Changes in health-related quality of life with long-term eltrombopag treatment in adults with persistent/chronic immune thrombocytopenia: Findings from the EXTEND study.

Patients with persistent/chronic immune thrombocytopenia (cITP) have low platelet counts, increased risk of bleeding and bruising, and often suffer from reduced health-related quality of life (HRQoL). cITP treatments may either improve HRQoL by increasing platelet counts or decrease it because of side effects. The open-label EXTEND study (June 2006 to July 2015) evaluated long-term safety, tolerability, and efficacy of eltrombopag (an oral thrombopoietin-receptor-agonist) in adults with cITP who completed a previous eltrombopag ITP trial. The final results of EXTEND were published and used to assess changes in patient-reported HRQoL over time and association between HRQoL and platelet response. Four validated HRQoL instruments were administered: SF-36v2 including physical component summary (PCS) and Mental Component Summary; Motivation and Energy Inventory Short Form (MEI-SF); Fatigue Subscale of FACIT (FACIT-Fatigue); and FACT-Thrombocytopenia Subscale Six-Item Extract (FACT-Th6). For the 302 patients enrolled, median duration of eltrombopag treatment was 2.37 years. All 4 HRQoL instruments demonstrated positive mean changes from baseline over time adjusted for patient baseline characteristics and rescue therapy use, and had positive association with platelet response (platelet count ≥30 × 109 /L; ≥50 × 109 /L; and ≥50 × 109 /L and >2 times baseline). Improvements from baseline started within 3 months and persisted through 5 years of treatment for FACIT-Fatigue and FACT-Th6 (P <.05 for nearly all time points); through 2.5 years for SF-36v2 PCS and less consistently for the MEI-SF. In conclusion, in addition to eltrombopag increasing platelet counts and reducing bleeding/bruising, it also alleviated fatigue, concerns about bleeding and bruising, and improved physical function in many patients, especially responders.

Patient-reported outcomes of multiple myeloma patients treated with panobinostat after ≥2 lines of therapy based on the international phase 3, randomized, double-blind, placebo-controlled PANORAMA-1 trial.

The phase 3 PANORAMA-1 trial led to regulatory approvals of panobinostat (PAN) in combination with bortezomib (BTZ) and dexamethasone (DEX) for the treatment of multiple myeloma after ≥2 prior regimens, including BTZ and an immunomodulatory drug. Patient-reported outcomes (PROs) were assessed in PANORAMA-1, with data available for 73 patients in the PAN + BTZ + DEX arm and 74 patients in the placebo (PBO) + BTZ + DEX arm. Per the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), global health status/quality of life (QoL) scores initially declined with PAN + BTZ + DEX during the first 24 weeks before approaching baseline scores and remaining steady during the next 24 weeks, with no difference between arms at Week 48. The EORTC QLQ-Myeloma module (EORTC QLQ-MY20) demonstrated initial improvements and subsequent stabilization of disease symptom scores in both arms and initial worsening and subsequent improvement of side effects of treatment scores, with the initial worsening more pronounced and recovery less pronounced with PAN + BTZ + DEX. Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity scores remained relatively stable and similar between the arms. Overall, these PRO findings support the addition of PAN to the BTZ+DEX regimen as an efficacious treatment option, with limited symptomatology and impact on patients' QoL. The reported results are based on a descriptive analysis of the data. No formal statistical tests have been performed.

A Discrete Choice Experiment to Elicit Patient Willingness to Pay for Attributes of Treatment-Induced Symptom Relief in Comorbid. Insomnia.

PURPOSE: Insomnia is a burdensome, commonly comorbid condition. How patients value various aspects of the safety and efficacy of available drugs has not been studied. The aim of the present study was to quantify patient-rated utility by studying willingness to pay (WTP) for attributes of symptom relief via a discrete choice experiment (DCE). METHODOLOGY: Adult primary care patients (West Virginia University Hospital) with comorbid insomnia were enrolled. The attributes and levels examined were sleep onset latency (SOL; 10, 20,30 minutes), awakenings (1, 2, 3), wake time after sleep onset (WASO; 15,45, 60 minutes), total sleep time (TST; 6, 7, 8 hours), hangover (none, mild, moderate), FDA-approved duration of use (short term, not restricted to short term, no restrictions), and out-of-pocket cost per month ($20, $35, $50). Willingness to pay (WTP) data were analyzed using a random effects binary logistic regression model. RESULTS: A total of 82 patients completed the DCE (74 analyzed). SOL, WASO, TST, and cost were all found to predict treatment choice. Higher values of SOL, WASO, and cost resulted in decreased preference for a particular treatment, while higher TST predicted increased preference. Modeling revealed an estimated marginal WTP of $66.69 for an example product that improved SOL by 10 minutes, reduced WASO by 15 minutes, and improved TST by 1 hour. CONCLUSION: Patient WTP for symptomatic relief in insomnia can help clinicians fine-tune interventions based on patient preferences, provide evidence for drug formulary and reimbursement decisions, and potentially guide the development of novel drugs.

