Does the choice of platinum doublet matter? A study to evaluate the impact of platinum doublet choice for treatment of platinum-sensitive ovarian cancer recurrence on the development of future PARP inhibitor and platinum resistance.

OBJECTIVES: The use of a platinum doublet for the treatment of platinum-sensitive epithelial ovarian cancer (EOC) recurrence is well established. The impact of the non­platinum chemotherapy used as part of a platinum doublet on PARP inhibitor (PARPi) and platinum sensitivity it not known. We aimed to describe oncologic outcomes in cases of recurrent EOC receiving PARPi as maintenance therapy based on preceding platinum doublet. METHODS: Retrospective study of patients with platinum-sensitive recurrent ovarian, fallopian tube or primary peritoneal cancer treated with platinum doublet followed by maintenance PARPi from 1/1/2015 and 1/1/2022. Comparisons were made between patients receiving carboplatin + pegylated liposomal doxorubicin (CD) versus other platinum doublets (OPDs). Descriptive statistics, Kaplan-Meier and univariate survival analyses were performed. RESULTS: 100 patients received PARPi maintenance following a platinum doublet chemotherapy regimen for platinum-sensitive recurrence. 25/100 (25%) received CD and 75/100 (75%) received OPDs. Comparing CD and OPDs, median progression-free survival was 8 versus 7 months (p = 0.26), median time to platinum resistance was 15 versus 13 months (p = 0.54), median OS was 64 versus 90 months (p = 0.28), and median OS from starting PARPi was 25 versus 26 months (p = 0.90), respectively. CONCLUSIONS: Using pegylated liposomal doxorubicin as part of a platinum doublet preceding maintenance PARPi for platinum-sensitive recurrence does not seem to hasten PARPi resistance or platinum resistance compared to OPDs. Although there was a non-significant trend towards increased OS among patients who received a platinum doublet other than CD prior to PARPi, the OS from PARPi start was similar between groups. Given the retrospective nature of this study and small study population, further research is needed to evaluate if the choice of platinum doublet preceding PARPi maintenance impacts PARPi resistance, platinum resistance and survival.

A clinical classification system for grading platinum hypersensitivity reactions.

OBJECTIVES: Current grading systems for platinum hypersensitivities (pHSR) rely on subjective features rather than objective clinical signs leading to inconsistencies in grading. To standardize classification of pHSR, a clinical grading system was developed at our institution. We report the clinical outcomes our classification system and evaluate its correlation with the classification systems currently published and used in practice. METHODS: This was a retrospective review of patients with pHSR from 2011 to 2017. Demographics, chemotherapeutic histories (CT), and details of their initial HSR were collected. Mild reactions were defined as local skin manifestations only. Moderate-low reactions included widespread skin, respiratory or GI findings. Moderate-standard reactions were defined as transient cardiovascular compromise (CVC), hypoxia or neurologic changes whereas sustained changes (>10 min) were used to define severe reaction. Fischer Exact Tests (p < .05) and binary logistic regression analyses were performed. Spearman correlation were used to assess relationships between our grading system and the NCCN and CTCAEv4.0 criteria. RESULTS: 87 patients were identified with most having ovarian cancer (n = 55, 63.2%), receiving carboplatin (n = 62, 71.3%), and on second-line CT (n = 34, 42.5%). Chest pain was associated with transient CVC (OR 10.0, 95% CI 1.148-87.133) while nausea/vomiting (OR 8.420, 95% CI 1.263-55.275) was associated with transient hypoxia albeit less closely than transient hypotension (OR 17.010, 95% CI 2.026-142.825). Only presyncope/syncope remained associated with sustained CVC (OR 38.0, 95% CI 2.815-512.912) on logistic regression. The classification system was most strongly correlated with the NCCN grading system (ρ 0.761, p < .001). CONCLUSIONS: This classification system offers an objective means of grading pHSR severity and correlates with currently-used grading systems.

Outpatient desensitization of patients with moderate (high-risk) to severe platinum hypersensitivity reactions.

