Fostamatinib for warm antibody autoimmune hemolytic anemia: Phase 3, randomized, double-blind, placebo-controlled, global study (FORWARD).

Warm antibody autoimmune hemolytic anemia (wAIHA) is characterized by hemolysis and symptomatic anemia with no approved treatment options. Fostamatinib is an oral spleen tyrosine kinase inhibitor approved in the US and Europe for treatment of adults with chronic immune thrombocytopenia. In this phase 3 study, patients with an insufficient response to ≥1 prior wAIHA treatment were randomized to fostamatinib or placebo. The primary endpoint was the proportion of patients to achieve a durable hemoglobin (Hgb) response (Hgb ≥10 g/dL and increase from baseline of ≥2 g/dL on 3 consecutive visits) during the 24-week treatment period. Ninety patients were randomized, 45 to each arm. Of the fostamatinib-treated patients, 35.6% achieved a durable Hgb response versus 26.7% on placebo (p = .398). A post hoc analysis revealed a large placebo response in Eastern European patients. Significantly more patients on fostamatinib from North America, Australia and Western Europe exhibited a durable Hgb response compared to placebo (36% vs. 10.7%, p = .030). After censoring for Hgb values impacted by steroid rescue received during screening and excluding 2 placebo patients found to likely not have wAIHA, a reanalysis demonstrated a difference in durable Hgb response between fostamatinib and placebo (15/45 [33.3%] vs. 6/43 [14.0%], p = .0395). At least 1 AE was reported in 42 (93.3%) and 40 (88.9%) patients receiving fostamatinib and placebo, respectively. The most common AEs in the fostamatinib group were diarrhea (26.7%), hypertension (24.4%), and fatigue (15.6%). In this study, fostamatinib demonstrated a clinically meaningful benefit for patients in Western regions, and no new safety signals were identified.

Regional differences in clinical phenotype of axial spondyloarthritis: results from the International Map of Axial Spondyloarthritis (IMAS).

OBJECTIVES: To explore differences in axial spondyloarthritis (axSpA) clinical phenotype around the world in a large sample of patients included in the International Map of Axial Spondyloarthritis (IMAS). METHOD: IMAS was a cross-sectional online survey (2017-2022) of 5,557 unselected axSpA patients from 27 countries. We analysed across five geographic regions the age at symptom onset, diagnostic delay, gender, HLA-B27, family history, extra-musculoskeletal manifestations, presence of comorbidities, disease activity (BASDAI), level of spinal stiffness, and treatments. RESULTS: Of 5,557 IMAS participants, 3,493 were from Europe, 770 from North America, 600 from Asia, 548 from Latin America, and 146 from South Africa. Age at symptom onset ranged between 25-30 years and was higher in Latin America. Diagnostic delay was longest in South Africa and lowest in Asia. The lowest HLA-B27 positivity was observed in Latin America and the highest in Asia. Extra-musculoskeletal manifestations were the lowest in Europe. Mean disease activity (BASDAI) was 5.4, with highest values in South Africa and lowest in Asia. Most of the patients had used NSAIDs for their condition and less than half had ever taken csDMARDS; both were more frequent in Latin America and South Africa. Almost half of the patients had ever taken bDMARDs, more frequent being in the Americas. CONCLUSIONS: There is great heterogeneity of axSpA clinical phenotype presentation around the world. AxSpA manifests differently in different regions, so further understanding of these differences of phenotypes is needed to achieve early diagnosis and initiation of optimal disease treatment in axSpA in the different regions.

A Cross-sectional Study of Patients and Physicians on the Impact of Myeloproliferative Neoplasms on Patient Health: The Landmark Survey From Taiwan.

Patients with myeloproliferative neoplasm (MPN), including myelofibrosis, polycythemia vera, and essential thrombocythemia, experience a pronounced symptom burden. This study aimed to collect information from physicians and patients in Taiwan to explore their perceptions regarding MPN, treatment goals, and satisfaction with disease management. A cross-sectional, online survey was conducted among patients and physicians from September 2018 to November 2018 in Taiwan as a subset of the expansion of the Landmark survey. Overall, 50 patients with MPN and 30 physicians participated in this study. The symptom burden was low, with the mean number of symptoms experienced being 1.8. The most frequent symptom per physicians' perception was fatigue, whereas it is not the most common symptom from MPN patients' perspective. Blood count was the key indicator to determine treatment success from patients' view, whereas presence of a new symptom was the key indicator from physicians' perspective. Concordant with previous studies, our study revealed a lack of alignment between physician and patient perceptions relating to treatment goals and disease management. Nevertheless, the physical, emotional, work/activities and financial impacts on patients were minimal in Taiwan.

