Intra-rater reliability of goniometry to measure scapular protraction and retraction.

STUDY DESIGN: Observational, descriptive design. BACKGROUND: Despite scapular mobility being essential for the completion of activities of daily living (ADLs), there is currently no established, a reliable goniometric technique to measure scapular protraction and retraction. A proposed method has shown clinically significant inter-rater reliability for a goniometric technique for these measurements. PURPOSE: This observational descriptive study examined the intra-rater reliability of a goniometric technique to assess scapular protraction and retraction among a sample of healthy adults. METHODS: An occupational therapist who is a certified hand therapist (CHT) and an occupational therapy student used goniometry to measure the neutral (resting), protracted, and retracted positions of the right and left scapula for a sample of healthy young adults (n = 54; a total of 108 data points for each measurement). These measurements were compared to analyze intra-rater and inter-rater reliability. RESULTS: For measurements of the scapula in neutral, protraction, and retraction, the standard error of measure (SEM) for repeat measures by the expert and novice raters was < 4.5° and < 3.9° respectively and ICC values ranged from poor to moderate (0.37-0.63). The SEM for measures between evaluators was < 5.0° and the ICC was poor (0.16-0.35). Minimum detectable change (MDC) values as a percentage of the mean (% MDC) ranged between 15.9 and 43.7% for intra-rater reliability and 21.9-52.8% for inter-rater reliability. DISCUSSION: The results of the study were mixed; variance of less than 5° for repeat measures by the same rater and measures between raters suggest clinically acceptable reliability. However, variance as a proportion of available motion (%MDC) demonstrates a broader range both above and below the threshold of 30% suggested for rehabilitation assessments. CONCLUSION: There are few efficient, reliable techniques to measure scapular mobility in clinical practice. The absolute reliability of goniometry to measure scapular protraction and retraction is similar to measurements of other joints. However, additional research and possible refinement of the technique is recommended to further address relative reliability and validity.

Feasibility, safety and oncological outcomes of minimally invasive oesophagectomy following neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma - Experience from a tertiary care centre.

Background: Neoadjuvant chemoradiotherapy (nCRT) has improved the resectability and survival of operable oesophageal squamous cell carcinoma (OSCC). We aimed to study if nCRT for OSCC makes minimally invasive oesophagectomy (MIO) technically more challenging and if the peri-operative and oncological outcomes are acceptable for MIO following nCRT. Materials and Methods: A retrospective review of patients with OSCC (cT1-2N1-2, cT3-4aN0-2) treated with nCRT and MIO between 2013 and 2019 was performed. The operative details including the technical difficulty in tumour dissection and lymphadenectomy, the post-operative complications and oncological outcomes were studied. Results: Seventy-five patients (male:female - 50:25; mean [range] age - 55.49 ± 8.43 [22-72] years; stage II - 34.7%; stage III - 37.3%; stage IVA - 28.0%) were enrolled. The concurrent chemotherapy course was completed by 25.3% of patients and the most common reason limiting the completion of chemotherapy was neutropaenia (66.0%). A thoraco-laparoscopic (n = 60) or hybrid (n = 15) McKeown's oesophagectomy with a two-field lymphadenectomy was performed. The increased surgical difficulty was reported in 41 (54.7%) patients, particularly for mid-thoracic tumours and tumours exhibiting incomplete response. The 30-day overall and major complication rate was 48.0% and 20.0%, respectively, and there was no mortality. The rate of R0 resection, pathological complete response and median lymph nodal yield were 93.3%, 48% and 8 (range: 1-25), respectively. The mean overall survival (OS) was 62.2 months (95% confidence interval [CI]: 52.6-71.8) and recurrence-free survival (RFS) was 53.5 months (95% CI: 43.5-63.5). The 1-, 2- and 3-year OS and RFS were 89.5%, 78.8% and 64.4% and 71.1%, 61.3% and 56.6%, respectively. Conclusion: Minimally invasive McKeown's oesophagectomy is feasible and safe in patients with OSCC receiving nCRT. The radiation component of nCRT increases the degree of operative difficulty, especially in relation to the supracarinal dissection and lymphadenectomy. However, this drawback did not adversely affect the short-term surgical or the long-term oncological outcomes.

Gene therapy for haemophilia.

