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BACKGROUND: Glioblastoma (GBM) patients have poor survival outcomes despite treatment advances and most recurrences occur within the radiation field. Survival outcomes after dose escalation through hypofractionated accelerated RT(HART) were evaluated in this study. We previously reported the study's initial results showing similar survival outcomes with acceptable toxicities. Updated results after 5 years are being analysed to determine long-term survival trends. PATIENTS AND METHODS: 89 patients of newly diagnosed GBM after surgery were randomized to conventional radiotherapy (CRT) or HART. CRT arm received adjuvant RT 60 Gy in 30 fractions over 6 weeks and the HART arm received 60 Gy in 20 fractions over 4 weeks, both with concurrent and adjuvant temozolomide. RESULTS: 83 patients were eligible for analysis. After a median follow-up of 18.9 months, the median OS was 26.5 months and 22.4 months in the HART and CRT arms respectively. 5 year OS was 18.4% in the HART arm versus 3.8% in the CRT arm. This numerical difference in overall survival between the two arms was not statistically significant. The median PFS was not significantly different. CONCLUSION: The long-term results of the trial support HART as a promising treatment option with comparable survival outcomes to the current standard of care. Phase III trials are required for further validation of this regimen which has the potential to become the new standard of care in GBM.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Temozolomida/uso terapêutico , Glioblastoma/tratamento farmacológico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/cirurgia , Intervalo Livre de Doença , Antineoplásicos Alquilantes/uso terapêuticoRESUMO
Opiates are generally used to relieve dyspnoea in advanced diseases such as cancer and lung diseases. However, little is known regarding the safety and efficacy of morphine for refractory dyspnoea in coronavirus disease 2019 (COVID-19) patients. We retrospectively reviewed records of 18 COVID-19-positive patients who were administered morphine for refractory dyspnoea during hospitalisation between May 2021 and June 2021. Details of morphine usage, vital signs, an 11-point dyspnoea numeric rating scale (DNRS) and adverse events at baseline, 24 h and 72 h after the start of treatment were abstracted from records. The final clinical outcome in terms of death or discharge was noted. All patients had severe refractory dyspnoea (DNRS score ≥7) at the time of administration of morphine and had not been relieved from standard care for the past 3 days. In the results, the mean (standard deviation [SD]) age was 47.1 (12) years, male was 13 (72.20%) patients and modified Medical Research Council Grade 4 was present in all 18 patients. The mean (SD) 1st day dose of morphine was 7.03 (1.53) mg and the mean (SD) duration of morphine use was 5.22 (3.00) days. Significant decreases in DNRS, respiratory rate and oxygen saturation were observed 24 h and 72 h after the start of morphine administration. Meanwhile, blood pressure and heart rate were not significantly altered after treatment. The finding of this single-centre retrospective study indicates that morphine may be considered for use in the management of refractory dyspnoea among COVID-19 patients.
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Introduction: Frontotemporal dementia (FTD) encompasses a clinically and pathologically diverse group of neurodegenerative disorders, yet little work has quantified the unique phenotypic clinical presentations of FTD among post-9/11 era veterans. To identify phenotypes of FTD using natural language processing (NLP) aided medical chart reviews of post-9/11 era U.S. military Veterans diagnosed with FTD in Veterans Health Administration care. Methods: A medical record chart review of clinician/provider notes was conducted using a Natural Language Processing (NLP) tool, which extracted features related to cognitive dysfunction. NLP features were further organized into seven Research Domain Criteria Initiative (RDoC) domains, which were clustered to identify distinct phenotypes. Results: Veterans with FTD were more likely to have notes that reflected the RDoC domains, with cognitive and positive valence domains showing the greatest difference across groups. Clustering of domains identified three symptom phenotypes agnostic to time of an individual having FTD, categorized as Low (16.4%), Moderate (69.2%), and High (14.5%) distress. Comparison across distress groups showed significant differences in physical and psychological characteristics, particularly prior history of head injury, insomnia, cardiac issues, anxiety, and alcohol misuse. The clustering result within the FTD group demonstrated a phenotype variant that exhibited a combination of language and behavioral symptoms. This phenotype presented with manifestations indicative of both language-related impairments and behavioral changes, showcasing the coexistence of features from both domains within the same individual. Discussion: This study suggests FTD also presents across a continuum of severity and symptom distress, both within and across variants. The intensity of distress evident in clinical notes tends to cluster with more co-occurring conditions. This examination of phenotypic heterogeneity in clinical notes indicates that sensitivity to FTD diagnosis may be correlated to overall symptom distress, and future work incorporating NLP and phenotyping may help promote strategies for early detection of FTD.
