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Objectives: Spirituality is a significant dimension of quality palliative care service provision. The purpose of our audit was to assess current practice and improve documentation of spiritual concerns of adult advanced cancer patients in a specialist palliative care (SPC) service in a tertiary care cancer centre. Materials and Methods: In a standard-based audit, we measured the percentage of patient assessment forms with documentation of assessed spiritual concerns at a baseline and reaudit after practice change measures. We set the optimum standard that at least 60% of the case forms would have patients’ spiritual concerns recorded. We implemented the following measures – (1) engaging our palliative care staff in team discussions on existing practice and identifying problems and (2) conducting a structured 2 h training module for assessment and documentation of patients’ spiritual concerns. Results: About 70.8% and 93.4% of the patient assessment forms included had documentation of assessed spiritual concerns which is higher than the standard we set at 60% and 90% at baseline and after implementing practice change, respectively. In the reaudit, we found that documentation specific to spirituality and overall psychological assessment improved. We identified that a persisting problem was the lack of recording of spiritual assessment in the patients’ follow-up notes. Conclusion: We achieved the benchmark of a standard-based audit on documentation of assessed spiritual concerns of advanced cancer patients in our SPC service. Regular audits in clinical service delivery and documentation should be integrated into quality improvement measures in palliative care.

Background Patients taking medication with high anticholinergic and sedative properties are at increased risk of experiencing poor cognitive and physical outcomes. Therefore, precise quantification of the cumulative burden of their drug regimen is advisable. There is no agreement regarding which scale to use to simultaneously quantify the burden associated with medications. Objectives The objective of this review was to assess the strengths and limitations of available tools to quantify medication-related anticholinergic burden and sedative load in older adults. We discuss specific limitations and agreements between currently available scales and models and propose a comprehensive table combining drugs categorized as high, moderate, low, or no anticholinergic or sedative activity as excerpted from the selected studies. Methods A targeted search was carried out using the National Library of Medicine through PubMed using medical subject heading terms and text words around the following search terms: (anticholinergic OR sedative) AND (load OR burden OR scale) for studies published between 1 January 1945 and 5 June 2021. In addition, the following databases were searched using the same terms: MEDLINE-EBSCO, APA PsycInfo, CINAHL Plus, Cochrane Library, Scopus, OAIster, OVID-MEDLINE, Web of Science, and Google Scholar. Screening by titles was followed by an abstract and full-text review. After blind evaluation, agreement between reviewers was reached to establish drug characteristics and categories. Results After 3163 articles were identified, 13 were included: 11 assigned risk scores to anticholinergic drugs and two to sedative drugs. Considerable variability between anticholinergic scales was observed; scales included between 27 and 548 drugs. We generated a comprehensive table combining the anticholinergic and sedative activities of drugs evaluated and proposed a categorization of these drugs based on available scientific and clinical evidence. Our table combines information about 642 drugs and categorizes 44, 25, 99, and 474 drugs as high, moderate, low, or no anticholinergic and sedative activity, respectively. Conclusions Variability and inconsistency exists among scales used to categorize drugs with anticholinergic or sedative burden. In this review, we provide a comprehensive table that proposes a new categorization of these drugs. A longitudinal study will be required to validate the new proposed anticholinergic and sedative burden catalog in an evidence-based manner. Supplementary Information The online version contains supplementary material available at 10.1007/s40266-021-00895-x.

Background The safety and effectiveness of live virus vaccines, such as the varicella-zoster vaccine, are unknown in patients with inflammatory diseases receiving immunomodulatory therapy such as tumor necrosis factor inhibitors (TNFis). Objective To evaluate the safety and immunogenicity of the live attenuated zoster vaccine (ZVL) in patients receiving TNFis. Design Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02538341). Setting Academic and community-based rheumatology, gastroenterology, and dermatology practices. Patients Adults aged 50 years or older receiving TNFis for any indication. Intervention Random assignment to ZVL versus placebo. Measurements Glycoprotein enzyme-linked immunosorbent assay (gpELISA) and enzyme-linked immunosorbent spot (ELISpot) from serum and peripheral blood mononuclear cells measured at baseline and 6 weeks after vaccination. Suspected varicella infection or herpes zoster was clinically assessed using digital photographs and polymerase chain reaction on vesicular fluid. Results Between March 2015 and December 2018, 617 participants were randomly assigned in a 1:1 ratio to receive ZVL (n = 310) or placebo (n = 307) at 33 centers. Mean age was 62.7 years (SD, 7.5); 66.1% of participants were female, 90% were White, 8.2% were Black, and 5.9% were Hispanic. The most common TNFi indications were rheumatoid arthritis (57.6%) and psoriatic arthritis (24.1%); TNFi medications were adalimumab (32.7%), infliximab (31.3%), etanercept (21.2%), golimumab (9.1%), and certolizumab (5.7%). Concomitant therapies included methotrexate (48.0%) and oral glucocorticoids (10.5%). Through week 6, no cases of confirmed varicella infection were found; cumulative incidence of varicella infection or shingles was 0.0% (95% CI, 0.0% to 1.2%). At 6 weeks, compared with baseline, the mean increases in geometric mean fold rise as measured by gpELISA and ELISpot were 1.33 percentage points (CI, 1.17 to 1.51 percentage points) and 1.39 percentage points (CI, 1.07 to 1.82 percentage points), respectively. Limitation Potentially limited generalizability to patients receiving other types of immunomodulators. Conclusion This trial informs safety concerns related to use of live virus vaccines in patients receiving biologics. Primary funding source The National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American College of Rheumatology.

Objectives: Patients needing palliative care prefer to be cared for in the comfort of their homes. Although private home health-care services are entering the health-care ecosystem in India, for the majority it is still institution-based. Here, we describe a model of home-based palliative care developed by the Tata Memorial Hospital, a government tertiary care cancer hospital. Materials and Methods: Data on patient demographics, services provided and outcomes were collected prospectively for patients for the year November 2013 - October 2019. In the 1st year, local general physicians were trained in palliative care principles, bereavement services and out of hours telephone support were provided. In the 2nd year, data from 1st year were analysed and discussed among the study investigators to introduce changes. In the 3rd year, the updated patient assessment forms were implemented in practice. In the 4th year, the symptom management protocol was implemented. In the 5th and 6th year, updated process of patient assessment data and symptom management protocol was implemented as a complete model of care. Results: During the 6 years, 250 patients were recruited, all suffering from advanced cancer. Home care led to good symptom control, improvement of quality of life for patients and increased satisfaction of caregivers during the care process and into bereavement. Conclusion: A home-based model of care spared patients from unnecessary hospital visits and was successful in providing client centred care. A multidisciplinary team composition allowed for holistic care and can serve as a model for building palliative care capacity in low- and middle-income countries.