BACKGROUND: Haemophilia is a genetic disorder characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy for haemophilia is a curative treatment modality currently under investigation. This is an update of a published Cochrane Review. OBJECTIVES: To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Date of last search: 17 April 2020. SELECTION CRITERIA: Eligible trials include randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation for individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. DATA COLLECTION AND ANALYSIS: No trials of gene therapy for haemophilia matching the inclusion criteria were identified. MAIN RESULTS: No trials of gene therapy for haemophilia matching the inclusion criteria were identified. AUTHORS' CONCLUSIONS: No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the safety and efficacy of gene therapy for haemophilia. Gene therapy for haemophilia is still in clinical investigation and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.

Splenectomy for people with thalassaemia major or intermedia.

BACKGROUND: Thalassaemia is a genetic disorder of the haemoglobin protein in red blood cells. It has been historically classified into thalassaemia minor, intermedia and major, depending on the genetic defect and severity of the disease. The clinical presentation of ß-thalassaemia varies widely from a mild asymptomatic form in thalassaemia minor, to a severe disease in thalassaemia major where individuals are dependant on life-long blood transfusions. The hallmark of thalassaemia syndromes is the production of defective red blood cells that are removed by the spleen resulting in an enlarged hyperfunctioning spleen (splenomegaly). Removal of the spleen may thus prolong red blood cell survival by reducing the amount of red blood cells removed from circulation and may ultimately result in the reduced need for blood transfusions. OBJECTIVES: To assess the efficacy and safety of splenectomy in people with ß-thalassaemia major or intermedia. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Review Group's Haemoglobinopathies Trials Register, compiled from searches of electronic databases and the handsearching of journals and conference abstract books. We also searched online trial registries and the reference lists of relevant articles and reviews (27 July 2018).Date of the most recent search of the Group's trials register: 02 August 2019. SELECTION CRITERIA: We included randomised controlled and quasi-randomised controlled studies of people of any age with thalassaemia major or intermedia, evaluating splenectomy in comparison to conservative treatment (transfusion therapy and iron chelation) or other forms of splenectomy compared to each other (laparoscopic, open, radio-frequency). DATA COLLECTION AND ANALYSIS: Two authors independently selected and extracted data from the single included study using a customised data extraction form and assessed the risk of bias. The quality of the evidence was assessed using GRADE. MAIN RESULTS: One study, including 28 participants was included in the review; the results were described, primarily, in a narrative manner. This study assessed the feasibility of splenectomy using a laparoscopic approach versus open surgery. Given the lack of detail regarding the study methods beyond randomisation, the overall risk of bias for this study was unclear. The study was carried out over a period of 3.5 years, with each participant followed up only until discharge (less than one week after the intervention); it did not assess the majority of the outcomes outlined in this review (including two of the three primary outcomes, frequency of transfusion and quality of life). A total of three serious post-operative adverse events (the review's third primary outcome) were reported in the laparoscopic splenectomy group (one case of atelectasis and two cases of bleeding), compared to two events of atelectasis in the open surgery group; however, there were no significant differences between the groups for either atelectasis, risk ratio (RR) 0.50 (95% confidence interval (CI) 0.05 to 4.90) or for bleeding, RR 5.00 (95% CI 0.26 to 95.61) (very low-quality evidence). In addition, the study also reported three serious cases of intra-operative bleeding in the laparoscopic group which mandated conversion to open surgery, although the difference between groups was not statistically significant, RR 7.00 (95% CI 0.39 to 124.14) (very low-quality evidence). These effect estimates are based on very small numbers and hence are unreliable and imprecise. From this small study, there appeared to be an advantage for the laparoscopic approach, in terms of post-operative hospital stay, although the group difference was not large (median difference of 1.5 days, P = 0.03). AUTHORS' CONCLUSIONS: The review was unable to find good quality evidence, in the form of randomised controlled studies, regarding the efficacy of splenectomy for treating thalassaemia major or intermedia. The single included study provided little information about the efficacy of splenectomy, and compared open surgery and laparoscopic methods. Further studies need to evaluate the long-term effectiveness of splenectomy and the comparative advantages of surgical methods. Due to a lack of high quality evidence from randomised controlled studies, well-conducted observational studies may be used to answer this question.

Gene therapy for haemophilia.

