Introduction Of New Medications Research Articles

Medication use evaluation of tocilizumab implementation in COVID-19 treatment guidelines: A causal inference approach.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Introduction of new medications to health-system formularies is often not accompanied by assessments of their clinical impact on the local patient population. The growing availability of electronic health record (EHR) data and advancements in pharmacoepidemiology methods offer institutions the opportunity to monitor the medication implementation process and assess clinical effectiveness in the local clinical context. In this study, we applied novel causal inference methods to evaluate the effects of a formulary policy introducing tocilizumab therapy for critically ill patients with coronavirus disease 2019 (COVID-19). We conducted a medication use evaluation utilizing EHR data from patients admitted to a large medical center during the 6 months before and after implementation of a formulary policy endorsing the use of tocilizumab for treatment of COVID-19. The impact of tocilizumab on 28-day all-cause mortality was assessed using a difference-in-differences analysis, with ineligible patients serving as a nonequivalent control group, and a matched analysis guided by a target trial emulation framework. Safety endpoints assessed included the incidence of secondary infections and liver enzyme elevations. Our findings were benchmarked against clinical trials, an observational study, and a meta-analysis. Following guideline modification, tocilizumab was administered to 69% of eligible patients. This implementation was associated with a 3.1% absolute risk reduction in 28-day mortality (odds ratio, 0.86; number needed to treat to prevent one death, 32) attributable to the inclusion of tocilizumab in the guidelines and an additional 8.6% absolute risk reduction (odds ratio, 0.65; number needed to treat to prevent one death, 12) linked to its administration. These findings were consistent with estimates from published literature, although the effect estimates from the difference-in-differences analysis exhibited imprecision. Evaluating formulary management decisions through novel causal inference approaches offers valuable estimates of clinical effectiveness and the potential to optimize the impact of new medications on population outcomes.

Therapeutical Approach to Arterial Hypertension - Current State of the Art.

Arterial hypertension (AH) is recognized as the most common illness within the group of cardiovascular diseases and the most massive chronic non-infectious disease in the world. The number of hypertensive patients worldwide has reached 1.28 billion, contributing to an increase in cardiovascular diseases and premature death globally. The high prevalence of hypertension emphasizes the importance of effectively treating this condition. Elevated blood pressure often leads to lethal complications (heart failure, stroke, renal disorders, etc.) if left untreated. Considering an increase in AH prevalence in the future, a successful therapeutical approach to this disease and its complications is essential. The goal of AH treatment is to maintain normotensive blood pressure through various approaches, including lifestyle changes, a well-balanced diet, increased physical activity, psychoeducation, and, when necessary, pharmacotherapy. The evolving pharmacotherapeutic landscape reflects the progress made in our understanding of hypertension and emphasizes the need for continuous innovation to meet the challenges posed by this prevalent global health concern. The journey toward more effective and tailored treatments for hypertension is ongoing, and the introduction of new medications plays a pivotal role in shaping the future of antihypertensive pharmacotherapy.

Pneumocystis jirovecii Pneumonia after Heart Transplantation: Two Case Reports and a Review of the Literature.

Post-transplant Pneumocystis jirovecii pneumonia (PcP) is an uncommon but increasingly reported disease among solid organ transplantation (SOT) recipients, associated with significant morbidity and mortality. Although the introduction of PcP prophylaxis has reduced its overall incidence, its prevalence continues to be high, especially during the second year after transplant, the period following prophylaxis discontinuation. We recently described two cases of PcP occurring more than one year after heart transplantation (HT) in patients who were no longer receiving PcP prophylaxis according to the local protocol. In both cases, the disease was diagnosed following the diagnosis of a viral illness, resulting in a significantly increased risk for PcP. While current heart transplantation guidelines recommend Pneumocystis jirovecii prophylaxis for up to 6-12 months after transplantation, after that period they only suggest an extended prophylaxis regimen in high-risk patients. Recent studies have identified several new risk factors that may be linked to an increased risk of PcP infection, including medication regimens and patient characteristics. Similarly, the indication for PcP prophylaxis in non-HIV patients has been expanded in relation to the introduction of new medications and therapeutic regimens for immune-mediated diseases. In our experience, the first patient was successfully treated with non-invasive ventilation, while the second required tracheal intubation, invasive ventilation, and extracorporeal CO2 removal due to severe respiratory failure. The aim of this double case report is to review the current timing of PcP prophylaxis after HT, the specific potential risk factors for PcP after HT, and the determinants of a prompt diagnosis and therapeutic approach in critically ill patients. We will also present a possible proposal for future investigations on indications for long-term prophylaxis.