OBJECTIVES: Platinum hypersensitivity reactions (HSR) affect approximately 5% of the general oncologic population. Here we report the efficacy and safety of outpatient platinum desensitization protocol (PD) in gynecologic oncology patients with moderate (high-risk) to severe platinum HSR. METHODS: This is a retrospective report of patients with gynecologic malignancies undergoing an outpatient PD for moderate (high-risk) to severe platinum HSR from 2011 to 2017. Patient demographics, chemotherapy histories, and PD outcomes were collected. Descriptive statistics were performed given the exploratory nature of the study. RESULTS: Forty-eight patients meeting inclusion criteria were identified. Most patients were being treated for ovarian cancer (56.3%) and were receiving carboplatin during their initial platinum HSR (75.0%). Patients received a mean of 10.3 platinum doses prior to their initial HSR. Transient hypertension was the most common sign of moderate (high-risk) HSR while persistent tachycardia was the most common sign of severe HSR. A total of 295 PD cycles were attempted with a successful completion rate of 96.6%. The mean number of PD cycles received by patients was 5.1. Almost 65% of patients experienced breakthrough reactions but over 58% of these breakthrough reactions were isolated to the first PD cycle. Only 8.3% of patients had severe breakthrough reactions, all of whom initially underwent shortened desensitization. Of these 4 patients, 2 successfully underwent desensitization with a prolonged protocol. CONCLUSION: Outpatient PD is safe and effective in patients with gynecologic malignancies. This may present a feasible option for institutions with multi-disciplinary teams experienced with the management of platinum HSR.

Outpatient desensitization in selected patients with platinum hypersensitivity reactions.

Platinum-based chemotherapies are a standard treatment for both initial and recurrent gynecologic cancers. Given this widespread use, it is important to be aware of the features of platinum hypersensitivity reactions and the subsequent treatment of these reactions. There is also increasing interest in the development of desensitization protocols to allow patients with a history of platinum hypersensitivity to receive further platinum based therapy. In this review, we describe the management of platinum hypersensitivity reactions and the desensitization protocols utilized at our institution. We also describe the clinical categorizations utilized to triage patients to appropriate desensitization protocols.

Oral Health-Related Quality of Life (OHRQoL) in Elderly Patients with and without Alzheimer's Disease - An Evaluative Study.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by the loss of intellectual functions. The disorder is usually seen after the age of 60 years, and these elderly patients tend to experience a progressive decline in their cognitive and behavioural abilities. AIM: The present study was carried out to assess the oral health-related quality of life (OHRQoL) in elderly patients suffering from AD as compared to subjects without the disease. MATERIALS AND METHOD: One hundred elderly subjects with AD and 150 subjects without AD were included in the study. The subjective assessment of OHRQoL was done using the General Oral Health Assessment Index (GOHAI). Demographic and oral characteristics were assessed for dentition status with the Decayed, Missing and Filled Teeth (DMFT) index, Oral Hygiene Index (OHI), prosthesis use, xerostomia and presence of oral pathologies. RESULTS: GOHAI values were found to be statistically higher ( P = 0.0003) in the subjects with AD. The subjects with AD were found to have a higher DMFT (mean difference = 4.11), Oral Hygiene Index (OHI) scores (mean difference = 1.54), xerostomia ( P = 0.0128) and number of oral pathologies. However, the educational level ( P = 0.2603) and number of natural teeth ( P = 0.0006) were found to be lower in the group with AD. CONCLUSION: The present study reported that the elderly subjects suffering from AD had poorer OHRQoL than those without the disease. There is a need to comprehensively evaluate the oral health conditions of elderly patients with AD and actively provide management to improve their OHRQoL.

Oral Health and Lifestyle Factors in Rural Adults of Jharkhand, India.

