Importance of Therapeutic Drug Monitoring of Rifampicin.

Therapeutic Drug Monitoring (TDM) is a routinely practised clinical laboratory technique which aids the clinicians with a clear clinical judgement of the drug therapy and optimize the doses if necessary. Rifampicin is the most important and potent component of first line therapy of tuberculosis (TB). Several factors like age, weight, gender, doses and formulations, gastro-intestinal disorders, ethnicity etc alter the absorption and bioavailability of rifampicin thus altering the drug levels. Low plasma levels of rifampicin may play a plausible role in slow response to therapy, treatment failure or relapse or acquired drug resistance. TB Patients with further complicated conditions like diabetes or HIV are at an increased risk for poor drug absorption and drug-drug interactions. A standard treatment regimen may be inadequate for some cases as the clinical status of patients vary from case to case. TDM can be used as a clinical tool for identifying patients at high risk of treatment failure, delayed response, drug-drug interactions and help optimization of therapy. In the past two decades numerous reports of TDM of anti-tuberculosis drugs have been reported wherein low rifampicin levels have been a major concern. Rifampicin exhibit concentration dependent killing of mycobacteria. A 2 hour post-dose sample approximates the peak plasma rifampicin concentration (Cmax) and is recommended for TDM of rifampicin. An additional 6 hour sample may be collected to distinguish between delayed absorption and malabsorption. Combined with clinical and bacteriological data, TDM can help clinicians treat slow response / complicated TB patients.

Indian Guidelines on Nebulization Therapy.

Inhalational therapy, today, happens to be the mainstay of treatment in obstructive airway diseases (OADs), such as asthma, chronic obstructive pulmonary disease (COPD), and is also in the present, used in a variety of other pulmonary and even non-pulmonary disorders. Hand-held inhalation devices may often be difficult to use, particularly for children, elderly, debilitated or distressed patients. Nebulization therapy emerges as a good option in these cases besides being useful in the home care, emergency room and critical care settings. With so many advancements taking place in nebulizer technology; availability of a plethora of drug formulations for its use, and the widening scope of this therapy; medical practitioners, respiratory therapists, and other health care personnel face the challenge of choosing appropriate inhalation devices and drug formulations, besides their rational application and use in different clinical situations. Adequate maintenance of nebulizer equipment including their disinfection and storage are the other relevant issues requiring guidance. Injudicious and improper use of nebulizers and their poor maintenance can sometimes lead to serious health hazards, nosocomial infections, transmission of infection, and other adverse outcomes. Thus, it is imperative to have a proper national guideline on nebulization practices to bridge the knowledge gaps amongst various health care personnel involved in this practice. It will also serve as an educational and scientific resource for healthcare professionals, as well as promote future research by identifying neglected and ignored areas in this field. Such comprehensive guidelines on this subject have not been available in the country and the only available proper international guidelines were released in 1997 which have not been updated for a noticeably long period of over two decades, though many changes and advancements have taken place in this technology in the recent past. Much of nebulization practices in the present may not be evidence-based and even some of these, the way they are currently used, may be ineffective or even harmful. Recognizing the knowledge deficit and paucity of guidelines on the usage of nebulizers in various settings such as inpatient, out-patient, emergency room, critical care, and domiciliary use in India in a wide variety of indications to standardize nebulization practices and to address many other related issues; National College of Chest Physicians (India), commissioned a National task force consisting of eminent experts in the field of Pulmonary Medicine from different backgrounds and different parts of the country to review the available evidence from the medical literature on the scientific principles and clinical practices of nebulization therapy and to formulate evidence-based guidelines on it. The guideline is based on all possible literature that could be explored with the best available evidence and incorporating expert opinions. To support the guideline with high-quality evidence, a systematic search of the electronic databases was performed to identify the relevant studies, position papers, consensus reports, and recommendations published. Rating of the level of the quality of evidence and the strength of recommendation was done using the GRADE system. Six topics were identified, each given to one group of experts comprising of advisors, chairpersons, convenor and members, and such six groups (A-F) were formed and the consensus recommendations of each group was included as a section in the guidelines (Sections I to VI). The topics included were: A. Introduction, basic principles and technical aspects of nebulization, types of equipment, their choice, use, and maintenance B. Nebulization therapy in obstructive airway diseases C. Nebulization therapy in the intensive care unit D. Use of various drugs (other than bronchodilators and inhaled corticosteroids) by nebulized route and miscellaneous uses of nebulization therapy E. Domiciliary/Home/Maintenance nebulization therapy; public & health care workers education, and F. Nebulization therapy in COVID-19 pandemic and in patients of other contagious viral respiratory infections (included later considering the crisis created due to COVID-19 pandemic). Various issues in different sections have been discussed in the form of questions, followed by point-wise evidence statements based on the existing knowledge, and recommendations have been formulated.

Central retinal vein occlusion in a patient after being commenced on sildenafil citrate for pulmonary arterial hypertension.

A 75-year-old female was commenced on sildenafil for the treatment of pulmonary arterial hypertension (PAH) secondary to chronic obstructive pulmonary disease (COPD). She reported blurring of vision within 72 hours after starting treatment and was found to have a central retinal vein occlusion (CRVO). Such an occurrence is the second case reported to date, and we review the possible mechanisms and literature on the subject.

A patient with hypercoagulable state due to tuberculosis.

A 55-year-old male patient presented with status epilepticus following prolonged fever. Investigations revealed miliary opacities in lungs that were diagnosed as tubercular after thoracoscopic lung biopsy. Wide derangement of coagulation parameters was found, indicating a pro-coagulent state. There was evidence of widespread thrombosis.

Hermansky-Pudlak syndrome.

We present a rare disease condition Hermansky-Pudlak syndrome in a 33-year-old male. He was born of a consanguineous marriage, had occulo-cutaneous albinism, nystagmus, decreased visual acuity, refractory errors, pulmonary fibrosis and granulomatous inflammation of the colon. In spite of all the classical features of this genetic disorder he was labeled to have disseminated tuberculous infection with a drug resistant strain for many years till the actual diagnosis was made on the basis of a strong clinical suspicion. We report this rare condition which might be misdiagnosed as tuberculosis.