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BACKGROUND: Neoadjuvant chemotherapy (NACT) with human epidermal growth factor receptor 2 (HER2) blockade is the preferred approach for treating early and locally advanced HER2-positive breast cancer. There is a lack of robust data comparing pathological complete response (pCR) and survival outcomes in anthracycline-free and anthracycline-containing regimens with single HER2-targeted therapy. OBJECTIVES: The present study retrospectively evaluated pCR between two groups: Single HER2-targeted therapy with and without anthracycline. METHODS: A total of 215 HER2-positive female breast cancer patients were analyzed who received eitheranthracycline-containing EC-TH (epirubicin and cyclophosphamide, followed by docetaxel and trastuzumab)oranthracycline-free TCH [docetaxel, carboplatin and trastuzumab]. Univariate and multivariate analyses identified prognostic factors for survival and pCR.Kaplan Meier survival curvesdetermined disease-free survival(DFS) and overall survival (OS). RESULTS: Baseline characteristics were comparable in both treatment groups. The pCR rate was 30.8% in the anthracycline-containing EC-TH group and 40.9% in the anthracycline-free TCH group; p = 0.140. Disease-free survival at 3 years (65.8% vs. 58.4%) and 5 years (49.2% vs. 55.2%) was similar between EC-TH and TCH groups, respectively (log-rank p = 0.550). Three-year (95.5% vs. 92.5%) and five-year (84.4% vs. 80.8%) OSwere also comparable between both groups (log-rank p = 0.485). The anthracycline-containing EC-TH group had a higher incidence of febrile neutropenia (6.4%. vs. 3.6%) and cardiac adverse events (7.7% vs. 4.4%) than the anthracycline-free TCH group. CONCLUSION: Neoadjuvant anthracycline-free chemotherapy has similar pCR and survival outcomeswith favourable cardiac and non-cardiac adverse effect profiles compared with anthracycline-containing chemotherapy.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Docetaxel/uso terapêutico , Antraciclinas , Terapia Neoadjuvante/efeitos adversos , Estudos Retrospectivos , Anticorpos Monoclonais Humanizados/uso terapêutico , Taxoides , Trastuzumab/efeitos adversosRESUMO
BACKGROUND: Dose-dense adjuvant chemotherapy has been shown to be associated with improved long-term survival outcomes in triple-negative breast cancer (TNBC). However, there is a lacuna of data on the benefits of dose-dense neoadjuvant chemotherapy (NACT) in TNBC. METHODS: This retrospective study included 217 newly diagnosed cases of TNBC treated with a sequential anthracycline and taxane-based NACT, followed by definitive surgery. Study groups consisted of 137 patients who received 3-weekly conventional chemotherapy (cNACT group) and 80 patients with 2-weekly dose-dense NACT (ddNACT group). Pathological complete response (pCR) rates, relapse-free survival (RFS), overall survival (OS), and grade-3/4 chemotoxicities were compared across the groups. RESULTS: No significant difference in the pCR rate (32.8% versus 31.3%; P = 0.808) was observed across the study groups. Relapse rate was lower in the ddNACT group compared to the cNACT group (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27-0.95). However, ddNACT had no RFS advantage over conventional chemotherapy (median RFS: not reached versus 56.1 months in cNACT; hazard ratio: 0.90, 95% CI: 0.52-1.53). OS was also comparable in both the groups with a 3-year survival rate of 78.8% (95% CI: 60.9-89.2) in the ddNACT group versus 84.3% (95% CI: 74.8-90.4) in the cNACT group. Younger age, menopause, the Eastern Cooperative Oncology Group ECOG status, and pCR were significantly associated with OS in our cohort. Grade-3 toxicities were comparable in both groups. CONCLUSIONS: This observational study focusing on ddNACT among TNBC patients demonstrated significant differences in the relapse rate with no survival benefits. Differential effects of ddNACT by tumor presentation (early vs. late), tumor size, tumor biology, and cost-benefits of granulocyte colony-stimulating factor support with such regimens need further exploration.
