The prevalence of metabolic syndrome parameters and their association with headache characteristics among migraineurs

Background: Migraine is associated with metabolic syndrome (MetS). There are evidences that components of MetS are more prevalent among migraine patients than non migraineurs. Since both migraine and MetS are associated with a high risk of cardiovascular events, it is likely that the parameters of MetS increase the occurrence of cardiovascular disease (CVD) in migraineurs. The present research project was conducted for the purpose of investigating the relationship between MetS parameters and different items of migraine headaches. Methods: This descriptive-analytical, cross-sectional study was performed on 240 migraineurs [according to International Headache Society (HIS) II criteria] within the 17+ age range. The participants were selected via consecutive and convenience sampling method. The evaluated parameters for each subject included 2 arms: migraine characteristics (intensity, frequency of attacks, subtype, duration, and treatment regimen) and indices of MetS according to the National Cholesterol Education Program’s Adult Treatment Panel III (NCEP ATP-III) report criteria [high-density lipoprotein-cholesterol (‎HDL-C), triglyceride (TG), fasting plasma glucose (FPG), height, waist circumference (WC), systolic and diastolic blood pressure (BP), and body mass index (BMI)]. All data were analyzed in SPSS software. Results: Total prevalence of MetS was 16.25% (39 patients). There was a statistically meaningful relationship between hypertriglyceridemia and gender (P = 0.021), hypertriglyceridemia and prophylactic antimigraine regimen (P = 0.022), hyperglycemia and age group (P = 0.010), hyperglycemia and the intensity of headache (P = 0.048), hyperglycemia and prophylactic treatment (P = 0.001), systolic hypertension and migraine subtype (P = 0.004), systolic hypertension and the duration of migraine disease (P = 0.005), diastolic hypertension and migraine subtype (P = 0.002), WC and gender (P = 0.001), WC and the intensity of headache (P = 0.028), WC and prophylactic medication (P = 0.017), HDL and gender (P = 0.001), HDL and the prophylactic regimen (P = 0.023), and MetS and gender (P = 0.005). The prevalence of MetS was increased with increase in the severity of migraine headache. Conclusion: Due to the relative increase in the prevalence of MetS in patients with more severe migraine, an evaluation of the mechanisms of MetS is recommended in this population.

Forest malaria and prospects for anti-malarial chemoprophylaxis among forest goers: findings from a qualitative study in Lao PDR

Background Despite significant decline in malarial incidence and mortality in countries across the Greater Mekong Subregion, the disease remains a public health challenge in the region; transmission continues mainly among people who visit forests in remote areas, often along international borders, where access to primary healthcare is limited. In the absence of effective vector-control measures and limited exposure periods, malaria chemoprophylaxis has been proposed as a strategy to protect forest goers. As a rarely used approach for indigenous populations, questions remain about its feasibility and acceptability. Drawing on in-depth interviews with forest goers and stakeholders, this article examines opportunities and challenges for implementation of anti-malarial chemoprophylaxis for forest goers in Lao PDR. Methods In-depth interviews were conducted with 16 forest goers and 15 stakeholders in Savannakhet province, Lao PDR. Interview topics included experience of malaria prevention and health services, and perceptions of prophylaxis as a potential component of malaria elimination strategy. The interviews were transcribed and coded using inductive and deductive approaches for qualitative thematic analysis. Results In ethnically and geographically diverse villages, awareness of malaria risk prompts forest goers to protect themselves, albeit sub-optimally using available preventive measures. Stakeholders highlighted challenges for targeting at-risk populations and approaches to address forest malaria in southern Lao PDR. Among policymakers, choice and cost of anti-malarials, particularly their efficacy and source of funding, were key considerations for the feasibility of malaria prophylaxis. Acceptability of prophylaxis among forest goers was also influenced by the complexity of the regimen, including the number of tablets and timing of doses. Implementation of prophylaxis may be affected by a lack of transportation and communication barriers in remote communities. Conclusion Adding prophylaxis to existing malaria control activities requires strengthening the capacity of local health workers in Lao PDR. Ideally, this would be part of an integrated approach that includes strategies to address the other febrile illnesses that forest goers describe as priority health concerns. The prophylactic regimen also requires careful consideration in terms of effectiveness and simplicity of dosing.