MERGE: A Multinational, Multicenter Observational Registry for Myeloproliferative Neoplasms in Asia, including Middle East, Turkey, and Algeria.

Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal disorders of the bone marrow, and are associated with a high disease burden, reduced quality of life (QOL), and shortened survival. This multinational, multicenter, non-interventional registry "MERGE" was initiated with an objective to collect data on the epidemiological indices of classical Ph-MPNs, existing treatment patterns, and impact of MPNs on health-related QOL in various countries/regions in Asia, including the Middle East, Turkey, and Algeria. Of the 884 eligible patients with MPNs, 169 had myelofibrosis (MF), 301 had polycythemia vera (PV), 373 had essential thrombocythemia (ET), and 41 had unclassified MPNs. The median age was 58 years (range, 47-66 years), and 50% of patients were males. The prevalence and incidence of MPNs were estimated to be 57-81 and 12-15 per 100 000 hospital patients per year over the last 4 years, respectively, in these countries. Total symptom score (mean [standard deviation; SD]) at baseline was highest in patients with MF (23.5 [17.47]) compared with patients with ET (14.6 [14.26]) and PV (16.6 [14.84]). Patients with ET had a lower mean (SD) number of inpatient visits (0.9 [0.77] days), and patients with MF had more outpatient visits (5.2 [3.17] days) on an average, compared with the entire MPN group. The study showed that patients with MPNs have a severe disease burden and reduced QOL. A discordance between physician and patient perception of symptom assessment was observed in this study (International clinical trials registry ID: CTRI/2014/05/004598).

Minimally invasive technique of placing a dual chamber permanent pacemaker in children.

OBJECTIVE: To share the experience of a minimally invasive technique in the implantation of a dual chamber permanent pacemaker in paediatric population. METHODS: The retrospective study was conducted at Aga Khan University Hospital, Karachi, and comprised data of patients aged up to 16 years who underwent epicardial dual chamber permanent pacemaker insertion via xiphisternal incision between April 2011 and August 2016. Demographic data included age, weight and gender of the patient. Indications for pacemaker insertion, electrocardiography findings, concomitant cardiac procedures and procedural complications were reviewed. Pacemaker thresholds and impedance at the time of implantation and throughout the course of follow-up were extracted from the clinical data. RESULTS: Of the 10 patients, 5(50%) were males and 5(50%)were females. The overall mean age was 3.4}3.8 years (range: 1 month - 13 years). The mean weight at the time of operation was 11.4}6.8 kg (range: 4.3-27kg). Indications for permanent pacemaker insertion included postoperative advanced or complete atrioventricular block in 7(70%) and complete congenital heart block in 3(30%). There was no reported morbidity. CONCLUSIONS: Dual chamber permanent pacemaker insertion via xiphisternal incision was found to be of benefit to the patients and the surgeons alike.

Estimating the Global Demand and Delivery of Cancer Surgery.

BACKGROUND: Cancer is a leading cause of death and disability globally. While surgery remains a vital part of cancer management, access to surgical care remains inconsistent. Our objective was to estimate the global need for cancer-related surgery and to identify disparities in the surgeon workforce. METHODS: The World Health Organization International Agency for Research on Cancer and the Global Cancer Observatory were queried for estimates on national incidences of 35 different malignancies. The proportion of patients requiring surgery for each of these cancers was extrapolated from the United States Surveillance, Epidemiology and End-Result database. The number of people requiring cancer surgery in each country was calculated and compared with the surgical workforce. Estimates were presented as choropleth maps. Associations were tested with country development indicators. RESULTS: An estimated 9,464,214 (95% CI 4,364,196-14,564,230) patients required cancer-related surgical care in 2018. An overall 1.24 people needed cancer surgery per 1000 population. This was related to income status (p < 0.01) and Human Development Index (r = 0.86, p < 0.001), with the largest need being in high-income countries. The number of people requiring cancer surgery per surgeon (CP-S ratio) ranged from 7.3 in the European region to 80 in the African regions. The CP-S ratio was 10 times higher for low- versus high-income countries (p < 0.001) and was inversely related to healthcare expenditure (r = -0.59, p < 0.001). CONCLUSIONS: An estimated 9.5 million people required cancer surgery globally. Low- and middle-income countries experience a severe and acute shortage of surgeons to provide for the cancer surgery needs of the population.