BACKGROUND: Haemophilia is a genetic disorder characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy has recently been prompted as a curative treatment modality. This is an update of a published Cochrane Review. OBJECTIVES: To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 18 August 2016. SELECTION CRITERIA: Eligible trials include randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation for individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. DATA COLLECTION AND ANALYSIS: No trials of gene therapy for haemophilia were found. MAIN RESULTS: No trials of gene therapy for haemophilia were identified. AUTHORS' CONCLUSIONS: No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the safety and efficacy of gene therapy for haemophilia. Gene therapy for haemophilia is still in its nascent stages and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.

Splenectomy for people with thalassaemia major or intermedia.

BACKGROUND: Thalassaemia is a genetic disease of the haemoglobin protein in red blood cells. It is classified into thalassaemia minor, intermedia and major, depending on the severity of the disease and the genetic defect. Thalassaemia major and intermedia require frequent blood transfusions to compensate for the lack of well-functioning red blood cells, although this need is significantly less in thalassaemia intermedia.Damaged or defective red blood cells are normally eliminated in the spleen. In people with thalassaemia there is a large quantity of defective red blood cells which results in an enlarged hyperfunctioning spleen (splenomegaly). Removal of the spleen may thus prolong red blood cell survival by reducing the amount of red blood cells removed from circulation and may ultimately result in the reduced need for blood transfusions. OBJECTIVES: To assess the efficacy and safety of splenectomy in people with beta-thalassaemia major or intermedia. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Review Group's Haemoglobinopathies Trials Register, compiled from searches of electronic databases and the handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of the most recent search: 25 April 2016. SELECTION CRITERIA: We included randomised controlled studies and quasi-randomised controlled studies of people of any age with thalassaemia major or intermedia, evaluating splenectomy in comparison to conservative treatment (transfusion therapy and iron chelation) or other forms of splenectomy compared to each other (laparoscopic, open, radio-frequency). DATA COLLECTION AND ANALYSIS: Two authors independently selected and extracted data from the single included study using a customised data extraction form and assessed the risk of bias. MAIN RESULTS: One study, including 28 participants was included in the review; the results were described, primarily, in a narrative manner. The study assessed the feasibility of splenectomy using laparoscopy in comparison to open surgery. Given the lack of detail regarding the study methods beyond randomisation, the overall risk of bias for this study was unclear. The study was carried out over a period of 3.5 years, with each participant followed up only until discharge (less than one week after the intervention); it did not assess the majority of the outcomes outlined in this review (including two of the three primary outcomes, frequency of transfusion and quality of life). A total of three serious post-operative adverse events (the review's third primary outcome) were reported in the laparoscopic splenectomy group (one case of atelectasis and two cases of bleeding), compared to two events of atelectasis in the open surgery group; however, there were no significant differences between the groups for either atelectasis, risk ratio 0.50 (95% confidence interval 0.05 to 4.90) or for bleeding, risk ratio 5.00 (95% confidence interval 0.26 to 95.61). In addition, the study also reported three serious cases of intra-operative bleeding in the laparoscopic group which mandated conversion to open surgery, although the difference between groups was not statistically significant, risk ratio 7.00 (95% confidence interval 0.39 to 124.14). These effect estimates are based on very small numbers and hence are unreliable and imprecise. From this small study, there appeared to be an advantage for the laparoscopic approach, in terms of post-operative hospital stay, although the group difference was not large (median difference of 1.5 days, P = 0.03). AUTHORS' CONCLUSIONS: The review was unable to find good quality evidence, in the form of randomised controlled studies, regarding the efficacy of splenectomy for treating thalassaemia major or intermedia. The single included study provided little information about the efficacy of splenectomy, and compared open surgery and laparoscopic methods. Further studies need to evaluate the long-term effectiveness of splenectomy and the comparative advantages of surgical methods. Due to a lack of high quality evidence from randomised controlled studies, well-conducted observational studies may be used to answer this question.

Gene therapy for haemophilia.

BACKGROUND: Haemophilia is a genetic disorder which is characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy has recently been prompted as a curative treatment modality. OBJECTIVES: To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 06 November 2014. SELECTION CRITERIA: Eligible trials included randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. DATA COLLECTION AND ANALYSIS: No trials of gene therapy for haemophilia were found. MAIN RESULTS: No trials of gene therapy for haemophilia were identified. AUTHORS' CONCLUSIONS: No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the effects of gene therapy for haemophilia. Gene therapy for haemophilia is still in its nascent stages and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.