Adherence With Oral Anticancer Therapies: Clinical Trial versus Real-World Experiences with a Focus on Prostate Cancer.

In this review, we address adherence rates in clinical settings, barriers to compliance with dosing schedules, and potential strategies to overcome challenges in maintaining high levels of adherence. Four studies reporting real-world adherence to prostate cancer medications, 52 studies describing barriers to adherence, and 16 studies on methods to minimize poor adherence were reviewed. Mean nonadherence rates of 25 to 51% have been identified in prostate cancer patients prescribed oral therapies, with higher rates in older patients. An extensive review of prostate cancer patients receiving gonadotropin hormone-releasing hormone agonist injections found an overall nonadherence rate of over 27%. Patients may encounter barriers to complying with dosing instructions related to the medication (eg, complex dosing schedules, the total burden of medication management, fasting or dietary requirements, high medication costs, adverse effects, and drug-drug interactions). Barriers may also be related to patient-specific factors (eg, suboptimal education regarding the importance of adherence, physical limitations and cognitive decline associated with advancing age, living alone without a care partner, high symptom burden, needle phobia, and comorbid mental disorders). Interventions to improve dosing adherence may include automated reminders, treatment diaries, educational materials, and the involvement of patients, family members, care partners, and healthcare teams. Many oral anticancer medications improve survival in men with prostate cancer and therefore it is vital to establish good adherence by understanding the pitfalls that patients may encounter. In situations where both oral and injectable drugs are interchangeable, injections of long-acting drugs lead to fewer opportunities for dosing nonadherence than oral therapies. In contrast, oral medicines do not require scheduling for injections and travel for injection appointments. Therefore, maximizing adherence to all treatment regimens will reduce the chance of efficacy failures and likely lead to improved clinical outcomes.

Critical Appraisal of Drug Promotional Literature in Accordance With WHO Guidelines.

BackgroundDrug promotional literature (DPL) is used as a marketing tactic to publicize the introduction of new medications. As drug companies are promoting the literature for their brand products, bias is possible. Various studies have demonstrated that printed DPLs disseminated by pharmaceutical companies are typically skewed.Material and methodA prospective, observational study was carried out in the outpatient departments of a tertiary care hospital to analyze the DPL of different pharmaceutical companies using WHO criteria for "Ethical criteria for medicinal drug promotion, 1988".ResultsOut of 192 DPLs analyzed, information regarding the generic name, brand name, amount of active ingredient, and manufacturer name was found in all the DPLs (100%). Though therapeutic uses were mentioned in 91% of DPLs, dosage schedule (regimen) was mentioned only in 60%. Drug safety information such as the side effects and significant adverse drug reactions, precautions and warnings, contraindications, and major drug interactions were present in 24%, 36%, and 20%, respectively. Address of the manufacturer and reference to scientific literature were present only in 63% and 53% of DPLs, respectively. References mainly were from journals, present in 71% of DPLs. Most of the claims made in DPLs were regarding efficacy (73%), followed by safety (34%). ConclusionIn our study, not a single DPL fulfilled all the nine WHO criteria. A doctor should rigorously evaluate study findings before prescribing because misleading and incorrect information is now frequently found in this literature.

Early sonographic response to a new medical therapy is associated with future treatment response or failure in patients with inflammatory bowel disease.

