Comparison of the Clinical Efficacy of Rituximab Infusion and Dexamethasone-Cyclophosphamide Pulse Therapy and Their Effect on Serum Th1, Th2, and Th17 Cytokines in Pemphigus Vulgaris-A Prospective, Nonrandomized, Comparative Pilot Study.

Background: Rituximab infusion and dexamethasone-cyclophosphamide pulse (DCP) are the two most popular regimens used in pemphigus vulgaris (PV) in India. Objective: The present study compared the clinical efficacy of rituximab and DCP in Indian PV patients and their effects on serum Th1,2, and 17 cytokine levels. Materials and Methods: A total of 37 patients received DCP (Group A, n = 22) or rituximab (Group B, rheumatoid arthritis protocol (n = 15)) as per patients' preference. They were monitored for clinical response, adverse events (AEs), changes in serum anti-desmoglein-1,3 antibody titers and Th1,2 and 17 cytokine levels at baseline and weeks 20 and 52. Results: The proportion of patients attaining disease control, remission, and relapse in groups A and B were 82% and 93%; 73% and 93%; and 27% and 50%, respectively, after a median duration of 2 months each for disease control; 4 and 4.5 months for remission; and 5 and 7 months for relapse post remission. The musculoskeletal AEs were the highest in the two groups. Significant and comparable decreases in anti-dsg1 and 3 titers from baseline to weeks 20 and 52 were observed in both groups. Th1 and Th17 cytokine levels decreased, while Th2 cytokines increased post-treatment in both groups. However, no correlation was found between change in body surface area of involvement by PV and anti-dsg titers and cytokine levels before and after therapy in both groups. Conclusion: Comparable clinical efficacy between DCP and rituximab was observed.

Impact of Bundled Intervention on Outcomes of Patients Undergoing Clean Orthopedic Surgeries With Hardware Implants: Small Prospective Randomized Controlled Trial.

Background: Prosthesis-related infections (PRIs) and surgical site infections (SSIs) remain one of the most devastating complications among patients undergoing clean orthopedic surgeries. Prevention strategies are critical to reduce infection rates in orthopedic surgeries. The current study aimed to determine the effectiveness of a set of evidence-based practices (bundled intervention) in reducing the incidence of PRIs and SSIs among patients undergoing clean orthopedic surgeries with hardware implants. Patients and Methods: A prospective, interventional randomized controlled trial was conducted for a period of three years. A total of 597 patients were enrolled, and depending on their Staphylococcus aureus carrier status were categorized into carrier group (n = 98) and non-carrier group (n = 499). Only carrier group patients were analyzed for effectiveness of bundled interventions, after being randomly assigned to two subgroups: interventional carrier group (ICG; n = 50) and non-interventional carrier group (NICG; n = 48). Results: Of the 597 patients, 98 (16.4%) were colonized with Staphylococcus aureus, among whom 9 (19.4%) had methicillin resistance. During follow-up, overall infection rate of 1.1% was observed (PRI, 0.3%; SSI, 0.8%). There was no case of PRI/SSI in the ICG. However, in the NICG, one patient developed SSI because of methicillin-resistant Staphylococcus aureus. An endogenous source of infection was demonstrated by pulsed field gel electrophoresis (PFGE). The SSI rate was higher in the NICG (p = 0.002). In the non-carrier group (n = 499), SSIs/PRIs occurred among 1.2% of the patients, because of organisms other than Staphylococcus aureus. Conclusions: Benefit of bundle intervention approach could be demonstrated. Further studies assessing the effectiveness of the individual components of the bundle can inform clinical practice greatly.

Assessment of renal allograft rejection with diffusion tensor imaging.