Facilitators and Barriers for Private Health Sector Engagement for TB Care in India: A Systematic Review and Meta-Synthesis of Qualitative Research.

INTRODUCTION: Private sector engagement is recognized as one of the most critical interventions to achieve the End TB goals in India. We conducted a systematic review and a meta-synthesis of qualitative studies to identify the barriers and facilitators for private sector engagement in TB care in India. METHODS: A systematic search in electronic databases was done. We assessed the methodological limitations of individual studies, synthesized the evidence using thematic analysis, and assessed our confidence in each finding. RESULTS: Of the 19 eligible articles included for the qualitative synthesis, 31.5% (6/19) were conducted in northern states of India. Included studies had details from 31 focus group discussions and 303 in-depth interviews conducted among various stakeholders. The synthesis revealed that barriers to engaging the private sector were lack of coordination mechanisms, lack of the National TB Elimination Program (NTEP) staff capacity to deal with the private sector, lack of private practitioners' knowledge on various programmatic aspects, and perceived complexity of the data exchange mechanism. The private sector felt that NTEP was not sensitive to the patient's confidentiality and demanded too much patient data. The private sector considered nonfinancial incentives like recognition, feedback, involving them in planning, and giving them equal status in partnership as powerful enablers for their engagement in TB care. CONCLUSION: Factors related to the context in which the engagement occurs, the architecture of the engagement, and interaction among the actors contribute to barriers to engaging the private sector for TB care in India. Strengthening policies to protect patient confidentiality, using behavior change communication to NTEP program managers, providing managerial and soft-skill training to NTEP staff, promoting nonfinancial incentives to private providers, establishing a coordination mechanism between the sectors, and simplifying the data exchange mechanisms need to be done to further strengthen the private-sector engagement.

Evaluation of immunogenicity and protective efficacy of bacteriophage conjugated haemagglutinin based subunit vaccine against equine influenza virus in a murine model.

Equine influenza (EI) is a highly contagious acute respiratory disease of equines caused by the H3N8 subtype of Influenza A virus i.e. equine influenza virus (EIV). Vaccination is an important and effective tool for the control of EI in equines. Most of the commercial influenza vaccines are produced in embryonated hen's eggs which has several inherent disadvantages. Hence, subunit vaccine based on recombinant haemagglutinin (HA) antigen, being the most important envelope glycoprotein has been extensively exploited for generating protective immune responses, against influenza A and B viruses. We hypothesized that novel vaccine formulation using baculovirus expressed recombinant HA1 (rHA1) protein coupled with bacteriophage will generate strong protective immune response against EIV. In the present study, the recombinant HA1 protein was produced in insect cells using recombinant baculovirus having cloned HA gene of EIV (Florida clade 2 sublineage) and the purified rHA1 was chemically coupled with bacteriophage using a crosslinker to produce rHA1-phage vaccine candidate. The protective efficacy of vaccine preparations of rHA1-phage conjugate and only rHA1 proteins were evaluated in mouse model through assessing serology, cytokine profiling, clinical signs, gross and histopathological changes, immunohistochemistry, and virus quantification. Immunization of vaccine preparations have stimulated moderate antibody response (ELISA titres-5760 ± 640 and 11,520 ± 1280 for rHA1 and rHA1-phage, respectively at 42 dpi) and elicited strong interferon (IFN)-γ expression levels after three immunizations of vaccine candidates. The immunized BALB/c mice were protected against challenge with wild EIV and resulted in reduced clinical signs and body weight loss, reduced pathological changes, decreased EIV antigen distribution, and restricted EIV replication in lungs and nasopharynx. In conclusion, the immune responses with moderate antibody titer and significantly higher cytokine responses generated by the rHA1-phage vaccine preparation without any adjuvant could be a novel vaccine candidate for quick vaccine preparation through further trials of vaccine in the natural host.

Reproducibility in Radiomics: A Comparison of Feature Extraction Methods and Two Independent Datasets.