Hepatic tuberculosis (HTB) is rare and mimics neoplastic liver lesions clinico-radiologically leading to misdiagnosis and even unnecessary surgery. We analysed 43 cases of HTB diagnosed at a referral cancer centre over 10 years. Clinical details, investigations and treatment received were noted. The median age was 46 years with a female preponderance (58%). HTB was diagnosed incidentally in 28% cases during surveillance imaging for a previous cancer. Constitutional symptoms (31, 72%), abdominal pain (25, 58%), fever (12, 28%), hepatomegaly (22, 51%), elevated alkaline phosphatase (34, 79%), elevated aminotransferases (18, 42%) and hypoalbuminemia (19, 45%) were common features. All cases had negative HIV serology and normal tumor markers. Twenty-two (52.5%) had solitary liver lesion and lesions > 2 cm in 28 (65%). Ultrasound showed hypoechoic lesions in 31 of 33 cases. Computed tomography showed hypodense lesions (43,100%) with mild peripheral enhancement (32, 74%). Calcifications (5, 12%) and capsular retraction (8, 19%) was uncommon. MRI was performed in seven cases commonly showed T1 hypointense, T2 hyperintense lesions with restricted diffusion. Histopathology showed granulomatous inflammation (42, 97.5%), Langhan’s giant cells (41, 95%) and caseation necrosis (35, 85%). Acid-fast stain and PCR positivity was uncommon. Extrahepatic organs were involved in 20 (46.5%). HTB mimicked cholangiocarcinoma (25, 58%), liver metastasis (11, 26%) and lymphoma (3, 7%). Six patients underwent liver resection with a presumptive diagnosis of cancer without a preoperative biopsy. All patients received antitubercular therapy, 37 had clinico-radiological response, there were 3 deaths and 3 patients were lost to follow-up. HTB is rare and can mimic a malignancy clinico-radiologically. Calcifications and pseudocapsule appearance on multiphase CT scan may help in differentiating HTB from hepatic malignancy. Tumor markers are normal while histopathology is generally diagnostic. A high index of suspicion is required to avoid unnecessary surgery as the patients respond well to ATT. This is a retrospective and observational study hence clinical trial registration is not applicable.

Spondyloarthritis (SpA) comprises a group of chronic inflammatory diseases with overlapping clinical, genetic and pathophysiological features including back pain, peripheral arthritis, psoriasis, enthesitis and dactylitis. Several cytokines are involved in the pathogenesis of SpA, variously contributing to each clinical manifestation. Many SpA-associated cytokines, including IL-23, IL-17, IL-6, type I/II interferon and tumour necrosis factor signal directly or indirectly via the Janus kinase (JAK)–signal transducer and activator of transcription pathway. JAK signalling also regulates development and maturation of cells of the innate and adaptive immune systems. Accordingly, disruption of this signalling pathway by small molecule oral JAK inhibitors can inhibit signalling implicated in SpA pathogenesis. Herein we discuss the role of JAK signalling in the pathogenesis of SpA and summarize the safety and efficacy of JAK inhibition by reference to relevant SpA clinical trials.

Objective: Cholesterol efflux capacity (CEC), the ability of extracellular acceptors to pick-up cholesterol from macrophages, is a clinically relevant cardiovascular biomarker. CEC is inversely associated with incident atherosclerotic cardiovascular disease events. However, CEC is only modestly associated with HDL-C (high-density lipoprotein cholesterol) levels, which may explain the failure of HDL-C raising therapies to improve atherosclerotic cardiovascular disease outcomes. Determinants of variation in CEC are not well understood. Thus, we sought to establish whether extreme high and low CEC is a robust persistent phenotype and to characterize associations with cholesterol, protein, and phospholipids across the particle size distribution. Approach and Results: CEC was previously measured in 2924 participants enrolled in the Dallas Heart Study, a multi-ethnic population-based study from 2000 to 2002. We prospectively recruited those who were below the 10th and above 90th percentile of CEC. Our study revealed that extreme low and high CEC are persistent, robust phenotypes after 15 years of follow-up. Using size exclusion chromatography, CEC to fractionated plasma depleted of apolipoprotein B (fraction-specific CEC) demonstrated significant differences in CEC patterns between persistent high and low efflux groups. Fraction-specific CEC was correlated with fraction-specific total phospholipid but not apolipoprotein A-I, cholesterol, or total protein. These correlations varied across the size distribution and differed among persistent high versus low efflux groups. Conclusions: Extreme high and low CEC are persistent and robust phenotypes. CEC patterns in fractionated plasma reveal marked variation across the size distribution. Future studies are warranted to determine specific molecular species linked to CEC in a size-specific manner.

This study was performed to assess the risk factors driving the epidemic of coronavirus disease 2019 (COVID-19)-associated mucormycosis (COVID-Mucor) in India that has accompanied the COVID-19 pandemic, particularly during the second wave. Risk factors were analysed among 164 participants: 132 COVID-Mucor (cases) and 32 non-COVID-Mucor (controls). Data from a prospective cohort study of mucormycosis over a period of 1 year were used. Diabetes mellitus remained a significant risk factor in both groups (97%), while uncontrolled diabetes mellitus (odds ratio (OR) 4.6; P = 0.026) and newly detected diabetes (OR 3.3; P = 0.018) were more common among the cases. Most patients with COVID-Mucor had mild COVID-19. Steroid use, often unwarranted, was highly associated with COVID-Mucor after adjusting for other risk factors (OR 28.4; P = 0.001). Serum ferritin was significantly higher (P = 0.041), while C-reactive protein was not, suggesting that alterations in iron metabolism may predispose to COVID-Mucor. Oxygen was used only in a small minority of patients with COVID-Mucor. The in-hospital mortality in both groups was low. In conclusion, the Indian COVID-Mucor epidemic has likely been driven by a convergence of interlinked risk factors: uncontrolled diabetes mellitus, unwarranted steroid use, and perhaps COVID-19 itself. Appropriate steroid use in patients with severe COVID-19 and screening and optimal control of hyperglycaemia can prevent COVID-Mucor.

Treatment and prevention of human immunodeficiency virus type one (HIV-1) infection was transformed through widespread use of antiretroviral therapy (ART). However, ART has limitations in requiring life-long daily adherence. Such limitations have led to the creation of long-acting (LA) ART. While nucleoside reverse transcriptase inhibitors (NRTI) remain the ART backbone, to the best of our knowledge, none have been converted into LA agents. To these ends, we transformed tenofovir (TFV) into LA surfactant stabilized aqueous prodrug nanocrystals (referred to as NM1TFV and NM2TFV), enhancing intracellular drug uptake and retention. A single intramuscular injection of NM1TFV, NM2TFV, or a nanoformulated tenofovir alafenamide (NTAF) at 75 mg/kg TFV equivalents to Sprague Dawley rats sustains active TFV-diphosphate (TFV-DP) levels ≥ four times the 90% effective dose for two months. NM1TFV, NM2TFV and NTAF elicit TFV-DP levels of 11,276, 1,651, and 397 fmol/g in rectal tissue, respectively. These results are a significant step towards a LA TFV ProTide., Antiretroviral therapy (ART) for the treatment of HIV-1 requires life-long daily adherence to supress viral replication, and nucleoside reverse transcriptase inhibitors that are commonly used in ART have not been converted into long-acting agents. Here, the authors report two lipophilic tenofovir (TVF) ProTide nanoformulations, NM1TFV and NM2TFV, which sustain drug levels above therapeutic concentrations for two months after a single intramuscular dose in rats.

Background Endometrial serous carcinoma (ESC) is an aggressive neoplasm wherein the recent studies have shown that it arises from its putative precursor namely the serous endometrial intraepithelial carcinoma (SEIC). SEIC usually arises in inactive/ atrophic endometrium but surprisingly is frequently associated endometrial polyps (EPs). The aim of this study was to assess the incidence of SEIC with or without invasion, its clinical behaviour and association with endometrial polyp. Materials and Methods After Institutional review board approval, a total of 205 samples (belonging to 120 patients); diagnosed as ESC from January 2009 to December 2015 were retrieved and reviewed for presence of in situ carcinoma and also for associated endometrial polyp. Results The mean age at diagnosis was 62.40 years with postmenopausal bleeding being the most common presenting symptom. The incidence of SEIC with or without invasive tumor was 40% (48/120). Of these 48 cases; 25 cases were associated with in-situ carcinoma arising in the EPs which amounted to 52% of the total cases. The overall three year survival and disease free survival in SEIC with or without invasion were 1.9% and 0.25%, indicating the aggressive nature of the disease. Conclusion SEIC is a difficult histopathological diagnosis and one should carefully look for these lesion, especially in the EPs which are frequently associated with them. Extensive sampling of the EP will be helpful to pick up in-situ carcinoma arising in EP. SEIC is an aggressive disease on its own with a propensity to develop distant metastasis even in the absence of myometrial invasion and hence should be treated with optimum surgical staging and if indicated aggressive adjuvant treatment protocols.

