Amikacin liposome inhalation suspension for chronic Pseudomonas aeruginosa infection in cystic fibrosis

BackgroundShortcomings of inhaled antibiotic treatments for Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) include poor drug penetration, inactivation by sputum, poor efficiency due to protective biofilm, and short residence in the lung.MethodsEligible patients with forced expiratory volume in 1 s (FEV₁) ≥25% of predicted value at screening and CF with chronic P. aeruginosa infection were randomly assigned to receive 3 treatment cycles (28 days on, 28 days off) of amikacin liposome inhalation suspension (ALIS, 590 mg QD) or tobramycin inhalation solution (TIS, 300 mg BID). The primary endpoint was noninferiority of ALIS vs TIS in change from baseline to day 168 in FEV₁ (per-protocol population). Secondary endpoints included change in respiratory symptoms by Cystic Fibrosis Questionnaire-Revised (CFQ-R).ResultsThe study was conducted February 2012 to September 2013. ALIS was noninferior to TIS (95% CI, −4.95 to 2.34) for relative change in FEV₁ (L) from baseline. The mean increases in CFQ-R score from baseline on the Respiratory Symptoms scale suggested clinically meaningful improvement in both arms at the end of treatment in cycle 1 and in the ALIS arm at the end of treatment in cycles 2 and 3; however, the changes were not statistically significant between the 2 treatment arms. Treatment-emergent adverse events (TEAEs) were reported in most patients (ALIS, 84.5%; TIS, 78.8%). Serious TEAEs occurred in 17.6% and 19.9% of patients, respectively; most were hospitalisations for infective pulmonary exacerbation of CF.ConclusionsCyclical dosing of once-daily ALIS was noninferior to cyclical twice-daily TIS in improving lung function.ClinicalTrials.gov Identifier: NCT01315678     

Dr PK Sen TAI gold medal oration

The current write-up is for Dr P.K.Sen TAI Gold Medal Oration Award for 2020 conferred to Dr Rupak Singla and delivered on 19 th December 2020. The title chosen for the oration was “Introduction and scale up of new anti-TB drugs in India: role of NITRD.? However, in the oration the role this institute has played for overall scale up of Drug-resistant TB services in India under National Tuberculosis Elimination Programme (NTEP) at different times from the beginning of national TB programme has also been presented. National Institute of TB and Respiratory Diseases has travelled with our country from beginning of DR-TB care. It demonstrated for the first time use of a Standardized Treatment Regimen with second line drugs for MDR-TB in field conditions. NITRD assisted NTEP for the concept of DST guided treatment. This institute guided NTEP for the management of MDR-TB failure patients with Pre-XDR and XDR-TB. Also, NITRD assisted India for the introduction of newer DR-TB drugs and scale up of newer drugs across the country. The strength of NITRD include clinical expertise, laboratory support and training division. NITRD commitment is strong and will continue to support NTEP for all endeavors in future also.     

Independent association of obstructive sleep apnea with left ventricular geometry and systolic function in resistant hypertension: the RESIST-POL study

ObjectiveWe investigated the impact of obstructive sleep apnea (OSA) and night blood pressure (BP) on left ventricular geometry and systolic function in patients with resistant hypertension (RHTN).Methods and ResultsData from 155 patients with RHTN were analyzed. All patients underwent biochemical evaluations, ambulatory blood pressure monitoring (ABPM), and polysomnography. Left ventricular mass index (LVMI), relative wall thickness (RWT), left ventricular ejection fraction (LVEF), midwall fractional shortening (mwFS) and global longitudinal strain (GLS) were measured. Patients were divided into four groups based on the presence of metabolic syndrome (MS) and OSA: group 1: OSA(−), MS(−) [n = 42]; group 2: OSA(+), MS(−) [n = 14]; group 3: OSA(–), MS(+) [n = 46]; and group 4: OSA(+), MS(+) [n = 53]. In group 3 and 4 concentric geometry was present in 53.2% and 79.6% respectively (P = 0.004). There were no differences in LVEF between groups. Group 3 and 4 had lower mwFS as compared with group 1 (16.40 ± 1.9 and 15.38 ± 2.2 vs 17.44 ± 1.9; P < 0.049 and P < 0.0001 respectively). Group 4 had significantly lower GLS as compared with group 1 (–12.64 ± 3.3 vs −15.59 ± 4.0; P < 0.001). In the multivariable analysis, factors independently associated with concentric geometry were age, nighttime SBP (OR –1.04; 95%Cl 1.019–1.082; P < 0.0001) and OSA (OR –3.97; 95%Cl 1.835–8.590; P < 0.0001). In the other multivariable analysis, factors independently associated with GLS were OSA (beta = 0.279; P = 0.001), and nighttime DBP (beta = 0.168; P = 0.048) whereas factors independently associated with mwFS were age, gender, nighttime SBP, concentric geometry, and metabolic syndrome.ConclusionsIn patients with true RHTN without diabetes concentric geometry and systolic dysfunction are independently associated with moderate and severe OSA and nighttime BP levels.