Radiomics involves the extraction of information from medical images that are not visible to the human eye. There is evidence that these features can be used for treatment stratification and outcome prediction. However, there is much discussion about the reproducibility of results between different studies. This paper studies the reproducibility of CT texture features used in radiomics, comparing two feature extraction implementations, namely the MATLAB toolkit and Pyradiomics, when applied to independent datasets of CT scans of patients: (i) the open access RIDER dataset containing a set of repeat CT scans taken 15 min apart for 31 patients (RIDER Scan 1 and Scan 2, respectively) treated for lung cancer; and (ii) the open access HN1 dataset containing 137 patients treated for head and neck cancer. Gross tumor volume (GTV), manually outlined by an experienced observer available on both datasets, was used. The 43 common radiomics features available in MATLAB and Pyradiomics were calculated using two intensity-level quantization methods with and without an intensity threshold. Cases were ranked for each feature for all combinations of quantization parameters, and the Spearman's rank coefficient, rs, calculated. Reproducibility was defined when a highly correlated feature in the RIDER dataset also correlated highly in the HN1 dataset, and vice versa. A total of 29 out of the 43 reported stable features were found to be highly reproducible between MATLAB and Pyradiomics implementations, having a consistently high correlation in rank ordering for RIDER Scan 1 and RIDER Scan 2 (rs > 0.8). 18/43 reported features were common in the RIDER and HN1 datasets, suggesting they may be agnostic to disease site. Useful radiomics features should be selected based on reproducibility. This study identified a set of features that meet this requirement and validated the methodology for evaluating reproducibility between datasets.

Tuberculosis preventive treatment in eight SEAR countries - Current practices, implementation challenges and operations research priorities.

Objectives: Countries in the South East Asian region face similar challenges in control of infectious diseases. There is limited access to experiences and learnings of neighboring countries. The Indian Council - of Medical Research (ICMR) has established a Regional Enabler for the South-East Asia Research Collaboration for Health (RESEARCH) Platform for South East Asian Region (SEAR) countries to address the above issues. This paper discusses about current practices, implementation challenges and operations research priorities of Tuberculosis Preventive therapy (TPT) in eight SEAR countries. Methods: A three day workshop on "Capacity Building for TB Research under Programmatic Settings". was conducted under the aegis of this RESEARCH platform jointly ICMR and the Union which was participated by eight SEAR countries. Data were collected from a semi-structured questionnaire prior to the workshop and open discussions during the workshop. Results: The various challenges faced for TPT implementation were broadly categorized as poor demand and low level of acceptance by the beneficiary, low level of acceptance to provide TPT among the providers, challenges in ruling out active TB, issues with supply and supply chain management of diagnostic tests and drugs. Many operations research priorities like person centric TPT driven models, capacity building for improving cascade of care for latent TB infection, health system strengthening and effective risk communication were identified. Conclusion: Full implementation of the TPT guidelines requires focused attention and coordinated action from all stakeholders of the country to attain the full benefit of TB preventive therapy and the ultimate TB elimination goal.

Patient reported outcome measures correlate with step-count in total hip arthroplasty.

BACKGROUND: Passive smartphone-based apps are becoming more common for measuring patient progress after total hip arthroplasty (THA). Optimum activity levels during early THA recovery have not been well documented. OBJECTIVES: Correlations between step-count and patient reported outcome measures (PROMs) during early recovery were explored. This study also investigated how demographics impact step-count during early post-operative recovery. METHODS: Smartphone captured step-count data from 666 THA patients was retrospectively reviewed. Mean age was 64 ± 11 years. 55% were female. Mean BMI was 29 ± 8kg/m2. Mean daily step-count was calculated for each patient over four time-windows: 60 days prior to surgery (preop), 42-49 days postop (6 weeks), 91-98 days postop (3 months), and 183-197 days postop (6 months). Spearman correlation coefficients and linear regression were used to assess the association between PROMs (HOOS-12, HOOS-Jr, and UCLA) were performed. Patients were separated into three step-count levels: low (< 2500 steps/day), medium (2500-5500 steps/day), and high (> 5500 steps/day). Age > 65 years, BMI > 35 kg/m2, and sex were used for demographic comparisons. Post hoc analyses were performed using Welch's unequal variances t-tests, or Wilcoxon rank-sum tests, both with Bonferroni corrections, where appropriate when comparing between groups. Chi-squared analyses were also used when comparing categorical variables. RESULTS: UCLA correlated with step-count at all time-windows (p< 0.001). HOOS12-Function correlated with step-count preoperatively, at 6 weeks, and at 3 months (p< 0.001). High step-count individuals had improved UCLA scores compared to low step-count individuals preoperatively (Δ1.5, p< 0.001), at 6 weeks (Δ0.9, p< 0.001), at 3 months (Δ1.4, p< 0.001), and at 6 months (Δ1.4, p< 0.001). High step-count individuals had improved HOOS12-Function scores compared to low step-count individuals preoperatively (Δ9.6, p< 0.001), at 6 weeks (Δ5.3, p< 0.001), and at 3 months (Δ6.1, p< 0.001). Males had greater step-count at all time points (p< 0.001). Younger patients and low BMI patients had greater step-count across all time points (p< 0.001). CONCLUSION: High step-count improved PROMs scores compared to low step-count. Early post-operative step-count was significantly impacted by age, sex, and BMI. Generic recovery profiles may not be appropriate across diverse populations.

