 35.7% of reported cases of osteoporosis (n = 15) followed by systemic antiviral drugs (n = 12). There was no spontaneous report for antacid drugs. For osteomalacia, the 2 main drug classes were systemic antiretroviral drugs (n = 18, 81.8%) followed by antiepileptics (n = 2, 9.0%). In both countries, concomitant administration of systemic corticosteroids with other suspected drugs did not significantly modify the time to onset of drug-induced osteoporosis. Conclusion Despite some differences between the French and Spanish PVDBs, our data consistently show that bone loss is not only restricted to glucocorticoids but also involves antivirals, antiepileptic drugs, antacid drugs or antidepressants. Further analysis might prove useful in exploring the characteristics of drug-induced bone loss on a larger scale.

Insulin resistance induced by olanzapine and other second-generation antipsychotics in Chinese patients with schizophrenia: a comparative review and meta-analysis Abstract Purpose This systematic review aimed to determine whether olanzapine is more likely than other second-generation antipsychotics (SGAs) to induce insulin resistance in patients with schizophrenia in China. Methods We reviewed all randomized controlled trials on insulin resistance and metabolic abnormalities caused by SGAs in the PubMed, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang databases. Retrieved articles were published on or before December 2018. Meta-analysis was performed to determine the effect size of the treatment on the insulin resistance index (IRI), fasting blood glucose (FBG), and fasting insulin (FINS). Results Forty studies (3725 participants in total) were included. All studies contained data suitable for comparing aripiprazole vs. olanzapine, ziprasidone vs. olanzapine, and risperidone vs. olanzapine. Patients treated with olanzapine had higher IRI, FBG, and FINS levels than did patients treated with aripiprazole, ziprasidone, or risperidone, with significant differences (aripiprazole vs. olanzapine: FBG: standardized mean difference [SMD] = 0.72, 95% confidence interval [95%CI] − 0.82, − 0.61; FINS: SMD = − 0.8, 95%CI − 1.00, − 0.61; IRI: SMD = − 0.80, 95%CI − 0.99, − 0.61; ziprasidone vs. olanzapine: FBG: SMD = − 1.19, 95%CI − 1.30, − 1.08; FINS: SMD = − 0.66, 95%CI − 0.85, − 0.47; IRI: SMD = − 0.71, 95%CI − 0.88, − 0.55; risperidone vs. olanzapine: FBG: SMD = − 0.17, 95%CI − 0.34, − 0.00). Conclusions Existing data suggest that olanzapine is associated with a significantly greater risk of IRI, FBG, and FINS, while other agents are associated with relatively lower risks. Thus, olanzapine is more likely to induce insulin resistance than are other SGAs in schizophrenic patients in China.

MIF plasma level as a possible tool to predict steroid responsiveness in children with idiopathic nephrotic syndrome Abstract Purpose Idiopathic nephrotic syndrome (INS) is the most frequent form of childhood nephrotic syndrome. Steroids represent the best therapeutic option; however, inter-individual differences in their efficacy and side effects have been reported. To date, there is no way to predict patients’ resistance and/or dependence. Alterations in the cytokine profile of INS patients might contribute to proteinuria and glomerular damage and affect drug sensitivity. Methods The cytokine plasma levels were measured in 21 INS children at diagnosis to investigate the association among cytokines pattern and clinical response. Patients were selected on the basis of their clinical response: 7 steroid sensitive (SS), 7 dependent (SD), and 7 resistant (SR). Significant results were then analyzed in 41 additional pediatric INS patients. Results Within the 48 cytokines analyzed, macrophage migration inhibitory factor (MIF) was a good predictor of steroid response. Indeed, SR patients showed significantly higher MIF plasma levels compared with all others (p = 0.022; OR = 4.3, 95%CI = 1.2–25.4): a cutoff concentration of MIF > 501 pg/ml significantly discriminated SR patients (sensitivity = 85.7%, specificity = 71.4%). On the contrary, SD patients showed lower MIF plasma levels compared with others (p = 0.010; OR = 0.12, 95%CI = 9.2 × 10−3–6.7 × 10−1). Significant results were confirmed in the entire cohort. Conclusions Our comprehensive cytokine analysis indicates that assessing MIF plasma levels at diagnosis could predict response to glucocorticoids in children with INS.

Thiopurines with low-dose allopurinol (ThiLDA)—a prospective clinical one-way crossover trial Abstract Purpose Many patients with Crohn’s disease (CD) and ulcerative colitis (UC) who have a high 6-methylmercaptopurine/6-thioguanine (6-MMP/6-TGN) ratio receive allopurinol 100 mg in addition to thiopurines to optimize metabolite concentrations. However, some patients do not tolerate allopurinol at this dosage. The aim of this study was to determine the intra-patient effect of reducing the allopurinol dosage from 100 to 50 mg, in terms of metabolite concentrations, enzyme activities, efficacy, and tolerability. Methods A prospective non-inferiority one-way crossover study was performed. CD and UC patients with stable disease using a thiopurine and allopurinol 100 mg were switched to 50 mg for 1 month. Primary outcomes were thiopurine metabolite concentrations. Secondary outcomes were enzyme activities of xanthine oxidase, thiopurine methyltransferase and hypoxanthine-guanine phosphoribosyltransferase, disease activity, and tolerability. Results Twenty-two patients were included. Treatment with allopurinol 50 mg compared with 100 mg resulted in a significant decrease in mean 6-TGN levels (761 to 625 pmol/8 × 108 RBC; p = 0.005) and a significant increase in mean 6-MMP levels (451 to 665 pmol/8 × 108 RBC; p = 0.01). However, the mean metabolite concentrations were still therapeutic. Enzyme activities, disease activity scores, and patient experiences did not alter significantly. Generally, UC patients were more positive about their improved treatment than CD patients. Conclusion Combination therapy with 50 mg allopurinol led to a decrease of 6-TGN levels compared with 100 mg allopurinol. Disease activity, side effects, and patient experience, however, were similar between allopurinol 100 and 50 mg. UC patients seem to benefit and prefer lower doses whereas the contrary is seen in CD patients. Trial registration EudraCT trial registry - number 2016-001638-84