Objective Families of children with cancer undergoing treatment during COVID‐19 pandemic represent a vulnerable population for psychological distress and early identification and remedial measures are imperative for wellbeing of both the children and the caregivers. This article reports the results of assessment of psychological distress in primary caregivers of children with cancer undergoing treatment at a tertiary care center. Methods Primary caregivers of children with cancer (≤15 years) taking treatment at our institute during the period of July 2020 to August 2020 were prospectively evaluated for psychological distress using Patient Health Questionnaire‐9 (PHQ‐9) and Generalized Anxiety Disorder‐7 (GAD‐7) tools over a telephonic call. There were 2 cohorts, A and B (50 participants each) depending on whether child was diagnosed with COVID‐19 or not respectively during the study period. Results The assessment tool, PHQ‐9 showed a score of ≥10 in 13% (n = 13) participants (95%CI:7.1%–21.2%) in the entire cohort and in 16% (n = 8, 95%CI:5.8%–26.2%) and 10% (n = 5, 95%CI:1.7%–18.3%) participants in cohort A and cohort B respectively. GAD‐7 showed a score of ≥8 in 18% (n = 18) participants (95%CI:11.0%–27.0%) in the entire cohort and in 20% (n = 10, 95%CI:8.9%–31.1%) and 16% (n = 8, 95%CI:5.8%–26.2%) participants in cohort A and cohort B respectively. All participants were assessed, and supportive psychotherapeutic interventions administered over telephonic call. Conclusions Primary caregivers should be assessed and followed up for psychological distress irrespective of other co‐existing factors. Robust support systems built over time could help withstand the exceptional strain of a major surge during a pandemic.

Drug safety is generally established from clinical trials, by pharmacovigilance programs and during observational phase IV safety studies according to drug intended or approved indications. The objective of this study was to estimate the risk of potential adverse drug events (ADEs) associated with drugs repurposed for coronavirus disease 2019 (COVID‐19) treatment in a large‐scale population. Drug claims were used to calculate a baseline medication risk score (MRS) indicative of ADE risk level. Fictitious claims of repurposed drugs were added, one at a time, to patients’ drug regimens to calculate a new MRS and compute a level of risk. Drug claims data from enrollees with Regence health insurance were used and sub‐payer analyses were performed with Medicare and commercial insured groups. Simulated interventions were conducted with hydroxychloroquine and chloroquine, alone or combined with azithromycin, and lopinavir/ritonavir, along with terfenadine and fexofenadine as positive and negative controls for drug‐induced Long QT Syndrome (LQTS). There were 527,471 subjects (56.6% women; mean [SD] age, 47 years [21]) were studied. The simulated addition of each repurposed drug caused an increased risk of ADEs (median MRS increased by two‐to‐seven points, p

Gametophytic self-incompatibility (SI) controlled by the multiallelic S-locus, that include tightly linked SRNase and SLF genes has been reported extensively in wild and diploid potatoes. The widely cultivated tetraploid are reported to overcome SI through a phenomenon called ‘competition interaction’ or ‘heteroallelic pollen’ effect. Here we report the activated Gametophytic SI in a tetraploid, non-fruiting popular Indian cultivar Kufri Girdhari through pollen and gene expressional studies. The results revealed highly stage-specific expression of S-RNase in contrast to ubiquitous SLFs in flower. Our preliminary studies found that S-RNase expressed in flower stigma and style after the pollination provide the evidence for the general mechanism SI. The recombination event and later fixing of the genetic composition may have lead to homomorphic condition that causes SI in the variety despite being a tetraploid. The study reveals the functional SI system acting in a tetraploid first time and further in-depth investigation of allele composition would provide complete understanding that would help in designing the future breeding programs.

Background Trastuzumab-dkst is a biosimilar of trastuzumab. The phase 3 HERITAGE trial demonstrated equivalent overall response rate (ORR) with trastuzumab-dkst or originator trastuzumab at 24 weeks in patients with HER2-positive metastatic breast cancer receiving chemotherapy. We now present the correlation of ORR with progression-free survival (PFS) for maintenance monotherapy with trastuzumab-dkst vs trastuzumab at 48 weeks of treatment, and the safety, tolerability, and immunogenicity. Methods HERITAGE is a multicenter, double-blind, randomized, parallel-group, phase 3 study. Patients were randomized 1:1 to receive trastuzumab-dkst or trastuzumab in combination with taxane followed by continued monotherapy until disease progression. The analysis included PFS at 48 weeks to support the primary efficacy endpoint of ORR and safety, tolerability, and immunogenicity of trastuzumab-dkst vs trastuzumab as maintenance monotherapy. Results Of 500 randomized patients, 342 entered the monotherapy phase; 214 patients received ≥48 weeks of treatment. There were no statistically significant differences between PFS, ORR, or interim overall survival at week 48 between trastuzumab-dkst and trastuzumab. Week 24 ORR was highly correlated with week 48 PFS (rb = 0.75). Cumulative treatment-emergent adverse events (TEAEs) and serious AEs were similar in both groups, with few grade ≥3 TEAEs. Immunogenicity was low and similar in both groups at 48 weeks. Conclusion The correlation between ORR and PFS supports the design of first-line metastatic trials assessing biosimilar trastuzumab. Overall, trastuzumab-dkst and trastuzumab were well tolerated with similar efficacy, including ORR and PFS, in combination with a taxane followed by monotherapy., Highlights • Trastuzumab-dkst is a biosimilar of trastuzumab. • Trastuzumab-dkst and trastuzumab had similar PFS, ORR, and OS at week 48. • Results support therapeutic equivalence between trastuzumab-dkst and trastuzumab. • Week 24 ORR was highly correlated with week 48 PFS. • ORR and PFS correlation supports ORR as a valid endpoint in clinical trials for MBC.

A simple, specific, precise, and accurate stability-indicating assay method using high performance thinlayer chromatography (HPTLC) is described for estimation of daclatasvir dihydrochloride (DCV) in bulk drug and in the tablet dosage form. The separations were achieved on prepared TLC plates precoated with silica gel 60 F254. The mobile phase developed and optimized for bringing out the separation involves toluene: methanol in the ratio of (6:4 V/V). The densitometric scanning wavelength selected was 312.0 nm. The compact bands of DCV were obtained at RF value of 0.702±0.032. The method developed was able to separate peaks of all the degradation products formed in ICH prescribed stress conditions with sufficient difference in their RF values. The developed method was validated for linearity and range, specificity, precision, accuracy, and robustness, and the results were found to be within acceptance criteria. The reliability of the method was evaluated when it was applied for the estimation of DCV in pharmaceutical tablet formulation and assay results gave good recovery.

