scholarly journals Pharmacogenetic association between NAT2 gene polymorphisms and isoniazid induced hepatotoxicity: trial sequence meta-analysis as evidence

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Saif Khan ◽  
Raju K. Mandal ◽  
Abdulbaset Mohamed Elasbali ◽  
Sajad A. Dar ◽  
Arshad Jawed ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
Meta Analysis ◽  
Term Treatment ◽  
Wild Type ◽  
Severe Problem ◽  
Trial Sequence ◽  
Increased Risk ◽  
Long Term Treatment ◽  
Nat2 Gene

Abstract Hepatotoxicity is a severe problem generally faced by tuberculosis (TB) patients. It is a well-known adverse reaction due to anti-TB drugs in TB patients undergoing long-term treatment. The studies published previously have explored the connection of N-acetyltransferase 2 (NAT2) gene polymorphisms with isoniazid-induced hepatotoxicity, but the results obtained were inconsistent and inconclusive. A comprehensive trial sequence meta-analysis was conducted employing 12 studies comprising 3613 controls and 933 confirmed TB cases using the databases namely, EMBASE, PubMed (Medline) and Google Scholar till December 2017. A significant association was observed with individuals carrying variant allele at position 481C>T (T vs. C: P = 0.001; OR = 1.278, 95% CI = 1.1100–1.484), at position 590G>A (A vs. G: P = 0.002; OR = 1.421, 95% CI = 1.137–1.776) and at position 857G>A (A vs. G: P = 0.0022; OR = 1.411, 95% CI = 1.052–1.894) to higher risk of hepatotoxicity vis-à-vis wild-type allele. Likewise, the other genetic models of NAT2 gene polymorphisms have also shown increased risk of hepatotoxicity. No evidence of publication bias was observed. These results suggest that genetic variants of NAT2 gene have significant role in isoniazid induced hepatotoxicity. Thus, NAT2 genotyping has the potential to improve the understanding of the drug–enzyme metabolic capacity and help in early predisposition of isoniazid-induced hepatotoxicity.

scholarly journals Do antipsychotic drugs lose their efficacy for relapse prevention over time?

2017 ◽  
Vol 211 (3) ◽  
pp. 127-129 ◽  
Author(s):  
Stefan Leucht ◽  
John M. Davis
Keyword(s):  
Relapse Prevention ◽  
Antipsychotic Drugs ◽  
Meta Analysis ◽  
Term Treatment ◽  
First Episode ◽  
Brain Volume Loss ◽  
New Findings ◽  
Long Term Treatment ◽  
Long Term Follow Up

SummaryThere is a debate about long-term treatment of schizophrenia with antipsychotic drugs, with some experts suggesting that these drugs should be discontinued. In this issue, Takeuchi et al demonstrated by a meta-analysis of 11 trials that antipsychotic drugs maintained their efficacy for relapse prevention for 1 year, whereas patients on placebo kept getting worse. We consider these findings in the light of the current discussion about possible dose-related brain volume loss, supersensitivity psychosis, the high variability of results in long-term follow-up studies and recent approaches to discontinue antipsychotics in patients with a first-episode. The new findings speak in favour of continuing antipsychotics at the same dose, at least in patients whose condition is chronic, but the topic is complex.

scholarly journals What does the latest meta-analysis really tell us about antidepressants?

2018 ◽  
Vol 27 (5) ◽  
pp. 430-432 ◽  
Author(s):  
J. Moncrieff
Keyword(s):  
Meta Analysis ◽  
Term Treatment ◽  
Significant Other ◽  
Brain Abnormality ◽  
Antidepressant Effects ◽  
Long Term Treatment ◽  
Clinically Significant ◽  
Meta Analyses ◽  
Chemical Imbalance

A recent meta-analysis of antidepressant trials is the largest conducted to date. Although it claims to prove antidepressant effectiveness beyond dispute, the main outcome is response rates, which are derived from continuous data in a process that can inflate differences between groups. The standardised mean difference of 0.3 is in line with other meta-analyses that show small differences between antidepressants and placebo that are unlikely to be clinically significant. Other factors likely to exaggerate the effects are discussed, and evidence on associations between antidepressant effects and severity and outcomes of long-term treatment is considered. Clinicians need to have open discussions with patients about the limitations of antidepressant research, the lack of evidence that antidepressants correct a chemical imbalance or other brain abnormality, and the range of adverse effects and mental and physical alterations they can produce.

Medical Consequences of Long-term Treatment of Acromegaly

2010 ◽  
Vol 06 ◽  
pp. 68
Author(s):  
Rosario Pivonello ◽  
Renata S Auriemma ◽  
Mariano Galdiero ◽  
Ludovica FS Grasso ◽  
Annamaria Colao ◽  
...  
Keyword(s):  
Signs And Symptoms ◽  
Premature Death ◽  
Term Treatment ◽  
Tumour Mass ◽  
Risk Of Death ◽  
Increased Risk ◽  
Long Term Treatment ◽  
A Minor ◽  
The Impact

This article discusses the impact of long-term treatment of acromegaly on cardiovascular, metabolic, respiratory and articular complications as well as on malignancies. The main goals of treatment of acromegaly include normalisation of biochemical markers of disease activity, improvement in signs and symptoms of the disease, removal or reduction of tumour mass and preservation of pituitary function, together with prevention of complications. Cardiovascular and respiratory complications are the main causes of morbidity and mortality, whereas neoplasms are a minor cause of increased risk of death. Other associated diseases are arthropathy, carpal tunnel syndrome and reproductive disorders. The prolonged elevation of growth hormone (GH) and insulin-like growth factor (IGF)-I levels results in premature death, whereas strong biochemical control improves wellbeing and restores life expectancy to normal.