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Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Terapia Neoadjuvante/efeitos adversos , Estudos Retrospectivos , Países em Desenvolvimento , Protocolos de Quimioterapia Combinada Antineoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Quimioterapia Adjuvante , RecidivaRESUMO
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects and alters various laboratory parameters that are predictors of disease severity and mortality, and hence, their prompt identification can aid in patient triaging and resource allocation. Objectives A retrospective study was conducted on 7416 admitted coronavirus disease 2019 (COVID-19) patients from 20 March 2020 to 9 August 2021 to identify crucial laboratory biomarkers as predictors of disease severity and outcome; also, their optimal cutoffs were also calculated. A comparison of laboratory markers between both COVID-19 waves was also performed. Results The majority of patients had mild disease (4295/7416, 57.92%), whereas 1262/7416 (17.02%) had severe disease. The overall fatal outcome was reported in 461 (6.22%) patients. Predictors for mortality were age (>52 years), albumin/globulin (A/G) ratio (≤1.47), chloride (≤101 mmol/L), ferritin (>483.89 ng/mL), lactate dehydrogenase (LDH) (>393 U/L), procalcitonin (>0.10 ng/mL), interleukin-6 (IL-6) (>8.8 pg/mL), fibrinogen (>403 mg/dL), international normalized ratio (INR) (>1.18), and D-dimer (>268 ng/mL). Disease severity predictors were neutrophils (>81%), lymphocyte (≤25.4%), absolute lymphocyte count (ALC) (≤1.38×103/µL), absolute eosinophil count (AEC) (≤0.03×103/µL), total bilirubin (TBIL) (≥0.51 mg/dL), A/G ratio (≤1.49), albumin (≤4.2 g/dL), ferritin (≥445.4 mg/dL), LDH (≥479 U/L), IL-6 (≥28.6 pg/mL), C-reactive protein/albumin (CRP/ALB) ratio (≥1.78), D-dimer (≥237 ng/mL), and fibrinogen (≥425 mg/dL). The majority of patients admitted in the second wave were older and had severe disease, increased fatality, and significantly deranged laboratory parameters than first wave patients. Conclusion Our findings suggested that several biomarkers are crucial for both severe disease and mortality in COVID-19 patients. Ferritin, LDH, IL-6, A/G ratio, fibrinogen, and D-dimer are important biomarkers for both severity and mortality, and when combined, they provide valuable information for patient monitoring and triaging. In addition to these, older age, INR, chloride, and procalcitonin are also significant risk factors for mortality. For severe COVID-19, TBIL, CRP/ALB, albumin, neutrophil percentage, lymphocyte percentage, ALC, and AEC are also important biomarkers. According to the study, the majority of the baseline laboratory parameters associated with COVID-19 mortality and severe disease were significantly higher during the second wave, which could be one of the possible causes for the high mortality rate in India during the second wave. So, the combination of all these parameters can be a powerful tool in emergency settings to improve the efficacy of treatment and prevent mortality, and the planning of subsequent waves should be done accordingly.