OBJECTIVES: To investigate the value of DTI in differentiation of renal allograft rejection from well-functioning stable allograft, using fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values. METHODS: In this prospective study, 22 transplant recipients with well-functioning stable allograft (group A) and 20 patients with renal allograft rejection (group B + C) were recruited over a period of 19 months from January 2018 to July 2019. DTI-MRI was performed in all the patients, and FA and ADC values were measured in cortical and medullary regions of the transplanted kidney. On biopsy, graft rejection was classified as acute (group B) (n = 7) and chronic graft rejection (group C) (n = 13) based on the BANNF scoring system. Statistical analysis was performed using STATA v.14.0. RESULTS: Statistically significant difference between group A and group B + C was noted for cortical (p < 0.001), and medullary (p = 0.003) FA values, and cortical (p = 0.020), and medullary (p = 0.046) ADC values. Cortical(p < 0.001) and Medullary(p = 0.020) FA values showed statistically significant difference between group A and group C, and cortical FA value(p = 0.012) also showed statistically significant difference between group B and group C. AUC (to differentiate between renal allograft rejection and well-functioning stable allograft) for cortical, and medullary FA values and cortical and medullary ADC values were 0.853(p < 0.001), 0.757(p = 0.004), 0.709(p = 0.021) and 0.736(p = 0.009), respectively. CONCLUSION AND ADVANCES IN KNOWLEDGE: DTI is a promising functional MRI technique for the non-invasive assessment of renal allograft function. Diffusion parameters, such as FA and ADC values, can be useful in the differentiation of renal allograft rejection from well-functioning stable allograft.

Quality of life in paediatric solid tumours: a randomised study of metronomic chemotherapy versus placebo.

OBJECTIVE: Health-related quality of life (HRQoL) is an important outcome for paediatric cancer studies. We compared the HRQoL between patients of progressive paediatric solid tumours randomised to metronomic chemotherapy versus placebo. METHODS: In this double-blinded, placebo-controlled randomised study of 108 children with progressive malignancies, HRQoL was evaluated using the PedsQOL Cancer module V.3 at baseline (A1), A2 (9 weeks or earlier if progressed) or A3 (18 weeks or earlier if progressed). RESULTS: There was no statistically significant difference in the change in quality of life produced by each arm from A1 to A2 in either mean total scores or individual domain scores, reported by children or their parents. On analysing the response according to the minimal clinically important difference, defined as an improvement by 4.5 points, we found no significant differences, be it among bone-sarcomas, other tumours, responders (those who received ≥9 weeks of treatment) or non-responders. CONCLUSIONS: The present study concludes that there was no significant difference in HRQoL, between the patients in the two arms at second and later assessments. This is consistent with the other survival endpoints in the study. TRIAL REGISTRATION NUMBER: Clinical trial registration: clinicaltrials.gov Identifier: NCT01858571.

Addition of aprepitant improves acute emesis control in children and adolescents receiving induction chemotherapy for acute myeloid leukaemia: a randomised, open-label trial.

OBJECTIVES: More than 50% patients develop emesis during induction therapy for acute myeloid leukaemia (AML). The addition of aprepitant for emesis control in children receiving induction for AML have not been explored. METHODS: A single-institutional randomised, open-label trial (NCT02979548) was conducted where children between 5 and 18 years with the diagnosis of AML being planned for 3+7 induction regimen were included. All study participants received ondansetron (0.15 mg/kg) every 8 hours for 8 days starting 30 min prior to chemotherapy. Children belonging to aprepitant group additionally received aprepitant capsules (15-40 kg=days 1-3, 80 mg; >40 kg=day 1, 125 mg and days 2-3, 80 mg) starting from 1 hour prior to chemotherapy. The proportion of patients with complete response (CR) in chemotherapy induced vomiting (CIV) in acute phase (day 1-8), delayed phase (day 9-13), overall and initial 96 hours were recorded along with severity of vomiting and adverse effects. RESULTS: Total 78 children were randomised (Aprepitant group: 37 and control group: 41). The proportion of patients with CR in CIV was significantly higher in Aprepitant group in acute phase (p=0.007), overall phase (p=0.007) and in initial 96 hours (p<0.001) but it was not different in delayed phase (p=0.07). The first episode of vomiting was also significantly delayed in aprepitant group (p=0.02). Adverse effect profile was similar in two groups. CONCLUSION: Aprepitant significantly improves emesis control in children receiving induction therapy for AML, especially in acute phase and should be routinely incorporated as part of antiemetic prophylaxis. TRIAL REGISTRATION NUMBER: The study was registered at ClinicalTrials.gov (NCT02979548).

Association of Common Mental Disorders with Diabetes Mellitus - Evidence from Community-based Matched Case-Control Study in North India.

