Search

Importance: Disparity in overall survival (OS) and differences in the frequency of driver gene variants by race and ethnicity have been separately observed in patients with colorectal cancer; however, how these differences contribute to survival disparity is unknown., Objective: To quantify the association of molecular, socioeconomic, and clinical covariates with racial and ethnic disparities in overall survival among patients with colorectal cancer., Design, Setting, and Participants: This single-center cohort study was conducted at a tertiary-level cancer center using relevant data on all patients diagnosed with colorectal cancer from January 1, 1973, to March 1, 2023. The relative contribution of variables to the disparity was determined using mediation analysis with sequential multivariate Cox regression models., Main Outcome: OS, from diagnosis date and from start of first-line chemotherapy., Results: The study population of 47 178 patients (median [IQR] age, 57.0 [49-66] years; 20 465 [43.4%] females and 26 713 [56.6%] males; 3.0% Asian, 8.7% Black, 8.8% Hispanic, and 79.4% White individuals) had a median (IQR) follow-up from initial diagnosis of 124 (174) months and OS of 55 (145) months. Compared with White patients, Black patients had worse OS (hazard ratio [HR], 1.16; 95% CI, 1.09-1.24; P <.001), whereas Asian and Hispanic patients had better OS (HR, 0.66; 95% CI, 0.59-0.74; P <.001; and 0.86; 95% CI, 0.81-0.92; P <.001, respectively). When restricted to patients with metastatic disease, the greatest disparity was between Black patients compared with White patients (HR, 1.2; 95% CI, 1.06-1.37; P <.001). Evaluating changes in OS disparity over 20 years showed disparity decreasing among Asian, Hispanic, and White patients, but increasing between Black patients and White patients (HRs, 1.18; 95% CI, 1.07-1.31 for 2008-2012; 1.24, 95% CI, 1.08-1.42 for 2013-2017; and 1.50; 95% CI, 1.20-1.87 for 2018-2023). Survival outcomes for first-line chemotherapy were worse for Black patients compared with White patients (median OS, 18 vs 26 months; HR, 1.30; 95% CI, 1.01-1.70). Among 7628 patients who had clinical molecular testing, APC, KRAS, and PIK3CA showed higher variant frequency in Black patients (false discovery rate [FDR], 0.01; < 0.001; and 0.01, respectively), whereas BRAF and KIT were higher among White patients (FDR, 0.001 and 0.01). Mediation analysis identified neighborhood socioeconomic status as the greatest contributor to OS disparity (29%), followed by molecular characteristics (microsatellite instability status, KRAS variation and BRAF variation, 10%), and tumor sidedness (9%)., Conclusions: This single-center cohort study identified substantial OS disparity and differing frequencies of driver gene variations by race and ethnicity. Socioeconomic status had the largest contribution but accounted for less than one-third of the disparity, with substantial contribution from tumor molecular features. Further study of the associations of genetic ancestry and the molecular pathogenesis of colorectal cancer with chemotherapy response is needed.