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Background COVID-19 has spread as two distinct surges of cases in many countries. Several countries have reported differences in disease severity and mortality in the two waves. Objective Compare the in-hospital mortality in the two COVID-19 waves at a tertiary care hospital in India. Methods We conducted a retrospective data collection. Distinct periods of surges in cases and admissions were defined as the first wave spanning from March 2020 to December 2020 and the second wave from April 2021 to June 21, 2021. The primary outcome of this study was to compare mortality rates in terms of total hospital mortality rate (TMR) and case fatality rate (CFR). Results Mortality rates of wave 2 were approximately 10 times that of wave 1 (TMR of 20.3% in wave 2 versus 2.4% in wave 1 and CFR of 1.5% versus 17.7% in wave 1 and 2, respectively). Mortalities in wave 2 had a larger proportion of severe disease at presentation, faster progression of symptoms to death, and more patients without any chronic comorbid condition dying due to the direct effect of COVID-19 acute respiratory distress syndrome (ARDS). Conclusion Our data matches the worldwide reported pooled hospital mortality figures and shows the comparative difference in disease severity between the two waves.
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BACKGROUND: Studies comparing the utility of dexmedetomidine with other drugs for sedation during medical thoracoscopy are lacking. In this pilot study, we compared dexmedetomidine with midazolam for sedation in thoracoscopy. METHODS: Consecutive subjects were randomized to receive either dexmedetomidine (n=30) (group D) or midazolam (n=30) (group M). All received fentanyl for procedural analgesia. The primary endpoint was pulmonologist-rated overall procedure satisfaction on the visual analog scale (satisfaction VAS). Key secondary outcomes were pulmonologist-rated cough on VAS (cough VAS), patient-rated faces pain scale scores, change in hemodynamic variables, total additional fentanyl dose, and adverse events during procedure. RESULTS: The satisfaction VAS score (mean±SD) was significantly greater in group D versus group M (7.5±1.4 and 6.5±1.1, respectively) ( P =0.003). The cough VAS scores (mean±SD) were 2.1±1.5 (group D) and 3.1±1.3 (group M) ( P =0.014). The scores (mean±SD) for patient-rated faces pain scale were 2.9±1.8 and 4.2±2.3 ( P =0.019) in group D and group M, respectively. The additional dose of fentanyl administered in group M was significantly greater than in group D ( P =0.001). The responses at the local anesthesia infiltration, skin incision, thoracoscope insertion, and biopsy between both groups were similar. The hemodynamic parameters were comparable in both groups. Also, more patients were willing for repeat thoracoscopy if needed; in the dexmedetomidine group. CONCLUSION: The findings of this pilot RCT indicate that dexmedetomidine may be more efficacious than midazolam for sedation in patients undergoing medical thoracoscopy. These observations need to be confirmed in an adequately powered RCT.
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Dexmedetomidina , Midazolam , Analgésicos Opioides/uso terapêutico , Sedação Consciente/métodos , Tosse/etiologia , Dexmedetomidina/uso terapêutico , Fentanila/uso terapêutico , Humanos , Hipnóticos e Sedativos/uso terapêutico , Midazolam/uso terapêutico , Dor , Projetos Piloto , ToracoscopiaRESUMO
Background: Hypoxia in patients with COVID-19 is one of the strongest predictors of mortality. Silent hypoxia is characterised by the presence of hypoxia without dyspnoea. Silent hypoxia has been shown to affect the outcome in previous studies. Methods: This was a retrospective study of a cohort of patients with SARS-CoV-2 infection who were hypoxic at presentation. Clinical, laboratory and treatment parameters in patients with silent hypoxia and dyspnoeic hypoxia were compared. Multivariate logistic regression models were fitted to identify the factors predicting mortality. Results: Among 2080 patients with COVID-19 admitted to our hospital, 811 patients were hypoxic with SpO2 <94% at the time of presentation. Among them, 174 (21.45%) did not have dyspnoea since the onset of COVID-19 symptoms. Further, 5.2% of patients were completely asymptomatic for COVID-19 and were found to be hypoxic only on pulse oximetry. The case fatality rate in patients with silent hypoxia was 45.4% as compared to 40.03% in dyspnoeic hypoxic patients (P = 0.202). The odds ratio of death was 1.1 (95% CI: 0.41-2.97) in the patients with silent hypoxia after adjusting for baseline characteristics, laboratory parameters, treatment and in-hospital complications, which did not reach statistical significance (P = 0.851). Conclusion: Silent hypoxia may be the only presenting feature of COVID-19. As the case fatality rate is comparable between silent and dyspnoeic hypoxia, it should be recognised early and treated as aggressively. Because home isolation is recommended in patients with COVID-19, it is essential to use pulse oximetry in the home setting to identify these patients.