BACKGROUND: Diabetes mellitus (DM) and depression are major public health problems globally. Evidence of linkage of common mental disorders (CMDs) including depression and anxiety disorders with DM is sparsely reported from community-based settings. OBJECTIVE: The present study aimed to study the association between CMDs and DM among adult population (>30 years) residing in a rural area of North India. MATERIALS AND METHODS: A community-based case-control study was conducted in 28 villages of Ballabgarh block of Faridabad district of Haryana. Cases (diabetes) were recruited from the community with at least 1 year of diabetes. Age- and sex-matched two neighborhood controls were selected from the same community. Diabetic status was confirmed using glycated hemoglobin. CMDs such as depression and anxiety disorders were screened using PRIME-MD Hindi version. Conditional logistic regression was used to study the relationship between diabetes and CMDs. RESULTS: Total 211 cases (diabetic) and 273 controls (nondiabetic) were approached for the study, of which 173 cases and 175 controls were analyzed. Cases and controls were comparable with respect to age, sex, and socioeconomic status. CMDs were found more among cases as compared to controls (67.5% vs. 37.5%) (P < 0.001). On conditional logistic regression analysis, CMDs were significantly higher among diabetes cases (adjusted odds ratio - 3.2, 95% confidence interval: 1.9-5.2). CONCLUSION: Strong evidence of coexistence of CMDs and DM from this population-based study necessitates the need of incorporation of management of CMDs into diabetes control program in India.

Azithromycin resistance and its molecular characteristics in Neisseria gonorrhoeae isolates from a tertiary care centre in North India.

Treatment guidelines for management of uncomplicated gonorrhoeae have been recently modified owing to alarming upsurge in azithromycin resistance. This study investigated the prevalence and genetic determinants of gonococcal azithromycin resistance in India. Four (5.7%) of 70 gonococcal isolates were resistant to azithromycin. Of 16 isolates investigated for molecular mechanisms of resistance, 13 (81.3%) and 6 (37.5%) isolates exhibited mutations in coding and promoter regions of mtrR gene, respectively. However, ermA, ermB and ermC genes or mutations in rrl gene were absent in all isolates. Azithromycin resistance is low in India posing no immediate threat to use of dual-therapy for syndromic management.

Plasmalyte-A Based del Nido Cardioplegia Versus Plain Ringer Based del Nido Cardioplegia: Double-Blind Randomized Trial.

Background: In this prospective randomized controlled trial, we compared the standard del Nido cardioplegia solution (SDN) with the modified del Nido cardioplegia solution (MDN) in which the base solution was the plain Ringer solution. Methods: A total of 80 patients aged < 12 years undergoing intracardiac repair of Tetralogy of Fallot were randomized into SDN (n = 39) or MDN (n = 41) groups. The primary outcome was a change in cardiac index (CI). Secondary outcomes were ventricular arrhythmias after the release of aortic-cross clamp, postoperative inotropic score (IS), time to peripheral rewarming, duration of mechanical ventilation, intensive care unit (ICU) length of stay, and hospital length of stay, and electron microscopic differences between the 2 groups. Cardiac Troponin-I, inflammatory markers tumor necrosis factor-α (TNF-α), and interleukin-L (IL-6) were measured. Results: Applying the noninferiority confidence interval approach, the difference between the changes in CI between the 2 groups was -0.093 L/min/m2 (95% CI: -0.46-0.27 L/min/m2) which was within the noninferiority threshold of -0.5 indicating that CI was similar in both SDN and MDN. Ventricular arrhythmias postclamp release (P = .91), IS (P = .09), duration of mechanical ventilation (P = .27), ICU length of stay (P = .50), hospital length of stay (P = .57), IL-6 (P = .19), TNF-α (P = .17), Troponin-I (P = .15), electron microscopy changes (P > .05) were not different between groups. Conclusion: MDN was shown to be noninferior to the SDN cardioplegia in terms of preservation of cardiac index. In addition, other metrics indicative of myocardial protection were similar between groups. In developing nations where SDN is not available or is expensive, MDN cardioplegia is an acceptable alternative.

N-terminal pro-brain natriuretic peptide is an independent predictor of mortality in patients with sepsis.

