Impact of Chronic Suppurative Otitis Media on Quality of Life and Psychological Well-Being: A Cross-Sectional Study.

BACKGROUND: Chronic suppurative otitis media (CSOM) is a prevalent and persistent middle ear condition that not only affects auditory health but also potentially influences various aspects of an individual's life. This study explores the correlation between CSOM, depression, anxiety, and stress, using the 21-item Depression, Anxiety, and Stress Scale (DASS 21), also assessing quality of life (QoL) using the Chronic Ear Survey (CES) questionnaire. The primary objective of this study was to gather prospective audiological data along with information on both disease-specific quality of life and psychological well-being, utilizing validated measurement instruments. METHODS: This cross-sectional study was conducted at a tertiary care center in Central India, involving 182 patients with CSOM. The study included individuals aged 18 years and above diagnosed with CSOM in at least one ear. Patients with a history of psychological disorders, head injury, and those with comorbidities such as diabetes, hypertension, and chronic heart diseases were excluded. Pure tone audiometry was employed for hearing evaluation, while the assessment of psychological well-being utilized the DASS 21 questionnaire. Furthermore, the quality of life was evaluated using the CES tool. RESULTS: From the initial cohort of 182 patients diagnosed with CSOM, 32 were excluded based on predefined criteria, resulting in a final sample of 150 patients. The cohort, with a mean age of 34.3 years, exhibited a predominantly female population (63.3%). Psychological assessments using DASS 21 revealed depression in 22 (14.7%) patients and anxiety in 23 (15.3%) patients. Among those with depression, majority of the participants had mild depression. Similarly, among those with anxiety, the majority were found to be experiencing mild anxiety. Bilateral CSOM demonstrated a higher prevalence of anxiety and depression, establishing a significant association. QoL parameters, assessed by the Chronic Ear Survey, indicated a more adverse impact in bilateral cases across all categories except symptoms. Correlation analysis between psychological well-being, quality of life, and hearing loss severity yielded statistically significant results. CONCLUSION: CSOM with the symptom of hearing loss can lead to reduced QoL and psychological well-being in the affected individuals. This study highlights the psychological impact of CSOM, particularly in bilateral cases and severe hearing loss. Integrating psychological support into treatment plans is crucial for comprehensive patient care. Regular assessments are essential for guiding timely interventions, ensuring a holistic approach to enhance both quality of life and psychological well-being in individuals affected by CSOM.

Ayurvedic formulations containing benzoic and ascorbic acids as additives: benzene formation during storage and impact of additives on quality parameters.

OBJECTIVES: Ayurvedic formulations are becoming the prior choice of people as health care supplements. The increasing demand for these formulations has led to extensive development of Ayurvedic pharmaceutical industries worldwide. The reaction between the preservatives (sodium benzoates and ascorbic acid) used in these formulations could generate benzene. Benzene is classified as class-1 human carcinogen and responsible for various short and long term health effects. METHODS: In this study, 25 formulations (containing ascorbic acid and sodium benzoate) of various manufacturers available as over the counter products were obtained and their benzene content were determined using gas chromatograph with flame ionization detector. RESULTS: The result showed that 64% of the formulations were free from benzene contamination whereas 36% of formulations were found to be contaminated with benzene. A simple, less time-consuming, economic, and validated gas chromatographic method for estimation of benzene in Ayurvedic formulations was also developed successfully in present study. CONCLUSIONS: The data revealed that the level of benzene was within permissible limits, yet the presence of a carcinogen in the marketed formulations intended for internal use is an alarming situation.

Comparison of efficacy of diclofenac and tramadol in relieving pain in patients of acute pancreatitis: A randomized parallel group double blind active controlled pilot study.