Background: There is a lack of health care facilities and poor oral health awareness among the rural adult population of Jharkhand which may significantly influence oral health status and lifestyle scores. Aim: To assess the oral hygiene status, lifestyle factors, and various risk factors associated with poor lifestyle scores in the rural adult population of Jharkhand. Materials and Methods: This cross-sectional study included 400 rural adults (35-44 years) populations. Face-to-face interviews were used to collect sociodemographic data and data on oral hygiene practices. Lifestyle factors were assessed using Health Practice Index (HPI). Oral health status was assessed using the oral health assessment proforma provided by the World Health Organization (WHO). Results: A significantly higher (p value < 0.0001) prevalence of tobacco consumption was reported by males (94.0%) compared to females (4.0%). The males (54.0%) reported significantly higher (p value < 0.0001) poor lifestyle scores compared to females (38.0%). A significantly higher (p value < 0.0001) number of oromucosal lesions (13.0%) was found in males compared to females (1.0%). There was a significant difference (p value < 0.0001) in the oral hygiene status between males and females with majority of males (60.0%) having poor oral hygiene. A bivariate analysis was performed, and unadjusted odds ratio was computed. The factors that became significant were then entered into logistic regression model (enter method). The results of logistic regression analysis showed that education (OR = 0.3, p value = 0.003), systemic diseases/long-term medication (OR = 2.9, p value = 0.004), tobacco consumption (OR = 2.9, p value = 0.006), oral hygiene status (OR = 2.4, p value = 0.007), and dental caries (OR = 2.9, p value = 0.004) were significant predictors of poor lifestyle scores. Conclusion: The rural adult population in Jharkhand has poor oral hygiene status and poor lifestyle scores. It is important to raise awareness regarding good oral hygiene and the negative effects of tobacco consumption. The dental visit should be encouraged, and the concept of preventive care needs to be instilled.

A Questionnaire Study to Assess the Belief and Barrier to Blood Donation and the Influence of Educational Intervention on Urban and Rural Patients.

OBJECTIVE:  Blood transfusion services are an essential part of any healthcare delivery system in today's clinical world with advanced medicines because blood is in high demand during various medical emergencies. Improving knowledge and hastening the development of a positive attitude toward blood donation in society should be the goal of developing an efficient strategy for sustaining a safe and adequate blood supply. AIM:  The study aims to explore the knowledge, attitude, and motivation toward blood donation among urban and rural patients attending the outreach program. MATERIALS AND METHODS:  Patients who attended the outreach program held by the Dental College of Uttar Pradesh were subjected to a questionnaire survey to determine their level of knowledge regarding blood donation. Further, an education-based intervention was done among the camp patients to assess the change in their learning after the intervention. The difference between the individual responses prior to and following the intervention was analyzed using the chi-square test. p≤0.05 was considered statistically significant. RESULTS:  Urban patients comprise 186 males (44.28%) and 234 females (55.72%). Among the rural patients, 205 (45.55%) were males and 245 were females (54.45%). About 48.80% of the urban patients and 48.88% of the rural patients were Hindus while the remaining were Muslims. Only 22.14% of urban patients and 16.88% of rural patients had donated blood till now. The comparison after the intervention for rural patients showed a significant improvement in the level of knowledge and awareness. CONCLUSION:  Although it is quite common knowledge that rural people require more awareness and education related to health, after the conduction of our study, we have resolute evidence that demands thorough IEC and health information activities for the welfare of rural people and to diminish the divide.

Evaluation of Dental Professionals' Knowledge and Attitude Regarding the Diagnosis of Oral Cancer Through Histopathological Examination of Granulation Tissue.

INTRODUCTION: The current cancer trend in India has reported an alarming increase in cancer of the lip, throat, and oral cavity. Few dentists are aware that malignant neoplasms can also occur in the form of granulation tissue and periapical granulomas. However, most dentists agree that biopsies are essential to diagnose oral cancer. This makes the timely diagnosis of oral cancer dependent upon the histopathological examination of the granulation tissue by the dentist. AIM:  The main aim of this study was to evaluate the knowledge and attitudes of dentists regarding the diagnosis of oral cancer through histopathological analysis of granulation tissue. METHOD: A cross-sectional study was conducted on dentists who were residents of Uttar Pradesh, India. Two hundred and fifty study participants enrolled to complete a self-structured questionnaire containing 15 closed-ended questions. The study was conducted over a period of three months, from June to August 2020. Descriptive statistics were analyzed using IBM SPSS Statistics for Windows, Version 21.0 (Released 2012; IBM Corp., Armonk, New York, United States, and the t-test was performed. A significance level of P ≤ 0.05 was used to determine the statistical significance of quantitative variables. RESULTS: The study findings revealed that only a small percentage of dentists (47.2%) were aware of the importance of biopsies in diagnosing oral cancer. Moreover, a minority (14.4%) had conducted biopsies and submitted samples for histopathological analysis. Of them, 10% were aware that in clinical practice, malignant tumors can also manifest as periapical granulomas, granulation tissue, gingivitis, and other conditions. CONCLUSION: Dentists should proactively submit any granulation tissue for histopathological examination. Oral healthcare providers must maintain a high level of suspicion, develop a range of potential or differential diagnoses for oral cancer, and take necessary measures to attain a definitive diagnosis. This may include considering a referral to a specialist for the treatment of oral cancer.