Purpose The phase 3 HERITAGE trial demonstrated that the biosimilar trastuzumab-dkst is well tolerated with similar efficacy (measured by overall response rate [ORR] and progression-free survival [PFS]) compared with originator trastuzumab combined with taxane followed by monotherapy in patients with HER2-positive metastatic breast cancer (MBC). Herein, we present final overall survival (OS) from HERITAGE. Methods HERITAGE is a multicenter, double-blind, randomized, parallel-group study. Patients were randomized 1:1 to receive trastuzumab-dkst or trastuzumab plus taxane followed by continued monotherapy until disease progression. Overall survival was to be assessed at 36 months or after 240 deaths, whichever occurred first, as observed from time of randomization of last patient. Results At the final analysis (36 months), 242 patients in the intention-to-treat population had died during the study: 116 and 124 in the trastuzumab-dkst and trastuzumab groups, respectively, and 1 untreated patient from each treatment group. Median OS by Kaplan–Meier analysis was 35.0 months with trastuzumab-dkst and 30.2 months with trastuzumab. Evaluation of PFS showed a median of 11.1 months in both treatment groups. No new safety concerns were reported from week 48 until the end of the survival follow-up. Conclusion This is the first phase 3 trial of a trastuzumab biosimilar to report long-term survival data similar to originator trastuzumab in patients with MBC. The comparable long-term OS between the trastuzumab-dkst and originator trastuzumab groups further supports the similarity of trastuzumab-dkst with originator trastuzumab and establishes trastuzumab-dkst as a safe and effective treatment option for patients with HER2-positive MBC. ClinicalTrials.gov NCT02472964; 6/16/2015

Objectives Peritoneal tuberculosis can mimic advanced abdominal malignancy. We describe clinical and laboratory characteristics in a series of female patients with peritoneal tuberculosis who were referred to a tertiary cancer center with a diagnosis of suspected advanced ovarian/primary peritoneal cancer. Materials and Methods Details of clinical features, laboratory results including serum tumor markers, radiological findings, and ascitic fluid evaluation were retrospectively collected from hospital records for patients diagnosed to have peritoneal tuberculosis and reported descriptively. Statistical Analysis Descriptive statistics was performed using SPSS Statistics for Windows software, version 20.0 (SPSS, Chicago, Illinois). Results Between January 2009 and December 2017, 120 patients of peritoneal tuberculosis with a median age 41 years (range, 15–79 years) were identified. Of these 112 (93.3%; 95% CI 88.9–97.8%) patients had ascites and 63 (52.5%; 95% CI 43.6–61.4%) had adnexal mass at presentation. Mean serum cancer antigen 125 (CA-125) level was 666.9 (range, 38–18,554) U/mL. Ascitic fluid was negative for malignant cells in all patients and lymphocyte rich exudate was seen in 103 (91.9%; 86.9–97.0%) patients. Ascitic fluid adenosine deaminase (ADA) level was more than 40 U/L in 107 (95.5%; 95% CI 91.7–99.4%). Ascitic fluid Ziel–Neelsen staining was positive in 4/62 (6.5%; 95% CI 0.3–12.6%) patients while ascitic fluid culture examination for mycobacterium tuberculosis was positive in 7/59 (11.9%; 95% CI 3.6–20.1%) patients. The diagnosis of tuberculosis was based on image-guided biopsy in 44 (36.7%) patients, surgical biopsy in 8 (6.7%) patients, and a combination of clinicoradiological and laboratory features in 68 (56.7%) patients. All patients received standard antitubercular treatment. Conclusions The study results suggest that peritoneal tuberculosis has clinical, radiological, and serological profile which may mimic advanced ovarian/primary peritoneal cancer. Peritoneal tuberculosis should be considered in the differential diagnosis of advanced abdominal malignancy.

Diffuse alveolar hemorrhage (DAH) is a rare but potentially life-threatening emergency that has both immune and non-immune etiologies. The objective of this investigation was to compare the risk factors and outcomes of immune and non-immune causes of DAH at a tertiary-care academic center. This was a retrospective observational study conducted at a University center. We reviewed all chest radiographs spanning 12 years (2007–2019) at our institute with the words “diffuse alveolar hemorrhage” in the body of their report, and ascertained cases of DAH through a detailed chart review. We used Chi-squared test to determine the differences in risk factors and outcomes between immune versus non-immune causes of DAH. We performed logistic regressions to assess whether baseline demographics and clinical features influence four critical outcomes: death, shock, renal failure, and severe anemia requiring transfusions. Over the 12-year period, there were 88 patients with DAH, 55 with non-immune and 33 with immune etiologies. Among immune causes of DAH, granulomatosis with polyangiitis (GPA) (10.2%), microscopic polyangiitis (MPA) (9%) and systemic lupus erythematosus (SLE) (9%) were most common. Among non-immune causes of DAH, coagulopathy (6.8%), decompensated heart failure (4.5%) and infection (3.4%) were most common. Patients with non-immune causes of DAH were 45.8% more likely to die and 20.7% less likely to experience sustained remission (p = 0.001). Patient with immune causes of DAH were 21% more likely to have extra-pulmonary findings and 23.7% more likely to have received hemodialysis (HD). The presence of extra-pulmonary findings was statistically significantly correlated with the number of blood products received, the need for HD and non-statistically significantly correlated with likelihood of death. Patients with immune causes of DAH were 71.5% more likely to receive multimodal therapy including corticosteroids. Immune-mediated DAH is associated with a better prognosis than non-immune DAH, despite its greater association with extra-pulmonary findings and requirement for hemodialysis.

Background Deprescribing is one way to reduce inappropriate polypharmacy in older adult patients. Although algorithms have been published to guide practitioners in deprescribing, it is still unknown how applicable these algorithms are to the general older adult population. Objectives The primary objective was to assess the applicability of published deprescribing protocols in hospitalized older adult patients. Methods This retrospective study included patients aged 65 years or greater who were discharged from an internal medicine team between January 1, 2017 and June 30, 2017. Along with age and admission to internal medicine wards, other eligibility criteria were extracted from published deprescribing protocols. The primary endpoint was the proportion of patients eligible for deprescribing based on published algorithms. Secondary endpoints included the proportion of patients receiving medications which were included in an algorithm, proportion of patients using medications included in the algorithms who were eligible for deprescribing, and proportion of patients with medications deprescribed during the hospital stay. Results Two hundred sixty-seven patients were included and 124 (46.4%) used a medication with a published deprescribing algorithm. Thirty-four percent of all patients and 74% (92/124) of patients prescribed medications included in algorithms were eligible for deprescribing. Seven percent (6/92) of patients eligible for deprescribing had medications deprescribed during the hospital stay. Conclusion The application of deprescribing algorithms in hospitalized older adults identified a significant opportunity to initiate deprescribing practices.

ObjectivesDuring the COVID-19 pandemic, much communication occurred online, through social media. This study aimed to provide patient perspective data on how the COVID-19 pandemic impacted people with rheumatic and musculoskeletal diseases (RMDs), using Twitter-based patient-generated health data (PGHD).MethodsA convenience sample of Twitter messages in English posted by people with RMDs was extracted between 1 March and 12 July 2020 and examined using thematic analysis. Included were Twitter messages that mentioned keywords and hashtags related to both COVID-19 (or SARS-CoV-2) and select RMDs. The RMDs monitored included inflammatory-driven (joint) conditions (ankylosing spondylitis, RA, PsA, lupus/SLE and gout).ResultsThe analysis included 569 tweets by 375 Twitter users with RMDs across several countries. Eight themes emerged regarding the impact of the COVID-19 pandemic on people with RMDs: (i) lack of understanding of SARS-CoV-2/COVID-19; (ii) critical changes in health behaviour; (iii) challenges in healthcare practice and communication with healthcare professionals; (iv) difficulties with access to medical care; (v) negative impact on physical and mental health, coping strategies; (vi) issues around work participation; (vii) negative effects of the media; and (viii) awareness-raising.ConclusionThe findings show that Twitter serves as a real-time data source to understand the impact of the COVID-19 pandemic on people with RMDs. The platform provided ‘early signals’ of potentially critical health behaviour changes. Future epidemics might benefit from the real-time use of Twitter-based PGHD to identify emerging health needs, facilitate communication and inform clinical practice decisions.