This study aims to evaluate the role of cardiac enzymes N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin-I (CTnI) as predictors of outcomes in patients with sepsis.78 cases with a diagnosis of sepsis were enrolled over a 2-year period. Baseline demographic, Acute Physiology and Chronic Health Evaluation-II (APACHE-II), Simplified Acute Physiology Score-II (SAPS-II), hematologic and biochemical parameters were noted. Serum NT-proBNP and CTnI were evaluated at 24 and 72 hours of admission along with echocardiography. Patients were prospectively followed up until death or discharge.Mean APACHE-II score was 19.8±9.6 and SAPS-II was 44.8±17.2. Survival rate in the study was 47.5% (36 of 78 patients). NT-proBNP was significantly higher in non-survivors with values over 4300 pg/mL at 24 hours and 5229 pg/mL at 72 hours associated with poor outcomes (p<0.05). CTnI was higher among non-survivors than in survivors, but the difference was not significant. APACHE-II score combined with NT-proBNP predicted a poor outcome in 51.2% cases compared with 14.6% cases with APACHE-II alone (p<0.05), while SAPS-II combined with NT-proBNP predicted a poor outcome in 53.6% cases as compared with 9.6% cases with SAPS-II alone (p<0.05). SAPS-II greater than 45 and NT-proBNP values at 72 hours were independent predictors of mortality in patients with sepsis.NT-proBNP is an independent predictor of mortality in patients with sepsis and its combination with APACHE-II and SAPS-II improves the predictive values of the scoring systems.

Efficacy of NB-UVB in Progressive Versus Non-Progressive Non-Segmental Vitiligo: A Prospective Comparative Study.

INTRODUCTION: Narrow-band (NB) ultraviolet B (UVB) phototherapy has been shown to halt disease progression in vitiligo, but whether there is any difference in the response to NB-UVB seen in patients with progressive vitiligo versus non-progressive vitiligo has not been evaluated. OBJECTIVES: To evaluate the effect of NB-UVB on progressive versus non-progressive non-segmental vitiligo. STUDY DESIGN: Prospective observational comparative study. DURATION: April 2016-November 2017. METHODS: Adult patients having non-segmental vitiligo involving 2-50% body surface area were divided into two subsets; patients developing >5 lesions in the last 1 month or >15 lesions in the last 3 months (progressive vitiligo, Group I) and patients with static disease for the last 6 months (non-progressive vitiligo, Group II). Both groups were treated with NB-UVB for 6 months (26 weeks) cumulatively and its efficacy in halting disease progression, re-pigmentation, side effects and psychosocial impact were evaluated. RESULTS: Nineteen out of 24 patients with progressive vitiligo had arrest of disease progression. Rest five patients developed lesions at a slower pace. Group II had earlier onset of re-pigmentation, while Group I had more NB-UVB fluence (34.73 J/cm2 vs 25.2 J/cm2, P value = 0.034), more time for the fluence to be fixed (P value = 0.001) and more pruritus (P value = 0.001). CONCLUSIONS: NB-UVB has the potential to halt disease progression in some patients with progressive vitiligo; but is associated with more total NB-UVB fluence and time taken for fixing it. Progressive vitiligo patients have more pruritus as compared to patients with non-progressive vitiligo.

Bone mass in newborns and its predictors.

OBJECTIVE: Optimal bone mass (a function of foetal programming and adequate intrauterine bone mineral accrual) is essential for prevention of osteoporosis. The present study was planned with the objectives to describe newborn bone mass (NBBM) and study the associated factors. DESIGN: Observational study Patients: Singleton pregnant women ≤16 weeks gestation. MEASUREMENTS: Maternal factors and antenatal events: Dietary assessment (3 days-24-h diet recalls at ≤16 and 32-34 weeks), fetal femoral volume (FFV) assessment at 19 and 34 weeks, serum 25 hydroxyvitamin D (S.25OHD) and placental weight. Newborn anthropometric parameters, cord S.25OHD & IGF-1 level and NBBM by DXA (whole-body bone mineral content (BMC), bone mineral density (BMD) and bone area). RESULTS: Total 224 subjects were studied: 198 full-term and 26 preterm. The mean BMC, BMD and bone area for term newborns was 46.5 g (95% confidence interval [CI]: 45.35-47.66), 0.209 g/cm2 (95% CI: 0.206-0.212) and 221.6 cm2 (95% CI: 218.52-224.62), respectively. The mean placental weight was 403.2 ± 75.01 g (n = 72) while FFV was 0.71 ± 0.28 ml (19 weeks; n = 59) and 4.4 ± 1.17 ml (34 weeks; n = 33). Factors significantly associated with NBBM -gestational age at delivery, gestational weight gain, FFV at 19 weeks, placental weight, third-trimester maternal serum albumin and newborn anthropometric parameters (univariable analysis) and newborn birth weight, placental weight and FFV at 19 weeks (multivariable analysis). CONCLUSION: This study described NBBM among term newborns and birth weight, second-trimester FFV and placental weight were the associated factors.