Introduction: One strategy to mitigate progressive multifocal leukoencephalopathy (PML) risk is to switch to other highly effective disease-modifying therapies (DMTs). However, the optimal switch DMT following natalizumab (NTZ) discontinuation is yet to be determined., Objective: The objective of the study is to determine the most effective and tolerable DMTs to switch to following NTZ discontinuation due to John Cunningham virus (JCV) antibody positivity., Methods: This is a multicenter observational cohort study that included all stable relapsing-remitting multiple sclerosis (MS) patients who were treated with NTZ for at least 6 months before switching therapy due to JCV antibody positivity., Results: Of 321 patients, 255 switched from NTZ to rituximab/ocrelizumab, 52 to fingolimod, and 14 to alemtuzumab, with higher annualized relapse rate (ARR) in fingolimod switchers (0.193) compared with rituximab/ocrelizumab or alemtuzumab (0.028 and 0.032, respectively). Fingolimod switchers also had increased disability progression ( p = 0.014) and a higher proportion developed magnetic resonance imaging (MRI) lesions compared with rituximab/ocrelizumab (62.9% vs. 13.0%, p < 0.001, and 66.6% vs. 24.0%, p < 0.001, respectively). Mean drug survival favored rituximab/ocrelizumab or alemtuzumab over fingolimod ( p < 0.001)., Conclusion: Our study shows superior effectiveness of rituximab/ocrelizumab and alemtuzumab compared with fingolimod in stable patients switching from NTZ due to JC virus antibody positivity., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.Z. has received honoraria for lectures from Biologix, Biogen, Janssen, Hikma Pharmaceuticals, Novartis, Merck, Roche, and Sanofi-Genzyme. She received travel grants from Novartis, Merck, and Roche and a research grant from Biogen. She received two research grants from Biogen, one research grant from Merck, and two research grants from MENACTRIMS. She has no conflict of interest related to this study. B.Y. has received speaker honoraria from Bayer, Biogen, Merck, Novartis, Roche, and Sanofi; research grants from Bayer, Biogen, Merck, Novartis, and Pfizer; and advisory board honoraria from Bayer, Biogen, Merck, Novartis, Roche, and Sanofi. He has no conflict of interest related to this study. A.A.-A. has received honoraria from Novartis, Sanofi, Biologix, Merck, Roche, Biogen, and Bayer. He serves on the scientific advisory boards of Novartis, Merck, and Roche. He has no conflict of interest related to this study. R.G. has received research grant from Roche and advisory board honoraria from Biogen, Hikma, Merck, Roche, and Sanofi. He has no conflict of interest related to this study. S.M. received a MENACTRIMS clinical research grant (2020) but has no conflict of interest related to this study. R.A.-R., S.F.A., S.K., N.E.-A., A.A.-M., J.A.-K., A.C., J.I., N.S., J.M., F.M.R.H.M., A.A.-H., P.S., H.D., and F.B. declare that there is no conflict of interest.

Background: There is a lack information regarding risk factors associated with worse COVID-19 outcomes in patients with multiple sclerosis (MS) in the MENA region., Methods: This is a multicenter, retrospective cohort study that included all MS patients with a suspected or confirmed COVID-19 infection using the MENACTRIMS registry. The association of demographics, disease characteristics, and use of disease-modifying therapies (DMTs) with outcomes and severity of COVID-19 were evaluated by multivariate logistic model., Results: A total of 600 MS patients with confirmed (n = 542) or highly suspected (n = 58) COVID-19 were analyzed. Seventy-three patients (12.2 %) had a COVID-19 severity score of ≥3 on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death] with a cutoff at 3 [hospitalized and not requiring supplemental oxygen]), and 15 patients (2.5 %) died. Out of 73 patients with a severity score ≥3, 90.4 % were on DMTs; 50.6 % of them were on anti-CD20, including ocrelizumab and rituximab. Multivariate logistic regression showed that older age (odds ratio per 10 years, 1.4 [95 %CI, 1.0-1.8]), disability (OR for EDSS 3.0-5.5, 2.9 [95 %CI. 1.5-5.7], OR for EDSS ≥6.0, 2.3 [95 %CI. 1.0-5.1]), obesity (OR, 3.0 [95 %CI, 1.5-6.0]), and treatment with rituximab (OR, 9.0 [95 %CI, 3.1-25.3]) or off-label immunosuppressive medications (OR, 5.6 [95 %CI. 1.1-27.8]) were risk factors for moderate or severe COVID-19., Conclusion: In this registry-based study of MS patients, age, sex, EDSS, obesity, progressive MS were risk factors for severe COVID-19. Moreover, there was an association found between exposure to anti-CD20 DMTs and COVID-19 severity., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Dynamic operations platforms allow for cross-platform data extraction, integration, and analysis, although application of these platforms to large-scale oncology enterprises has not been described. This study presents a pipeline for automated, high-fidelity extraction, integration, and validation of cross-platform oncology data in patients undergoing treatment for rectal cancer at a single, high-volume institution., Methods: A dynamic operations platform was used to identify patients with rectal cancer treated at MD Anderson Cancer Center between 2016 and 2022 who had magnetic resonance imaging (MRI) imaging and preoperative treatment details available in the electronic health record (EHR). Demographic, clinicopathologic, tumor mutation, radiographic, and treatment data were extracted from the EHR using a methodology adaptable to any disease site. Data accuracy was assessed by manual review. Accuracy before and after implementation of synoptic reporting was determined for MRI data., Results: A total of 516 patients with localized rectal cancer were included. In the era after institutional adoption of synoptic reports, the dynamic operations platform extracted T (tumor) category data from the EHR with 95% accuracy compared with 87% before the use of synoptic reports, and N (lymph node) category with 88% compared with 58%. Correct extraction of pelvic sidewall adenopathy was 94% compared with 78%, and extramural vascular invasion accuracy was 99% compared with 89%. Neoadjuvant chemotherapy and radiation data were 99% accurate for patients who had synoptic data sources., Conclusion: Using dynamic operations platforms enables automated cross-platform integration of multiparameter oncology data with high fidelity in patients undergoing multimodality treatment for rectal cancer. These pipelines can be adapted to other solid tumors and, together with standardized reporting, can increase efficiency in clinical research and the translation of actionable findings toward optimizing patient outcomes.

