Autologous Stem Cell Transplantation in Adult Hodgkin Lymphoma at a Tertiary Care Center in India: Analysis of Outcomes and Prognostic Factors.

High-dose chemotherapy and autologous stem cell transplant (ASCT) is the standard of care treatment in relapsed/refractory Hodgkin lymphoma (rrHL). Published long-term follow-up data concerning this modality from the Indian subcontinent is lacking. In this retrospective study, the data on adults (> 16 years) with biopsy-confirmed rrHL who were autografted from 1 January 2000 to 31 December 2021 at our transplant unit were analyzed. Progression-free survival (PFS) was defined as time from transplant to disease progression or death due to any cause. Overall survival (OS) was determined from date of transplant to date of death due to any cause. Overall, 134 patients with Hodgkin lymphoma underwent ASCT. At a median follow-up of 38.2 (range, 0.1-240) months, 5 years PFS was 45.3% (95% CI 35.4-54.4). The probability of OS at 5 years was 60.5% (95% CI 49.6-69.6). Eleven (8.2%) patients suffered transplant-related mortality by 100 days. Post-transplant persistent disease, pre-transplant serum hypoalbuminemia (< 3.5 g/dl) and chemo-resistance (< PR after last salvage regimen) of tumour at transplant were independent prognostic factors associated with worse PFS in multivariable analysis. Likewise, age ≥ 30 years, ECOG performance status ≥ 1 and residual disease after transplantation correlated with inferior OS. Long-term outcomes of rrHL patients undergoing ASCT in India match those from the developed world in the era of peripheral blood stem cell transplantation. Pre-transplant performance status, chemo-sensitivity of disease, serum albumin and post-transplant remission status determined survival in our cohort. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01690-x.

Sexual and reproductive health and rights of migrant women attending primary care in England: A population-based cohort study of 1.2 million individuals of reproductive age (2009-2018).

Background: Evidence on the sexual and reproductive health and rights (SRHR) of migrants is lacking globally. We describe SRHR healthcare resource use and long-acting reversible contraceptives (LARCs) prescriptions for migrant versus non-migrant women attending primary care in England (2009-2018). Methods: This population-based observational cohort study, using Clinical Practice Research Datalink (CPRD) GOLD, included females living in England aged 15 to 49. Migration was defined using a validated codelist. Rates per 100 person years at risk (pyar) and adjusted rate ratios (RRs) were measured in migrants versus non-migrants for consultations related to all-causes, six exemplar SRHR outcomes, and LARC prescriptions. Proportions of migrants and non-migrants ever prescribed LARC were calculated. Findings: There were 25,112,116 consultations across 1,246,353 eligible individuals. 98,214 (7.9 %) individuals were migrants. All-cause consultation rates were lower in migrants versus non-migrants (509 vs 583/100pyar;RR 0.9;95 %CI 0.9-0.9), as were consultations rates for emergency contraception (RR 0.7;95 %CI 0.7-0.7) and cervical screening (RR 0.96;95 %CI 0.95-0.97). Higher rates of consultations were found in migrants for abortion (RR 1.2;95 %CI 1.1-1.2) and management of fertility problems (RR 1.39;95 %CI 1.08-1.79). No significant difference was observed for chlamydia testing and domestic violence. Of 1,205,258 individuals eligible for contraception, the proportion of non-migrants ever prescribed LARC (12.2 %;135,047/1,107,894) was almost double that of migrants (6.91 %;6,728/97,364). Higher copper intrauterine devices prescription rates were found in migrants (RR 1.53;95 %CI 1.45-1.61), whilst hormonal LARC rates were lower for migrants: levonorgestrel intrauterine device (RR 0.63;95 %CI 0.60-0.66), subdermal implant (RR 0.72;95 %CI 0.69-0.75), and progesterone-only injection (RR 0.35;95 %CI 0.34-0.36). Interpretation: Healthcare resource use differs between migrant and non-migrant women of reproductive age. Opportunities identified for tailored interventions include access to primary care, LARCs, emergency contraception and cervical screening. An inclusive approach to examining health needs is essential to actualise sexual and reproductive health as a human right.

End Users' Perceived Engagement with Clinical Dashboards: A Rapid Review.