Technical Varieties of Ross Procedure: A Case Series.

Replacement of aortic valve with the pulmonary autograft is carried out through the Ross procedure due to its potential for growth, durability in pediatric population, and absence of anticoagulation. This case series reports the postoperative outcome of two technical variations of Ross procedure in eight patients who underwent surgery from January 2007 to December 2016. The dominant valvular hemodynamic indication was aortic regurgitation. The techniques employed for Ross procedure included free standing root replacement in six patients and modified root replacement with autograft stabilisation using Dacron interposition graft in two patients. Right ventricular outflow tract (RVOT) conduit reconstruction was achieved by utilisation of Contegra bio prosthesis in four patients; and use of manually constructed valved conduit comprising of PTFE (polytetrafluoroethelene) membrane and bovine pericardial tube in remaining four patients. There was no mortality and no re-intervention. The technical varieties of Ross procedure offer freedom from need of anti-coagulation, mortality, and RVOT conduit failure in younger adults.

Malignant Pheochromocytoma with Widespread Bony and Pulmonary Metastases.

Pheochromocytoma is a rare benign tumor of the adrenal gland. A select few cases may be malignant, and metastatic cases are exceedingly rare. It often presents with symptoms of catecholamine excess, such as sweating, palpitations, headaches, and characteristic paroxysmal hypertension. Due to its diffuse symptoms, it is difficult to diagnose and is often diagnosed late. We describe the unique case of a 44-year-old female patient who presented with uncontrolled hypertension and vomiting, accompanied by lower back pain. She was diagnosed with malignant pheochromocytoma with multiple metastases to the lungs, vertebrae, scapulae, and skull. Because of the advanced state of her disease, the patient was started on treatment with the chemotherapeutic combination of cyclophosphamide, vincristine, and dacarbazine. However, she had a complicated hospital course and died because of aspiration pneumonia and sepsis.

Prevention and management of radiation-induced dermatitis, mucositis, and xerostomia.

PURPOSE: Current strategies for preventing and managing radiation-induced dermatitis, mucositis, and xerostomia are reviewed, with an emphasis on pharmacologic interventions. SUMMARY: Nearly two thirds of all patients with cancer receive radiation therapy during the course of treatment, frequently resulting in acute skin and mucosal toxicities. The severity of radiotherapy-associated toxicities varies according to multiple treatment- and patient-related factors (e.g., total radiation dose and dose fractionation schedule, volume of organ or tissue irradiated, use of concurrent versus sequential chemotherapy, comorbid conditions, functional performance status). Three major radiation toxicities encountered in clinical practice are (1) radiation dermatitis, typically managed with a variety of topical agents such as water-based moisturizing creams or lotions, topical steroids, antiinflammatory emulsions, and wound dressings, (2) radiation-induced oral mucositis, which can be managed through proper basic oral care practices, appropriate pain management, and the use of medicated mouthwashes and oral rinses and gels, and (3) radiation-induced xerostomia, which can be alleviated with saliva substitutes, moistening agents, and sialagogues. Pharmacists involved in the care of patients receiving radiotherapy can play an important role in optimizing symptom control, educating patients on self-care strategies, and adverse effect monitoring and reporting. CONCLUSION: Radiation-induced dermatitis, mucositis, and xerostomia can cause significant morbidity and diminished quality of life. Pharmacologic interventions for the prevention and treatment of these toxicities include topical agents for dermatitis; oral products, analgesics, and palifermin for mucositis; and amifostine, saliva substitutes, and pilocarpine for xerostomia.

Sewage treatment by anaerobic hybrid reactor.

Attempts were made to utilize anaerobic hybrid reactor for sewage treatment. The reactor was seeded with digested sewage sludge and a HRT of 24 hrs. was kept in the start up. The HRT was subsequently decreased to 20, 16, 12, 8 and 4 hrs. A maximum COD removal efficiency of 74% was achieved at minimum HRT. The pH, alkalinity, solids and VFA of the effluent were within the permissible limits.