Appendiceal cancer is a rare, orphan disease with no therapies currently approved by the FDA for its treatment. Given the limited data regarding drug efficacy, these tumors have historically been treated with chemotherapy designed for colon cancer. However, an overwhelming body of molecular data has demonstrated that appendiceal adenocarcinoma is a distinct entity with key molecular differences from colon cancer, notably rare APC mutation. Recognizing that APC loss-of-function is thought to contribute to taxane resistance and that taxanes are effective in the treatment of other gastrointestinal tumors, including gastric, esophageal, and small bowel adenocarcinoma, we completed a single-center retrospective study to assess efficacy. In a cohort of 13 patients with metastatic appendiceal adenocarcinoma, treated with taxane chemotherapy the median overall survival was 8.8 months. Of 10 evaluable patients, we observed 3 responses, 4 patients with stable disease, and 3 with progression (30% response rate, 70% disease control rate). The results of this study showing activity of taxane-based chemotherapy in appendiceal adenocarcinoma support further clinical investigation of taxane therapy in this orphan disease., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Multiple sclerosis (MS) management varies markedly between different countries of the Middle East and North Africa (MENA) region based on the availability and accessibility of disease-modifying therapies (DMTs)., Objective: To evaluate the accessibility to DMTs in each MENA country, identify barriers to treatment and make recommendations for improved access to DMTs across the region., Methods: This is a descriptive, survey-based study whereby we extracted data collected, between October 2019 and April 2020, for countries in the MENA region by the Multiple Sclerosis International Federation (MSIF) through their Atlas of MS survey., Results: 16 out of 19 countries in the MENA region were included in this study. Sudan and Syria did not have any originator DMTs approved. Interferons were the most widely low-efficacy originator approved DMTs. Three countries did not have any high efficacy DMTs approved. Moreover, follow-on DMTs were approved in half (50%) of the countries. Cost of treatment was the most important barrier, reported in nearly half (47%) of the MENA countries., Conclusion: Although most MENA countries have access to DMTs, more than half of countries report problems with treatment continuation, highlighting the need for a targeted regional strategy to address the variations in access to MS treatments., Competing Interests: Declaration of Competing Interest Maya Zeineddine has received honororia for lectures from Biologix, Biogen, Janssen, Hikma Pharmaceuticals, Novartis, Merck, Roche and Sanofi-Genyme. She received travel grants from Novartis, Merck and Roche and a research grant from Biogen. She has no conflict of interest related to this study. Amal Al-Hajje declares that there is no conflict of interest. Pascale Salameh declares that there is no conflict of interest. Anne Helme and Michael Gunnar Thor declare the following: Multiple Sclerosis International Federation (MSIF) is an alliance of national multiple sclerosis (MS) organizations. MSIF receives income from a wide range of sources, including healthcare and other companies, individuals, member organizations, campaigns, foundations and trusts. Over the last 5 years, MSIF received funding from the following companies: Biogen, BristolMyersSquibb, Coloplast, Janssen, Merck, Mylan, Novartis, Roche and Sanofi – all of which is publicly disclosed. MSIF has not received any funding from industry for its access to medicines work in 2019, 2020, 2021 or 2022. Farid Boumediene declares that there is no conflict of interest. Bassem Yamout has received speaker honoraria from Bayer, Biogen, Merck, Novartis, Roche and Sanofi; research grants from Bayer, Biogen, Merck, Novartis and Pfizer; and advisory board honoraria from Bayer, Biogen, Merck, Novartis, Roche and Sanofi. He has no conflict of interest related to this study., (Copyright © 2023. Published by Elsevier B.V.)