Numerical approaches for the rapid analysis of prophylactic efficacy against HIV with arbitrary drug-dosing schemes

Pre-exposure prophylaxis (PrEP) is an important pillar to prevent HIV transmission. Because of experimental and clinical shortcomings, mathematical models that integrate pharmacological, viral- and host factors are frequently used to quantify clinical efficacy of PrEP. Stochastic simulations of these models provides sample statistics from which the clinical efficacy is approximated. However, many stochastic simulations are needed to reduce the associated sampling error. To remedy the shortcomings of stochastic simulation, we developed a numerical method that allows predicting the efficacy of arbitrary prophylactic regimen directly from a viral dynamics model, without sampling. We apply the method to various hypothetical dolutegravir (DTG) prophylaxis scenarios. The approach is verified against state-of-the-art stochastic simulation. While the method is more accurate than stochastic simulation, it is superior in terms of computational performance. For example, a continuous 6-month prophylactic profile is computed within a few seconds on a laptop computer. The method’s computational performance, therefore, substantially expands the horizon of feasible analysis in the context of PrEP, and possibly other applications.

Forest Malaria and Prospects for Antimalarial Chemoprophylaxis Among Forest Goers: Findings From a Qualitative Study in Lao PDR

Background Despite significant decline in malarial incidence and mortality in countries across the Greater Mekong Subregion, the disease remains a public health challenge. Transmission continues mainly among people who visit forests in remote areas, often along international borders, where access to primary healthcare is limited. In the absence of effective vector-control measures and limited periods of exposure, malaria chemoprophylaxis has been proposed as a strategy to protect forest goers. As a rarely used approach for indigenous populations, questions remain about its feasibility and acceptability. Drawing on in-depth interviews with forest goers and stakeholders, this article examines opportunities and challenges for implementation of antimalarial chemoprophylaxis for forest goers in Lao PDR.Methods In-depth interviews were conducted with 16 forest goers and 15 stakeholders in Savannakhet province, Lao PDR. Interview topics included experience of malaria prevention and health services, and perceptions of prophylaxis as a potential component of malaria elimination strategy. The interviews were transcribed and coded using inductive and deductive approaches for qualitative thematic analysis.Results In ethnically and geographically diverse villages, awareness of malaria risk prompts forest goers to protect themselves, albeit suboptimality using available preventive measures. Stakeholders highlighted challenges for targeting at-risk populations and approaches to address forest malaria in southern Laos. Among policymakers, choice and cost of antimalarials, particularly their efficacy and source of funding, were key considerations for the feasibility of malaria prophylaxis. Acceptability of prophylaxis among forest goers was also influenced by the complexity of the regimen, including the number of tablets and timing of doses. Implementation of prophylaxis may be affected by a lack of transportation and communication barriers in remote communities. Conclusion Adding prophylaxis to existing malaria control activities requires strengthening the capacity of local health workers in Lao PDR. Ideally, this would be part of an integrated approach that includes strategies to address the other febrile illnesses that forest goers describe as priority health concerns. The prophylactic regimen also requires careful consideration in terms of effectiveness and simplicity of dosing.

Belgian Consensus Recommendations to Prevent Vitamin K Deficiency Bleeding in the Term and Preterm Infant

Neonatal vitamin K prophylaxis is essential to prevent vitamin K deficiency bleeding (VKDB) with a clear benefit compared to placebo. Various routes (intramuscular (IM), oral, intravenous (IV)) and dosing regimens were explored. A literature review was conducted to compare vitamin K regimens on VKDB incidence. Simultaneously, information on practices was collected from Belgian pediatric and neonatal departments. Based on the review and these practices, a consensus was developed and voted on by all co-authors and heads of pediatric departments. Today, practices vary. In line with literature, the advised prophylactic regimen is 1 or 2 mg IM vitamin K once at birth. In the case of parental refusal, healthcare providers should inform parents of the slightly inferior alternative (2 mg oral vitamin K at birth, followed by 1 or 2 mg oral weekly for 3 months when breastfed). We recommend 1 mg IM in preterm <32 weeks, and the same alternative in the case of parental refusal. When IM is perceived impossible in preterm <32 weeks, 0.5 mg IV once is recommended, with a single additional IM 1 mg dose when IV lipids are discontinued. This recommendation is a step towards harmonizing vitamin K prophylaxis in all newborns.

