Multiple sclerosis in Pakistan: Current status and future perspective.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) which commonly leads to disability. We reviewed articles on MS from Pakistan using PubMed, Google Scholar and Pak Medinet to present different aspects of the disease and the status of disease modifying treatments in Pakistan and South Asia. MS is not as uncommon in Pakistan as it has been previously thought to be. Estimated prevalence of MS in Pakistan may be 10 per 100,000 population. Data suggests that most features of MS found in Pakistan are similar to those found in the West. These features include a female preponderance, mean age of onset in the third decade of life and similar risk factors including viral infections, smoking, and vitamin D deficiency, as well as genetic risk factors. Relapsing-remitting multiple sclerosis (RRMS) is the most common disease pattern seen in Pakistan which is also consistent with data from other regions. Treatment modalities in Pakistan include immunomodulatory and immunosuppressive drugs. In order to improve care for MS patients in Pakistan, it is extremely important to obtain a population-based prevalence of MS in the country and a national MS registry, along with implementing programs for patients' awareness and the training of doctors, especially internists. There are many disease modifying therapies (DMT) available in Pakistan but no data is available on the utilization and impact of these DMTs.

Achieving effective patient and public involvement in international clinical trials in neurology.

There is a growing need for patient and public involvement (PPI) to inform the way that research is developed and performed. International randomized controlled trials are particularly likely to benefit from PPI, but guidance is lacking on how or when it should be incorporated. In this article, we describe the PPI process that occurred during the design and initiation of an international treatment clinical trial in MS. PPI was incorporated using a structured approach, aiming to minimize bias and achieve equivalence in study design, implementation, and interpretation. Methods included PPI representation within the study research team, and the use of focus groups, analyzed using thematic framework analysis. We report the outcomes of PPI and make recommendations on its use in other neurology clinical trials. By sharing our model for PPI, we aim to maximize effectiveness of future public involvement and to allow its effect to be better evaluated.

Sphingosine 1-Phosphate Receptor Modulators for the Treatment of Multiple Sclerosis.

Sphingosine 1-phosphate receptor (S1PR) modulators possess a unique mechanism of action in the treatment of multiple sclerosis (MS). Subtype 1 of the S1PR is expressed on the surface of lymphocytes and is important in regulating egression from lymph nodes. The S1PR modulators indirectly antagonize the receptor's function leading to sequestration of lymphocytes in the lymph nodes. Fingolimod was the first S1PR modulator to receive regulatory approval for relapsing-remitting MS after 2 phase III trials demonstrated potent efficacy, safety, and tolerability. Fingolimod can cause undesirable effects as a result of its interaction with other S1PR subtypes, which are expressed in diverse tissues, including cardiac myocytes. As such, agents that more selectively target subtype 1 of the S1PR are of interest and are at various stages of development. These include ponesimod (ACT128800), siponimod (BAF312), ozanimod (RPC1063), ceralifimod (ONO-4641), GSK2018682, and MT-1303. Data from phase II trials and early results from phase III studies have been promising and will be presented in this review. Of special interest are results from the EXPAND study of siponimod, which suggest a potential role for S1PR modulators in secondary progressive MS.

Rates of Adverse Events and Outcomes among Stroke Patients Admitted to Primary Stroke Centers.

BACKGROUND AND PURPOSE: To identify the beneficial effects of primary stroke centers (PSCs) certification by Joint Commission (JC), we compared the rates of in-hospital adverse events and discharge outcomes among ischemic stroke patients admitted to PSCs and those admitted to non-PSC hospitals in the United States. METHODS: We obtained the data from the Nationwide Inpatient Sample from 2010 and 2011. The analysis was limited to states that publicly reported hospital identity. PSCs were identified by matching the Nationwide Inpatient Sample hospital files with the list provided by JC. The analysis was limited to patients (age ≥18 years) discharged with a principal diagnosis of ischemic stroke (International Classification of Disease, 9th Revision, codes 433.x1, 434.x1). RESULTS: We identified a total of 123,131 ischemic stroke patients from 28 states. A total of 72,982 (59.3%) patients were admitted to PSCs. After adjusting for age, gender, race or ethnicity, comorbidities, All Patients Refined Diagnosis Related Groups (APR-DRG)-based disease severity, and hospital teaching status, patients admitted to PSCs were at lower risk of in-hospital adverse events complications: pneumonia (odds ratio [OR], .8; 95% confidence interval [CI], .7-.8) and sepsis (OR, .7; 95% CI, .6-.8). Patients admitted to PSCs were more likely to receive thrombolysis (OR, 1.6; 95% CI, 1.5-1.7). The mean cost of hospitalization (95% CI) of the patients was significantly higher in patients admitted at PSCs compared with those admitted at non PSC hospitals $47621 (47099-48144) vs. $35229 (34803-35654), P < .0001). The patients admitted to PSCs had lower inpatient mortality (OR, .8; 95% CI, .8-.9) and were more likely to be discharged with none to minimal disability (OR, 1.1; 95% CI, 1.0-1.1). CONCLUSIONS: Compared with non-PSC admissions, patients admitted to PSCs are less likely to experience hospital adverse events and more likely to experience better discharge outcomes.