Clinical dashboards are an emerging and fast-evolving technology used to support frontline clinicians' practice. Understanding end users' perceived engagement with clinical dashboards is essential to co-design, implementation, and adoption. There is a lack of literature exploring the integration of dashboards into clinical workflow. This rapid review explores clinical end users' perceived engagement with dashboards that support workflow. We conducted a literature search in PubMed and CINAHL. Four articles met our eligibility criteria. Findings reveal variations in taxonomy and measures used to evaluate clinicians' perceived engagement. There are also a variety of reported barriers and facilitators to adoption. Standardized frameworks and vocabulary are needed to facilitate a common understanding of clinical end users' perceived engagement with dashboards.

Developing a Quality Improvement Implementation Taxonomy for Organizational Employee Wellness Initiatives.

BACKGROUND: Standardized taxonomies (STs) facilitate knowledge representation and semantic interoperability within health care provision and research. However, a gap exists in capturing knowledge representation to classify, quantify, qualify, and codify the intersection of evidence and quality improvement (QI) implementation. This interprofessional case report leverages a novel semantic and ontological approach to bridge this gap. OBJECTIVES: This report had two objectives. First, it aimed to synthesize implementation barrier and facilitator data from employee wellness QI initiatives across Veteran Affairs health care systems through a semantic and ontological approach. Second, it introduced an original framework of this use-case-based taxonomy on implementation barriers and facilitators within a QI process. METHODS: We synthesized terms from combined datasets of all-site implementation barriers and facilitators through QI cause-and-effect analysis and qualitative thematic analysis. We developed the Quality Improvement and Implementation Taxonomy (QIIT) classification scheme to categorize synthesized terms and structure. This framework employed a semantic and ontological approach. It was built upon existing terms and models from the QI Plan, Do, Study, Act phases, the Consolidated Framework for Implementation Research domains, and the fishbone cause-and-effect categories. RESULTS: The QIIT followed a hierarchical and relational classification scheme. Its taxonomy was linked to four QI Phases, five Implementing Domains, and six Conceptual Determinants modified by customizable Descriptors and Binary or Likert Attribute Scales. CONCLUSION: This case report introduces a novel approach to standardize the process and taxonomy to describe evidence translation to QI implementation barriers and facilitators. This classification scheme reduces redundancy and allows semantic agreements on concepts and ontological knowledge representation. Integrating existing taxonomies and models enhances the efficiency of reusing well-developed taxonomies and relationship modeling among constructs. Ultimately, employing STs helps generate comparable and sharable QI evaluations for forecast, leading to sustainable implementation with clinically informed innovative solutions.

Developing a Quality Improvement Implementation Taxonomy for Organizational Employee Wellness Initiatives.

BACKGROUND: Standardized taxonomies (STs) facilitate knowledge representation and semantic interoperability within health care provision and research. However, a gap exists in capturing knowledge representation to classify, quantify, qualify, and codify the intersection of evidence and quality improvement (QI) implementation. This interprofessional case report leverages a novel semantic and ontological approach to bridge this gap. OBJECTIVES: This report had two objectives. First, it aimed to synthesize implementation barrier and facilitator data from employee wellness QI initiatives across Veteran Affairs health care systems through a semantic and ontological approach. Second, it introduced an original framework of this use-case-based taxonomy on implementation barriers and facilitators within a QI process. METHODS: We synthesized terms from combined datasets of all-site implementation barriers and facilitators through QI cause-and-effect analysis and qualitative thematic analysis. We developed the Quality Improvement and Implementation Taxonomy (QIIT) classification scheme to categorize synthesized terms and structure. This framework employed a semantic and ontological approach. It was built upon existing terms and models from the QI Plan, Do, Study, Act phases, the Consolidated Framework for Implementation Research domains, and the fishbone cause-and-effect categories. RESULTS: The QIIT followed a hierarchical and relational classification scheme. Its taxonomy was linked to four QI Phases, five Implementing Domains, and six Conceptual Determinants modified by customizable Descriptors and Binary or Likert Attribute Scales. CONCLUSION: This case report introduces a novel approach to standardize the process and taxonomy to describe evidence translation to QI implementation barriers and facilitators. This classification scheme reduces redundancy and allows semantic agreements on concepts and ontological knowledge representation. Integrating existing taxonomies and models enhances the efficiency of reusing well-developed taxonomies and relationship modeling among constructs. Ultimately, employing STs helps generate comparable and sharable QI evaluations for forecast, leading to sustainable implementation with clinically informed innovative solutions.