Efficacy of Thyroid Hormone Suppression for Benign Thyroid Nodules: Meta-Analysis of Randomized Trials

2005 ◽  
Vol 133 (3) ◽  
pp. 391-396 ◽  
Author(s):  
Matthew T. Sdano ◽  
Mercedes Falciglia ◽  
Jeffrey A. Welge ◽  
David L. Steward
Keyword(s):  
Thyroid Nodule ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Term Treatment ◽  
Volume Reduction ◽  
Benign Thyroid Nodule ◽  
Long Term Treatment ◽  
Nodule Volume ◽  
Benign Thyroid

OBJECTIVE: To determine the efficacy of thyroid hormone suppressive therapy (THST) to decrease benign thyroid nodule volume. DESIGN: Meta-analysis. METHODS: Systematic search using electronic databases (PubMed, Medline, Cochrane Library) through August 2004, paper review, and contacting experts and drug manufacturers. Only randomized controlled studies of THST vs no treatment or placebo, for reduction of benign thyroid nodule volume, were included. Exclusion criteria were: >6-month treatment, lack of ultrasound volume measurement, and region of endemic goiter. Primary outcome was clinically relevant nodule volume reduction (>50%), with a random effects model (RevMan4.2). RESULTS: Nine randomized trials were included (609 subjects). Subjects were 88% more likely to experience >50% nodule volume reduction with THST than placebo or no treatment (relative risk = 1.88; 95% CI = 1.18-3.01; P = 0.008). However, 8 subjects must be subjected to the risk of cardiac and skeletal side effects from THST, for one to benefit from therapy (number needed to treat = 8, risk difference = 0.13; 95% CI = 0.06-0.19; P = 0.0003). Sensitivity analysis reveals that 15 null studies would have to have been missed to reverse statistical significance (fail-safe N = 15). Review of the only study with long-term treatment (5 years) suggests no significant difference in nodule volume reduction between THST and placebo. Further, studies with follow-up after THST withdrawal demonstrate rapid increase in thyroid nodule and goiter volumes. CONCLUSION: THST appears more likely than placebo or no treatment to significantly reduce benign thyroid nodule volume, but long-term treatment may be less effective and regrowth is likely following cessation of therapy. Given the risks of THST, routine use is not recommended for benign nodules.

The Role of Long Acting Antipsychotics in Bipolar Disorder

2017 ◽  
Vol 41 (S1) ◽  
pp. S15-S15
Author(s):  
E. Vieta
Keyword(s):  
Bipolar Disorder ◽  
Meta Analysis ◽  
Term Treatment ◽  
Patient Profile ◽  
Long Term Treatment ◽  
Short And Long Term ◽  
Competing Interest ◽  
Long Acting

Antipsychotics are widely used for the short and long-term treatment of bipolar disorder. Depot and long-acting injectable formulations (LAIs) can be particularly useful for certain subgroups of patients. This lecture will discuss the available data from randomized controlled trials of LAIs in bipolar disorder. A recently published meta-analysis and individual studies assessing depot medications, as well as modern LAIs such as risperidone, paliperidone and aripiprazole, will be reviewed, looking carefully into the prevention of either pole of illness and tolerability. Potential indications and patient profile, based on data and clinical experience, will be discussed.Disclosure of interestThe author has not supplied his declaration of competing interest.

Osteochondritis Dissecans of the Medial Trochlear Ridge of the Talus in the Dog

1989 ◽  
Vol 02 (04) ◽  
pp. 168-176 ◽  
Author(s):  
K. A. Spaulding ◽  
T. D. Braden ◽  
G. J. Breur
Keyword(s):  
Osteochondritis Dissecans ◽  
Meta Analysis ◽  
Normal Function ◽  
Term Treatment ◽  
Medial Malleolus ◽  
Treatment Results ◽  
Limb Function ◽  
Long Term Treatment ◽  
Labrador Retrievers

SummaryThe medical records of 12 dogs with osteochondritis dissecans (OCD) of the medial trochlear ridge of the talus were reviewed. Long-term treatment results were obtained from client questionnaires and clinical and radiographic re-examinations. After a mean follow-up time of 52 months, only three of 12 dogs treated for OCD of the medial trochlear ridge of the talus had regained full function of the affected joint(s). In all cases available for radiographic re-examination, osteoarthritic changes had progressed. The medial approach to the hock joint by osteotomy of the medial malleolus was associated with a high complication rate.A meta-analysis of 38 cases (55 joints) of previous clinical studies and the present clinical study indicated that the Labrador Retriever and the Rottweiler were the most frequently affected breeds. Seventy-five percent of the affected Labrador Retrievers and Bull Terriers had bilateral involvement. The data suggested that in young dogs with an acute lameness, due to osteochondritis dissecans of the medial trochlear ridge in the talus, treatment resulted in 18% of the affected limbs in a normal limb function, in 27% in an intermittent lameness and in 55% in a chronic lameness. In dogs with a more chronic lameness, treatment results were better and approximately 40% of the affected limbs returned to normal function, while chronic lameness following treatment was unusual. In dogs older than a year at the time of treatment initiation, treatment became less successful because of the presence of severe osteoarthritic changes before treatment. Only 24% obtained normal limb function following treatment, while in 42% of the dogs treatment resulted in a chronic lameness.

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