BACKGROUND: Opioids and non steroidal anti inflammatory drugs (NSAIDs) are commonly used for pain relief in acute pancreatitis (AP). Opioids carry risk of sphincter of oddi constriction. Although diclofenac prevents post endoscopic retrograde cholangio-pancreatography (ERCP) pancreatitis, few reports of diclofenac associated AP are also present. Although, both tramadol and diclofenac are commonly used for pain relief in AP, no study has evaluated their comparative efficacy and safety. MATERIALS AND METHODS: Forty-six eligible participants were randomized to either diclofenac or tramadol. Primary objectives of our study were improvement in pain intensity on visual analogue scale (VAS pain score after 1 hr of drug administration) and number of patients requiring supplementary analgesia. The secondary objectives were total number of times of supplementary analgesia requirement, time to significant decrease (33%) in VAS pain score from baseline, number of painful days (VAS pain score >5), VAS pain score on 7th day, side effects, all cause death and complications of pancreatitis between the two groups. RESULTS: Although 46 patients were randomized, the final analysis included 41 participants. Five patients were withdrawn from the study (intubation = 3, altered sensorium = 2). No significant difference was seen in terms of VAS score after 1 hr of drug administration, number of patients requiring supplementary analgesic and number of painful days. However, time taken to significant reduction of pain was lower in the diclofenac group (p = .028). Both the agents were comparable in terms of safety. Although complications were less in the diclofenac group, the difference was not statistically significant. CONCLUSION: Both diclofenac and tramadol are equally effective in controlling pain in AP with similar safety profile. SIGNIFICANCE: There are no studies that have compared the safety and efficacy of two commonly used analgesics for pain relief in patients with AP. We found that both diclofenac and tramadol are equally effective in decreasing the pain associated with AP. There is also no significant difference in the incidence of side effects between both the groups. Hence both diclofenac and tramadol can be used safely and effectively for pain control in AP. TRIAL REGISTRATION: The trial was registered with clinical trials registry India (Number- CTRI/2018/05/014309).

Daratumumab in multiple myeloma.

The development of effective monoclonal antibodies for the treatment of myeloma has been a long journey of clinical and drug development. Identification of the right target antigen was a critical part of the process. CD38 as a target has been considered for some time, but clinically, daratumumab, a CD38 monoclonal antibody, was the first to be tested, and it has delivered the best clinical responses as a single agent to date. Its proven safety and efficacy in combination with other antimyeloma agents have led to several US Food and Drug Administration approvals for treating myeloma. Furthermore, the results of early trials in the induction therapy setting have demonstrated a beneficial role when it is added to the existing induction regimens. This review summarizes the importance of CD38 as a target and examines the clinical development of the CD38 monoclonal antibody daratumumab and its clinical significance in combination regimens in both patients with relapsed/refractory myeloma and patients with newly diagnosed myeloma.

Bioinformatics-Based Tools and Software in Clinical Research: A New Emerging Area.

Nowadays, drug discovery is a long process which includes target identification, validation, lead optimization, and many other major/minor steps. The huge flow of data has necessitated the need for computational support for collection, storage, retrieval, analysis, and correlation of data sets of complex information. At the beginning of the twentieth century, it was cumbersome to elaborate the experimental findings in the form of clinical outcomes, but current research in the field of bioinformatics clearly shows ongoing unification of experimental findings and clinical outcomes. Bioinformatics has made it easier for researchers to overcome various challenges of time-consuming and expensive procedures of evaluation of safety and efficacy of drugs at a much faster and economic way. In the near future, it may be a major game player and trendsetter for personalized medicine, drug discovery, drug standardization, as well as food products. Due to rapidly increasing commercial interest, currently probiotic-based industries are flooding the market with a range of probiotic products under the banner of dietary supplements, natural health products, food supplements, or functional foods. Most of the consumers are attracted toward probiotic formulations due to the rosy picture provided by the media and advertisements about high beneficial claims. These products are not regulated by pharmaceutical regulatory authorities in different countries of origin and are rather regulated as per their intended use. Lack of stipulated quality standard is a major challenge for probiotic industry; hence there would always be a possibility of marketing of ineffective and unsafe products with false claims. Hence it is very important and pertinent to ensure the safety of probiotic formulations available as over-the-counter (OTC) products for ignorant society. At the same time, probiotic industry, being in its initial stages in developing and underdeveloped countries, requires to ensure safe, swift, and successful usage of probiotics. In the absence of harmonized regulatory guidelines, safety, quality, as well as the efficacy of the probiotic strain does not remain a mandate but becomes a choice for the manufacturer. Hence there is an urgent need to screen already marketed probiotic formulations for their safety with respect to specific strains of probiotic. Various conventional methods used by the manufacturers for the identification of probiotic microbes create a blurred image about their status as probiotics. The present manuscript focuses on a bioinformatics-based technique for validation of marketed probiotic formulation using 16s rRNA sequencing and strain-level identification of bacterial species using Ez Texan and laser gene software. This technique gives a clear picture about the safety of the product for human use.