Objectives The aim of this study was to compare the symptoms, treatment patterns, and quality of life (QoL) of ankylosing spondylitis (AS) patients to non-radiographic axial spondyloarthritis (nr-axSpA) patients in the USA. Method A cross-sectional survey was conducted with rheumatologists and their consulting patients in the USA from June through August 2018. Patients who had a rheumatologist confirmed diagnosis of AS and nr-axSpA were eligible to participate. Patient demographics, symptoms, and medication use were reported by the rheumatologist, while work disability and QoL measures were reported by the patient. Patient demographics, symptoms, QoL and treatment patterns of AS and nr-axSpA patients were compared using parametric tests and non-parametric tests when appropriate. Results A total of 515 AS patients and 495 nr-axSpA patients were included in this analysis. A higher proportion of AS patients were male (p < 0.001), older (p = 0.014), and more likely to be prescribed a biologic (p < 0.0001). On average, AS patients experienced slightly more symptoms at diagnosis (p = 0.023); however, nr-axSpA patients were more likely to experience enthesitis (p = 0.048) and synovitis (p = 0.003). Patient reported outcomes such as the ASAS Health Index (p = 0.171), ASQoL (p = 0.296), BASDAI (p = 0.124), and WPAI (p = 0.183) were similar between AS and nr-axSpA patients after adjusting for confounding variables such as medication use. Conclusions AS and nr-axSpA patients share the same clinical features. The burden of the disease, as assessed by QoL measurements, is also similar in AS and nr-axSpA patients; however, despite these similarities, patients with nr-axSpA are less likely to be treated with a biologic. Key Points • Ankylosing spondylitis and non• radiographic axial spondyloarthritis patients share similar clinical features and burden of disease.• Quality of life is similar among ankylosing spondylitis and non• radiographic axial spondyloarthritis after adjusting for current treatment patterns.

Background Early palliative care (EPC) is an important aspect of cancer management but, to our knowledge, has never been evaluated in patients with head and neck cancer. Hence, we performed this study to determine whether the addition of EPC to standard therapy leads to an improvement in the quality of life (QOL), decrease in symptom burden, and improvement in overall survival. Methods Adult patients with squamous cell carcinoma of the head and neck region planned for palliative systemic therapy were allocated 1:1 to either standard systemic therapy without or with comprehensive EPC service referral. Patients were administered the revised Edmonton Symptom Assessment Scale and the Functional Assessment of Cancer Therapy for head and neck cancer (FACT-H&N) questionnaire at baseline and every 1 month thereafter for 3 months. The primary endpoint was a change in the QOL measured at 3 months after random assignment. All statistical tests were 2-sided. Results Ninety patients were randomly assigned to each arm. There was no statistical difference in the change in the FACT-H&N total score (P = .94), FACT-H&N Trial Outcome Index (P = .95), FACT-general total (P = .84), and Edmonton Symptom Assessment Scale scores at 3 months between the 2 arms. The median overall survival was similar between the 2 arms (hazard ratio for death = 1.01, 95% confidence interval = 0.74 to 1.35). There were 5 in-hospital deaths in both arms (5.6% for both, P = .99). Conclusions In this phase III study, the integration of EPC in head and neck cancer patients did not lead to an improvement in the QOL or survival.

Mentors at seven United States and Australian academic institutions partnered with seven leading Indian academic palliative care and cancer centers to undertake a program combining remote and in-person mentorship, didactic instruction, and project-based learning in quality improvement. From its inception in 2017 to 2020, the Promoting Assessment and Improvement of the Cancer Experience (PC-PAICE) Program conducted three cohorts for capacity building of 22 Indian palliative care and cancer programs. Indian leadership established a Mumbai training hub in 2019 with philanthropic support, Quality Improvement Hub (e.g., QI-Hub) India. In 2020 the project which now focuses on both palliative care and cancer teams as EQuIP-India. EQuIP now leads ongoing Indian national collaboratives and training in quality improvement and is integrated into India's National Cancer Grid. PC-PAICE demonstrates a feasible model of international collaboration and capacity building in palliative care and cancer quality improvement. It is one of several networked, blended learning approaches with potential for rapid scaling of evidence-based practices.

Introduction Clinical remission in patients with ankylosing spondylitis (AS) has been determined using composite indices such as the AS Disease Activity Score inactive disease (ASDAS-ID), Assessment of SpondyloArthritis international Society criteria partial remission (ASAS-PR), and low Bath AS Disease Activity Index (BASDAI) scores. The objective of this exploratory analysis was to evaluate the proportion of secukinumab-treated patients with AS achieving remission defined based on the ASDAS-ID (score < 1.3), ASAS-PR or BASDAI score ≤ 2. Methods The analysis pooled data from the MEASURE 1 and 2 studies over 3 years. The proportion of patients who achieved ASDAS-ID, ASAS-PR, or BASDAI ≤ 2 with secukinumab was compared with placebo at week 16; results for secukinumab-treated patients were summarized through week 156. Sustainability of each criterion was assessed from week 16 to 156 using shift analysis. The association between each of these criteria and specific patient-reported outcomes (PROs), such as health-related quality of life, function, fatigue, and work impairment, was also explored. Results At week 16, a higher proportion of secukinumab-treated patients versus placebo achieved ASDAS-ID (17.6 vs. 3.5%), ASAS-PR (15.4 vs. 4.1%), or BASDAI ≤ 2 (22.3 vs. 6.4%) criteria (all P

Purpose In 2018, the International Federation of Gynecology and Obstetrics (FIGO) proposed a new staging for cervical cancer. The present study was designed to reclassify patients with locally advanced cervix cancer and perform a comparative evaluation with FIGO 2009. Methods and Materials Patients with locally advanced cervical cancer (stage IB2-IVA) who had baseline cross-sectional imaging and received (chemo-) radiation and brachytherapy were included. Survival outcomes were analyzed according to FIGO 2009. Patients were then reclassified according to FIGO 2018, and TNM classification outcomes were analyzed. FIGO stage and known prognostic factors were included in univariate analysis, and multivariate analysis was performed to investigate the prognostic value of clinical stage. Results Six hundred thirty-two patients were included. Overall, 185 (29.3%) patients had pelvic adenopathy, and 51 (8.2%) had positive paraortic nodes. At a median follow-up of 33 months, 116 (18.3%) patients had recurrence. Three-year disease-free survival (DFS) according to FIGO 2009 for stage IB, IIA, IIB, IIIA, IIIB, and IVA was 86%, 91%, 76%, 57%, 65%, and 61%, respectively. The 3-year DFS after restaging according to FIGO 2018 for stage IB, IIA, IIB, IIIA, IIIB, IIIC1, IIIC2, and IVA was 100%, 93%, 84%, 53%, 77%, 74%, 61%, and 61%, respectively. Patients with clinically significant lymphadenopathy had inferior outcomes compared with node-negative patients (62.9% vs 77.8%; P = .002). Patients with ≥3 paraortic nodes had poorer DFS than patients with 30 cm3 had worse 3-year DFS than those with primary tumor volume ≤30 cm3 (67.4% vs 78.5%; P = .002). Conclusions FIGO 2018 modification is associated with heterogenous outcomes in node-positive patients that are affected by primary tumor and nodal volume. We propose a modification to the existing TNM staging system to allow more robust classification of outcomes.