Prevention of Fetal/Neonatal Alloimmune Thrombocytopenia in a Preclinical Model By Monoclonal Anti-HPA-1a Antibody Prophylaxis: Structural and Functional Properties of Antibody Variant Isoforms

Maternal alloantibodies to paternally inherited platelet antigens can cause fetal/neonatal alloimmune thrombocytopenia (FNAIT), rendering the fetus or newborn prone to bleeding and intracranial hemorrhage (ICH) with risk of lifelong disabilities or death. In Caucasians, the vast majority of cases are due to antibodies to the Human Platelet Antigen (HPA)-1a epitope on glycoprotein (GP)IIIa. To date, there are neither any means to prevent or reduce the risk of alloimmunization and subsequent FNAIT, nor safe and efficient treatment during affected pregnancies. Thus, a prophylactic regimen by administration of monoclonal antibodies to women at risk would be highly beneficial. Knowledge about the optimal functional design of prophylactic monoclonal antibodies for antenatal or post-natal use is however still limited. We have previously isolated and characterized a fully human anti-HPA-1a monoclonal antibody, mAb26.4. In the current study we have explored the prophylactic potential of this antibody by testing a panel of different IgG1 designs, including the wild-type mAb26.4, variants with modified Fc-region N-glycans, as well as an effector silent variant. We performed analyses of properties relevant for immunosuppression: in vitro Fc-receptor binding and capacity to induce phagocytosis, in vivo half-life measurements in humanized FcRn mice and platelet clearance in a recently developed transgenic mouse strain with a recreated HPA-1a epitope on murine GPIIIa. The prophylactic capacity by antibody-mediated immune suppression in vivo, were further tested in the FNAIT pre-clinical murine model, in which BALB/c females can be immunized by transfusion of HPA-1a-expressing platelets from the transgenic mice and where subsequent breeding of pre-immunized mice with transgenic males cause thrombocytopenia in off-springs mimicking FNAIT. By intravenous administrations of mAb26.4 variants prior to platelet transfusions, the mice generated no or low anti-platelet responses compared to control mice, and normal platelet counts in pups upon subsequent breeding. Our data thus successfully demonstrates efficient immunosuppression and prevention of FNAIT by anti-HPA-1a human monoclonal variants, providing further support for potential use in humans. Disclosures Skogen: Prophylix Pharma AS: Current holder of individual stocks in a privately-held company. Newman: Rallybio: Consultancy, Research Funding.

PHYTOREMEDIAL POTENTIAL OF HYDROALCOHOL EXTRACT OF SEEDS OF SORGHUM BICOLOR AGAINST DRUG-INDUCED NEPHROTOXICITY

The gravity of the impact of drug induced nephrotoxicity is more prominent in society. The present study was undertaken to evaluate the potential of hydroalcoholic extract of seeds of Sorghum bicolor against cisplatin and doxorubicin- induced nephrotoxicity in Wistar albino rats. The nephrotoxicity was modeled by intraperitoneal injection of cisplatin (5 mg/kg b.w.) in cisplatin model and doxorubicin (15 mg/kg b.w.) in doxorubicin-induced model in rats. Nephroprotection of hydroalcoholic extract of seeds of S. bicolor was evaluated at two different doses of 200 and 400mg/kg b.w. The nephroprotective activity was assessed by the determination of various serum and urinary parameters, anti-oxidant studies, histological and immunohistochemical studies. The results indicated that injection of cisplatin and doxorubicin led to marked nephrotoxicity in animals. Treatment with extract in cisplatin-induced model resulted in significant nephroprotective activity in a curative regimen whereas in prophylactic regimen the extract prevented the induction of nephrotoxicity only up to a considerable level. But the extract failed to attenuate the doxorubicin induced nephrotoxicity, as evident by biochemical, histological and immunohistochemical studies. From the findings, it is concluded that the seeds of S. bicolor can be used as a novel approach in the treatment of cisplatin-induced nephrotoxicity.