Reliability of specific finger dermatoglyphic patterns and their association with dental caries.

The etiology of dental caries is generally agreed to be a complex problem with many indirect factors that may obscure the direct cause or causes. There is substantial evidence that heredity plays an important role in this disease. Dermatoglyphics is a study that can be used to indicate congenital abnormalities. This study sought to determine a correlation between the prevalence of dental caries and dermatoglyphic fingerprint patterns, and thus assess the reliability of such patterns for identifying a susceptibility to dental caries. The results showed that the association between people with dental caries and whorls in their fingerprints was 60.4% . The association between people without caries who had loops in their fingerprints was 55.7%. These associations had a statistical significance of P < 0.001.

Analgesic and anti-inflammatory activity of ß-sitosterol isolated from Nyctanthes arbortristis leaves.

Nyctanthes arbortristis Linn. (Oleaceae) is one of the well-known Indian medicinal plant. Various extracts of leaves of the plant were screened for analgesic activity by hot plate test and acetic acid-induced writhings and anti-inflammatory activity by carrageenan-induced hind paw edema method at the dose of 50 mg/kg, i.p. Petroleum ether extract was found to be most active and hence subjected to activity-guided fractionation. Results showed that ß-sitosterol (5, 10 and 20 mg/kg, i.p.) was responsible for the significant and dose-dependent activity comparable with the standard extract. ß-Sitosterol from N. arbortristis leaves might be responsible for analgesic and anti-inflammatory activity.

Use of Cordia dichotoma bark in the treatment of ulcerative colitis.

CONTEXT: The plant Cordia dichotoma Forst. f. (Boraginaceae) is commonly known as "Bhokar" in Marathi. This tree species has been of interest to researchers because traditionally its bark is reported in the treatment of ulcer and colic pain. OBJECTIVE: The present work was undertaken to validate its folk use in the treatment of ulcerative colitis (UC) by using scientific methods. MATERIALS AND METHODS: Dried bark powder was extracted with methanol and this crude methanol extract was fractionated using various solvents. These fractions were tested for effectiveness against UC. Macroscopical study and histopathology of the colon, level of myeloperoxidase (MPO) and malondialdehyde (MDA) in colon and blood were studied for the assessment of the activity. Antioxidant activity of these fractions was screened by using various methods. RESULTS: Animals treated with the methanol fraction of the crude methanol extract showed lower pathological scores and good healing. This fraction reduced MPO and MDA levels significantly in blood and tissue. It showed antioxidant potential [in DPPH (1,1-diphenyl-2-picrylhydrazyl) assay IC50 value is 26.25; trolox equivalent (TE) antioxidant capacity µg/ml TE/g of plant material on dry basis in ABTS (2,2'-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid) and FRAP (ferric reducing antioxidant potential) assay is 2.03 and 2.45, respectively]. The fraction contains a high level of phenolics. DISCUSSION AND CONCLUSION: The methanol fraction of crude methanol extract of C. dichotoma bark is effective in the treatment of UC.

Potential of Vitex negundo roots in the treatment of ulcerative colitis in mice.

CONTEXT: Vitex negundo Linn. (Verbenaceae) is an indigenous tree species in India. This tree species has been of interest to researchers because traditionally its roots are reported in the treatment of ulcer and colic pain. OBJECTIVE: The present work was undertaken to validate its folk use in the treatment of ulcerative colitis (UC) by using the method of acetic acid-induced colitis in mice. MATERIALS AND METHODS: Ethanol and aqueous extracts of roots of V. negundo (100 mg/kg) were screened for use in the treatment of UC by the method of acetic acid-induced UC in mice. Macroscopical study of the colon, level of myeloperoxidase (MPO), malondialdehyde (MDA) in colon tissue and blood and histopathology of the colon tissue were studied for the assessment. RESULTS: Ethanol extract (100 mg/kg) reduced the level of MPO in blood from 355 ± 0.39 to 240 ± 0.36 U/mL and from 385 ± 0.35 to 257 ± 0.36 U/mg in tissue. Similarly, it reduced the level of MDA in blood from 9.40 ± 0.42 to 6.10 ± 0.36 nmol/mL and from 9.38 ± 0.56 to 5.89 ± 0.56 U/mg in tissue. Both the results are comparable with the standard drug, prednisolone (5 mg/kg). This preventive effect was observed by morphological and histopathological study. DISCUSSION AND CONCLUSION: Results showed that ethanol extract of V. negundo root is effective in the treatment of UC and results are comparable with the standard drug, prednisolone, and thus possessing a great potential in the treatment of UC.

Cholesterol granuloma of maxillary sinus.