Multi-centre radiomics for prediction of recurrence following radical radiotherapy for head and neck cancers: Consequences of feature selection, machine learning classifiers and batch-effect harmonization.

Background and purpose: Radiomics models trained with limited single institution data are often not reproducible and generalisable. We developed radiomics models that predict loco-regional recurrence within two years of radiotherapy with private and public datasets and their combinations, to simulate small and multi-institutional studies and study the responsiveness of the models to feature selection, machine learning algorithms, centre-effect harmonization and increased dataset sizes. Materials and methods: 562 patients histologically confirmed and treated for locally advanced head-and-neck cancer (LA-HNC) from two public and two private datasets; one private dataset exclusively reserved for validation. Clinical contours of primary tumours were not recontoured and were used for Pyradiomics based feature extraction. ComBat harmonization was applied, and LASSO-Logistic Regression (LR) and Support Vector Machine (SVM) models were built. 95% confidence interval (CI) of 1000 bootstrapped area-under-the-Receiver-operating-curves (AUC) provided predictive performance. Responsiveness of the models' performance to the choice of feature selection methods, ComBat harmonization, machine learning classifier, single and pooled data was evaluated. Results: LASSO and SelectKBest selected 14 and 16 features, respectively; three were overlapping. Without ComBat, the LR and SVM models for three institutional data showed AUCs (CI) of 0.513 (0.481-0.559) and 0.632 (0.586-0.665), respectively. Performances following ComBat revealed AUCs of 0.559 (0.536-0.590) and 0.662 (0.606-0.690), respectively. Compared to single cohort AUCs (0.562-0.629), SVM models from pooled data performed significantly better at AUC = 0.680. Conclusions: Multi-institutional retrospective data accentuates the existing variabilities that affect radiomics. Carefully designed prospective, multi-institutional studies and data sharing are necessary for clinically relevant head-and-neck cancer prognostication models.

Individuals' Vulnerability Based Active Surveillance for TB: Experiences from India.

Community-based active TB case finding (ACF) has become an essential part of TB elimination efforts in high-burden settings. In settings such as the state of Kerala in India, which has reported an annual decline of 7.5% in the estimated TB incidence since 2015, if ACF is not well targeted, it may end up with a less-than-desired yield, the wastage of scarce resources, and the burdening of health systems. Program managers have recognized the need to optimize resources and workloads, while maximizing the yield, when implementing ACF. We developed and implemented the concept of 'individuals'-vulnerability-based active surveillance' as a substitute for the blanket approach for population/geography-based ACF for TB. Weighted scores, based on an estimate of relative risk, were assigned to reflect the TB vulnerabilities of individuals. Vulnerability data for 22,042,168 individuals were available to the primary healthcare team. Individuals with higher cumulative vulnerability scores were targeted for serial ACF from 2019 onwards. In 2018, when a population-based ACF was conducted, the number needed to screen to diagnose one microbiologically confirmed pulmonary TB case was 3772 and the number needed to test to obtain one microbiologically confirmed pulmonary TB case was 112. The corresponding figures in 2019 for individuals'-vulnerability-based ACF were 881 and 39, respectively. Individuals'-vulnerability-based active surveillance is proposed here as a practical solution to improve health system efficiency in settings where the population is relatively stationary, the TB disease burden is low, and the health system is strong.

Analysis of Early Impact of COVID-19 on Presentation and Management of Oral Cancers - an Experience from a Tertiary Care Hospital in South India.