COVID-19 has been associated with a variety of multi-organs complications, with an increasing proportion of patients presenting with neurologic manifestations. There is still an uncertainty in the relationship between stroke and COVID-19. Therefore, in this study, the authors report 18 cases of acute stroke occurring in the setting of COVID-19 infection, including 11 ischaemic strokes and 7 haemorrhagic strokes and identified in a Lebanese tertiary hospital. In this case series, patients with ischaemic and haemorrhagic stroke had elevated markers of inflammation and coagulation. Ischaemic stroke patients were treated with different regimens of anti-platelets, anticoagulants, and thrombolytic therapies. Death was the most common outcome observed and was associated with the severity of COVID-19 infection., Competing Interests: The authors declare that they have no competing interests and the research is not funded by any funding agency., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Concerns regarding potential neurologic complications of COVID-19 are being increasingly reported worldwide. Our objective was to investigate the neurologic complications of COVID-19 among a cohort of Lebanese patients with SARS-CoV-2 infection admitted to Rafik Hariri University Hospital (RHUH), the leading COVID-19 testing and treatment center in Lebanon., Methods: This is a retrospective, single-center, observational study conducted from March to July 2020 at RHUH, Lebanon., Results: Of 169 hospitalized patients with confirmed SARS-CoV-2 infection (mean {SD} age was 45.75 {19} years and 62.7% were men), 91 patients (53.8%) had severe infection and 78 patients (46.2%) had non-severe infection according to the American Thoracic Society guidelines for community-acquired pneumonia. Overall, 112 patients (66.3%) developed neurologic symptoms: CNS (46.1%), PNS (43.7%), and skeletal muscle injury (2.4%). Compared with patients with non-severe infection, patients with severe infection were significantly older, were male and more likely to have underlying disorders, especially diabetes and cardiac or cerebrovascular disease. Moreover, those patients experienced more typical COVID-19 symptoms at onset of illness such as fever, cough and fatigue. However, there was no significant difference in the frequency of all nervous system manifestations between the severe and the non-severe infection groups (57 {62.6%} vs 55 {70.5%}; p =0.316), except for impaired consciousness, where seven patients had impaired consciousness in the severe group compared to none in the non-severe group (p=0.012)., Conclusion: A wide variety of neurologic symptoms were detected in our Lebanese cohort of hospitalized COVID-19 patients. A comprehensive knowledge of the neurologic manifestations will help healthcare providers to be more attentive to these complications., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, El Hajj et al.)

Background: Most Middle East and North Africa (MENA) countries record pancreatic cancer incidence rates that are above the world's average. Reducing this burden requires evidence-based policies. This bibliometric review aims to examine the status of pancreatic cancer research in the MENA world, while systematically categorising publications across cancer care pathways., Methods: We searched Scopus, Medline and PubMed for peer-reviewed publications related to both pancreatic cancer and MENA countries by using controlled vocabulary and keywords. The results were screened for duplicates and later included in the analysis based on preset eligibility criteria. A structured data extraction form was used to collect data related to each article, its methodology, its cancer care pathway, funding status and authorship., Results: A total of 5,848 publications resulted from our search, from which 1,098 articles remained after applying the eligibility criteria. Trends show a steady increase in pancreatic cancer research by MENA. Case reports are the most common, whereas a lack in high-evidence clinical studies as well as public health and epidemiological research was evident. Most studies were not funded and had no female contributions. Funding, if present, came mostly from foreign states. There exists a much greater focus in research on diagnosis and treatment among other cancer care pathways. Most MENA-based studies did not involve collaborations with other countries. Country gross domestic product and population are both correlated to the research output., Conclusion: This bibliometric analysis identified significant gaps and limitations in pancreatic cancer research in MENA countries. Vital domains requiring research investment have also been highlighted as a first step towards evidence-based health policies., Competing Interests: The authors declare no conflicts of interest., (© the authors; licensee ecancermedicalscience.)

