Clinical profile of patients with Juvenile Idiopathic Arthritis

Introductions: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of disorders with different manifestations. There is lack of data locally. In this study, we describe the clinical profile and functional outcome of patients with JIA attending two rheumatology clinics in Lalitpur, Nepal. Methods: This cross sectional study wasconducted at Patan Hospital and Aarogya Health Home, Lalitpur, Kathmandu, Nepal. The medical records of patients with juvenile arthritis during the period between Jan 2013 to Dec 2015 were retrospectively reviewed for clinical profile and functional outcome of disease. Results: A total of 81 patients with arthritis diagnosed before age 16 years were seen during this period. Seventy eight patients with JIA included 41 males and 37 females. Mean age of onset was 9.21 years. Polyarticular JIA was seen 32 (42.2%), oligoarticular in 24 (30.7%), enthesitis-related 13 (16.6%), and systemic-onset in 6 (7.7%). Systemic complications were seen in 14 (17.9%) cases. Five cases had uveitis. Joint deformities were present in 28 (35.8%). Sixty seven (86%) children continued their education. Functional limitation (Steinbrocker’s functional class III and IV) was seen in 4 (5.1%). One child with oligoarticular JIA died. Conclusions: The clinical profile of JIA in Nepalese patients is similar to studies from other parts of the World. During the short follow up, functional limitation was not a major problem. Keywords:  clinical profile, functional outcome, juvenile idiopathic arthritisÂ

Clinical characteristics and outcome of Vasculitides

Introductions: Vasculitides can cause significant morbidity and mortality if not treated on time. There is lack of data locally. This study aim to define the pattern, clinical characteristics, and outcome of vasculitides. Methods: This was a cross sectional study  between January 2011 to December 2015 at Patan Hospital, Patan Academy of Health Sciences, Lalitpur, Nepal. The medical records of patients diagnosed with vasculitides in adults rheumatology service of the hospital were reviewed. Results: Ninety six patients were diagnosed with vasculitides during the study period. The mean age was 42.2 years. Sixty nine (71.8%) patient had small vessel, 20 (20.8%) large vessel and five (5.2%) had variable vessel vasculitides. Seventy five patients (78.1%) had primary and 21 (21.8%) secondary vasculitides. Cutaneous leucocytoclasticangitis was seen in 27 (28.1%), Takayasu arteritis in 17 (17.7), Henoch-Schonlein purpure in 11 (11.4%) and Rheumatoid arthritis associated vasculitis in nine patients. Purpura was present in all 96 (100%). The overall mortality was 9 (9.3%). Conclusions: Primary vasculitides were more common than secondary forms. Small vessel vasculitis was the most common. Cutaneous symptoms were predominant features. The mortality was attributed to active disease, sepsis, and complications of the primary disease. Keywords: Clinical characteristics, outcome, vasculitis, Patan Hospital, Nepa

Patan hospital experience in treating philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukemia patients with gleevec (imatinib mesylate); the first generation specific tyrosine kinase inhibitor

<p>Abstract</p> <p>Background</p> <p>Chronic Myeloid Leukemia (CML) is caused by the abnormal fusion protein BCR-ABL1, a constitutively active tyrosine kinase and product of the Philadelphia chromosome. Gleevec (Imatinib mesylate) is a selective inhibitor of this kinase. Treatment with this agent is known to result in hematologic, cytogenetic, and molecular responses. Patan hospital (Patan, Nepal) is one of the Gleevec International Patient Assistance Program (GIPAP) centers for patients with CML.</p> <p>Methods</p> <p>A total of 106 Philadelphia positive CML patients were enrolled in our center between Feb 2003 and Jun 2008, and 103 of them were eligible for cytogenetic and/or hematologic response analyses.</p> <p>Results</p> <p>Out of 103 patients, 27% patients underwent cytogenetic analysis. Imatinib induced major cytogenetic responses in 89% and complete hematologic responses in almost 100% of the patients with confirmed CML. After a mean follow up of 27 months, an estimated 90% of the patients on imatinib remained in hematologic remission and more than 90% of the patients are still alive. About 30% of patients developed some form of manageable myelosuppression. A few patients developed non-hematologic toxic side effects such as edema and hepatotoxicity.</p> <p>Conclusions</p> <p>Our study demonstrates that imatinib is safe to use in a developing country. Furthermore, we demonstrate that imatinib is very effective and induced long lasting responses in a high proportion of patients with Ph chromosome/BCR-ABL1 positive CML. Imatinib is well tolerated by our patients. The lack of cytogenetic analysis in the majority of our patients hindered our ability to detect inadequate responses to imatinib and adjust therapy appropriately.</p

Azithromycin and cefixime combination versus azithromycin alone for the out-patient treatment of clinically suspected or confirmed uncomplicated typhoid fever in South Asia: a randomised controlled trial protocol.