Oral cancers are the leading cause of cancer-related death in Indian men. Currently steps to contain the transmission and treatment of COVID-19 pandemic have crippled the entire health care system. With hospitals running short of resources, the oncological practice became standstill, especially during the initial phase. This is a retrospective study among patients who presented to our tertiary care hospital in early 3 months of COVID-19 era(ECE) with respect to pre-COVID-19 era(PCE). The study includes patients discussed in multidisciplinary tumor board(MDT)(421 in ECE Vs 31 in PCE) and those who underwent surgery(192 in ECE Vs 26 in PCE). The presentation and outcomes of oral carcinoma were compared between the two eras. There was a significant drop in the number of patients who presented during ECE. Though mean age and gender remained comparable between groups, there was a statistical difference in relation to demographic profile of patient (p value < 0.001). Among operated during ECE, 80% had a significantly advanced tumor stage (p value < 0.034) and advanced composite stage (p value < 0.049). Among patients discussed in MDT during ECE, 38.7% were deemed inoperable which is double the number when compared with PCE (p value < 0.009). Results of our study showed a higher incidence of advanced stage disease during ECE, with many patient turning inoperable. Thus, the survival of newly diagnosed oral carcinoma patients will be worser. In the management of oral cancer both early stage and advanced stage should have the same priority. Immediate resumption of safe oncology services is mandatory to curtail the current issues.

Framework for Machine Learning of CT and PET Radiomics to Predict Local Failure after Radiotherapy in Locally Advanced Head and Neck Cancers.

CONTEXT: Cancer Radiomics is an emerging field in medical imaging and refers to the process of converting routine radiological images that are typically qualitatively interpreted to quantifiable descriptions of the tumor phenotypes and when combined with statistical analytics can improve the accuracy of clinical outcome prediction models. However, to understand the radiomic features and their correlation to molecular changes in the tumor, first, there is a need for the development of robust image analysis methods, software tools and statistical prediction models which is often limited in low- and middle-income countries (LMIC). AIMS: The aim is to build a framework for machine learning of radiomic features of planning computed tomography (CT) and positron emission tomography (PET) using open source radiomics and data analytics platforms to make it widely accessible to clinical groups. The framework is tested in a small cohort to predict local disease failure following radiation treatment for head-and-neck cancer (HNC). The predictors were also compared with the existing Aerts HNC radiomics signature. SETTINGS AND DESIGN: Retrospective analysis of patients with locally advanced HNC between 2017 and 2018 and 31 patients with both pre- and post-radiation CT and evaluation PET were selected. SUBJECTS AND METHODS: Tumor volumes were delineated on baseline PET using the semi-automatic adaptive-threshold algorithm and propagated to CT; PyRadiomics features (total of 110 under shape/intensity/texture classes) were extracted. Two feature-selection methods were tested for model stability. Models were built based on least absolute shrinkage and selection operator-logistic and Ridge regression of the top pretreatment radiomic features and compared to Aerts' HNC-signature. Average model performance across all internal validation test folds was summarized by the area under the receiver operator curve (ROC). RESULTS: Both feature selection methods selected CT features MCC (GLCM), SumEntropy (GLCM) and Sphericity (Shape) that could predict the binary failure status in the cross-validated group and achieved an AUC >0.7. However, models using Aerts' signature features (Energy, Compactness, GLRLM-GrayLevelNonUniformity and GrayLevelNonUniformity-HLH wavelet) could not achieve a clear separation between outcomes (AUC = 0.51-0.54). CONCLUSIONS: Radiomics pipeline included open-source workflows which makes it adoptable in LMIC countries. Additional independent validation of data is crucial for the implementation of radiomic models for clinical risk stratification.

Patterns of Recurrence in Locally Advanced Resectable Oesophageal Carcinoma: Retrospective Review from a Tertiary Cancer Centre in South India.

PURPOSE: The study aims to analyse patterns of recurrence following neoadjuvant treatment and surgery in carcinoma oesophagus with an intent to postulate optimal nodal radiation. METHODOLOGY: A retrospective review of patients who presented to our centre within a 5-year period (2014-2018), with recurrence following sequential neoadjuvant treatment and radical surgery, was conducted in this single-institution study. The patterns of recurrence and duration of disease-free survival were analysed. RESULTS: Twenty-one patients (14 men, 7 women) presented with recurrence, of which 13, 7, and 1 patient(s) had received NACT, NACTRT, or both, respectively. Six patients who did not receive neoadjuvant radiotherapy received adjuvant RT. Among the 10 patients who had nodal recurrence after RT (either neoadjuvant or adjuvant), 6 and 4 patients had in-field and out-of-field nodal recurrences, respectively-the latter were equally distributed within 5 cm and outside 5 cm of the PTV margin. CONCLUSION: Among the patients who presented with recurrence, more than half had not received neoadjuvant RT (treated in the 'pre-CROSS era' or due to long-segment disease), reasserting the therapeutic superiority of NACTRT. Increased regularity of recurrences in the draining nodal region was not noted in this study, but large-scale, prospective, randomised head-to-head comparative trials to determine optimal nodal irradiation in carcinoma oesophagus are required.