Objective: To conduct a scoping review examining the status of prostate cancer research in Arab countries and systematically map publications across the cancer care pathway. Prostate cancer incidence has been rising in the Arab world and tackling its increasing burden will require evidence-based policies., Methods: We searched Medline, PubMed and Scopus for peer-reviewed publications related to both our research topic and countries of interest by using controlled vocabulary and keywords. Search results were limited for the period between 2000 and 2020, screened for duplicates, and then included in our study based on pre-specified eligibility criteria. We used a structured data extraction form to extract information related to the article, its methodology, its cancer care pathway, funding status, and authorship., Results: A total of 4142 publications were retrieved from our search, of which 874 articles remained after applying eligibility criteria. Trends show a steady increase in prostate cancer research in the Arab world. Most studies were focussed on diagnosis and treatment, whereas a lack in studies concerning screening and prevention, as well as epidemiological data, was evident. Most studies were not funded and had no female author. Country gross domestic product and population were positively correlated with its research output. The USA had the highest number of corresponding authors. The majority of Arab-based studies did not involve collaborations with other countries. Most research conducted was basic or clinical studies with a low level of evidence., Conclusion: Our present review identified significant gaps and limitations in prostate cancer research in Arab countries. Priority areas for research investment have also been highlighted as a first step towards context-specific health policies., Abbreviations: ASR: age-standardised rate; COVID-19: coronavirus disease 2019; GDP: gross domestic product; HDI: Human Development Index; KSA: Kingdom of Saudi Arabia; UAE: United Arab Emirates., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Patients with multiple sclerosis (MS) should be vaccinated against COVID-19. All COVID-19 vaccines are effective and do not appear to carry any additional risk for patients with MS. Patients with MS should get a COVID-19 vaccine as soon as it becomes available. The risks of COVID-19 disease outweigh any potential risks from the vaccine. Even if vaccinated, patients with MS should continue to practice standard and recommended precautions against COVID-19, such as wearing a face mask, social distancing and washing hands. There is no evidence that patients with MS are at higher risk of complications from the mRNA, non-replicating viral vector, inactivated virus or protein COVID-19 vaccines, compared to the general population. COVID-19 Vaccines are safe to use in patients with MS treated with disease-modifying therapies (DMTs). The effectiveness of vaccination may be affected by few of the DMTs but yet some protection is still provided. For certain DMTs we may consider coordinating the timing of the vaccine with the timing of the DMT dose to increase vaccine efficacy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The epidemiology of multiple sclerosis (MS) has been studied in many countries of the Middle East but the prevalence and incidence of MS in Lebanon is still unknown., Objectives: To determine the incidence and prevalence of MS in Lebanon., Methods: Lebanese patients diagnosed with MS between January 2018 and December 2018 were identified using the database of governmental third-party payers. The crude, age- and sex-specific 2018 prevalence and incidence among Lebanese patients were calculated., Results: 2248 MS patients were identified of whom 67.1% were women (female: male ratio 2:1) with a mean age of 41.8 ± 12.96 years. The 2018 prevalence of MS was 62.91 cases per 100,000 persons (95% CI: 60.41 - 65.41). The overall incidence of MS in Lebanon was 8.36 cases per 100,000 (95% CI: 7.45 - 9.27) with a mean age at onset of 34.5 ± 12.5 years., Conclusion: This is the first study to assess prevalence and incidence of MS in Lebanon, confirming that Lebanon is a moderate to high-risk area for MS. Those high rates are commensurate with recently published studies from the Middle East, pointing to a significant rise in incidence and prevalence of this disease in our region., (Copyright © 2021. Published by Elsevier B.V.)