Gastrointestinal ultrasound (GIUS) accurately assesses inflammation and is responsive to changes in inflammatory bowel disease. This study aimed to determine the prognostic utility of sonographic response in the first 14 weeks of a newly-instituted therapy with therapeutic response at 46 weeks and to compare its performance with standard clinical assessment tools. Patients with sonographic evidence of inflammation were assessed by GIUS, clinical activity, serum C-reactive protein and faecal calprotectin again 2, 6 and 14 weeks after commencing a new biologic or thiopurine. Treatment failure was defined as undergoing surgery, hospitalisation, escalation of dosage or introduction of new medication over 46-weeks' follow-up. Sonographic response was defined as a decrease in bowel wall thickness and improved vascularity. In 31 patients (median age 49 years, 74% Crohn's disease), sonographic response at 14 weeks [OR 19.3, 95% confidence interval (CI), 3.23-101.10; P = 0.0054] and faecal calprotectin (P = 0.018), but no clinical disease activity or C-reactive protein, were predictive of subsequent treatment response. Sonographic response alone was predictive at week 6 (P = 0.016), but not week 2. 16% reduction in bowel wall thickness at 6 weeks (area-under-the-receiver-operator-curve=0.86; P = 0.002; sensitivity 72%, specificity 90%), with similar performance for 10% at 14 weeks, was associated with treatment response. Sonographic response as early as 6 weeks after initiation of a new therapy may accurately predict treatment outcomes over 46 weeks and is superior to other markers used to monitor disease activity.

Prevalence of neural tube defects, maternal HIV status, and antiretroviral therapy from a hospital-based birth defect surveillance in Kampala, Uganda.

Background:The estimated prevalence of neural tube defects (NTDs) in Africa is 11.7 per 10,000 live births; however, data on the impact of antiretroviral therapy (ART) during pregnancy and the risk for birth defects in Africa are limited.Methods:Data from a hospital-based surveillance program at four hospitals in Kampala, Uganda were used to estimate the baseline prevalence of NTDs and assess potential associations with HIV status and ART use. All live births, stillbirths, and spontaneous abortions delivered at the participating hospitals affected with selected birth defects between August 2015 and December 2018 were included. Trained midwives collected data from hospital records, maternal interviews, photographs, and narrative descriptions of birth defects. We estimated NTD prevalence per 10,000 births (live, stillbirths, spontaneous abortions), prevalence ratios, and 95% confidence intervals (CIs).Results:A total of 110,752 births from 107,133 women were included in the analysis; 9,394 (8.8%) women were HIV-infected and among those with HIV infection, 95.6% (n = 8,977) were on ART at delivery. Overall, 109 births were affected with NTDs, giving a prevalence of 9.8 (95% CI [8.2, 11.9]). Spina bifida (n = 63) was the most common type of NTD, with a prevalence of 5.7 (95% CI [4.4, 7.3]), followed by anencephaly (n = 31), with a prevalence of 2.8 (95% CI [2.0, 4.0]).Conclusion:The prevalence of NTDs among births in Kampala, Uganda is consistent with current estimates for Africa. With the continued introduction of new medications that may be taken during pregnancy, sustainable birth defect surveillance systems and pharmacovigilance are indicated.

Trends of Industry Payments in Neurology Subspecialties.

BackgroundOpen Payments is a national disclosure program to promote transparency by the public disclosure of financial relationships between the pharmaceutical and medical device industries and physicians.ObjectiveTo explore payments from the industry to physicians in various neurology subspecialties.MethodsOpen Payments Program (OPP) data (https://openpaymentsdata.cms.gov) on industry-to-physician payments for the years 2014-2018 were extracted for general neurology, neuromuscular, neurophysiology, and vascular neurology. The data were then analyzed to explore trends in payments for various subspecialties and to identify the possible factors underlying these trends.ResultsOverall, industry-to-physician payments for neurology subspecialties increased by 16% from 2014 to 2018. The introduction of newer drugs in a subspecialty was likely the driving factor for higher industry payments. Nearly half of the total industry-to-physician payments were for the subspecialty of multiple sclerosis (MS)/Neuroimmunology; this coincided with Aubagio and Copaxone being the top two medications associated with the highest industry payments in 2014, Aubagio, and Lemtrada in 2018. A significant increase in spending percentages for headache, neuromuscular disorders, and movement disorders was observed while a relative decrease in the payments for MS/neuroimmunology and epilepsy was identified; these trends coincide with the introduction of new drugs such as Aimovig, Neuplazid, Nusinersen, and Austedo for headache, neuromuscular and movement disorders.ConclusionsFrom 2014 to 2018, the total industry-to-physician payments for neurology subspecialties increased while the distribution of industry-to-physician payments for various neurology subspecialties showed notable changes. The introduction of newer medications in a subspecialty coincided with higher industry payments. Identification of these trends and potential motives of the industry spending is critical to address any potential physician bias in prescribing medications.