Quality of life assessment in testicular non-seminomatous germ cell tumour survivors.

PURPOSE: Patients with Germ cell tumours (GCT) are at risk of long-term toxicities due to multimodality therapy. It is debatable whether there is an impact on the quality of life(QoL) of GCT survivors. METHODS: A case-control study was conducted at a tertiary care centre in India, using the EORTC QLQ C30 questionnaire, to compare the QoL between GCT survivors(disease free > 2 years) and healthy matched controls. A multivariate regression model was used to identify factors affecting QoL. RESULTS: A total of 55 cases and 100 controls were recruited. Cases had a median age of 32 years (interquartile range, IQR 28-40 years), ECOG PS of 0-1(75%), advanced stage III (58%), chemotherapy (94%) and 66% were > 5 years from diagnosis. The median age of controls: 35 years (IQR 28-43 years). A statistically significant difference was seen for emotional (85.8 ± 14.2 vs 91.7 ± 10.4, p 0.005), social(83.0 ± 22.0 vs 95.2 ± 9.6, p < 0.001) and global scales (80.4 ± 21.1 vs 91.3 ± 9.7, p < 0.001). Cases had more nausea and vomiting(3.3 ± 7.4 vs 1.0 ± 3.9, p 0.015), pain(13.9 ± 13.9 vs 4.8 ± 9.8, p < 0.001), dyspnea(7.9 + 14.3 vs 2.7 ± 9.1, p 0.007), and appetite loss(6.7 ± 14.9 vs 1.9 ± 7.9, p 0.016) and greater financial toxicity(31.5 ± 32.3 vs 9.0 ± 16.3, p < 0.001). Adjusting for age, performance status, BMI, stage, chemotherapy, RPLND, recurrent disease, and time since diagnosis, no predictive variables were significant. CONCLUSION: There is a detrimental impact of history of GCT in long term survivors of GCT.

Sclerosing epithelioid fibrosarcoma of the kidney.

A woman in her 20s presented with headache and back pain and was found to have a left renal mass with bony metastases. She underwent nephrectomy, and on histopathology was initially diagnosed with stage 4 clear cell sarcoma of the kidney. She underwent palliative radiation and chemotherapy; however, the disease progressed and she came to our centre. We started her on second-line chemotherapy and submitted her tissue blocks for review. Due to her age and lack of sclerotic stroma in the tissue, we had our doubts about the diagnosis and hence, tissue sample was submitted for next-generation sequencing (NGS). NGS detected an EWSR1::CREBL1 fusion, clinching the final diagnosis of sclerosing epithelioid fibrosarcoma of the kidney, a singular diagnosis rarely reported in the literature. Currently, the patient is post her third line of chemotherapy, is on maintenance, and is doing well and has resumed her daily activities.

The proactive-reactive classification of intimate partner violence offenders: A multi-method approach to classification.

BACKGROUND: Men who commit violence against an intimate partner differ in their motives. Classifying the proactivity of men's partner violence may reveal important differences that could be treatment targets. AIMS: To examine the differences between proactive and reactive partner violence based on coded descriptions of past violent events. METHOD: Community cohabiting couples reporting intimate partner violence were recruited via advertisements. Men and women were independently interviewed about past male-to-female violent events. The narratives of a male perpetrator and a female victim were coded using a Proactive-Reactive coding system, yielding three categories of violence: reactive, mixed proactive/reactive and proactive. The three categories were compared for differences in personality disorder features, attachment, psychophysiological reactivity during a conflict discussion task, and a self- and partner report of men's proactive and reactive aggressive tendencies. RESULTS: The results revealed a 54% classification agreement between perpetrator and victim reports. No differences were found on personality or attachment measures between the groups regardless of gender of the reporter. Reactive violence was related to a tendency to self-report more reactive aggression and higher heart rate reactivity during a laboratory conflict discussion compared to the group reporting both proactive and reactive violent incidents. CONCLUSION: This study suggests that a coding system for intimate partner violence can be applied to community volunteers, and it is a reliable report and valid. However, there are discrepancies when the coding is based on the perpetrator or victim reports.

Improving the performance status in advanced non-small cell lung cancer patients with chemotherapy (ImPACt trial): a phase 2 study.