Epidemiological Trends and Factors Associated With Mortality Rate in Psychoactive Substance Use-Related Mental and Behavioral Disorders: A CDC-WONDER Database Analysis.

Background The persisting challenge of substance use disorder's impact on society prompts the need for insights into its mortality trends. This study examines epidemiological patterns and factors tied to mortality rates in individuals with psychoactive substance-related mental and behavioral disorders from 1999 to 2020. Methodology This study used a retrospective observational design. The study analyzed the Centers for Disease Control and Prevention's (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) database information, encompassing mortality and population-based data. Data extraction focused on specific criteria such as age, sex, race/ethnicity, and geographic location. Descriptive statistics were employed to depict the study population and reveal epidemiological trends. Results The study encompassed data from 239,573 individuals who died due to psychoactive substance use-related mental and behavioral disorders between 1999 and 2020. The overall mortality rate was 3.55 per 100,000 individuals (95% confidence interval (CI) = 3.55-3.54) across the study period. Noticeable discrepancies in mortality rates emerged among various geographic regions, genders, races, and age groups. Males (5.32 per 100,000 individuals) experienced notably higher mortality rates than females (1.80 per 100,000 individuals), while the 55-64 age group faced elevated mortality risks (8.24 per 100,000 individuals) compared to the 25-34 age group (1.71 per 100,000 individuals). Significant variations in mortality rates were also evident across different racial and ethnic groups. Conclusions Between 1999 and 2020, the study explored mortality rates in individuals with psychoactive substance use-related mental and behavioral disorders. This analysis revealed variations in mortality across genders, ages (with the 55-64 age group facing higher risks compared to the 25-34 age group), and ethnicities. Notably, males exhibited higher mortality than females. Additionally, divergent rates were observed among different geographic regions. These insights can inform public health initiatives and support the development of targeted strategies to reduce mortality rates and improve the well-being of affected individuals.

Prevalence and Predictors of Seizure Clusters in Pediatric Patients With Epilepsy: The Harvard-Yale Pediatric Seizure Cluster Study.

BACKGROUND: Determine the prevalence of seizure clusters (two or more seizures in six hours), use of rescue medications, and adverse outcomes associated with seizure clusters in pediatric patients with a range of epilepsy severities, and identify risk factors predictive of seizure clusters. METHODS: Prospective observational two-center study, including phone call and seizure diary follow-up for 12 months in patients with epilepsy aged one month to 18 years. We classified patients into three risk groups based on seizures within the prior year: high, seizure cluster (two or more seizures within one day); intermediate, at least one seizure but no days with two or more seizures; low, no seizures. RESULTS: One-third (32.3%; high risk, 72.4%; intermediate risk, 30.4%; low risk, 3.1%) of 297 patients had a seizure cluster during the study, including half (46.2%) of the patients with active seizures at baseline (intermediate- and high-risk groups combined). Emergency room visits or injuries were no more likely due to a seizure cluster than an isolated seizure. Rescue medications were utilized in 15.8% of patients in the high-risk group and 19.2% in the intermediate-risk group. History of status epilepticus (adjusted odds ratio [aOR], 2.13; confidence interval [CI], 1.09 to 4.16]), seizure frequency greater than four per month (aOR, 4.27; CI, 1.92 to 9.50), and high-risk group status (aOR, 6.42; CI, 2.97 to 13.87) were associated with greater odds of seizure cluster. CONCLUSIONS: Seizure clusters are common in pediatric patients with epilepsy. High seizure frequency was the strongest predictor of clusters. Rescue medications were underutilized. Future studies should evaluate the applicability and effectiveness of these medications for optimization of pediatric seizure cluster treatment and reduction of seizure-related emergency department visits, injuries, and mortality.

Acquaintance and Approach in the Direction of Tobacco Cessation Among Dental Practitioners-A Systematic Review.