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Background: While long-term studies on the correlates of protection, vaccine effectiveness, and enhanced surveillance are awaited for SARS-CoV-2 vaccine, studies on breakthrough infections help understand the nature and course of this illness among vaccinated individuals and guide in public health preparedness. This study aims to compare the differences in the hospitalization outcomes SARS-CoV-2 infection of fully vaccinated individuals with with those of unvaccinated and partially vaccinated individuals. Materials and Methods: Single institution observational cohort study. This study compared the differences in clinical, biochemical parameters and the hospitalization outcomes of 53 fully vaccinated individuals with those of unvaccinated (1464) and partially vaccinated (231) individuals, among a cohort of 2,080 individuals hospitalized with SARS-CoV-2 infection. Descriptive statistics and propensity-score weighted multivariate logistic regression analysis adjusting for clinical and laboratory parameters were used to compare the differences and to identify factors associated with outcomes. Results: Completing the course of vaccination protected individuals from developing severe COVID-19 as evidenced by lower proportions of those with hypoxia, abnormal levels of inflammatory markers, requiring ventilatory support, and death compared to unvaccinated and partially vaccinated individuals. There were no differences in these outcomes among patients who received either vaccine type approved in India. Conclusions: Efforts should be made to improve the vaccination rates as a timely measure to prepare for the upcoming waves of this highly transmissible pandemic. Vaccination rates of the communities may also guide in the planning of the health needs and appropriate use of medical resources.
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INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a recognized military service-connected condition. Prior prevalence studies of ALS among U.S. war Veterans were not able to address concerns related to neurodegenerative sequelae of traumatic brain injury (TBI) and disregarded risk heterogeneity from occupational categories within service branches. MATERIALS AND METHODS: We identified the prevalence of definite and possible ALS and cumulative incidence of definite ALS among Post-9/11 U.S. Veterans deployed in support of Post-9/11 conflicts (mean age 36.3) who received care in the Veterans Health Administration during fiscal years 2002-2015. Using a case-control study design, we also evaluated the association of TBI and major military occupation groups with ALS adjusting for demographics and comorbidities. RESULTS: The prevalence of ALS was 19.7 per 100,000 over 14 years. Both prevalence and cumulative incidence of definite ALS were significantly higher among Air Force personnel compared to other service branches and among tactical operation officers and health care workers compared to general and administrative officers. Neither TBI nor younger age (<45 years) was associated with ALS. Depression, cardiac disease, cerebrovascular disease, high blood pressure, and obstructive sleep apnea were clinical comorbidities significantly associated with ALS in this population of Veterans. CONCLUSION: This study among a cohort of relatively young Veterans showed a high ALS prevalence, suggesting an early onset of ALS among deployed military service members. The higher prevalence among some military specific occupations highlights the need to determine which occupational exposures specific to these occupations (particularly, Air Force personnel, tactical operations officers, and health care workers) might be associated with early onset ALS.