The introduction of new medications in pediatric multiple sclerosis: Open issues and challenges

Disease-modifying drugs (DMDs) for multiple sclerosis (MS) have been evaluated in pediatric patients in observational studies demonstrating a similar, even better clinical effect compared to adults, with a similar safety. Only fingolimod has been tested in a randomized controlled trial (RCT) and is approved for pediatric multiple sclerosis (ped-MS). Numerous methodological, practical, and ethical issues underline that RCTs are difficult to conduct in ped-MS. This also creates a lack of safety information. To facilitate the availability of new agents in ped-MS, we encourage to develop a different approach based on pharmacokinetic/pharmacodynamic studies to yield information on optimal doses and implementation of obligatory registries to obtain information on safety as primary endpoint.

Update on the NAEPPCC Asthma Guidelines: The wait is over, or is it?

As an asthma specialist, one is often asked to discuss the asthma guidelines. The challenge that one faces is deciding which guidelines to use as a resource for discussion or presentation. It often comes down to the following questions: What is the question? What message does one want to deliver? Where is the most current information? and Who is the target audience? This commentary will help answer those questions as it guides the reader through the new update of the National Heart, Lung and Blood Institute/National Asthma Education and Prevention Program guidelines and then outlines differences between 2 widely used strategies for the management of asthma: the Global Initiative for Asthma and the National Heart, Lung and Blood Institute/National Asthma Education and Prevention Program Guidelines for the Diagnosis and Management of Asthma.

A Short Review on Anti-diabetics for Uncontrolled Type 2 Diabetes Mellitus

Introduction: This article reviews the treatments available for patients with T2DM, with an emphasis on agents introduced within the last decade. Materials and Methods: This review is based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. Subject heading and key words used include type 2 diabetes mellitus, prevalence, current diagnosis, and current treatment. Only articles in English were included.
 Materials & Methods: Screening and diagnosis is still based on World Health Organization (WHO) and American Diabetes Association (ADA) criteria which include both clinical and laboratory parameters. No cure has yet been found for the disease; however, treatment modalities include lifestyle modifications, treatment of obesity, oral hypoglycemic agents, and insulin sensitizers is still the recommended first line medication. Other effective medications include non-sulfonylurea secretagogues, thiazolidinediones, alpha glucosidase inhibitors, and insulin. Recent research into the pathophysiology of type 2 DM has led to the introduction of new medications like glucagon-like peptide 1 analogoues: dipeptidyl peptidase-IV inhibitors, inhibitors of the sodium-glucose cotransporter 2 and 11ß-hydroxysteroid dehydrogenase 1, insulin-releasing glucokinase activators and pancreatic-G-protein-coupled fatty-acid-receptor agonists, glucagon-receptor antagonists, metabolic inhibitors of hepatic glucose output and quick-release bromocriptine.
 Discussion: Screening and diagnosis is still based on World Health Organization (WHO) and American Diabetes Association (ADA) criteria which include both clinical and laboratory parameters. No cure has yet been found for the disease; however, treatment modalities include lifestyle modifications, treatment of obesity, oral hypoglycemic agents, and insulin sensitizers is still the recommended first line medication. Other effective medications include non-sulfonylurea secretagogues, thiazolidinediones, alpha glucosidase inhibitors, and insulin. Recent research into the pathophysiology of type 2 DM has led to the introduction of new medications like glucagon-like peptide 1 analogoues: dipeptidyl peptidase-IV inhibitors, inhibitors of the sodium-glucose cotransporter 2 and 11ß-hydroxysteroid dehydrogenase 1, insulin-releasing glucokinase activators and pancreatic-G-protein-coupled fatty-acid-receptor agonists, glucagon-receptor antagonists, metabolic inhibitors of hepatic glucose output and quick-release bromocriptine.
 Conclusion: Metformin remains the first choice of treatment for most patients. Other alternative or second-line treatment options should be individualized depending on the characteristics of each patient.
 Medicine Today 2019 Vol.31(2): 120-127

