Pharmacokinetics of rifampicin, isoniazid & pyrazinamide during daily & intermittent dosing: A preliminary study

Background & objectives: The National Tuberculosis (TB) Control Programme has transitioned from thrice-weekly to daily drug treatment regimens in India. This preliminary study was conceived to compare the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) in TB patients being treated with daily and thrice weekly anti-TB treatment (ATT). Methods: This prospective observational study was undertaken in 49 newly diagnosed adult TB patients receiving either daily ATT (n=22) or thrice-weekly ATT (n=27). Plasma RMP, INH and PZA were estimated by high-performance liquid chromatography. Results: The peak concentration (Cmax) of RMP was significantly higher (RMP: 8.5 ?g/ml vs. 5.5 ?g/ml; P=0.003) and Cmax of INH was significantly lower (INH: 4.8 ?g/ml vs. 10.9 ?g/ml; P<0.001) in case of daily dosing compared to thrice-weekly ATT. Cmax of drugs and doses was significantly correlated. A higher proportion of patients had subtherapeutic RMP Cmax (8.0 ?g/ml) during thrice-weekly compared to daily ATT (78% vs. 36%; P=0.004). Multiple linear regression analysis showed that Cmax of RMP was significantly influenced by the dosing rhythm, pulmonary TB and Cmax of INH and PZA by the mg/kg doses. Interpretation & conclusions: RMP concentrations were higher and INH concentrations were lower during daily ATT, suggesting that INH doses may need to be increased in case of a daily regimen. Larger studies are, however, required using higher INH doses when monitoring for adverse drug reactions and treatment outcomes.

Lack of Utility of Thoracoscore in Evaluating Fitness for Surgery in Lung Cancer.

Background. The thoracic surgery scoring system (Thoracoscore) is a multivariate scoring system with nine parameters used for predicting inpatient mortality after thoracic surgery. In clinical practice, the value of the thoracoscore in evaluating the fitness of individual patients for surgery is not clear. Objective. The study objective was to evaluate the performance of thoracoscore in evaluating fitness for surgery for lung cancer and compare it with cardiopulmonary exercise test (CPEX). Methods. We retrospectively analysed data over a 2-year period from the CPEX database of patients referred for preoperative assessment prior to surgery for lung cancer. Results. Twenty-two patients who had borderline lung function impairment had CPEX to assess fitness for surgery. Fifteen (68%) were deemed fit and went on to have thoracic surgery while 7 (32%) were considered high risk and were turned down. The predicted death rate based on thoracoscore for patients who had surgery was 3.5+2.8 as compared to 3.4+2.0 for patients who did not have surgery (p>0.05). The mean peak VO2 (peak oxygen uptake during CPEX) among those who had surgery was significantly higher than those who did not have surgery (14.2 mL/kg/min versus 10.1 mL/kg/min). There was no correlation of thoracoscore with lung function parameters, duration of hospital stay and peak VO2. Conclusions. Our study showed that CPEX remains a standard and useful tool for functional assessment prior to lung cancer resection. There is no correlation between thoracoscore and either CPEX or pulmonary function parameters. Thoracoscore should not be used to assess fitness for surgery.

Tuberculosis risk in health care workers.

Risk to health care workers (HCW) is of paramount importance in the global fight against tuberculosis (TB). There is mounting evidence that they are at increased risk of contracting TB infection as well as developing the disease. This occupational risk is at alarming proportions in the low- and middle-income countries (LMIC), because of increased exposure and lack of preventive measures. Although tuberculin skin test has been used for a long time to detect latent TB infection (LTBI), it has significant drawbacks. Interferon-gamma release assays arrived with a lot of promise, but the expected benefit of more specific diagnosis has not yet been proved. The treatment of LTBI is an area, which is not well studied in LMIC. Effective environmental and personal protective measures along with education to the patients and the HCW needs to be carried out expeditiously, to reduce the occupational risk of TB.

Pain assessment and analgesic prescription for cancer patients in a medical ward: The influence of an educational intervention.

Background. Pain is present in more than 75% of patients with advanced cancer and is often under-treated. Adequate pain control is an essential component of patient care. By correctly following the WHO analgesic ladder, pain can be controlled in nearly 90% of patients with cancer. Clinical audits help to improve patient care. Hence, an audit was done on documentation of pain and prescription of analgesics in patients with cancer admitted to a medical ward. Methods. We conducted a retrospective audit of inpatient charts to assess the adequacy of documentation of pain and prescription of analgesics. Following this, we introduced an educational intervention in the form of teaching, provision of pocket guidelines and displaying a poster with the WHO analgesic guidelines. Subsequently, we conducted a prospective audit of documentation of pain and prescribing practices against the following standards: documentation of pain, intensity and response, prescription of analgesics based on WHO guidelines, prescribing breakthrough analgesics and prescribing stimulant laxatives with strong opioids. Results. The retrospective audit included 39 patients and the prospective audit had 34 patients. Pain was documented in 89.7% and 82.4%, pain intensity in 12.8% and 8.8%, and pain response in 12.8% and 11.8%, in the retrospective and prospective audits, respectively. WHO principles were correctly followed in 74.3% and 88.2%, and breakthrough analgesics prescribed in 38.4% and 61.8%, respectively. Conclusion. There was improvement in correctly following the WHO analgesic guidelines and prescribing breakthrough analgesics but not in documentation of pain. Clinical audits and interventions such as teaching, pocket guidelines and posters can result in better patient care.