BACKGROUND: Nowadays, tobacco consumption has become one of the major public health problems and is the leading cause of escapable illness and death. A significant role is played by dental professionals in the identification of smokers; they are, thus, in a better position to offer preventive care. The aim of the present study was to systemically review the knowledge and attitude of dental practitioners toward tobacco cessation. METHODS: A literature search was performed in PubMed Central and Cochrane Library, Medline-PubMed, Embase, Google Scholar up to 2018 to identify appropriate studies. Full-text original research articles of the cross-sectional design were only included in the study. Our target was to systemically review the knowledge and attitude of dental practitioners toward tobacco cessation. RESULTS: The present review included a total of nine articles (studies) that fulfilled the eligibility criteria. Two articles which were hand searched and one article which was obtained through contact with experts were included. The results of the review revealed that the dental practitioners in most of the included studies lack satisfactory knowledge and were unaware of existing referral pathways to specialist smoking cessation services. At the same time, most of the dentists have a positive attitude toward tobacco cessation. CONCLUSIONS: Dental professionals are aware of their obligations toward smoking cessation counseling for patients but certain barriers including lack of time, confidence, and training prevent them from practicing the same in their daily routine. The dental professionals should obtain appropriate training and attain knowledge along with quantifiable skills for the prevention and cessation of tobacco use.

Assessment of implementation and compliance of (COTPA) Cigarette and Other Tobacco Products Act (2003) in open places of Delhi.

BACKGROUND: The use of tobacco in modern life leads to major epidemic disease resulting in social, financial, and environmental problems. In 1975, the first anti-tobacco legislation was passed which was incompetent; however, in 2003 "Cigarettes and Other Tobacco Products Bill" was passed which represents effectiveness in tobacco control. Thus, the aim was to assess the implementation of various sections of COTPA like Sections 4, 5, 6-a, and 6-b, and 7, 8, and 9 in public places of Delhi. MATERIALS AND METHODS: The study was conducted in open places of Delhi in which 376 public places were visited for observing the compliance of Section 4 of COTPA, 350 places for observing the compliance of Section 5 of COTPA, and 70 educational institutions for observing the compliance of Section 6(a) and 6(b) of COTPA, and data were recorded through direct observation. RESULTS: From a total of 376 places visited, smoking was seen in 59.28% of the places visited in Delhi which is against Section 4 of COTPA. For the compliance of Section 5, 97.42% were as per the COTPA specification; however, the compliance of Section 6-a was 68.57% and Section 6-b was 52.85%. In Delhi, 100% compliance of Sections 7, 8, and 9 has been observed. CONCLUSION: The finding of our study suggests that after years of implementation of the COTPA Act 2003, it is executed only to a certain degree in Delhi. For effective implementation of act, various health policy makers, institutions, media, NGOs, and so on can help in minimizing the usage.

Assessment of knowledge and attitude regarding management of patients with substance usage in dental clinics in Modinagar- A cross-sectional study.

INTRODUCTION: The consequences of oral issues among drug users necessitate the implementation of a comprehensive dental care program. Integrated oral health-care services should be programmed for the management of drug addiction as a multi-organ disease needs a multi-disciplinary approach. AIM: The aim of the present study was to assess the knowledge and attitude regarding the management of patients with substance usage at a dental clinic. METHODOLOGY: A cross-sectional study was conducted among 208 dentists working as clinicians. A self-structured 27-item questionnaire consisting of questions related to the management of patients with substance usage at a dental clinic was distributed to them. Data were analyzed using Statistical Package for Social Sciences (SPSS) 20.0 (SPSS Inc., Chicago, IL, USA) and descriptive and analytical tests, including mean, standard deviation, and Chi-square test were used. P < 0.05 was considered statistically significant. RESULTS: Majority of the dentist irrespective of qualification were unaware of the modalities regarding the management of the patients with substance usage at the dental clinic. Most dental clinicians were having a positive attitude regarding such patients and agreed that abuser should be identified and managed in dental settings. CONCLUSION: Educating dental graduates and postgraduates about the oral implications of substance usage and making it a part of the dental curriculum may help us deal with the global issues of substance usage. The dental setting is recognized increasingly as an untapped venue for the delivery of medical screenings, given the long-term nature and frequent contacts associated with the patient-dentist relationship.

A tandem three-phase reaction for preparing secondary amines with minimal side products.

[reaction: see text] A new method for the preparation of secondary amines has been reported. Complementary solution-phase and solid-phase synthesis highlight the process. Amines are obtained in good yields free from the usual byproducts of reductive amination. Secondary amines are unreactive, so overalkylation does not occur. The procedure can be used interchangeably for traditional or parallel synthesis settings.