Background: Typhoid and paratyphoid fever (enteric fever) is a common cause of non-specific febrile infection in adults and children presenting to health care facilities in low resource settings such as the South Asia.  A 7-day course of a single oral antimicrobial such as ciprofloxacin, cefixime, or azithromycin is commonly used for its treatment. Increasing antimicrobial resistance threatens the effectiveness of these treatment choices. We hypothesize that combined treatment with azithromycin (active mainly intracellularly) and cefixime (active mainly extracellularly) will be a better option for the treatment of clinically suspected and culture-confirmed typhoid fever in South Asia. Methods: This is a phase IV, international multi-center, multi-country, comparative participant-and observer-blind, 1:1 randomised clinical trial. Patients with suspected uncomplicated typhoid fever will be randomized to one of the two interventions: Arm A: azithromycin 20mg/kg/day oral dose once daily (maximum 1gm/day) and cefixime 20mg/kg/day oral dose in two divided doses (maximum 400mg bd) for 7 days, Arm B: azithromycin 20mg/kg/day oral dose once daily (max 1gm/day) for 7 days AND cefixime-matched placebo for 7 days. We will recruit 1500 patients across sites in Bangladesh, India, Nepal, and Pakistan. We will assess whether treatment outcomes are better with the combination after one week of treatment and at one- and three-months follow-up. Discussion: Combined treatment may limit the emergence of resistance if one of the components is active against resistant sub-populations not covered by the other antimicrobial activity. If the combined treatment is better than the single antimicrobial treatment, this will be an important result for patients across South Asia and other typhoid endemic areas. Clinicaltrials.gov registration: NCT04349826 (16/04/2020)

An Open Randomized Comparison of Gatifloxacin versus Cefixime for the Treatment of Uncomplicated Enteric Fever

OBJECTIVE: To assess the efficacy of gatifloxacin versus cefixime in the treatment of uncomplicated culture positive enteric fever. DESIGN: A randomized, open-label, active control trial with two parallel arms. SETTING: Emergency Room and Outpatient Clinics in Patan Hospital, Lagankhel, Lalitpur, Nepal. PARTICIPANTS: Patients with clinically diagnosed uncomplicated enteric fever meeting the inclusion criteria. INTERVENTIONS: Patients were allocated to receive one of two drugs, Gatifloxacin or Cefixime. The dosages used were Gatifloxacin 10 mg/kg, given once daily for 7 days, or Cefixime 20 mg/kg/day given in two divided doses for 7 days. OUTCOME MEASURES: The primary outcome measure was fever clearance time. The secondary outcome measure was overall treatment failure (acute treatment failure and relapse). RESULTS: Randomization was carried out in 390 patients before enrollment was suspended on the advice of the independent data safety monitoring board due to significant differences in both primary and secondary outcome measures in the two arms and the attainment of a priori defined endpoints. Median (95% confidence interval) fever clearance times were 92 hours (84-114 hours) for gatifloxacin recipients and 138 hours (105-164 hours) for cefixime-treated patients (Hazard Ratio[95%CI] = 2.171 [1.545-3.051], p&lt;0.0001). 19 out of 70 (27%) patients who completed the 7 day trial had acute clinical failure in the cefixime group as compared to 1 out of 88 patients (1%) in gatifloxacin group(Odds Ratio [95%CI] = 0.031 [0.004 - 0.237], p&lt;0.001). Overall treatment failure patients (relapsed patients plus acute treatment failure patients plus death) numbered 29. They were determined to be (95% confidence interval) 37.6 % (27.14%-50.2%) in the cefixime group and 3.5% (2.2%-11.5%) in the gatifloxacin group (HR[95%CI] = 0.084 [0.025-0.280], p&lt;0.0001). There was one death in the cefixime group. CONCLUSIONS: Based on this study, gatifloxacin is a better treatment for uncomplicated enteric fever as compared to cefixime. TRIAL REGISTRATION: Current Controlled Trials ISRCTN75784880

Organophosphorus Poisoning

Acute poisoning by organophosphorus (OP) compounds is a major global clinical problem, with thousands of deaths occurring every year. Most of these pesticide poisoning and subsequent deaths occur in developing countries following a deliberate self ingestion of the poison. Metacid (Methyl parathion) and Nuvan (Dichlorovos) are commonly ingested OP pesticides; Dimethoate, Profenofos, and Chlorpyrifos are other less frequently ingested compounds in Nepal. The toxicity of these OP pesticides is due to the irreversible inhibition of acetylcholinesterase (AChE) enzyme leading to accumulation of acetylcholine and subsequent over-activation of cholinergic receptors in various parts of the body. Acutely, these patients present with cholinergic crisis; intermediate syndrome and delayed polyneuropathy are other sequel of this form of poisoning. The diagnosis depends on the history of exposure to these pesticides, characteristic manifestations of toxicity and improvements of the signs and symptoms after administration of atropine. The supportive treatment of OP poisoning includes the same basic principles of management of any acutely poisoned patient i.e., rapid initial management of airways, breathing, and circulation. Gastric lavage and activated charcoal are routinely used decontamination procedures, but their value has not been conclusively proven in this poisoning. Atropine is the mainstay of therapy, and can reverse the life threatening features of this acute poisoning. However, there are no clear cut guidelines on the dose and duration of atropine therapy in OP poisoning. Cholinesterase reactivators, by regenerating AChE, can reverse both the nicotinic and muscarinic effects; however, this benefit has not been translated well in clinical trials. All these facts highlight that there are many unanswered questions and controversies in the management of OP poisoning and there is an urgent need for research on this aspect of this common and deadly poisoning. Key Words: poisoning, organophosphorus insecticides, decontamination, antidote

Paroxysmal Nocturnal Hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hemolytic disorder of acquired origin and is clinically manifested by chronic hemolysis, thromboses in various sites, and bone marrow failure. The disease is so rare that the delay in the diagnosis is not uncommon and this bears a tremendous impact on patient management. We present this case to draw attention to this uncommon cause of hemolytic anemia, which should be considered in any patient, of any age, who has signs of chronic hemolysis. Key Words: Paroxysmal Nocturnal Hemoglobinuria, Hemolytic anemia