A Systematic Literature Review of the Economic Evaluations of Treatments for Patients with Chronic Myeloid Leukemia.

BACKGROUND AND OBJECTIVES: The management of chronic myeloid leukemia is associated with an extensive economic burden, and as novel interventions are being tested in this disease, understanding the comparative effectiveness is of interest. Findings and conclusions of this important issue continue to evolve with improvements in clinical research and economic understanding. This systematic literature review aims to conduct a comprehensive assessment of economic evaluations in chronic phase chronic myeloid leukemia. METHODS: Embase®, MEDLINE®, and the National Health Service Economic Evaluation Database were searched on 4 July, 2022 to identify economic evaluations of chronic myeloid leukemia. Health technology assessment websites and key conference proceedings were also searched. Economic evaluations comparing treatment options in adult patients with chronic phase chronic myeloid leukemia were included. The quality of the studies were assessed using Drummond's checklists. RESULTS: The search retrieved 47 studies and 16 health technology assessments that fulfilled the eligibility criteria. Most were cost-utility analyses (23 studies and 11 health technology assessments) and were from the USA (n = 15) and China (n = 7). Twenty-seven studies and six health technology assessments included only patients with chronic phase chronic myeloid leukemia. Most models had a Markov structure, a 1 year to lifetime time horizon, and a 1-month cycle length. Commonly assessed treatments were various tyrosine kinase inhibitors (imatinib, nilotinib, dasatinib, bosutinib, and ponatinib) and other interventions such as interferon-α, hydroxyurea, and allogeneic stem cell transplant. CONCLUSIONS: In patients with newly diagnosed chronic myeloid leukemia, imatinib regimens were cost effective, mostly owing to the availability of generics. Nilotinib and dasatinib were generally cost effective as second-line agents for patients who were resistant or intolerant to imatinib. Though progress has been made to better characterize the cost effectiveness of first-line and second-line chronic myeloid leukemia therapies, the paucity of published cost-effectiveness studies of third-line treatments increases the uncertainty associated with economic evaluations of later lines of therapy.

In vitro and in vivo evaluation of clastogenicity of second-line antitubercular drug loaded PLGA nanoparticles.

Sustained release nanoformulations of second line antitubercular drugs levofloxacin and ethionamide had shown promise in pharmacokinetics and acute and sub-acute toxicity studies. The present study evaluated the clastogenicity potential of the nanoformulations of these antitubercular agents. Clastogenicity was evaluated by (a) in vitro micronucleus assay (b) in vivo micronucleus assay in Swiss albino mice and (c) sister chromatid exchange (SCE) in CHO cell lines. Ethionamide and levofloxacin loaded nanoparticles were 312 ± 64 nm and 245 ± 24 nm in size respectively and drug encapsulation was 35.2 ± 3.1% w/w and 45.6 ± 9.4% w/w, respectively. The frequency of MN-NCE/1000 NCE and MN-PCE/1000 PCE were significantly reduced in mice treated with ethionamide nanoparticle (3.5 ± 0.9, 13.8 ± 16.68) and levofloxacin nanoparticles (5.6 ± 2.7, 16.7 ± 12.7) compared to the mice treated with free ethionamide (11.5 ± 4.1, p = 0.23 and 45.19 ± 19.21, p = 0.38) and free levofloxacin (14.7 ± 1.88, p < 0.0001 and 54.6 ± 18.1, p = 0.0017), respectively. For in vitro, micronucleus assay frequencies of micronuclei per thousand bi-nucleated cells (MN-BN/1000 BN) was 188.3 ± 20.20 and 148 ± 20.42 for ethionamide and levofloxacin nanoparticles as compared to 232.6 ± 16.04 (p = 0.52) and 175 ± 5.56 (p = 0.45) for free ethionamide and levofloxacin, respectively. The average number of SCE per cell for nanoformulation of ethionamide were not different from that of free drug (4.9 ± 0.51 vs 4.1 ± 0.55, p = 0.86). The SCE per cells were not significant difference for nanoformulation of levofloxacin (2.33 ± 1.36 vs 5.46 ± 0.25, p = 0.88). In vitro and in vivo assays have shown relatively less clastogenic potential of equivalent dose of ethionamide nanoparticles as compared to the conventional formulation.

A meta-analysis to assess usefulness of procalcitonin-guided antibiotic usage for decision making.

BACKGROUND & OBJECTIVES: Development of antibacterial resistance and its association with antibiotic overuse makes it necessary to identify a specific and sensitive biomarker for the diagnosis of bacterial infection and guiding antibiotic therapy. Procalcitonin (PCT), as a sepsis biomarker, may play a role in guiding antibiotics treatment in hospital settings. The aim of the current meta-analysis was to analyze the utility of PCT on various outcomes of interest in inpatients. METHODS: Different databases were searched for randomized controlled trials comparing PCT-guided therapy with standard therapy in admitted patients with bacterial infections. Twenty six articles were found suitable for full text search and of these, 16 studies were considered finally for data extraction. RESULTS: There were no significant differences found in total mortality [pooled odds ratio (OR) 1.04, 95% confidence interval (CI) 0.89-1.22, P=0.63], 28-day mortality (pooled OR 0.97, 95% CI 0.80-1.19, P=0.79), need of Intensive Care Unit admission (OR=0.80, 95% CI 0.59-1.09, P=0.16) and duration of stay in hospital (pooled mean difference -0.01, 95% CI -0.50-0.49, P=0.98) between treatment and control groups. PCT-guided treatment significantly decreased the duration of antibiotic treatment (pooled mean difference -2.79, 95% CI -3.52--2.06, P<0.00001). INTERPRETATION & CONCLUSIONS: PCT-guided therapy significantly decreased antibiotics exposure and thus treatment cost. However, the hard endpoints did not demonstrate any significant benefits, possibly due to low power to detect differences and/or the presence of comorbidities.