Background There were 142,101 new cases of non-melanomatous skin cancers reported by the UK National Cancer Statistics in 2015. The UK statistics published that the incidence is highest in the 90+ population and that this represented an overall 61% increase in skin cancer incidence in the UK in the last decade. This article aims to first provide an understanding of the change in service requirement over the last 25 years for skin cancer management in nonagenarians, and second, understand the subtypes of skin cancer and possible differences in the management for this cohort. Methods All skin cancer biopsies received by a UK university teaching hospital dermato-histopathology department were analysed over a five-year period spanning 2013–2017. This was compared with snap shot data at five-year intervals dating back to 1993. The patient demographics including age, sex and anatomical region were seen along with the types of skin cancers and histological subtypes. Results A total of 1050 skin cancers were managed with surgical input between January 2013 and December 2017 in 733 patients. The number of biopsies/year has increased 7-fold from 1993 (33) to 2017 (231). The annual cost of the surgical element to this service has dramatically increased, and in 2017, it was £220k compared to £33k in 1993. Conclusion Partly because of the ageing UK population, there has been a dramatic increase in the demand on the surgical service regarding managing skin cancers in those over the age of 90. There is a higher rate of incomplete excision in this population than that reported in the national British Association of Dermatologists (BAD) guidelines. Despite higher incomplete excision rates, there is a low re-operation rate in this population probably due to patient comorbidities affecting reconstructive options, patient preference and clinical decisions on surgical morbidity versus benefit.

Tumor necrosis factor inhibitors (TNFi) are indicated to treat ankylosing spondylitis (AS), also termed radiographic axial spondyloarthritis (axSpA). The main indication for TNFi is symptom relief, and whether they retard spinal structural damage as assessed by radiography is debated. Hips are the most common "non-spinal" joints involved in AS patients leading to major incapacitation. No major treatment guidelines mention measures to prevent peripheral joint damage, especially hips, in individuals with AS. We present our experience of prevention of structural damage in hips by TNFi in 4 AS patients from our practice. We conducted a literature review looking for articles describing prevention of structural damage progression in hips by TNFi. Over a 10-year period, three out of four patients were treated with TNFi and had no progression in hip damage as assessed by imaging. Only one patient that withdrew the TNFi due to infectious complications developed rapid worsening and required hip arthroplasty. Our literature review showed multiple case series with similar results suggesting that use of TNFi in patients with AS may prevent structural damage and at least postpone a hip replacement at a young age. Based on our experience, as well as from the literature review, we believe that treatment guidelines in axSpA should recommend prompt institution of TNFi following identification of hip involvement in patients to prevent a major source of disability. Whether interleukin (IL)-17 inhibitors or targeted synthetic anti-rheumatic drugs have hip sparing effects in patients with AS should also be investigated. Key Points • Hip involvement in ankylosing spondylitis is a major source of disability. • TNFi prevent hip damage in ankylosing spondylitis. • Prompt institution of TNFi should follow suspicion of hip involvement in ankylosing spondylitis.

Objective: To report the primary (1-year) results from PREVENT, the first phase III study evaluating secukinumab in patients with active nonradiographic axial spondyloarthritis (SpA). Methods: A total of 555 patients were randomized (1:1:1) to receive subcutaneous secukinumab 150 mg with a loading dose (loading dose [LD] group), secukinumab 150 mg without a loading dose (non–loading dose [NL] group), or placebo weekly and then every 4 weeks starting at week 4. The NL group received placebo at weeks 1, 2, and 3 to maintain blinding. Switch to open-label secukinumab or standard of care was permitted after week 20. The study had 2 independent analysis plans, per European Union and non-US (plan A; week 16) and US (plan B; week 52) regulatory requirements. The primary end point was 40% improvement in disease activity according to the Assessment of SpondyloArthritis international Society (ASAS40) criteria at week 16 (in the LD group) and at week 52 (in the NL group) in tumor necrosis factor inhibitor (TNFi)–naive patients. Safety analyses included all patients who received ≥1 dose of study treatment. Results: Overall, 481 patients completed 52 weeks of treatment, including 84.3% (156 of 185) in the LD group, 89.7% (165 of 184) in the NL group, and 86.0% (160 of 186) in the placebo group. The proportion of patients who switched to open-label or standard of care between weeks 20 and 48 was 50.8% in the LD group, 47.3% in the NL group, and 64.0% in the placebo group. Both primary and all secondary end points were met at week 16. The proportion of TNFi-naive patients who met ASAS40 was significantly higher for LD at week 16 (41.5%) and NL at week 52 (39.8%) versus placebo (29.2% at week 16 and 19.9% at week 52; both P < 0.05). No new safety findings were reported. Conclusion: Our findings indicate that secukinumab 150 mg provides significant and sustained improvement in signs and symptoms of nonradiographic axial SpA through 52 weeks. Safety was consistent with previous reports.

PURPOSE Women with recurrent, multiply-treated epithelial ovarian cancer (EOC) have unfavorable prognosis with limited treatment options after failure of platinum-based regimens. We report here a retrospective analysis of women with recurrent, platinum-resistant EOC treated with an oral regimen of pazopanib and cyclophosphamide. PATIENTS AND METHODS Women with recurrent platinum-resistant or -refractory EOC were treated with pazopanib (600 mg orally daily in 2 divided doses, 400 and 200 mg) and cyclophosphamide (50 mg orally daily for 21 days every 28 days) until disease progression or unacceptable toxicity. RESULTS Twenty patients (17 with platinum-resistant and 3 with platinum-refractory disease) were treated between April 2014 and April 2018. Patients had a median age of 52 years (range, 40-60 years) and median of 4 previous lines of chemotherapy (range, 2-8 previous lines), including 3 patients with progressive disease on bevacizumab. Patients received a median of 6 cycles (range, 2-48 cycles) of pazopanib and cyclophosphamide, with best responses of partial response in 9 patients (45%, including 1 of 3 patients treated previously with bevacizumab), stable disease in 6 patients (30%), and disease progression in 5 patients (25%). The median progression-free survival time was 5.5 months, and median overall survival was 9.5 months. Common adverse events (grade 3 or 4) were fatigue (25%), diarrhea (15%), hand-foot syndrome (10%), mucositis (10%), transaminitis (5%), and hypertension (5%). Dose reduction as a result of toxicity was required in 14 patients (70%), and no patient stopped treatment as a result of toxicity. CONCLUSION Pazopanib plus oral cyclophosphamide is a well-tolerated regimen with clinically relevant benefit in patients with platinum-resistant or -refractory EOC.