Evaluation of the Prevalence, Regional Phenotypic Variation, Comorbidities, Risk Factors, and Variations in Response to Different Therapeutic Modalities Among Indian Women: Proposal for the Indian Council of Medical Research-Polycystic Ovary Syndrome (ICMR-PCOS) Study.

BACKGROUND: There is scanty data in India on polycystic ovary syndrome (PCOS) from several small, undersized, convenience-based studies employing differing diagnostic criteria and reporting varied regional prevalence. It is difficult to draw clear-cut conclusions from these studies; therefore, the present multicentric, well-designed, large-scale representative countrywide epidemiological study on PCOS across India was conceived with the aim to generate the actual prevalence rates of PCOS in India with a total sample size of approximately 9000 individuals. OBJECTIVE: The primary objectives of the study are to estimate the national prevalence of PCOS in India and the burden of comorbidities and to compare the variation in efficacy of standard therapeutic modalities for metabolic dysfunction in women with PCOS. METHODS: This multicentric umbrella study consists of three different substudies. Substudy 1 will involve recruitment of women aged 18-40 years using a multistage sampling technique from randomly selected polling booths across urban and rural areas to estimate national prevalence, phenotypic variation, and risk factors among regions. Substudy 2 involves recruitment of subjects from the community pool of substudy 1 and the institutional pool for quantitation of comorbidities among women with PCOS. Substudy 3, an interventional part of the study, aims for comparison of variation in efficacies of common treatment modalities and will be conducted only at 2 centers. The eligible consenting women will be randomized in a 1:1 ratio into 2 arms through a blinding procedure. All these women will undergo clinical, biochemical, and hormonal assessment at baseline and at 3 and 6 months. The data generated will be analyzed using the reliable statistical software SPSS (version 26). RESULTS: The study is ongoing and is likely to be completed by April 2022. The data will be compiled and analyzed, and the results of the study will be disseminated through publications. CONCLUSIONS: The Indian Council of Medical Research-PCOS study is the first of its kind attempting to provide accurate and comprehensive data on prevalence of PCOS in India. TRIAL REGISTRATION: Clinical Trials Registry-India CTRI/2018/11/016252; ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=26366. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/23437.

Modified ultrafiltration and postoperative course in patients undergoing repair of tetralogy of fallot.