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Esclerose Lateral Amiotrófica , Militares , Veteranos , Adulto , Esclerose Lateral Amiotrófica/epidemiologia , Estudos de Casos e Controles , Humanos , Incidência , Pessoa de Meia-Idade , Estados UnidosRESUMO
OBJECTIVE: To determine the validity of diagnoses indicative of early-onset dementia (EOD) obtained from an algorithm using administrative data, we examined Veterans Health Administration (VHA) electronic medical records (EMRs). METHOD: A previously used method of identifying cases of dementia using administrative data was applied to a random sample of 176 cases of Post-9/11 deployed veterans under 65 years of age. Retrospective, cross-sectional examination of EMRs was conducted, using a combination of administrative data, chart abstraction, and review/consensus by board-certified neuropsychologists. RESULTS: Approximately 73% of EOD diagnoses identified using existing algorithms were identified as false positives in the overall sample. This increased to approximately 76% among those with mental health conditions and approximately 85% among those with mild traumatic brain injury (TBI; i.e. concussion). Factors related to improved diagnostic accuracy included more severe TBI, diagnosing clinician type, presence of neuroimaging data, absence of a comorbid mental health condition diagnosis, and older age at time of diagnosis. CONCLUSIONS: A previously used algorithm for detecting dementia using VHA administrative data was not supported for use in the younger adult samples and resulted in an unacceptably high number of false positives. Based on these findings, there is concern for possible misclassification in population studies using similar algorithms to identify rates of EOD among veterans. Further, we provide suggestions to develop an enhanced algorithm for more accurate dementia surveillance among younger populations.
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Demência/diagnóstico , Registros Eletrônicos de Saúde/tendências , Testes Neuropsicológicos/normas , Veteranos/psicologia , Algoritmos , Estudos Transversais , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Use of illegal and prescription drugs has significantly increased in recent years all over the world in most populations. Greater worldwide awareness in this regard has substantially improved the epidemiological understanding of substance use, its risk factors, and impact on life. People with intellectual disabilities constitute 0.5%-1.5% of the world's population. It can be conjectured that they might be experiencing similar or even a greater burden of substance use in their lives. This article highlights some important aspects of substance use among this population in low- and middle-income countries that need urgent attention.
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BACKGROUND: Depression is a growing health issue in both developed and developing countries. General unawareness at the population level, lack of training among health care providers and scarcity of resources including treatment opportunities may conceal the real burden of depression in developing countries, and more epidemiological studies on its prevalence and risk factors are critically needed. AIM: This study reports the prevalence of depression and its associated risk factors among female garment factory workers in Bangladesh - a major supplier country of clothes for the Western market. This research should generate useful evidence for national and international stakeholders who have an interest in improving health, safety and well-being of outsourced factory workers. METHODS: A survey was conducted on a sample of 600 lower socio-economic status working women including garment workers. This survey collected data on demographic and health profile of these workers. The primary outcome was depression as measured by Patient Health Questionnaire 9. It also obtained data on traumatic life events and post-traumatic stress disorder. RESULTS: The prevalence of depression was 23.5%: 20.9% among garment workers and 26.4% among others. Part-time employment (odds ratio-OR): 2.36, 95% confidence interval (95% CI): 1.01-5.51), chronic pain (OR: 1.67, 95% CI: 1.01-2.78), two or more traumatic life events (OR: 6.43, 95% CI: 2.85-14.55) and dysuria (OR: 2.50, 95% CI: 1.02-6.15) were found to be significantly associated with depression among these workers in multivariate regression model. Depression prevalene lowered by 11% among these workers for every additional monthly earning of 1,000 taka (US$12). CONCLUSION: Depression is a multifaceted health issue with many personal, social, economic and health determinants and consequences. This study demonstrates that the prevalence of moderate-to-severe depression among working women in Bangladesh is quite high. Prevention and treatment of depression in developing countries and societies can reduce suffering, lower incidence of suicide, and prevent economic loss. Creating awareness on outsourced workers' poor mental health may help in developing initiatives to protect and preserve their well-being.