A Combination Antibiogram Evaluation for Pseudomonas aeruginosa in Respiratory and Blood Sources from Intensive Care Unit (ICU) and Non-ICU Settings in U.S. Hospitals.

Pseudomonas aeruginosa is an important pathogen associated with significant morbidity and mortality. U.S. guidelines for the treatment of hospital-acquired and ventilator-associated pneumonia recommend the use of two antipseudomonal drugs for high-risk patients to ensure that ≥95% of patients receive active empirical therapy. We evaluated the utility of combination antibiograms in identifying optimal anti-P.aeruginosa drug regimens. We conducted a retrospective cross-sectional analysis of the antimicrobial susceptibility of all nonduplicate P.aeruginosa blood and respiratory isolates collected between 1 October 2016 and 30 September 2017 from 304 U.S. hospitals in the BD Insights Research Database. Combination antibiograms were used to determine in vitro rates of susceptibility to potential anti-P.aeruginosa combination regimens consisting of a backbone antibiotic (an extended-spectrum cephalosporin, carbapenem, or piperacillin-tazobactam) plus an aminoglycoside or fluoroquinolone. Single-agent susceptibility rates for the 11,701 nonduplicate P.aeruginosa isolates ranged from 72.7% for fluoroquinolones to 85.0% for piperacillin-tazobactam. Susceptibility rates were higher for blood isolates than for respiratory isolates (P < 0.05). Antibiotic combinations resulted in increased susceptibility rates but did not achieve the goal of 95% antibiotic coverage. Adding an aminoglycoside resulted in higher susceptibility rates than adding a fluoroquinolone; piperacillin-tazobactam plus an aminoglycoside resulted in the highest susceptibility rate (93.3%). Intensive care unit (ICU) isolates generally had lower susceptibility rates than non-ICU isolates. Commonly used antipseudomonal drugs, either alone or in combination, did not achieve 95% coverage against U.S. hospital P.aeruginosa isolates, suggesting that new drugs are needed to attain this goal. Local institutional use of combination antibiograms has the potential to optimize empirical therapy of infections caused by difficult-to-treat pathogens.

Ethanol content in traditionally fermented ayurvedic formulations: Compromised Good Manufacturing Practice regulations - compromised health.

BACKGROUND: A large part of the population of India prefers the traditional medicine (ayurvedic formulations) for primary health care. However, the effective quality control of herbal medicine is still a big challenge. Numerous reports indicate noncompliance with Compromised Good Manufacturing Practice (GMP) guidelines by the manufacturers which may lead to adverse drug reactions or toxic effects. Asava and arishta are the classical herbal dosage forms wherein fermentation occurs during production leading to the generation of ethanol. The presence of ethanol in these preparations may lead to their misuse. The self-generated ethanol is responsible for extraction of active constituents and acts as a self-preservative. As the procedure for preparation for asava and arishta is same, the ethanol content is also expected to be the same irrespective of the manufacturer. OBJECTIVE: The objective of the present study was to assess and compare the ethanol content of some traditionally fermented ayurvedic formulations available in the market. METHOD: In this study, 20 formulations from 3 different manufacturers available as over-the-counter products were obtained and their ethanol contents were determined using gas chromatograph with flame ionization detector. RESULTS: Statistically significant differences were noted in the ethanol content of various ayurvedic formulations. A simple, less time-consuming, economic, and validated gas chromatographic method for estimation of ethanol in fermented ayurvedic formulations was also developed successfully in present study. CONCLUSION: The data generated during study reflected poor compliance of GMP guidelines by the manufacturers and hence the quality is being grossly compromised posing a safety hazard.

