Toxic effects and chemoresistance are major hurdles in chemotherapy and to avoid these problems caused by traditional chemotherapeutic regimens, a new modality of drug administration called “metronomic chemotherapy” has emerged. Such regimen involves the frequent administration of conventional chemotherapeutic agents at very low doses to target activated endothelial cells in tumors, the advantages of which include minimal adverse effects and a rare chance of developing acquired drug resistance. Previously it was thought that they act by targeting angiogenesis, but recently additional mechanisms have been discovered which has established metronomic chemotherapy as a type of multi-targeted therapy. The knowledge gained from the preclinical studies of metronomic chemotherapy, along with clinical experience, will help to design better therapeutic protocols against cancer. Detailed pharmacogenomic and pharmacoproteomic studies on tumor endothelial cells and large multi-centered clinical trials, integrating bio-marker analyzes, are needed to investigate and validate the best treatment combinations for each tumor type and patient population.

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Objective The aim of the study was to compare the effects of single intra-articular platelet-rich plasma (PRP) and corticosteroid (CS) injections in patients with adhesive capsulitis of the shoulder. Design Patients aged 18–70 yrs of either sex, diagnosed with adhesive capsulitis of shoulder, with less than 6-mo duration, were included. In intra-articular corticosteroid (IA-CS, control) group, 30 patients received a single injection (4 ml) of IA-CS and in IA-PRP (test) group, 30 patients received single IA-PRP injection (4 ml) into the glenohumeral joint under ultrasound guidance. All patients were prospectively followed for 12 wks. Results Twenty-eight patients in IA-PRP group and 27 in IA-CS group finished the entire 12-wk study period. At 12 wks, decrements in visual analog scale and total shoulder pain and disability index scores, in IA-PRP group, were 58.4 and 55.1, compared with 48.7 and 45.8 in IA-CS group. In range of movement, IA-PRP group showed significant improvement in passive abduction (−50.4 vs. −39.4), internal (−36.8 vs. −25.8), and external rotations (−35.4 vs. −25.9) compared with IA-CS group, respectively. No major complications were observed in any patients. Conclusions At 12-wk follow-up, a single dose of IA-PRP injection was found to be more effective than an IA-CS injection, in terms of improving pain, disability, and shoulder range of movement in patients with adhesive capsulitis of the shoulder.

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive, neuromodulatory tool, has been used to reduce craving in different substance use disorders. There are some studies that have reported conflicting and inconclusive results; therefore, this meta-analysis was conducted to evaluate the effect of high-frequency rTMS on craving in substance use disorder and to investigate the reasons behind the inconsistency across the studies. The authors searched clinical trials from MEDLINE, Cochrane databases, and International Clinical Trials Registry Platform. The PRISMA guidelines, as well as recommended meta-analysis practices, were followed in the selection process, analysis, and reporting of the findings. The effect estimate used was the standardized mean difference (Hedge's g), and heterogeneity across the considered studies was explored using subgroup analyses. The quality assessment was done using the Cochrane risk of bias tool, and sensitivity analysis was performed to check the influences on effect size by statistical models. After screening and assessment of eligibility, finally 10 studies were included for meta-analysis, which includes six studies on alcohol and four studies on nicotine use disorder. The random-model analysis revealed a pooled effect size of 0.75 (95% CI=0.29 to 1.21, p=0.001), whereas the fixed-model analysis showed a large effect size of 0.87 (95% CI=0.63 to 1.12, p<0.00001). Subgroup analysis for alcohol use disorder showed an effect size of -0.06 (95% CI=-0.89 to 0.77, p=0.88). In the case of nicotine use disorder, random-model analysis revealed an effect size of 1.00 (95% CI=0.48 to 1.55, p=0.0001), whereas fixed-model analysis also showed a large effect size of 0.96 (95% CI=0.71 to 1.22). The present meta-analysis identified a beneficial effect of high-frequency rTMS on craving associated with nicotine use disorder but not alcohol use disorder.