Identification of potential carcinogenic and chemopreventive effects of prescription drugs: a protocol for a Norwegian registry-based study

IntroductionSurveillance of unintended effects of pharmaceuticals (pharmacovigilance or drug safety) is crucial, as knowledge of rare or late side effects is limited at the time of the introduction of new...

Pediatric Post-anesthesia Care Unit Challenges Update

The purpose of this review is to discuss the current management of various challenges the health care provider faces in the pediatric post-anesthesia care unit (PACU). Efforts to ameliorate and manage PACU issues in the pediatric patient continue to evolve as new medications and methods of anesthesia delivery are introduced and incorporated into the perioperative period. In this review, emergence delirium (ED), postoperative nausea and vomiting (PONV), residual neuromuscular blockade, and tracheal extubation in the operating room versus the PACU are addressed. As ED may be self-limited, pharmacologic treatment may only be indicated if there is a concern for patient harm. Midazolam, fentanyl, and propofol have all been shown to be effective in the treatment of emergence delirium. Dexmedetomidine has been shown to decrease the incidence of ED when administered preoperatively or intraoperatively. This has led practitioners to use dexmedetomidine to treat ED in the PACU, though this has not been studied. Postoperative nausea is difficult to assess in the pediatric patient leading to under treatment. In order to capture these children, the BARF score, initially validated for use in oncologic pediatric patients, is validated for use in postoperative pediatric patients 6 years and older. The approach to treating breakthrough PONV in the PACU is guided by the medications administered intraoperatively for prophylactic treatment. Rescue medications from a different class should be selected if fewer than 6 h have passed since the administration of prophylactic antiemetics. Inadequate reversal of neuromuscular blockade intraoperatively results in adverse respiratory events in the PACU. In the past, when maximum doses of reversal agents are administered, the only recourse in the PACU is to provide assisted ventilation. With the introduction of sugammadex, assisted ventilation can be avoided since sugammadex is capable of reversing dense neuromuscular blockade by vecuronium or rocuronium. In the current environment of achieving greater OR efficiency and cost savings, some institutions are moving tracheal extubation from the operating room by trained anesthesiologists to the PACU by trained nurses with physicians immediately available. This practice in two different children’s hospitals is shown to be safe with no greater incidence of adverse respiratory events and with the added benefit of decreasing operating room time. PACU challenges in the pediatric patient continue to occur despite changes in anesthetic practice and introduction of newer medications. It is important to keep abreast of these newer modalities to best manage these PACU conditions.

The role of musculoskeletal ultrasound in psoriatic arthritis

Psoriatic arthritis (PsA) may develop in up to a third of people with psoriasis and can be erosive in 40-60% of patients early on, resulting in functional impairment and reduced quality of life. In recent years with the introduction of new medications and wider use of musculoskeletal ultrasound (US) imaging in clinical practice, the possibility of earlier US diagnosis in patients with psoriasis in the pre-clinical phase of PsA has been examined. US detection of subclinical synovitis and enthesitis in psoriasis patients without musculoskeletal involvement will be discussed. The clinical spectrum of PsA is broad with five target areas of joints, tendons, entheses, skin and nails. Each domain will be discussed with their relevant US findings, focussing on synovitis, enthesitis and dactylitis. Specifically, features of enthesitis on US can be divided into those of reversible soft tissue inflammation and irreversible tissue damage. There is increasing use of US in evaluating nail involvement in psoriasis as this feature increases the probability of developing PsA. In patients with predominantly hand involvement, US enables differentiation of PsA from other inflammatory arthritides, such as rheumatoid arthritis, using specific extra-synovial US patterns of inflammation. Examples include peritenonitis of the extensor digitorum tendon at the metacarpophalangeal joints. Thickening of the flexor tendon pulleys may be predictive of PsA in the setting of early arthritis. Psoriatic related polyenthesitis without clinically swollen joints or increased inflammatory markers can mimic fibromyalgia with multiple tender points. US detection of enthesitis especially if power Doppler positive may assist by providing an objective assessment of disease activity. More recently, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) US Working Group has developed a PsA US enthesitis scoring system, addressing the elementary inflammatory and structural components and determining which entheseal sites should be scanned. The utility of US in monitoring disease activity in PsA to support clinical assessment will be discussed, including guidance in tapering therapy in clinical remission. The ongoing prospective US in PsA Treatment Study (UPSTREAM) aims to identify clinical and US predictors of treatment response in PsA. Future research should address issues such as the optimal combination for US screening of joints, tendons and entheses, the predictive value of subclinical US inflammatory lesions for future development of PsA and whether US provides any added prognostic value in PsA in those achieving minimal disease activity on therapy.