PURPOSE: This phase II trial is designed to test whether the performance status (PS) of metastatic non-small cell lung cancer (mNSCLC) patients (pts) can improve with chemotherapy if their poor PS (Eastern Cooperative Oncology Group (ECOG) PS of ≥ 2) is due to disease burden rather than comorbidities. METHODS: Age18-65 years, Charlson's comorbidity index < 9, serum albumin ≥ 3.5 g/dl, adequate bone marrow and organ function, & ECOG PS ≥ 2 as judged by the worst score of three independent physicians were administered 3 doses of weekly paclitaxel at 60 mg/m2/dose. The primary endpoint was an improvement in ECOG PS by 1 point at 4 weeks; others: toxicity (CTCAE v 5.0), quality of life (QoL) assessment at baseline and 4 weeks by EORTC QLQ-C30 and EORTC QLQ-LC13. Optimal Simon's 2-stage design was used. RESULTS:  Forty-six patients were included with a median age of 56 years (interquartile range, IQR 54-59), 12 (26%) had comorbid conditions, and 87% with ECOG PS 3/4. PS improved in 11 pts at 4 weeks and in 7 beyond this time point. Grade 3/4 toxicities are seen in 20% (most common: anemia and diarrhea). At a median follow-up of 4.8 m (95% CI 3.27-14.9), the median progression-free survival and overall survival were 3.3 months (95% CI 2.36-5.6) and 6.8 months (95% CI 2.47-8.8), respectively. QoL improved for global QoL, role functioning, pain, dyspnea, insomnia, pain in the chest, pain in other parts, and worsened for alopecia and sore mouth. CONCLUSIONS:  Abbreviated chemotherapy is a useful, well-tolerated strategy in carefully selected poor PS mNSCLC patients that can improve PS and QoL. CLINICAL TRIAL: Clinical trial information: CTRI/2020/01/022617.

Autologous stem cell transplant for multiple myeloma: Impact of melphalan dose on the transplant outcome.

We evaluated impact of melphalan dose on transplant outcomes for multiple myeloma. Between 1995 and 2019 459 consecutive patients received a transplant; 69(15%) received melphalan ≤150 mg/m2 (Mel 150 cohort) and 390 (85%) melphalan 200 mg/m2 (MEL 200 cohort). The primary outcome was overall survival (OS) from the date of transplant. Progression-free survival (PFS), engraftment, transplant response, and cumulative relapse at 2 years were secondary outcome measures. Patients in Mel 150 cohort had adverse clinical and laboratory parameters at base line. Transplant response was better for Mel 200 cohort (p < 0.024). Median OS at a median follow-up of 88 months was similar in the two cohorts; 100 Vs 102 months (Mel 200), p = 0.817. Median PFS (60.0 Vs 53 months, p = 0.746), relapse at two years (32.4% Vs 30.9%, p = 0.745) and grade 3-4 mucositis (p = 0.823) were similar. Initial treatment prepares patients better for subsequent similar transplant outcomes despite differences in baseline characteristics.

Interventions to improve health and the determinants of health among sex workers in high-income countries: a systematic review.

Many sex worker populations face high morbidity and mortality, but data are scarce on interventions to improve their health. We did a systematic review of health and social interventions to improve the health and wider determinants of health among adult sex workers in high-income countries. We searched MEDLINE, Embase, PsycINFO, CINAHL, the Cochrane Library, Web of Science, EthOS, OpenGrey, and Social Care Online, as well as the Global Network of Sex Work Projects and the Sex Work Research Hub for studies published between Jan 1, 2005 and Dec 16, 2021 (PROSPERO CRD42019158674). Quantitative studies reporting disaggregated data for sex workers were included and no comparators were specified. We assessed rigour using the Quality Assessment Tool for Quantitative Studies. We summarised studies using vote counting and a narrative synthesis. 20 studies were included. Most reported findings exclusively for female sex workers (n=17) and street-based sex workers (n=11). Intervention components were divided into education and empowerment (n=14), drug treatment (n=4), sexual and reproductive health care (n=7), other health care (n=5), and welfare (n=5). Interventions affected a range of mental health, physical health, and health behaviour outcomes. Multicomponent interventions and interventions that were focused on education and empowerment were of benefit. Interventions that used peer design and peer delivery were effective. An outreach or drop-in component might be beneficial in some contexts. Sex workers who were new to working in an area faced greater challenges accessing services. Data were scarce for male, transgender, and indoor-based sex workers. Co-designed and co-delivered interventions that are either multicomponent or focus on education and empowerment are likely to be effective. Policy makers and health-care providers should improve access to services for all genders of sex workers and those new to an area. Future research should develop interventions for a greater diversity of sex worker populations and for wider health and social needs.

