Precautions before starting tofacitinib in persons with rheumatoid arthritis

Tofacitinib is an immunosuppressive and disease-modifying therapy in rheumatoid arthritis. It may result in many infections flaring up. It is important to take precautions of all kinds (cardiovascular, malignancy, infections etc.) before starting tofacitinib. In this article, we have highlighted important steps where we need to take precautions before starting tofacitinib.     

Epirubicin as a single agent therapy for the treatment of breast cancer — A pharmacokinetic and clinical study

Sixty women with breast cancer (mean age: 61 years; range 36-78 years) were treated with Epirubicin (4’epi-Dox-orubicin), 60 mg m^-2 , as single drug therapy. The drug was administered as 2 hours’ constant rate infusions. The pharmacokinetics of the drug during the first course of treatment was evaluated by measurements of the plasma concentration of Epirubicin at the end of the infusion period. There was a five-fold inter-individual variation of the dose-normalized maximum plasma concentration, which increased with increasing age of the patients. There was no correlation between this pharmacokinetic parameter and degree of obesity.     

Evaluation of low dose prostaglandin E1 treatment for ductus dependent congenital heart disease

This study reports our experience with low-dose prostaglandin E₁ (PGE₁) treatment of 91 newborns with ductus dependent congenital heart disease (CHD). PGE₁ efficacy, side-effects as well as the cardiovascular and respiratory profile of the patients were analysed. PGE₁ doses > 0.02 g/kg per minute were used for only 5.3% of the total 23 656 h of treatment. The mean systolic blood pressures did not differ from the normal mean for patients with cyanotic CHD, while the diastolic values were lowered. Respiratory support was required only during 13.7% of the total treatment time. Apnoeas occurred in 21 (38%) of the 55 spontaneously breathing infants, who all had a cyanotic CHD. The incidence of apnoeas was lower during treatment with doses < 0.01 g/kg per minute.     

Gastro-intestinal toxicity of chemotherapeutics in colorectal cancer:The role of inflammation

Chemotherapy-induced diarrhea(CID)is a common and often severe side effect experienced by colorectal cancer(CRC)patients during their treatment.As chemotherapy regimens evolve to include more efficacious agents,CID is increasingly becoming a major cause of dose limiting toxicity and merits further investigation.Inflammation is a key factor behind gastrointestinal(GI)toxicity of chemotherapy.Different chemotherapeutic agents activate a diverse range of pro-inflammatory pathways culminating in distinct histopathological changes in the small intestine and colonic mucosa.Here we review the current understanding of the mechanisms behind GI toxicity and the mucositis associated with systemic treatment of CRC.Insights into the inflammatory response activated during this process gained from various models of GI toxicity are discussed.The inflammatory processes contributing to the GI toxicity of chemotherapeutic agents are increasingly being recognised as having an important role in the development of anti-tumor immunity,thus conferring added benefit against tumor recurrence and improving patient survival.We review the basic mechanisms involved in the promotion of immunogenic cell death and its relevance in the treatment of colorectal cancer.Finally,the impact of CID on patient outcomes and therapeutic strategies to prevent or minimise the effect of GI toxicity and mucositis are discussed.     

A new early cognitive screening measure to detect cognitive side-effects of electroconvulsive therapy?

Cognitive side-effects from electroconvulsive therapy (ECT) can be distressing for patients and early detection may have an important role in guiding treatment decisions over the ECT course. This prospective study examined the utility of an early cognitive screening battery for predicting cognitive side-effects which develop later in the ECT course. The screening battery, together with the Mini Mental Status Examination (MMSE), was administered to 123 patients at baseline and after 3 ECT treatments. A more detailed cognitive battery was administered at baseline, after six treatments (post ECT 6) and after the last ECT treatment (post treatment) to assess cognitive side-effects across several domains: global cognition, anterograde memory, executive function, speed and concentration, and retrograde memory. Multivariate analyses examined the predictive utility of change on items from the screening battery for later cognitive changes at post ECT 6 and post treatment. Results showed that changes on a combination of items from the screening battery were predictive of later cognitive changes at post treatment, particularly for anterograde memory (p < 0.01), after controlling for patient and treatment factors. Change on the MMSE predicted cognitive changes at post ECT 6 but not at post treatment. A scoring method for the new screening battery was tested for discriminative ability in a sub-sample of patients. This study provides preliminary evidence that a simple and easy-to-administer measure may potentially be used to help guide clinical treatment decisions to optimise efficacy and cognitive outcomes. Further development of this measure and validation in a more representative ECT clinical population is required.     

Exploring the associations between drug side-effects and therapeutic indications

Drug therapeutic indications and side-effects are both measurable patient phenotype changes in response to the treatment. Inferring potential drug therapeutic indications and identifying clinically interesting drug side-effects are both important and challenging tasks. Previous studies have utilized either chemical structures or protein targets to predict indications and side-effects. In this study, we compared drug therapeutic indication prediction using various information including chemical structures, protein targets and side-effects. We also compared drug side-effect prediction with various information sources including chemical structures, protein targets and therapeutic indication. Prediction performance based on 10-fold cross-validation demonstrates that drug side-effects and therapeutic indications are the most predictive information source for each other. In addition, we extracted 6706 statistically significant indication-side-effect associations from all known drug-disease and drug-side-effect relationships. We further developed a novel user interface that allows the user to interactively explore these associations in the form of a dynamic bipartitie graph. Many relationship pairs provide explicit repositioning hypotheses (e.g., drugs causing postural hypotension are potential candidates for hypertension) and clear adverse-reaction watch lists (e.g., drugs for heart failure possibly cause impotence). All data sets and highly correlated disease-side-effect relationships are available at http://astro.temple.edu/∼tua87106/druganalysis.html.     

缓解柳氮磺吡啶治疗溃疡性结肠炎引起胃肠道反应15例分析

回顾分析SASP治疗溃疡性结肠炎引起胃肠道不良反应15例患者的临床表现。给予降低SASP剂量；恶心、食欲不振或上腹胀者用多潘立酮；上腹不适或烧灼感者用PPI；二者皆有给予多潘立酮及PPI两种药物治疗等。15例患者中发生恶心、食欲不振11例，上腹不适7例，上腹烧灼感2例，上腹胀1例。降低SASP剂量5例，给予多潘立酮3例，雷贝拉唑等PPI2例，多潘立酮及PPI治疗5例，15例患者皆症状减轻更好耐受治疗。降低剂量、用多潘立酮或／及质子泵抑制，可能缓解SASP引起的胃肠道不良反应，溃疡性结肠炎患者更易耐受治疗。     

High single-dose alternate-day corticosteroid regimens in treatment of polymyositis

Summary High single-dose alternate-day prednisolone therapy (ADT) was compared with daily-dose prednisolone therapy (DDT) for treatment of polymyositis. Thirty patients with polymositis were treated with ADT for an average of 33.9 months. The combined number of improvements was 21 out of 30, a response rate of 70%. Side-effects were very rare and mild. On the other hand, 9 of 17 patients treated with DDT for an average 18.5 months improved, a response rate of 53%. The incidence of side-effects was strikingly higher than with ADT. ADT is therefore strongly advocated for treatment of polymyositis to avoid infectious complications and lessen cushingoid side-effects.