BACKGROUND: Expected benefits of modified ultrafiltration (MUF) include increased hematocrit, reduction of total body water and inflammatory mediators, improved left ventricular systolic function, and improved systolic blood pressure and cardiac index (CI) following cardiopulmonary bypass (CPB). This prospective randomized trial tested this hypothesis. METHODS: Seventy-nine patients undergoing intracardiac repair of tetralogy of fallot were randomized to conventional ultrafiltration (CUF) + MUF (n = 39) or only CUF group (n = 40). The primary outcome was a change in hematocrit. Secondary outcomes were changes in peak airway pressures, ventilatory support, blood transfusions, time to peripheral rewarming, mean arterial pressure, central venous pressure, inotrope score (IS), and CI. Serum inflammatory markers were measured. RESULTS: Baseline hematocrit was 50.6 ± 10.02 in the only CUF group whereas it was 43.9 ± 5.55 in the CUF + MUF group (p = .36). Following MUF, the CUF + MUF group had higher hematocrit (44.7 ± 0.50 g/dl) compared to the only CUF group (37.2 ± 0.49 g/dl), p ≤ .001 after adjusting for baseline hematocrit. Central venous pressure (mmHg) immediately following sternal closure was 9.27 ± 3.12 mmHg in the CUF + MUF group and 10.52 ± 2.2 mmHg in the only CUF group (p = .04). In the intensive care unit (ICU), they were 11.52 ± 2.20 mmHg in the only CUF group and 10.84 ± 2.78 mmHg in the CUF + MUF group (p = .02). Time to peripheral rewarming was 6.30 ± 3.91 h in the CUF + MUF group and 13.67 ± 3.91 h in the only CUF group (p = .06). Peak airway pressures in ICU were 17 ± 2 mmHg versus 20.55 ± 2.97 mmHg in CUF + MUF group & only CUF group, respectively, p < .001). Duration of mechanical ventilation was 6.3 ± 2.7 h in CUF + MUF group compared to 14.7 ± 3.5 h in the only CUF group (p = .002). IS was 11.52 ± 2.20 in the only CUF group compared to 10.84 ± 2.78 in CUF + MUFs group. Eight of 39 (20.5%) patients in the CUF + MUF group had IS > 10 compared to 22 of 40 (55%) patients in the only CUF group (p = .02). Serum Troponin-T and interleukin-6 levels were lower in the CUF + MUF group; TNF-α and CPK-MB were similar. ICU and hospital stay were similar. CONCLUSION: Patients undergoing a combination of CUF and MUF had higher postoperative hematocrit, decreased duration of mechanical ventilation, lower need for inotropes and lower interleukin-6 and Troponin-T levels. This group had better postoperative outcomes. This study was registered with the Clinical trials registry of India (CTRI/2017/11/010512) before commencement.

Histological analyses of trucut liver biopsies from patients with noncirrhotic portal fibrosis and extra-hepatic portal vein obstruction.

BACKGROUND: Both noncirrhotic portal fibrosis (NCPF) and extrahepatic portal venous obstruction (EHPVO) are important causes of noncirrhotic portal hypertension (PH) in the Asian region. In this study, we analyzed the histopathological changes of liver needle-core biopsies from patients with NCPF and EHPVO. PATIENTS AND METHODS: The patients were diagnosed as per the Asia Pacific Association for the Study of Liver (APASL) criteria. Minimum adequacy criteria for liver core biopsies were defined, and finally, 69 liver biopsies from patients with NCPF and 100 liver biopsies from patients with EHPVO were analyzed. All histological parameters were predefined, and three experienced pathologists analyzed the biopsies after reaching consensus. Institute ethics committee clearance was taken. RESULTS: Although some histological features were overlapping, phlebosclerosis of intra-hepatic branches of the portal vein (PV), periportal aberrant vascular channels, remnant portal tracts, and hepatic fibrosis beyond the portal tracts without the formation of complete hepatic nodules (P < 0.001 for all) were common histological characteristics of NCPF on core-needle liver biopsies; while maintained lobular architecture, nonspecific dilatation of PV branches, absence of intra-hepatic PV phlebosclerosis, aberrant vascular channels, and significant fibrosis were characteristics of EHPVO. CONCLUSIONS: Despite the considerable histological overlap between NCPF and EHPVO, careful histological evaluation, supplemented by clinical features, radiological and biochemical findings can help in making a conclusive diagnosis. Patients with NCPF and EHPVO with clinical jaundice show transaminitis, high serum alkaline phosphatase level, more variceal bleed, and histological evidences of nodular regenerative hyperplasia.

Pazopanib based oral metronomic therapy for platinum resistant/refractory epithelial ovarian cancer: A phase II, open label, randomized, controlled trial.