Bioactivity-guided isolation of potent anxiolytic compounds from leaves of Citrus paradisi.

CONTEXT: Citrus fragrances have been attributed with mood-enhancing properties by aromatherapists. Leaves of this plant have been reported to exert anti-anxiety activity. Till date, no specific phytoconstituent responsible for this has been identified. OBJECTIVE: Isolation of anxiolytic constituent of Citrus paradisi using bioactivity-guided fractionation. MATERIALS AND METHODS: Leaf extracts of four varieties of C. paradisi in petroleum ether, chloroform, methanol and water were evaluated for anti-anxiety activity in mice using elevated plus-maze apparatus. Because of activity in methanol extract, it was used for safety evaluation/acute toxicity studies in animals. Bioactive fraction of methanol extract was subjected to column chromatography and structure of the isolated compound was elucidated by melting point, ultraviolet, infrared, nuclear mass reactor and mass spectroscopy. The isolated constituents were further evaluated for anti-anxiety activity using light/dark model and hole-board model of anxiety. RESULTS: Results showed no mortality at a dose up to 2000 mg/kg body weight that indirectly reflects the safety profile of the leaf extracts. Fractionation of methanol extract led to the isolation of four flavonoids (rutin, quercetin, kaempferol and myricetin). The isolated compounds exhibited significant anxiolytic activity in different animal models. CONCLUSION: The study confirms the presence of four flavonoids responsible for anti-anxiety activity.

Ashtawarga plants - Suffering a triple standardization syndrome.

Ayurveda is one of the oldest known holistic health care systems recommending diverse medicinal uses of plants for prevention and cure of diseases and illness. World Health Organization (WHO) estimates that the holistic system is gaining more popularity due to its easy availability, low cost, congeniality, better accessibility and higher safety than allopathic medicine. Demand of herbal drugs is increasing day-by-day because of increasing popularity of herbal drugs; however market fails to meet this supply due to numerous factors, one of the important factors being the extinction of these plants from local flora. About 560 herbal species of India have been included in the Red List of Threatened species. Hence to overcome problem of non-availability of endangered species, Department of AYUSH, Govt. of India has permitted the substitution of rare herbal drugs with available substitutes on the basis of Ayurvedic concepts. Due to this, herbal drug industry has started exploiting the situation and now Ayurvedic products are suffering from a serious problem of adulteration with addition of spoiled, inferior, spurious drugs that are inferior in therapeutic/chemical properties and used to enhance profits. Adulteration with other plants degrades the quality and credibility of Ayurvedic medicine. Ashtawarga plants being an important part of many Ayurvedic formulations are also available in a very limited amount and likely to be substituted by cheap adulterants. Keeping in view the above situation, a metadata analysis has been conducted to find out types of adulteration/substitutions malpractices going on for Ashtawarga plants.

Innate antioxidant activity of some traditional formulations.

Herbal medicine is the oldest form of healthcare known to humanity. Recently, much attention is being directed toward the use of antioxidants. There are some very commonly used Ayurvedic preparations that might have inbuilt antioxidant activity, and their therapeutic potential can be partially attributable to its antioxidant activity. Hence, it was proposed to find out antioxidant activity of such common formulations. Estimation of innate antioxidant activity of some commonly used traditional formulations. In this study, five formulations were evaluated for antioxidant activity in comparison to gallic acid (standard) using the in vitro reducing power method and superoxide radical scavenging activity by dimethyl sulfoxide method followed by calculation of scavenging activity and inhibitory concentration 50% (IC50). The result shows that Ayurvedic drug extracts possess good reducing power and antioxidant activity. Laxmivilas Ras shows higher reducing power ranging from 117 ± 0.021 to 0.176 ± 0.012 as compared to other extracts. The drug extracts were also found to be an efficient scavenger of superoxide radical. The IC50 values for Laxmivilas Ras, Agnitundi Vati, Ajmodadi Churna, Tribhuvankirti Rasa, gallic acid (standard) and Sitopladi Churna, were found to be 50.07, 98.41, 105.13, 116.39, 176.80, and 200.17, respectively. From this study, it can be concluded that the above Ayurvedic formulations possess antioxidant property. However, work could be initiated on the isolation and identification of these antioxidant components.