Propelling the Pediatric HIV Therapeutic Agenda With Science, Innovation, and Collaboration.

Background:A number of well-described obstacles to the pediatric therapeutic agenda have resulted in substantial delays in the introduction of new medications, formulations, strategies, and approaches to treat infants, children, and adolescents living with HIV.Setting:Global landscape.Methods:The authors will provide a summary of current and emerging initiatives to accelerate the pediatric therapeutic agenda including illustrative case studies of innovations and scientific discovery in diagnosis and treatment of very young children with HIV infection.Results:The challenges posed by rapid physiologic and developmental changes that characterize the trajectory of childhood as well as the complex regulatory and fiscal milieu of HIV therapeutics have hampered pediatric HIV therapeutic research. Recent efforts to accelerate this agenda include prioritizing agents and formulations, defining dosing by weight bands, applying innovative study designs, synergizing work across research networks to achieve common goals, and the establishment of a global prioritized research agenda. A case study of initiatives to diagnose and effectively treat newborns and infants will illustrate the critical role of basic science research and novel approaches to study design and implementation that are informing global efforts to end AIDS.Conclusions:A pediatric therapeutic agenda informed by basic science and achieved through innovation and global cooperation is essential to achieve an AIDS-free generation.

Patents and Recent Innovations in Topical Membrane Therapy of Refractory Rhinosinusitis.

Chronic Rhinosinusitis (CRS), one of the commonest chronic inflammatory disorders, is encountered daily in all healthcare settings. In its refractory form, CRS seems to prevail over most up-to-date surgical interventions and systemic medical remedies, owing to our poor understanding of its perplexing pathophysiology. Although several systemic influences impinge on the progression of inflammation, the true interplay between offensive and defensive factors takes place on-site, i.e. across the sinonasal epithelial coating. Therefore, current treatment strategies shift the weight of CRS management toward topical modalities, which combine the benefits of surgical approach with the healing effect of conventional medications. An explosive emergence of relevant patents is still in progress, emphasizing the need for classification and comparison. Novel delivery methods of medications into the sinus cavities include modifications of traditional rinses, state-of-the-art nebulizing devices, and the revolutionary concept of sustained drug application utilizing carrier gels or nasal implants. As far as the introduction of new medications is concerned, recent patents propose alterations to the physical and chemical properties of irrigating solutions, as well as the local use of antiseptics, hydragogues, and anti-biofilm agents. This review focuses on the local pathophysiologic events of CRS and the most exciting innovations regarding its topical management.

Thiazide-Induced Hyperglycemia in a 6 Years Old Girl: A Case Report and Review of the Literature

Various factors may affect glucose homeostasis in children resulting in rare clinical scenarios. Alterations in glucose regulation and hyperglycemia may result from pharmacologic interventions and the introduction of new medications. Although used most commonly to control fluid balance, an uncommon adverse effect of the thiazide diuretics is hyperglycemia. We present a 6-year-old girl with congenital heart disease who developed clinically significant hyperglycemia when a thiazide diuretic was added to her medication regimen. Previous reports of similar responses are reviewed, physiologic mechanisms are postulated, and treatment strategies are proposed. J Med Cases. 2016;7(2):49-51 doi: http://dx.doi.org/10.14740/jmc2403w

Utility and cost-effectiveness of uroflowmetry in a busy pediatric urology practice.