Objective To assess performance of psoriatic arthritis (PsA) composite indices and evaluate guselkumab’s effect on achieving low disease activity or remission. Methods In this phase II trial, patients with active PsA (≥3 tender and ≥3 swollen joints, C‐reactive protein level ≥0.3 mg/dl, ≥3% body surface‐area with psoriasis involvement) were randomized 2:1 to subcutaneous guselkumab 100 mg (n = 100) or placebo (n = 49) at week 0, week 4, and every 8 weeks through week 44. At week 16, patients with

Evaluate the effect of intravenous golimumab on health-related quality of life (HRQoL) in patients with ankylosing spondylitis (AS) through week 28 of the phase III, multicenter, randomized, double-blind, placebo-controlled GO-ALIVE study.Adult patients (n = 208) were randomized to IV golimumab 2 mg/kg (n = 105) at weeks 0, 4, and 12 and every 8 weeks or placebo (n = 103) at weeks 0, 4, and 12, with crossover to golimumab 2mg/kg at weeks 16, 20, and every 8 weeks. General HRQoL was evaluated using the Short Form Health Survey (SF-36) Physical Component Summary/Mental Component Summary (PCS/MCS), and the EQ VAS, and AS disease-specific HRQoL was assessed using the Ankylosing Spondylitis Quality of Life (ASQoL) instrument.Mean improvements from baseline in SF-36 PCS were greater in the golimumab group versus the placebo group at weeks 8 and 16 (6.8 vs 2.1 and 8.5 vs 2.9, respectively; P.001); similar results were observed for SF-36 MCS (5.6 vs 1.7 and 6.5 vs 0.8, respectively; P.001). Mean improvement in each of 8 subscale scores of the SF-36 were also greater for golimumab-treated patients versus placebo at weeks 8 and 16. Mean improvements in EQ VAS and ASQoL were greater in the golimumab group versus placebo at week 8 and week 16. Greater proportions of golimumab-treated patients had clinically meaningful improvement in SF-36 PCS, SF-36 MCS, EQ VAS, and ASQoL at weeks 8 and 16; improvements in SF-36 PCS/MCS, EQ VAS, and ASQoL were maintained through week 28.Golimumab-treated patients had greater mean improvements in HRQoL measures compared with placebo through week 16. Clinically meaningful improvements were observed as early as week 8 and continued through week 28.

The effect of intravenous (IV) golimumab on health-related quality of life (HRQoL) and productivity in patients with ankylosing spondylitis (AS) was evaluated. Patients were randomized to IV golimumab 2 mg/kg (n = 105) at weeks 0, 4, then every 8 weeks (q8w) through week 52 or placebo (n = 103) at weeks 0, 4, 12, with crossover to golimumab 2 mg/kg at weeks 16, 20, then q8w through week 52. Changes from baseline in EuroQol-5 dimension-5 level (EQ-5D-5L) index and visual analog scale (EQ-VAS), daily productivity VAS, Work Limitations Questionnaire (WLQ), and Ankylosing Spondylitis Quality of Life (ASQoL) were assessed. Correlations between these outcomes and disease activity and patient functioning outcomes were evaluated post hoc. At week 16, changes from baseline (mean ± standard deviation) in EQ-5D-5L index (0.17 ± 0.16 vs 0.05 ± 0.14), EQ-VAS (20.3 ± 24.6 vs 4.8 ± 23.5), daily productivity VAS (− 2.9 ± − 2.9 vs − 1.1 ± − 2.5), WLQ productivity loss score (− 3.5 ± − 5.3 vs − 1.9 ± − 4.0), and ASQoL (− 5.4 ± − 5.0 vs − 1.8 ± − 4.5) were greater in the IV golimumab versus placebo group, respectively. At week 28, changes from baseline were similar between the IV golimumab and placebo-crossover groups (EQ-5D-5L index: 0.18 ± 0.17 and 0.16 ± 0.16, EQ-VAS: 20.5 ± 27.9 and 22.5 ± 23.1, daily productivity VAS: − 3.1 ± − 3.0 and − 3.1 ± − 2.8, WLQ productivity loss: − 3.9 ± − 5.5 and − 4.5 ± − 4.5, and ASQoL: − 5.3 ± − 5.2 and − 5.3 ± − 4.8, respectively); improvements were maintained through week 52. HRQoL and productivity outcomes were generally moderately correlated with disease activity and functioning outcomes. In patients with AS, IV golimumab produced sustained improvements in HRQoL and productivity through 1 year, which correlated with improvements in disease activity and functioning. ClinicalTrials.gov registry number is NCT02186873.

Axial spondyloarthritis (axSpA) is a chronic inflammatory immune-mediated disease resulting in inflammatory low back pain and other inflammatory manifestations in peripheral joints and entheses. AxSpA encompasses both ankylosing spondylitis (AS), in which patients present with definitive sacroiliitis visible on radiographic imaging, as well as nonradiographic axSpA (nr-axSpA), in which such changes may not be discernable. Emerging evidence suggests that women and men experience axSpA differently. Although the prevalence of AS is approximately 2- to 3- fold higher in men than in women, nr-axSpA occurs with roughly equal frequency in women and men. The goal of this review is to increase awareness of sex differences in axSpA by exploring the distinct manifestations of disease and disease characteristics in women, the overall clinical burden, recommendations for diagnosis, and potential treatment options. We summarize and contextualize the results of recent studies that illuminate sex differences in nr-axSpA and AS, including differences in disease manifestation and progression. It is important that sex differences in axSpA are understood and considered when diagnosing and treating the spectrum of axSpA, including AS and nr-axSpA.

ObjectivesBimekizumab selectively neutralises both interleukin (IL)-17A and IL-17F. We report efficacy and safety in a phase IIb dose-ranging study in patients with active ankylosing spondylitis (AS).MethodsAdults with AS (fulfilling modified New York criteria) were randomised 1:1:1:1:1 to bimekizumab 16 mg, 64 mg, 160 mg, 320 mg or placebo every 4 weeks for 12 weeks (double-blind period). At week 12, patients receiving bimekizumab 16 mg, 64 mg or placebo were re-randomised 1:1 to bimekizumab 160 mg or 320 mg every 4 weeks to week 48; other patients continued on their initial dose (dose-blind period). The primary end point was Assessment of SpondyloArthritis international Society (ASAS) 40 response at week 12 (non-responder imputation (NRI) for missing data).Results303 patients were randomised: bimekizumab 16 mg (n=61), 64 mg (n=61), 160 mg (n=60), 320 mg (n=61) or placebo (n=60). At week 12, significantly more bimekizumab-treated patients achieved ASAS40 vs placebo (NRI: 29.5%–46.7% vs 13.3%; pConclusionsBimekizumab provided rapid and sustained improvements in key outcome measures in patients with active AS, with no unexpected safety findings versus previous studies.Trial registration numberNCT02963506.

Objective To compare the relative efficacy of intravenous golimumab (GOL IV) and infliximab (IFX) for active ankylosing spondylitis (AS). Methods Propensity score (PS) methods were used to compare the efficacy of GOL IV 2 mg/kg and IFX 5 mg/kg using individual patient data (IPD) from the active arms of the phase 3 GO-ALIVE and ASSERT studies. Outcomes included the proportion of patients with a ≥ 20% improvement in the Assessment of Spondyloarthritis International Society Criteria (ASAS20), change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) score, and change from baseline in C-reactive protein (CRP) levels from weeks 4–52. Results Before matching, 105 patients were treated with GOL IV and 201 patients were treated with IFX. After matching on all covariates, 118 patients were included in the ASAS20 analysis, 96 in the BASFI analysis, and 160 in the CRP analysis. After matching, GOL IV showed significantly greater improvement in ASAS20 response than IFX for weeks 28–44 (e.g., OR = 9.05 [95% CI 1.62–50.4] at week 44) and was comparable in change from baseline in BASFI scores and CRP levels to IFX at all time points. Results were robust for inclusion of different sets of covariates in scenario analyses. Conclusions This is the first analysis of its kind to leverage clinical trial data to compare two biologics using PS methods in the treatment of active AS. Overall, GOL IV was associated with greater improvement in ASAS20 response than IFX in patients with AS at 28, 36, and 44 weeks of follow-up. Key Points• Although intravenous golimumab (GOL IV) and infliximab (IFX) are the only two IV-based tumor necrosis factor (TNF) inhibitors with demonstrated phase 3 clinical efficacy in patients with ankylosing spondylitis (AS), no study has evaluated their comparative efficacy in a head-to-head trial.• Propensity score matching was used to derive indirect treatment comparisons of GOL IV and IFX for ≥ 20% in the Assessment of Spondyloarthritis International Society Criteria (ASAS20), change in Bath Ankylosing Spondylitis Functional Index (BASFI), and change in C-reactive protein (CRP) using individual patient data from the GO-ALIVE and ASSERT phase 3 trials.• Propensity score matched indirect comparisons showed improved relative efficacy of GOL IV compared to IFX; after matching for up to 16 baseline covariates, GOL IV was associated with significantly greater odds of ASAS20 response at weeks 28, 36, and 44 than IFX as well as equivalent changes from baseline in BASFI and CRP.• This novel application of propensity score matching using data from phase 3 trials, the first analysis of its kind in AS, allowed adjustment for important imbalances in prognostic factors between trials to generate estimates of comparative efficacy between GOL IV and IFX in the absence of a head-to-head trial between these treatments.