A Comparison of Sexual Minority and Heterosexual College Students on Gendered Sexual Scripts and Sexual Coercion Perpetration.

Prior work has identified endorsement of gendered sexual script beliefs as predictive of sexual coercion perpetration among heterosexual individuals, primarily men. This research is lacking among sexual minority individuals and may be important in informing inclusive and effective sexual coercion prevention efforts. The current study sought to (1) assess the level of adherence to gendered sexual script beliefs, (2) report relative rates of general sexual coercion and sexual intimate partner violence (IPV), and (3) examine the relationship between gendered sexual script beliefs and self-reported sexually coercive behavior among sexual minority and heterosexual college men and women. Undergraduate students (n = 1,199; 182 sexual minorities) completed self-report measures assessing gendered sexual script beliefs, sexual coercion perpetration, and sexual IPV. Results from Gender × Sexual Minority group ANOVAs and logistic regression analyses indicated similar rates of perpetration across sexual orientation groups, with men overall reporting the most perpetration. Furthermore, men and heterosexual individuals adhered more strongly to gendered sexual scripts than women and sexual minority individuals, respectively. Results of path models revealed no moderation by sexual orientation, and that adherence to gendered sexual scripts was positively related to sexual IPV perpetration among the full sample of heterosexual and nonheterosexual individuals, though this effect was small. Gendered sexual scripts did not significantly relate to general sexual coercion perpetration among the full sample, suggesting that traditional sexual script beliefs may not be as relevant to perpetration in a contemporary college sample. This study adds to limited literature on sexual coercion perpetration among sexual minority individuals and is an important step in understanding relationships between endorsement of gendered sexual script beliefs and sexual coercion perpetration among sexual minority and heterosexual college students.

Lifestyle Medicine Interventions for Personal and Planetary Health: The Urgent Need for Action.

The deterioration of planetary health-from threats such as climate change, environmental pollution, biodiversity loss, and ocean acidification-are a growing hazard to the foundation of health and the "healthspan." For those with chronic conditions-a large and growing subset of the global population-the health dangers are even greater. Climate change is a threat to the very pillars of lifestyle medicine that we rely on to prevent and manage chronic disease. Already, the planetary crisis is limiting our ability to prescribe healthy nutrition, safe outdoor physical activity, stress management strategies, social connection, restorative sleep, and toxic substance avoidance. In this article, we discuss the proceedings of our workshop at the American College of Lifestyle Medicine (ACLM) annual conference LM2021, "Lifestyle Medicine for Personal and Planetary Health." We examine how lifestyle medicine (LM) interventions are a prescription for individual, community, and planetary health. Our prescriptions work to not only restore the health of individuals and families, but also to bolster health equity while allowing us to mitigate and adapt to the health impacts of the planetary crises.

Migrants' primary care utilisation before and during the COVID-19 pandemic in England: An interrupted time series analysis.

Background: How international migrants access and use primary care in England is poorly understood. We aimed to compare primary care consultation rates between international migrants and non-migrants in England before and during the COVID-19 pandemic (2015-2020). Methods: Using data from the Clinical Practice Research Datalink (CPRD) GOLD, we identified migrants using country-of-birth, visa-status or other codes indicating international migration. We linked CPRD to Office for National Statistics deprivation data and ran a controlled interrupted time series (ITS) using negative binomial regression to compare rates before and during the pandemic. Findings: In 262,644 individuals, pre-pandemic consultation rates per person-year were 4.35 (4.34-4.36) for migrants and 4.60 (4.59-4.60) for non-migrants (RR:0.94 [0.92-0.96]). Between 29 March and 26 December 2020, rates reduced to 3.54 (3.52-3.57) for migrants and 4.2 (4.17-4.23) for non-migrants (RR:0.84 [0.8-0.88]). The first year of the pandemic was associated with a widening of the gap in consultation rates between migrants and non-migrants to 0.89 (95% CI 0.84-0.94) times the ratio before the pandemic. This widening in ratios was greater for children, individuals whose first language was not English, and individuals of White British, White non-British and Black/African/Caribbean/Black British ethnicities. It was also greater in the case of telephone consultations, particularly in London. Interpretation: Migrants were less likely to use primary care than non-migrants before the pandemic and the first year of the pandemic exacerbated this difference. As GP practices retain remote and hybrid models of service delivery, they must improve services and ensure primary care is accessible and responsive to migrants' healthcare needs. Funding: This study was funded by the Medical Research Council (MC_PC 19070 and MR/V028375/1) and a Wellcome Clinical Research Career Development Fellowship (206602).