The cholesterol granuloma is a particular form of granulation tissue developing as part of a variety of tissue reactions. It is usually associated with chronic middle ear disease and is common in the mastoid antrum of temporal bone. Cholesterol granuloma is rare in maxillary antrum. A case is reported of cholesterol granuloma in the maxillary sinus of a 42-year-old man, with the unique feature that the soft tissue lesion is enclosed by thick bone, entirely within the sinus.

Cytomegalovirus and Mucoepidermoid carcinoma: A possible causal relationship? A pilot study.

BACKGROUND: Human cytomegalovirus (CMV) infection has tropism for salivary gland ductal epithelium and establishes a persistent and lifelong infection. Mucoepidermoid carcinoma (MEC) is the most common salivary gland tumor. Recent studies have established that mouse CMV-induced tumorigenesis displays histologic and molecular characteristics similar to human MEC. We wished to explore further down the lane by analyzing the expression of pp65 and the key oncogenic signaling pathway in cases of MEC and their etiological relevance in the Indian scenario as a pilot study. MATERIALS AND METHODS: Histopathologically confirmed cases of MEC (n = 4) and normal salivary gland tissue (n = 4) were subjected to immunohistochemical analysis using the markers pp65 and epidermal growth factor receptor (EGFR). RESULTS: The pp65 antigen expression was found to be negative in all the studied cases and one case of high-grade MEC showed EGFR expression. CONCLUSION: The purpose of the study was to explore the role of CMV in the development of MEC, as it might help to exploit this etiological agent as a therapeutic target. Similar to human papillomavirus (HPV), these might identify a subset of neoplasms with a varied biological behavior and alternative therapies. However, this vision is obscured by contradicting evidence in the literature. As of today, surgery remains the only best possible management for these patients unless proven otherwise.

Use of apigenin from Cordia dichotoma in the treatment of colitis.

Cordia dichotoma f. (Boraginaceae) is a small deciduous tree from India. The bark of was used in the treatment of ulcerative colitis (UC) and colic pain traditionally hence present work was undertaken to identify the phytoconstituent responsible for this activity. Apigenin is isolated by column chromatography from methanol fraction of crude methanol extract of C. dichotoma bark. Structure of apigenin is established by various spectroscopic studies. Apigenin (5mg/kg, p.o.) showed significant healing and reduction in inflammatory enzymes when screened for UC. It can be concluded that apigenin from C. dichotoma bark may be responsible for the treatment of UC.

Morphometry of buccal mucosal cells in fluorosis--a new paradigm.

STUDY BACKGROUND: Fluorosis is one of the manifestations of chronic poisoning from long-term exposure to high levels of fluoride. An estimated 62 million people in 17 states in India are affected with dental and skeletal fluorosis. OBJECTIVE: To evaluate the cytological morphology of exfoliated oral mucosal cells among various stages of fluorosis patients compared with controls. DESIGN AND METHODS: Exfoliative cytology PAP-stained smears of 21 cases of fluorosis and 21 controls subjected to morphometric analysis using image Proplus software. For the assessment parameters like maximum and minimum diameter of the nucleus, cell and perimeter of the cell and nucleus were considered. RESULTS: An increase in maximum and minimum diameter of nucleus, perimeter of nucleus and cell in cases when compared to controls. CONCLUSIONS: Fluorosis induces oxidative stress, DNA damage and apoptosis which can be the reasons for the increase in the nuclear size and decrease in the cell size. Community dental and medical programmes should be stringently implemented in fluorosis-endemic areas, to create awareness regarding the toxic effects of fluoride to the body, especially within the oro-facial region.

Prevalence and cost of insomnia in a state Medicaid fee-for-service population based on diagnostic codes and prescription utilization.

OBJECTIVES: The aims of this research were to estimate prevalence of insomnia, describe the utilization patterns of physician office services and prescription medications for insomnia, and estimate related costs in a Medicaid population. METHODS: A cross-sectional descriptive analysis using data from the West Virginia (WV) Medicaid fee-for-service paid claims records for the year 2003 was conducted. Recipients with a diagnosis related to insomnia or a prescription claim for an FDA-approved drug for insomnia or trazodone were selected as the study sample. Costs were from the perspective of WV Medicaid. RESULTS: The overall prevalence of insomnia was 74.3 per 1000 recipients. Adults 45-64years of age, females, and whites had the highest prevalence and office visit rates for insomnia among demographic groups. A majority of dollars spent on insomnia treatment was for prescription drugs. Zolpidem and trazodone accounted for 88% of prescription claims; however, 84% of the total dollars paid for prescriptions was for zolpidem. CONCLUSIONS: Among the WV Medicaid population, rates of insomnia and office visit use for insomnia varied by demographic groups. There was greater use of zolpidem and trazodone than benzodiazepine drugs. This study provides baseline estimates that can be used for ongoing surveillance of insomnia.