Food loss and food waste occur along the food supply chain, negatively impacting the environment, global economy, and food security. There is a growing global interest in tackling this issue to mitigate or handle the waste generated and limit its repercussions, as one in eight people suffer from undernourishment worldwide. In the Arab world, where there is a high dependency on imports and limited potential of increasing local food production, addressing food loss and waste becomes substantial. Research has mainly been focused on household food waste generation, while data on post-consumer plate food waste in the foodservice sector remains scarce. In this study, managers from a representative sample of 222 restaurants located in Municipal Beirut, Lebanon, were surveyed about food waste generation. Plate food waste was measured to establish baseline information. Multiple Tobit regression analyses were performed to explore the determinants for plate food waste generation. Plate waste generation was also compared between Lebanese and non-Lebanese cuisine restaurants. Results revealed that 1,620 tons of plate food waste are generated per year in Beirut, equivalent to 0.15% of Lebanon's total organic waste. Furthermore, Lebanese cuisine restaurants serving Mediterranean Mezze were found to generate 34 kg of organic waste per day more than restaurants that serve international non-Lebanese cuisine. The type of cuisine, kind of service, and menu planning were significantly associated with post-consumer food waste generation. This study revealed an increasing concern towards the amount of plate waste generated in Beirut, and thereby further research is needed to create baseline information at the national level., Competing Interests: The authors have declared that no competing interests exist.

Background: Fingolimod is associated with different infections including lower respiratory tract, herpes virus, cryptococcal meningitis, histoplasmosis, progressive multifocal leukoencephalopathy, atypical mycobacterial infections, kaposi sarcoma and reactivation of hepatitis c., Objectives: To describe five cases of skin warts in MS patients treated with fingolimod at the American University of Beirut Medical Center (AUBMC) MS center (MSC)., Methods: We reviewed all MS patients treated with fingolimod at our MSC and identified patients who developed skin warts during treatment. We also reviewed a control group of patients treated with different interferons matched for age and sex., Results: Of 220 patients treated with fingolimod at our MSC, 5 (2.2%) developed skin warts. In 220 patients treated with different interferons and matched for age and sex, no cases of skin warts could be detected., Conclusions: In conclusion, we report five patients who developed skin warts during fingolimod therapy, especially HPV-related, for an overall incidence of 2.2%. Larger cohorts are needed to confirm this proposed higher susceptibility of fingolimod-treated patients to HPV infections., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Relapse rate in women with Multiple Sclerosis (MS) is reduced during pregnancy especially in the third trimester according to the previous studies., Objectives: To measure the annual relapse rate (ARR) in women with MS during pregnancy., Methods: A retrospective study was conducted using prospectively collected data from two MS registries in Kuwait and Lebanon. Demographics, clinical characteristics including relapses, disease modifying therapies (DMTs) and their washout periods were extracted. The annual relapse rates pre and post pregnancies were compared and the relationship between relapses and prior use of different DMTs was assessed., Results: Data of 164 pregnancies (132 MS patients) was reviewed. Mean age and disease duration at the time of pregnancy confirmation were 32.4 ± 5.3 and 7.8 ± 4.7 years respectively. Most patients (91.7%; n = 121) were on DMTs in the year prior to pregnancy. The pre-pregnancy ARR was 0.10 (95% CI: 0.04 - 0.13), which increased to 0.20 (95% CI: 0.13- 0.29) during pregnancy. Most relapses occurred either during the 1 st (ARR = 0.24; 95% CI: 0.12 - 0.44) or 3 rd (ARR = 0.32; 95%CI: 0.17 - 0.53) trimesters. Fingolimod (31.8%) and natalizumab (22.7%) were the most commonly prescribed DMTs in patients who sustained relapses during pregnancy. The mean washout period was significantly longer among subjects with relapses (9.3 ± 6.6 vs. 2.5 ± 3.9; p < 0.001) than those of without relapses., Conclusions: Relapse rate during pregnancy was higher than previous studies conducted in patients on platform therapies or untreated. Longer washout period prior to conception was associated with increased relapses especially in fingolimod and natalizumab treated patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Fingolimod is a daily oral medication used