Bendamustine in combination with pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: A phase II trial.

Treatment of patients with resistant/refractory multiple myeloma (MM) is an unmet need. In this phase II study, we evaluated the role of bendamustine, pomalidomide and dexamethasone combination in this setting. Between February 2020 and December 2021, 28 patients were recruited. Patients received bendamustine 120 mg/m2 day 1, pomalidomide 3 mg days 1-21, and dexamethasone 40 mg days 1, 8, 11, 22, regimen given for a maximum of six cycles. The median (range) age of the patients was 54 (30-76) years and 15 (53.6%) were males. Patients had received a median (range) of three (two-six) prior lines and 85.7% were refractory to both lenalidomide and bortezomib. The primary end-point was the overall response rate (ORR) defined as ≥partial response after at least three cycles. Secondary objectives were toxicity, progression-free survival (PFS), time to progression and overall survival (OS). An intent-to-treat analysis was done. An ORR of 57.6% was achieved. Patients with extramedullary myeloma had a better response rate. At a median follow-up of 8.6 months, the median PFS and OS were 6.2 and 9.7 months respectively. Toxicity was manageable; mainly haematological (neutropenia, 46.4%; anaemia, 42.8%; and thrombocytopenia, 7.1%). Bendamustine, pomalidomide and dexamethasone could be a novel combination for the heavily pretreated, lenalidomide-refractory myeloma population.

Long-Term Outcomes and Safety Trends of Autologous Stem-Cell Transplantation in Non-Hodgkin Lymphoma: A Report From A Tertiary Care Center in India.

PURPOSE: Published experience with autologous stem-cell transplantation (ASCT) in non-Hodgkin lymphoma (NHL) from the Indian subcontinent is extremely limited. Here, we describe the activity and outcomes of this treatment modality at a large tertiary care center in India. PATIENTS AND METHODS: We retrospectively analyzed adult patients with NHL who were eligible for ASCT and autografted between January 1, 2002, and December 15, 2020, at our transplant unit. Toxicities, complications, and long-term outcomes were compared between patients who underwent transplant during 2002-2012 (group A) and 2013-2020 (group B). RESULTS: Overall, 80 patients (group A, n = 37; group B, n = 43) underwent ASCT using peripheral blood stem cells. At a median follow-up of 57.6 months, the 5-year event-free survival (EFS) and overall survival (OS) were 43.5% and 47.6%, respectively, for all patients. More recently (group B), patients had reduced 100-day transplant-related mortality (2.3% v 21.6%, P < .01), improved 3-year EFS (52.9% v 37.3%, P = .04), and superior OS (at 3-year; 63.4% v 43.2%, P = .02). Patients in group B also tolerated the procedure better, with improved resource utilization. In multivariate analysis, an International Prognostic Index (IPI) ≥ 3 at diagnosis adversely affected EFS (hazard ratio [HR] = 2.82, P = .009) and OS (HR = 2.84, P = .01) after ASCT. Low pretransplant serum albumin levels were associated with inferior EFS (HR = 2.68, P = .02) and transplant-related mortality (odds ratio = 10.80, P = .02) after ASCT. CONCLUSION: It is feasible to achieve comparable short- and long-term outcomes in patients with NHL undergoing ASCT in a resource-poor country with improved supportive care and expertise of the transplant team and center.

Moment of truth-adding carboplatin to neoadjuvant/adjuvant chemotherapy in triple negative breast cancer improves overall survival: An individual participant data and trial-level Meta-analysis.