Characterization of different tissue changes in normal, betel chewers, potentially malignant lesions, conditions and oral squamous cell carcinoma using reflectance confocal microscopy: correlation with routine histopathology.

The goal of this study was to characterize the features of normal mucosa, mucosa in betel chewers and smokers, potentially malignant lesions and squamous cell carcinoma of oral mucosa using reflectance confocal microscopy. Oral cavity biopsies were acquired from 25 patients from College of Dental Surgery, Saveetha University who underwent screening for suspected lesions of Oral precancer and Oral cancer along with normal patients who underwent impaction. Biopsies were acquired from the clinically suspicious area and immediately placed in Dulbecco modified eagles growth medium (DMEM). Reflectance confocal images were obtained at multiple image plane depths from biopsies within 6h of excision. After imaging, biopsies were fixed in 10% formalin and submitted for routine histopathological examination by an experienced oral and maxillofacial pathologist. Reflectance confocal images were compared with histological images from the same sample to determine the tissue features which contribute to early cellular changes, image contrast and early diagnosis. The confocal images were obtained to a depth of up to 150 microns on intact biopsy specimens and subsequent 3-dimensional images, keratin thickness measurements, cell measurements, cell density analysis and graphical representations were performed using Leica image analysis software. In normal mucosa keratin deposition were seen as alternating dark and bright stacks and in different cell layers the nuclei were seen as disks of varying intensities. In pre-cancerous lesions the keratin thickness and cell nuclear density were found to be increased when compared to normal controls. In OSMF cases confocal images of fibrosis show scattering from individual fibres as hyperdense areas. Oral squamous cell carcinoma cases demonstrated extensive variations in cell size, nuclear size and nuclear morphology. At cellular level, dysplastic features like increased nuclear density, increased nuclear cytoplasmic ratio, nuclear and cellular pleomorphism with loss of cohesiveness were identified in all five cases. Our results support the potential of reflectance confocal microscopy to play a significant role in clinical evaluations of oral lesions, early diagnosis of potentially malignant and malignant oral lesions and real time identification of tumour margins.

Unilocular cystic sebaceous lymphadenoma: a rare tumour.

A unique variant of the sebaceous lymphadenoma, so-called unilocular cystic sebaceous lymphadenoma, occurred in a 28-year-old male with a painless swelling in the left parotid region. The recognition of key histological features will readily allow differentiation of this unique neoplasm from its benign and malignant mimics. To our knowledge, out of 21 cases of sebaceous lymphadenoma reported, only 3 unilocular cystic variants have been recorded.

Pleomorphic adenoma in the infra-temporal space: the first case report.

The infratemporal fossa is a deep retromaxillary space corresponding to the inferior aspect of the middle cranial fossa. Tumours in the infratemporal fossa are very rare; therefore experience in their diagnosis and therapeutic management is very limited. Tumors that are reported commonly in the infratemporal region are nasopharyngeal carcinomas, juvenile angiofibromas and adenoid cystic carcinomas. To the best of our knowledge, this is the first report in the English language literature of a pleomorphic adenoma presenting in the infratemporal space and probably arising from an ectopic minor salivary gland, along with a brief description of the surgical technique.

Stromal changes in apparently normal mucosa of smokers and pan chewers: a multi-parametric approach

Aim: To compare and contrast the various changes in the connective tissue among patients with the habits of smoking, pan chewing and controls by using fluorescence spectroscopy, histopathology and transmission electron microscopy. Method: Thirty subjects were categorized into three groups: pan chewers, smokers and controls without any oral lesions. Fluorescence spectroscopy was carried out using FLUOROMAX-2. Excitation spectroscopy was performed at 280 and 320nm respectively and Emission spectroscopy was performed at 340 and 390nm excitation. Subsequently, histopathological evaluation and transmission electron microscopy was done for biopsies taken from test groups and controls. Results: The mean, standard deviation and test of significance of mean values between different groups for intensity-380nm, intensity–420nm and intensity – 460nm at 320 nm excitations, showed that the Mean values in group I and group II were significantly higher than the mean value in group III with a p-value of less than 0.001. Considering the histopathological parameters, the pattern of the sub-epithelial connective tissue, the presence of chronic inflammatory cells and lysis of connective tissue was significant. The ultrastructural analysis revealed the presence of epithelioid, spindle or elongated and stellate shaped fibroblasts in the connective tissue. Conclusion: In this pilot study, we could find variations in emission characteristics of various amino acids which correlated with histopathology and electron microscopy. Our study suggests that there are connective tissue changes in oral mucosa among smokers and pan chewers, though it is apparently normal in clinical presentation. These initial connective tissue changes could determine the progression of altered mucosa to a pre-cancer or cancer, which is further related to other complex interactions. Elaborate studies are required to evaluate the significance of our hypothesis.