to treat relapsing multiple sclerosis (MS). Clinicians often adopt less frequent dosing for patients with profound drug-induced lymphopenia or other adverse events. Data on the effectiveness of alternate dose fingolimod are limited., Methods: We conducted a multicenter, retrospective, observational study at 14 sites and identified 170 patients with MS taking alternate doses of fingolimod for ≥1 month. Clinical and radiologic outcomes were collected and compared during daily and alternate fingolimod dosing., Results: Profound lymphopenia (77%), liver function abnormalities (9%), and infections (7%) were the most common reasons for patients to switch to alternate fingolimod dosing. The median follow-up was 12 months on daily dose and 14 months on alternate dose. Most patients (64%) took fingolimod every other day during alternate dosing. Disease activity was similar on alternate dose compared to daily dose: annualized relapse rate was 0.1 on daily dose vs 0.2 on alternate dose ( p = 0.25); proportion of patients with contrast-enhancing MRI lesions was 7.6% on daily vs 9.4% on alternate ( p = 0.55); proportion of patients with cumulative MS activity (clinical and radiologic disease) was 13.5% on daily vs 18.2% on alternate ( p = 0.337). Patients who developed contrast-enhancing lesions while on daily dose were at higher risk for breakthrough disease while on alternate dose fingolimod (odds ratio 11.4, p < 0.001)., Conclusions: These data support the clinical strategy of alternate dosing of fingolimod in patients with good disease control but profound lymphopenia or other adverse events while on daily dose., Classification of Evidence: This study provides Class IV evidence that for patients with MS on daily dose fingolimod with adverse events, alternate dose fingolimod is associated with disease activity similar to daily dose fingolimod.

Aim: Playing music during painful procedures has shown inconsistent benefits for preterm infants. This study observed preterm infants during a heel stick procedure to assess whether listening to the music their mothers listened to during pregnancy had any impact on their pain and physiological and behavioural parameters., Methods: We randomly exposed 42 preterm infants, with a mean gestational age of 31.8 ± 2.79 weeks, to the music their mothers listened to during pregnancy, recorded lullabies and no music, before, during and after a heel stick. Pain responses were measured using the Neonatal Pain, Agitation and Sedation Scale (N-PASS), and physiological and behavioural responses were recorded by a nurse blinded to the intervention., Results: N-PASS pain scores were lowest during mothers' music, with a mean of 1.40 (±1.28), compared to 2.33 (±1.64) for no music and 1.62 (±2.27) for the lullabies [F(3/121) = 4.86, p = 0.009]. Physiological parameters were not significantly different between the conditions. During the mothers' music, infants spent more time in a quiet alert state, with a significant decrease in their respiratory rates., Conclusion: The music mothers listened to during pregnancy was more beneficial for preterm infants, as it decreased pain and improved behavioural states during a heel stick., (©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objectives: To estimate JCV seroprevalence and risk of seroconversion against JCV among MS patients in the Middle East., Methods: This multicenter study was conducted by implementing a cross-sectional design to assess JCV seroprevalence, and a longitudinal design to assess the risk of JCV seroconversion. Multivariable logistic and Poisson regression analyses were used to assess the relationship between clinical variables and JCV seropositivity and risk of seroconversion., Results: Of 581 MS patients, 64.9% patients were females. Mean age and mean disease duration were 33.9 and 8.4years respectively. JCV seroprevalence was 48.7%. Male gender (p=0.002), age at onset (p=0.001) and disease duration of 20 or more years (p=0.007) were significantly associated with JCV seropositivity. Among patients (n=125), followed longitudinally, the risk of JCV seroconversion was 17.6% (95% CI: 11.4%-25.4%) during a median follow-up of 18months. The proportion of seroreverted and pseudoconverted patients was 4% and 3.2% respectively., Conclusions: JCV seroprevalence among MS patients in the Middle East was lower than international figures. Male gender, age at onset and disease duration were significantly associated with JCV seropositivity. Risk of JCV seroconversion was higher than previously reported figures. Observed JCV sero-reversion or pseudo-conversion entail watchful period before embarking on a clinical decision., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Long-term studies have been the backbone of population ecology. The red grouse Lagopus lagopus scoticus is one species that has contributed