Safety and Efficacy of Stosstherapy in Nutritional Rickets.

OBJECTIVE: Stosstherapy has been used since early 19th century for treating nutritional rickets. However, there are no clear cut guidelines for the biochemical monitoring of this treatment. Repeated blood tests at short intervals increase the cost of therapy and noncompliance. METHODS: A prospective study was conducted on 191 cases of nutritional rickets below 10 years of age to evaluate the effectivity of stosstherapy. All cases were treated with a single intramuscular injection of vitamin D (600.000 IU) along with oral calcium (50 mg/kg) and vitamin D (400 IU per day) until radiological resolution. Dietary modifications and adequate sunlight exposure were also recommended. RESULTS: The mean age of presentation was 2 years 9 months. Mean sunlight exposure was 17 minutes/week with 90% having low sunlight exposure (<30 minutes/week). Prolonged breast feeding (>6 months) was found in 93.7% of the cases. With treatment, the clinical features started resolving by 1 month with complete resolution of most of the features over a period of 1 year. By 6 months, all the study subjects had complete radiological resolution. Serum levels of calcium and alkaline phosphatase (ALP) were restored by 6 months in most cases while phosphate and vitamin D levels normalized by 6 weeks. CONCLUSION: Stosstherapy is a safe, cheap and effective method of treating nutritional rickets. Biochemical tests at initial presentation followed by vitamin D assay at 6 weeks and calcium, phosphate and ALP assays at 6 months is recommended in the monitoring of these patients. For regular monitoring, only ALP assay is recommended, provided one abstains from repeat injection of vitamin D based on high ALP levels.

Molecular determinants of substrate specificity revealed by the structure of Clostridium thermocellum arabinofuranosidase 43A from glycosyl hydrolase family 43 subfamily 16.

The recent division of the large glycoside hydrolase family 43 (GH43) into subfamilies offers a renewed opportunity to develop structure-function studies aimed at clarifying the molecular determinants of substrate specificity in carbohydrate-degrading enzymes. α-L-Arabinofuranosidases (EC 3.2.1.55) remove arabinose side chains from heteropolysaccharides such as xylan and arabinan. However, there is some evidence suggesting that arabinofuranosidases are substrate-specific, being unable to display a debranching activity on different polysaccharides. Here, the structure of Clostridium thermocellum arabinofuranosidase 43A (CtAbf43A), which has been shown to act in the removal of arabinose side chains from arabinoxylan but not from pectic arabinan, is reported. CtAbf43A belongs to GH43 subfamily 16, the members of which have a restricted capacity to attack xylans. The crystal structure of CtAbf43A comprises a five-bladed ß-propeller fold typical of GH43 enzymes. CtAbf43A displays a highly compact architecture compatible with its high thermostability. Analysis of CtAbf43A along with the other member of GH43 subfamily 16 with known structure, the Bacillus subtilis arabinofuranosidase BsAXH-m2,3, suggests that the specificity of subfamily 16 for arabinoxylan is conferred by a long surface substrate-binding cleft that is complementary to the xylan backbone. The lack of a curved-shaped carbohydrate-interacting platform precludes GH43 subfamily 16 enzymes from interacting with the nonlinear arabinan scaffold and therefore from deconstructing this polysaccharide.

Oily fish, coffee and walnuts: Dietary treatment for nonalcoholic fatty liver disease.