BACKGROUND: Treatment of patients with platinum resistant/refractory epithelial ovarian cancer (EOC) is an unmet need. We evaluated the role of oral metronomic therapy in this setting. PATIENTS AND METHODS: Between October 2017 and September 2019 seventy five patients with platinum resistant/refractory EOC were enrolled. Patients received oral etoposide (50 mg, day 1 to 14, cyclophosphamide 50 mg, day 1 to 28, every 4 weeks (Arm A, n = 38). Patients in Arm- B (n = 37) received Pazopanib (400 mg once daily) in addition to etoposide and cyclophosphamide. Quality of life (QoL) was evaluated using the EORTC questionnaire. Serum VEGF and PDGF were estimated at baseline, after 3rd and 6th cycle. The primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and QoL. RESULTS: Patients characteristics were well matched. Median PFS was higher in arm B, 5.1 months (95% CI 3.13 to10.33) compared to 3.4 months (95% CI 3.0 to 6.53) in arm A, p = 0.045. Median OS has 'not reached' in Arm B compared to 11.2 months (95% CI, 5.66 - not reached) in arm A, p = 0.032. Therapy was tolerated well; oral mucositis (p = 0.36) and fatigue (p = 0.08) being more in arm B. QoL assessment revealed modest improvement in 'symptom scales' in Arm B. Serum VEGF and PDGF levels decreased with therapy in both arms (Arm A-p < 0.0001, Arm B-p < 0.016). CONCLUSION: Addition of pazopanib to etoposide and cyclophosphamide could be a novel oral combination for metronomic therapy for platinum resistant/refractory EOC. TRIAL REGISTRATION: CTRI/2017/10/010219.

Molecular characterization of decreased susceptibility to ceftriaxone and genotyping of Neisseria gonorrheae isolates in New Delhi, India.

Data on genetic characteristics of Neisseria gonorrhoeae isolates exhibiting decreased susceptibility to extended-spectrum cephalosporins in India is deficient. In this study, we have sequenced penA, porB, mtrR and ponA and blaTEM genes in 70 clinical isolates of NG with varying ceftriaxone MICs. Amongst these, 22 (31.4%) were PPNG. Additionally, N. gonorrheae Multiantigen Sequence Typing was performed. Fisher exact and χ2 were used to evaluate significance of mutations with MICs. A total of six non-mosaic penA (Penicillin binding protein 2 [PBP2]) amino acid patterns were seen (II, IV, IX, XII, XIX, XXII) of which, pattern IX was significantly associated with decreased susceptibility to ceftriaxone. Other significant associations were noted in porB & mtrR genes. There were no mutations in blaTEM gene. ST6069 was significantly associated with decreased susceptibility to ceftriaxone. To conclude, development of decreased susceptibility to ceftriaxone in gonococci involves cumulation of different mutations in the four chromosomal genes investigated.

Impact of a Psychodermatological Education Package on the Subjective Distress, Family Burden, and Quality of Life among the Primary Caregivers of Children Affected with Epidermolysis Bullosa.

BACKGROUND: Epidermolysis bullosa (EB) has profound effect on the subjective distress, family burden, and quality of life (QOL) of the primary caregivers (PCG). Knowledgeable PCG can efficiently manage children with these skin diseases and also improve their QOL. OBJECTIVES: To assess the subjective distress, family burden, and QOL, to develop and assess the short-term effectiveness of a psycho-dermatological education package (PDEP) for the PCG of children with EB. METHODS: In this interventional study, 30 PCG of EB were assessed for subjective distress, family burden, and QOL. PDEP, a structured educational tool explaining the disease and its care and stress management, was developed by the authors for the PCG and administered to them after one month of enrolment. They were reassessed after three months and compared with the baseline assessment scores. For comparison, 37 PCG of CI were also studied. RESULTS: The mean age (years) of the subjects was 28.7 ± 6.7 for EB and 30.5 ± 4.6 for CI. The mean or median (range) baseline scores for subjective distress, family burden and QOL of PCG (n = 20) of EB were 8.4 ± 7.9, 6.5 (0-30); 28.5 ± 17.5, 24 (7-77) and 12.6 ± 6.7, 11.5 (4-28) and for PCG (n = 14) of CI were 12 ± 4.3, 38.9 ± 16.2 and 17.7 ± 3.6 respectively. The PDEP improved the QOL (p = 0.01), knowledge (p < 0.01) and practices (p < 0.001) for PCG of EB and it improved subjective distress (p < 0.001), QOL (p < 0.01) and knowledge (p < 0.01) for PCG of CI. CONCLUSIONS: PDEP is an effective educational tool in improving the QOL and knowledge of PCG, which in turn provides efficient management and psychological support to children affected with EB and CI. It should, therefore, be routinely used for educating the PCG of children with EB and CI.