Introduction The Food and Drug Administration (FDA) approved certolizumab-pegol, the first biologic for the treatment of non-radiographic axial spondyloarthritis (nr-axSpA), for use in the United States (US) in March of 2019. The objective of this study was to investigate biologic use and reasons for switching therapy among patients with nr-axSpA in the US. Methods This was a real-world, cross-sectional study of rheumatologists conducted in the US. Data were collected from June to August of 2018 via rheumatologist-completed patient record forms. Data from patients who had a rheumatologist-confirmed diagnosis of nr-axSpA were included in the study. Rheumatologists provided information on current medication use and reasons for switching biologics. Results Eighty-eight rheumatologists collected data on 495 nr-axSpA patients. Over half of nr-axSpA patients were male (53.3%), with a mean age of 44.2 years, and 69.8% of patients reported working full-time. Of the 495 nr-axSpA patients, 48.1% were receiving a biologic and no conventional synthetic disease-modifying anti-rheumatic drug (csDMARD), 18.4% csDMARD (no biologic), 18.2% non-steroidal anti-inflammatory drug (NSAIDs)/COX-2 (no biologic or csDMARD), 11.5% a biologic and a csDMARD, 2.0% were receiving no therapy, and 1.8% other therapy (no biologic, csDMARD, or NSAID/COX-2). Of 295 patients receiving a biologic, 77.8% were receiving their first, 13.8% their second, and 8.3% their third or more biologic. Of 74 nr-axSpA patients who switched from a previous biologic to their current biologic, rheumatologists reported that 51.4% switched due to condition worsening, 48.6% had a loss of response over time, 27.0% switched due to a lack of pain alleviation, and 25.7% of patients switched because remission was not induced. Conclusions This study suggests that around 60% of nr-axSpA patients were receiving biologic therapy prior to the approval of certolizumab pegol. Switching of biologics is frequent in nr-axSpA patients and is usually due to lack of efficacy, loss or response, and effort to accomplish remission.

R-Lacosamide (RLC) is a new approved antiepileptic drug for adjunctive use and monotherapy for partial-onset seizures in some countries. RLC use in other epilepsies and diseases is under study. Research is also going on the activities exhibited by the S-enantiomer (SLC). Taking into consideration further perspectives, the development of direct chiral method that can selectively estimate R-isomer in the presence of S-isomer from human plasma is needed. Plasma samples were spiked with RLC, deuterated internal standard, and SLC. Deuterated RLC as the internal standard enabled us to precisely measure the concentration of RLC by minimizing variations associated with the extraction, ionization, and separation. Target compounds were recovered by liquid-liquid extraction from human plasma using methyl tert-butyl ether. The percentage recovery was found to be 68%.The isomers were resolved completely using DIACEL-IC3 column in the reverse phase mode. The retention times of R- and S-isomers were found to be 6.20 ± 0.5 and 8.00 ± 0.5 min, respectively. The proposed method was found to be linear in a concentration range from 1.00 × 102 to 1.50 × 104 ng/mL. Direct chiral HPLC tandem mass spectrometric method that can quantify R-lacosamide in the presence of S-isomer from human plasma without any carry-over and matrix effects was successfully developed. This method is very simple, fast, economic, sensitive, and validated as per EMA guidelines.

Objective: Bacterial vaginosis (BV) is a common reproductive tract infection (RTI) reported among Indian women. BV can influence the persistence of high-risk oncogenic human papillomavirus, a causative factor for cervical cancer. BV and cervical cancer are major public health issues in a developing country like India. It becomes important for a resource-constrained country like India with poor healthcare access to implement control measures to screen and treat RTI in an attempt to prevent the risk for cervical cancer. Papanicolaou (Pap) smear is an established screening tool for cervical cancer and the diagnosis of RTIs, forms a part of its evaluation. The present study explores the validity of conventional Pap smear in diagnosing BV. Methodology: Pap smear and Gram stain smear were collected for 254 women with clinically evident cervicitis/cervicovaginitis (genital infection). Using the Nugent score on Gram stain as a gold standard, we determined the sensitivity and specificity of Pap smear to diagnose BV. Results: The overall prevalence of BV in the study population was 44% using the Nugent score. Pap smear showed sensitivity and specificity of 70.9%. (CI- 61.5% - 79.2%) and 56.8% (CI – 48.2%–65.2%), respectively. The positive predictive value of Pap smear to diagnose BV was 56.5% (CI – 47.8%–64.9%), and the negative predictive value was 71.2% (CI – 61.8%–79.4%). Conclusion: In the present study, conventional Pap smear demonstrates good accuracy to detect BV. Pap testing for cervical cancer screening can additionally serve as an effective screening tool for diagnosing BV among women with genital infection in healthcare settings.

Introduction/Objectives Ankylosing spondylitis (AS) is a chronic inflammatory immune-mediated condition. We compared AS diagnosis, treatment, and burden in Central Eastern European countries (CEE), where this has been less researched, and the United States (US) from a real-world perspective. Methods Point-in-time survey of rheumatologists and their AS patients was conducted in the US (Apr–Oct 2018) and CEE (Aug–Nov 2019) via physician- and patient-completed record forms, including clinical and patient-reported outcomes. Statistical analysis included descriptive statistics, t-tests, Fisher’s exact tests, and generalized linear models. Results In total, 487 patients were recruited from 88 rheumatologists in the US and 922 patients from 126 rheumatologists in CEE. Time from onset of symptoms to final AS diagnosis was longer in CEE than the US (4.2 vs 2.7 years, p p p p p p p Conclusions AS patients in CEE vs the US faced slower diagnosis and worse access to biologics, disease activity, and QoL. Whether early access to biologics can improve symptoms, QoL, and daily activities in AS patients in CEE remains to be seen. Key Points• The study provided evidence on the real-world approach to the diagnosis, treatment, and burden of axSpA (axial spondyloarthritis) in CEE compared with the US.• The study reported patients in CEE experienced longer delays in diagnosis and poorer access to biologics than in the US.• This may have resulted in higher disease activity, greater levels of pain, and poorer outcomes, as reported by patients with axSpA in CEE.

Background & objectives Aetiology of cervical cancer (CaCx) is multifactorial. Besides human papillomavirus (HPV) infection, many immunogenetic factors are involved in this complex process. The present study was carried out to investigate one such factor, interleukin-6 (IL-6), a central pro-inflammatory cytokine and a polymorphism at its promoter region -174 G/C (rs1800795) with CaCx. Methods HPV-infected women with or without CaCx were enrolled in group I and II, respectively. Another group of uninfected healthy women was also included as group III for comparison. Polymorphism in IL-6-174 G/C and IL-6 levels were analyzed by sequence-specific primer PCR (PCR-SSP) and ELISA, respectively. Results Groups I (n=111) and II (n=87) had significantly higher frequency of IL-6-174 GG genotype [odds ratios (OR)=3.9; P