widely to this field since the 1950s. This paper reviews the trajectory and profound impact that these studies have had. Red grouse research has combined long-term studies of marked individuals with demographic studies over wide geographical areas and replicated individual- and population-level manipulations. A main focus has been on understanding the causes of population cycles in red grouse, and in particular the relative importance of intrinsic (behaviour) and extrinsic (climate, food limitation and parasite) mechanisms. Separate studies conducted in different regions initially proposed either the nematode parasite Trichostrongylus tenuis or changes in male aggressiveness in autumn as drivers of population cycles. More recent experiments suggest that parasites are not a necessary cause for cycles and have highlighted that behavioural and parasite-mediated mechanisms are interrelated. Long-term experiments show that parasites and aggressiveness interact. Two outstanding questions remain to be tested experimentally. First, what intrinsic mechanism causes temporal variation in patterns of male aggressiveness? The current favoured mechanism is related to patterns of kin structuring although there are alternative hypotheses. Second, how do the dual, interacting mechanisms, affect population dynamics? Red grouse studies have had an important impact on the field of population ecology, in particular through highlighting: (1) the impact of parasites on populations; (2) the role of intrinsic mechanisms in cyclic dynamics and (3) the need to consider multiple, interacting mechanisms., (© 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.)

Aim: To evaluate the current practice of stress ulcer prophylaxis (SUP) in Lebanese Health care centers., Methods: A multi-center prospective chart review study was conducted over 8 mo. A questionnaire was distributed to pharmacy students who collected data on demographics, SUP medications, dose, route, duration and associated risk factors. The appropriateness of SUP use was determined as per American Society of Health-System Pharmacists guidelines. Institutional review board approval was obtained from each hospital center., Results: A total of 1004 patients were included. 67% of the patients who received prophylaxis did not have an indication for SUP. The majority (71.6%) of the patients who were administered parenteral drugs can tolerate oral medications. Overall, the regimen of acid-suppressant drugs was suboptimal in 87.6% of the sample. This misuse was mainly observed in non-teaching hospitals., Conclusion: This study highlighted the need, in Lebanese hospitals, to establish clinical practice guidelines for the use of SUP; mainly in non-critical care settings.

Shrimp-shaped periodic regions embedded in chaotic regions in two-dimensional parameter spaces are of specific interest for physical and biological systems. We provide the first observation of these shrimp-shaped stability regions in a parameter space of a continuous time-delayed population model, obtained by taking the delays as bifurcation parameters. The parameter space organization is governed by the presence of infinitely many periodicity hubs, which trigger the spiraling organization of these shrimp-shaped periodic regions around them. We provide evidence that this spiraling organization in the parameter space is a consequence of the existence of homoclinic orbits in the phase space., (© 2010 American Institute of Physics.)

The existence of semelparity or "big bang" reproduction (reproducing only once in a lifetime) and iteroparity (reproducing more than once in a lifetime) has led to many questions investigating the evolution or persistence of these strategies. Here we investigate semelparity and iteroparity for their evolutionary importance. A mathematical model is used to illustrate how a population's ability to evolve depends on this life-history trait, and how this rate of evolution impacts the individual. We find that the ability of a trait to evolve is greater toward a semelparous strategy and this expresses a fitness advantage. This leads to an optimality between survival, population tracking ability, and lifetime fecundity.

The characteristics governing the dynamics of populations can evolve and this evolution can either be towards stability or chaos. Yet it is not obvious how or why such population characteristics can evolve through selection on individuals. In this paper we construct a mathematical model, inspired by experimental results, illustrating the dynamics of a population of competing Drosophila. We demonstrate how selection of life history characteristics and stability influence one another as a population interacts with its environment. We generalize this result and show that population stability can evolve as a consequence of selection on individuals.