Presence of depression and its risk factors in patients with chronic obstructive pulmonary disease.

BACKGROUND & OBJECTIVES: Although depression is a significant co-morbid condition in chronic illnesses, little is known about the prevalence or risk factors for depressive symptoms in patients with chronic obstructive pulmonary disease (COPD) in India. This study was undertaken to investigate the presence and risk factors of depression in the COPD patients attending a tertiary care health facility in north India. METHODS: COPD was classified according to GOLD stages based on forced expiratory volume in one second (FEV 1 ) in 126 stable patients. Depression was examined by administering the nine-item Hindi version of Patient Health Questionnaire-9 (PHQ-9). Linear regression model was used to examine association between predictor variables and risk of depression with adjustment of age and sex. Cronbach alpha was calculated to assess internal consistency of PHQ-9. RESULTS: In the study population as whole, 33.3 per cent patients showed moderate to severe depressive symptoms whereas 20.6 per cent patients had major depressive disorder on PHQ-9 Scale. Educational and occupational status, body mass index, FEV 1, respiratory symptoms, physical impairment and dyspnoea were found to be potential predictors of depression in COPD patients. INTERPRETATION & CONCLUSIONS: One fifth of the patients with COPD had severe symptoms of related to depression, which was especially higher with severity of COPD. Hence, the patients with COPD should focus on management of these two conditions. Further, future studies should be conducted to assess the role of depression management and timely treatment of it in patients with COPD.

Effect of HDL-raising drugs on cardiovascular outcomes: a systematic review and meta-regression.

BACKGROUND: Substantial residual cardiovascular risk remains after optimal LDL lowering in patients of established coronary artery disease. A number of therapeutic agents that raise HDL-C have been tested in clinical trials to cover this risk. However, the results of clinical trials are conflicting. OBJECTIVES: To determine whether raising HDL-C with pharmacologic therapies translates into beneficial cardiovascular outcomes and to find out if this change was proportional to the percentage change in HDL levels. METHODS: Electronic and printed sources were searched up to August, 2013 for randomised controlled trials (RCTs) using at least one of the HDL raising therapies for secondary prevention of adverse cardiovascular events over optimal LDL levels. Data from eligible studies were pooled for the following outcomes: all cause mortality, cardiovascular disease mortality, hospitalization for unstable angina, non-fatal myocardial infarction, coronary revascularization and ischemic stroke. Mantel Haensnzel fixed effect model was used preferentially. Meta-regression was done to see the correlation of change in HDL levels and cardiovascular outcomes. Pooled odds ratios with 95% confidence interval (CI) were calculated. RESULTS: A total of 12 RCTs including 26,858 patients with follow up period ranging from 1 year to 6.2 years were included in the analysis. Pooled analysis showed no significant difference in all-cause mortality between the treatment and control group (Pooled OR 1.07; 95% CI 0.98-1.16, p = 0.15). No significant difference was found between the groups for any of the secondary outcomes. Similarly no correlation was seen between percentage change in HDL and adverse cardiovascular outcomes on meta-regression analysis. CONCLUSION: Increasing HDL levels via pharmacological manipulation beyond optimal lipid lowering therapy for secondary prevention is not beneficial.

Terminalia arjuna in Chronic Stable Angina: Systematic Review and Meta-Analysis.

Background. Terminalia arjuna is a popular Indian medicinal plant with its bark been used for over centuries as cardiotonic. The bark has been found to contain several bioactive compounds including saponins and flavonoids. A number of experimental and clinical studies have been conducted to explore therapeutic potential of Terminalia arjuna in cardiovascular ailments specially in patients of coronary heart disease. A number of narrative reviews have been done but no systematic review has been conducted to date. Objective. To systematically review and conduct a meta-analysis on the available literature evaluating the efficacy of Terminalia arjuna in patients of chronic stable angina. Study selection. We included randomised, pseudo-randomized and before-after comparative studies which compared Terminalia arjuna/commercial preparation of Terminalia arjuna with current standard/ conventional treatment regimens in patients with chronic stable angina. Findings. Studies were found to be of poor methodological design. We found no significant difference in the Terminalia arjuna group as compared to control arm in the outcomes for which we were able to pool data and undertake meta-analysis. Conclusions. Currently, the evidence is insufficient to draw any definite conclusions in favour of or against Terminalia arjuna in patients of chronic stable angina. Further, well-controlled multicentric clinical trials need to be conducted in large number of patients to explore the therapeutic potential of Terminalia arjuna if any.