Rates of non-alcoholic fatty liver disease (NAFLD) are increasing worldwide in tandem with the metabolic syndrome, with the progressive form of disease, non-alcoholic steatohepatitis (NASH) likely to become the most common cause of end stage liver disease in the not too distant future. Lifestyle modification and weight loss remain the main focus of management in NAFLD and NASH, however, there has been growing interest in the benefit of specific foods and dietary components on disease progression, with some foods showing protective properties. This article provides an overview of the foods that show the most promise and their potential benefits in NAFLD/NASH, specifically; oily fish/ fish oil, coffee, nuts, tea, red wine, avocado and olive oil. Furthermore, it summarises results from animal and human trials and highlights potential areas for future research.

Effects of ruxolitinib treatment on metabolic and nutritional parameters in patients with myelofibrosis from COMFORT-I.

BACKGROUND: In the COMFORT (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy)-I study, the Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib provided significant reductions in splenomegaly, improvements in myelofibrosis (MF)-related symptoms, and a survival advantage relative to placebo in patients with intermediate-2 or high-risk MF. In this post hoc analysis, we assessed the effects of ruxolitinib treatment on measures of metabolic and nutritional status. PATIENTS AND METHODS: Patients were randomized to receive ruxolitinib (n = 155; 15 or 20 mg twice a day for patients with baseline platelet counts of 100-200 × 10(9)/L or > 200 × 10(9)/L, respectively) or placebo (n = 154). The primary end point was the proportion of patients with a ≥ 35% spleen volume reduction from baseline to week 24. A secondary end point was the proportion of patients with ≥ 50% improvement in Total Symptom Score (TSS) from baseline to week 24, measured using the modified Myelofibrosis Symptom Assessment Form version 2.0. Weight, cholesterol, and albumin were measured at specified time points throughout the study. RESULTS: Compared with placebo, ruxolitinib treatment was associated with increased weight (mean change: 3.9 kg vs. -1.9 kg), total cholesterol (mean percentage change: 26.4% vs. -3.3%), and albumin levels (mean percentage change: 5.8% vs. -1.7%) at week 24; sustained improvements were observed with longer-term ruxolitinib therapy. Relative to placebo, increases in mean weight, total cholesterol, and albumin levels were observed with ruxolitinib treatment regardless of the degree of spleen volume and TSS reductions at 24 weeks. CONCLUSION: Treatment with ruxolitinib improved measures of metabolic and nutritional status of patients with intermediate-2 or high-risk MF.

In vitro evaluation of antimicrobial activity of Kutajghan vati - an Ayurvedic formulation.

The present investigation focuses to determine the antimicrobial potential of an Ayurvedic formulation Kutajghan vati. In this study the activity of this formulation was compared with the standard antibiotics like Amikacin and Norfloxacin. Ethanol, methanol and acetone extract of Kutajghan vati demonstrated good antimicrobial activity and thus can form the basis for the development of a novel antibacterial formulation.

Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths, controversies, and unknowns.

Progress in the last decade has improved the understanding of leukemia biology. Molecular markers in combinations with cytogenetics have improved the risk stratification of acute myeloid leukemia (AML) and informed decision-making. In parallel, several important advances in the transplant field, such as better supportive care, improved transplant technology, increased availability of alternative donors, and reduced-intensity conditioning have improved the safety as well as access of allogeneic hematopoietic cell transplantation (HCT) for a larger number of patients. In this review, the positioning of HCT in the management of patients with AML is evaluated in view of changing risk/benefit ratios associated with both conventional treatments and transplantation, and some of the controversies are addressed in light of emerging data. Increasing data demonstrate outcomes of alternative donor transplantation approaching HLA-identical sibling donors in high-risk AML supporting the inclusion of alternative donors in trials of prospective studies evaluating post remission strategies for high-risk AML. The use of reduced-intensity conditioning has expanded the eligibility of HCT to older patients with AML, and outcome data are encouraging. Continued study of HCT versus alternative therapies is required to optimize patients' outcomes in AML.