Numerical approaches for the rapid analysis of prophylactic efficacy against HIV with arbitrary drug-dosing schemes

Pre-exposure prophylaxis (PrEP) is an important pillar to prevent HIV transmission. Because of experimental and clinical shortcomings, mathematical models that integrate pharmacological, viral- and host factors are frequently used to quantify clinical efficacy of PrEP. Stochastic simulations of these models provides sample statistics from which the clinical efficacy is approximated. However, many stochastic simulations are needed to reduce the associated sampling error. To remedy the shortcomings of stochastic simulation, we developed three numerical methods that allow predicting the efficacy of arbitrary prophylactic regimen directly from a viral dynamics model, without sampling. We apply the methods to various hypothetical dolutegravir (DTG) prophylaxis scenarios. The approaches are verified against one another, as well as state-of-the-art stochastic simulation. While the methods are more accurate than stochastic simulation, they are superior in terms of computational performance. For example, a continuous 6-month prophylactic profile is computed within a few seconds on a laptop computer. The methods' computational performance, therefore, substantially expands the horizon of feasible analysis in the context of PrEP, and possibly other applications.

Transplant-associated thrombotic microangiopathy in pediatric patients: pre-HSCT risk stratification and prophylaxis

Transplant-associated thrombotic microangiopathy (TA-TMA) is an endothelial injury syndrome that complicates hematopoietic stem cell transplant (HSCT). Morbidity and mortality from TA-TMA remain high, making prevention critical. We describe our retrospective single-center experience of TA-TMA after pediatric allogeneic HSCT and present a novel pre-HSCT risk-stratification system and prophylaxis regimen. From January 2012 through October 2019, 257 patients underwent 292 allogeneic HSCTs. Prospective risk stratification was introduced in December 2016. High-risk (HR) patients were treated with combination prophylaxis with eicosapentaenoic acid and N-acetylcysteine. The 1-year cumulative incidence of TA-TMA was 6.3% (95% confidence interval [CI], 3.2-9.4). Age ≥10 years, myeloablative conditioning with total body irradiation, HLA mismatch, diagnosis of severe aplastic anemia or malignancy, prior calcineurin inhibitor exposure, and recipient cytomegalovirus seropositivity were found to be pre-HSCT risk factors for development of TA-TMA. Before routine prophylaxis, TA-TMA rates were significantly different between the HR and standard-risk groups, at 28.2% (95% CI, 0-12.7) vs 3.2% (0.1-6.3), respectively (P &lt; .001). After introduction of prophylaxis, the 1-year cumulative incidence of TA-TMA in the HR group decreased to 4.5% (95% CI, 0-13.1; P = .062, compared with the incidence before prophylaxis). Multicenter pediatric studies are needed to validate these risk criteria and to confirm the efficacy of the prophylactic regimen.

Does atorvastatin have augmentative effects with sodium valproate in prevention of migraine with aura attacks? A triple-blind controlled clinical trial

Background Migraine is a painful and disabling nervous disorder which negatively affects the quality of life. Migraineurs may suffer from a generalized vasomotor dysfunction. Statins improve vasomotor and vascular function, with their pleiotropic effects. We aimed to assess efficacy and safety of adding Atorvastatin to prophylactic regimen in better control of migraine with aura. Methods This triple-blind controlled clinical trial was on 68 patients with migraine with aura. An interval of at least 1 month was given to evaluate vitamin D3 level and eligibility. In patients with vitamin D3 deficiency, the correction with vitamin D supplementation was provided. The patients were randomly assigned to receive atorvastatin 20 mg plus sodium valproate 500 mg or placebo plus sodium valproate 500 mg once a day for 2 months. The patients were evaluated based for the number of attacks and pain severity based on Visual Analogue Scale. Results There was a significant (p = 0.0001) improvement in severity of pain and number of migraine attacks by adding Atorvastin to the prophylactic regimen of patients with migraine with aura. After controlling for variable parameters, the differences between two arms of the study was yet statistically significant (p = 0.0001). A significant number of participants in intervention group were satisfied by their treatment (p = 0.001) with no remarkable side effects (P = 0.315). Conclusions Adding atorvastatin to migraine with aura preventive regimen may help reduce the number of acute attacks and pain severity without causing considerable side effects and led to a better patient satisfaction. Trial registration IRCT20180106038242N1. Registered: 7 February 2018.