Population Attributable Risk of Tuberculosis Vulnerabilities in Kerala, India.

BACKGROUND: A robust disaggregated understanding of the determinants of tuberculosis (TB) in each local setting is essential for effective health system and policy action to control TB. OBJECTIVES: The objective of the study was to identify population attributable risk (PAR) for TB disease based on the locally available evidences for Kerala, India. METHODS: Systematic review was done for risk factors of TB in the state. The second set of searches was done to understand the prevalence of the identified risk factors in general population in Kerala. With all available studies and reports, an expert group consensus was made to finalize state-specific prevalence of risk factors. Population attributable fractions were calculated for identified risk factors. RESULTS: PAR for TB disease in Kerala obtained was 24% for undernutrition, 15% for diabetes, 15% for tobacco use, and 1% for HIV. CONCLUSION: Kerala state's PAR for TB was comparatively lower for HIV but higher for diabetes mellitus. Similar exercises for summarizing population risk factors need to happen at all states for making plans to effectively combat TB.

Paradigm shift in efforts to end TB by 2025.

TB is a deadly infectious disease, in existence since time immemorial. This article traces the journey of TB developments in the last few decades and the path breaking moments that have accelerated the efforts towards Ending TB from National Tuberculosis Control Program (NTCP 1962-1992) to Revised National Tuberculosis Control Program (RNTCP - 1992-2019) and to National Tuberculosis Elimination Program (NTEP) as per the vision of Honorable Prime Minister of India. From increased funding for TB, the discovery of newer drugs and diagnostics, increased access to health facilities, greater investment in research and expanded reach of public health education, seasoned with TB activism and media's proactive role, private sector participation to political advocacy and community engagement, coupled with vaccine trials has renewed the hope of finding the elusive and miraculous breakthrough to END TB and it seems the goal is within the realms of the possibility. The recent paradigm shift in the policy and the drive of several states & UTs to move towards TB free status through rigorous population-based vulnerability mapping and screening coupled with active case finding is expected to act as the driving force to lead the country towards Ending TB by 2025. Continued investments in research, innovations and availability of more effective drugs and the vaccines will add to existing armamentarium towards Ending TB.

Higher risk of developing active TB among adult diabetics exposed to TB during childhood: A study from Kerala, India.

INTRODUCTION: Factors associated with tuberculosis (TB) in Kerala, the southern Indian state that notifies approximately 33 microbiologically confirmed new cases per 100,000 population every year for the past two decades, are still unclear. We did a community-based case-control study in Kollam district, Kerala, to identify the individual-level risk factors for TB. METHODS: Structured questionnaire was applied to 101 microbiologically confirmed new TB cases registered under Revised National Tuberculosis Control Program and 202 age- and gender-matched neighborhood controls without present or past TB. Information was sought on socioeconomic status (SES), smoking, consumption of alcohol, close contact with active TB during childhood or recent past, diabetes mellitus (DM), and other comorbid conditions. RESULTS: Close contact with TB during childhood [odds ratio (OR) 15.88, 95% confidence interval (CI) 3.21-78.55], recent close contact with TB (OR 4.81, 95% CI 2.09-11.07), DM (OR 1.64, 95% CI 1.04-3.06), SES (OR 2.16, 95% CI 1.16-4.03), smoking more than 10 cigarettes/beedis per day (OR 3.32, 95% CI 1.27-8.96), consuming more than 10 standard drinks per week (OR 2.91, 95% CI 1.33-6.37), and the interaction term of having close contact with TB during childhood and DM at present (OR 7.37, 95% CI 1.18-50.29) were found to be associated with TB. CONCLUSION: Close contact with a case of TB, presence of DM, lower SES, smoking, and alcohol consumption were associated with active TB in Kollam. Having close contact with a case of TB during childhood and development of DM in later life together are significantly associated with active TB in the study population. The findings also direct further studies to confirm and explore mechanisms of interaction of diabetes with childhood exposure to TB.