IMPORTANCE: Carboplatin increases the pathological complete remission (pCR) rate in triple negative breast cancer (TNBC) when added to neoadjuvant chemotherapy, however, evidence on its effect on survival outcomes is controversial. METHODS: The study was prospectively registered at PROSPERO (CRD42021228386). We systematically searched PubMed, Embase, Cochrane Central Register of Clinical Trials, and conference proceedings from January 1, 2004 to January 30, 2022 for relevant randomized clinical trials (RCTs) of (neo)adjuvant chemotherapy in TNBC patients, with carboplatin in the intervention arm and standard anthracycline taxane (AT) in the control arm. PRISMA guidelines were used for this review. Data were pooled using fixed and random effects models as appropriate on extracted hazard ratios (HR). Individual patient data (IPD)for disease free survival (DFS) and overall survival (OS) were extracted from published survival curves of included RCTs; DFS and OS curves for each trial and the combined population were reconstructed, and HR estimated. The primary outcome was DFS; OS, pCR, and toxicity were secondary outcomes. RESULTS: Eight trials with 2425 patients were included. Carboplatin improved DFS (HR 0.60; 95% CI 0.47 to 0.78; I2 45%, p < 0.001) compared with AT at trial level and IPD level (HR 0.66; 95%CI, 0.55 to 0.80, p < 0.001) analysis. The OS also improved with carboplatin at both trial level (HR 0.69, 95%CI 0.50 to 0.95, I2 41%, p = 0.02) and IPD level (HR 0.68; 95%CI, 0.54 to 0.87, p = 0.002) analysis. The pCR as expected, was better in the carboplatin arm (OR 2.11; 95% CI = 1.44-3.08; I2 67%, p = 0.009). Anaemia and thrombocytopaenia were higher in the carboplatin arm. CONCLUSION: and relevance: Carboplatin added to (neo)adjuvant chemotherapy in TNBC improves survival, as shown in both trial level and IPD analysis.

Modified Protocol of Nivolumab in Relapsed/Refractory Hodgkin Lymphoma: A Brief Communication of Real World Data.

Immune check point inhibitors such as nivolumab are changing the treatment paradigm of relapsed/refractory Hodgkin lymphoma (r/rHL). Data from single arm studies have shown nivolumab to be an effective and safe therapy. Real world data from resource constrained settings are limited. Our study is a retrospective single center analysis of nivolumab in r/rHL from India. Data regarding baseline and pretreatment characteristics were collected for 20 patients treated with nivolumab from January 2016 to March 2021. Of 20, 15 patients received nivolumab in modified protocol, because of financial limitations. Postnivolumab therapy, the overall response rate was 90%, with 40% in complete remission. The median progression free survival was 13.1 month (95% confidence interval 8.33 mo, not reached) and median overall survival not reached, at a follow up of 24.3 months. No patients discontinued nivolumab because of side effects. Univariate and multivariate analysis showed no effect of dose reduction or increased duration of administration. Most common adverse effect seen was autoimmune hypothyroidism. Possible delayed immune-related side effects were seen in 3 out 5 patients in peritransplant period, in those who received nivolumab as salvage regimen before autologous stem cell transplant. In conclusion, nivolumab shows comparable efficacy and safety even with compromised dosing and schedule of administration of the drug in real world setting.

Comparative study on costs incurred for treatment of patients with bacterial and fungal keratitis - A retrospective analysis.

Purpose: To compare the costs associated with medications and travel of patients with smear-proven bacterial keratitis and fungal keratitis in a tertiary care center in India. Methods: Retrospective analysis of case records of a cohort of patients who presented between April 2017 and March 2018 to a tertiary care center in India, with infectious keratitis who were smear-positive for bacteria or fungi, and whose costs of treatment and travel were supported by a philanthropic program. Results: In total, 672 case records of 177 smear-positive bacterial keratitis (BK) and 495 smear-positive fungal keratitis (FK) were included in the study. Further, 62% of BK and 75% of FK received more than one antimicrobial drug (P < 0.001). The mean total medication cost (INR) was significantly more in FK (959.1 ± 675.2) compared to BK (674.9 ± 463.7) (P < 0.0001). The mean medication cost (INR) per visit was also more for FK (201.1 ± 109.4) compared to BK (155.2 ± 84.1) (P < 0.0001). The mean total medication cost was significantly more for FK for both patients who healed with medical treatment (611.6 ± 395.6 for BK, 801.5 ± 599.9 for FK, P = 0.0005) and for patients who required TPK (953.7 ± 653.1 for BK, 1374.6 ± 701.5 for FK, P = 0.0023) compared to their respective counterparts in BK. Conclusion: Patients with fungal keratitis incurred significantly more on medications compared to patients with bacterial keratitis irrespective of whether they had healed with successful medical treatment or required therapeutic keratoplasty. Prolonged duration of treatment and the high costs of antifungal medications account for the significant economic burden of fungal keratitis.