Uroflowmetry (UF) is frequently employed in daily pediatric urology practice for diagnostic and follow-up purposes. We assess the utility and cost-effectiveness of UF in the management of patients seen at a tertiary care centre. We retrospectively reviewed the charts of consecutive patients who had a UF between January 1, 2010 and March 31, 2010. We collected data on demographics, diagnosis, UF parameters and the impact of the UF on management. The impact on management was defined as indication for surgery, introduction of new medications and bladder retraining based on clinical and UF findings. In total, 524 patients were included in the study. In 63 (12%) patients, UF was performed as part of the evaluation at the first clinic appointment. The most common diagnoses were voiding dysfunction (VD) 41%, hypospadias 26%, vesicoureteric reflux (VUR) 16%, monosymptomatic nocturnal enuresis (NE) 8%, posterior urethral valves 5% and meatal stenosis (MS) 4%. In the VD group, UF contributed to a management decision in 25.2% of patients. In the MS group, surgical intervention was based on symptoms and supported by the UF in 41% of patients; in the PUV group, 50% of patients demonstrated high (>20 cc) post-void residual, which aided in management decisions. In contrast, there were virtually no changes in management supported by the UF in the NE, VUR and hypospadias groups. Overall, UF parameters had a direct influence in the management decisions in only 67 (12.8%) patients. Nonetheless, a repeat test was ordered for 44.5% of patients. In an era of financial restraints and in a busy tertiary pediatric urology practice, judicious use of UF for specific indications may translate into a more cost-effective use of time and resources. As expected, patients with VD were the ones that benefited most from the test, as did patients with symptomatic MS and PUV.

Low dose aspirin for MS-related fatigue: Results of a pilot, double-blind, randomized trial

Fatigue is one of the most common and disabling symptoms in multiple sclerosis (MS), occurring in more than 60% of patients during the course of the disease. Despite /INS;high prevalence of fatigue in MS patients, its pathophysiology was not understood completely yet and/INS; this would difficult introduction of new medication for this symptom. Wingerchuk et al. for the first time assess the effectiveness of Aspirin (ASA) on MS related fatigue and show high dose ASA (1300mg) would significantly decrease fatigue in these patients.

Type 2 diabetes mellitus: a review of current trends.

Type 2 diabetes mellitus (DM) is a chronic metabolic disorder in which prevalence has been increasing steadily all over the world. As a result of this trend, it is fast becoming an epidemic in some countries of the world with the number of people affected expected to double in the next decade due to increase in ageing population, thereby adding to the already existing burden for healthcare providers, especially in poorly developed countries. This review is based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. Subject heading and key words used include type 2 diabetes mellitus, prevalence, current diagnosis, and current treatment. Only articles in English were included. Screening and diagnosis is still based on World Health Organization (WHO) and American Diabetes Association (ADA) criteria which include both clinical and laboratory parameters. No cure has yet been found for the disease; however, treatment modalities include lifestyle modifications, treatment of obesity, oral hypoglycemic agents, and insulin sensitizers like metformin, a biguanide that reduces insulin resistance, is still the recommended first line medication especially for obese patients. Other effective medications include non-sulfonylurea secretagogues, thiazolidinediones, alpha glucosidase inhibitors, and insulin. Recent research into the pathophysiology of type 2 DM has led to the introduction of new medications like glucagon-like peptide 1 analogoues: dipeptidyl peptidase-IV inhibitors, inhibitors of the sodium-glucose cotransporter 2 and 11ß-hydroxysteroid dehydrogenase 1, insulin-releasing glucokinase activators and pancreatic-G-protein-coupled fatty-acid-receptor agonists, glucagon-receptor antagonists, metabolic inhibitors of hepatic glucose output and quick-release bromocriptine. Inhaled insulin was licensed for use in 2006 but has been withdrawn from the market because of low patronage.