Explore the vast range of titles available.

Study Objectives: To compare the efficacy of adjustable and fixed oral appliances for the treatment of OSA. Methods: Retrospective review of consecutive patients with OSA treated with either adjustable or fixed oral appliances. Polysomnography was conducted before and during therapy. Effective treatment was defined as an apnea-hypopnea index (AHI) < 5 events/h or < 10 events/h with resolution of sleepiness (Epworth < 10). We compared efficacy rates between fixed and adjustable appliances and sought to identify factors associated with greater success. Results: We included 805 patients, 602 (74.8%) treated with an adjustable and 203 (25.2%) a fixed oral appliances. Among the cohort, 86.4% were men; mean age was 41.3 ± 9.2 years. Mean AHI was 30.7 ± 25.6, with 34.1% having mild (AHI 5–14.9), 29.2% moderate (AHI 15–29.9), and 36.8% severe (AHI ≥ 30) OSA. Successful therapy was significantly more common with adjustable appliances. Obstructive events were reduced to < 5/h in 56.8% with adjustable compared to 47.0% with fixed appliances (p = 0.02). Similarly, a reduction of events to < 10 with resolution of sleepiness occurred in 66.4% with adjustable appliances versus 44.9% with fixed appliances (p < 0.001). For both devices, success was more common in younger patients, with lower BMI and less severe disease. Conclusions: Adjustable devices produced greater reductions in obstructive events and were more likely to provide successful therapy, especially in moderate-severe OSA. Fixed appliances were effective in mild disease, but were less successful in those with higher AHIs. Given these findings, the baseline AHI should be considered when selecting the type of oral appliance. Citation: Lettieri CJ; Paolino N; Eliasson AH; Shah AA; Holley AB. Comparison of adjustable and fixed oral appliances for the treatment of obstructive sleep apnea. J Clin Sleep Med 2011;7(5):439–445.

Chronic pain occurs with greater frequency in women, with a parallel sexually dimorphic trend reported in sufferers of many autoimmune diseases. There is a need to continue examining neuro-immune-endocrine crosstalk in the context of sexual dimorphisms in chronic pain. Several phenomena in particular need to be further explored. In patients, autoantibodies to neural antigens have been associated with sensory pathway hyper-excitability, and the role of self-antigens released by damaged nerves remains to be defined. In addition, specific immune cells release pro-nociceptive cytokines that directly influence neural firing, while T lymphocytes activated by specific antigens secrete factors that either support nerve repair or exacerbate the damage. Modulating specific immune cell populations could therefore be a means to promote nerve recovery, with sex-specific outcomes. Understanding biological sex differences that maintain, or fail to maintain, neuroimmune homeostasis may inform the selection of sex-specific treatment regimens, improving chronic pain management by rebalancing neuroimmune feedback. Given the significance of interactions between nerves and immune cells in the generation and maintenance of neuropathic pain, this review focuses on sex differences and possible links with persistent autoimmune activity using sciatica as an example.

Background From October 2019–March 2020, several clusters of mumps cases were identified in the Netherlands. Our objective was to describe cluster-associated mumps virus transmission using epidemiological and molecular information in order to help future mumps outbreak investigation and control efforts. Methods An epidemiological cluster includes ≥ 2 mumps cases with at least an epidemiological-link to a laboratory-confirmed mumps case. A molecular group includes ≥ 2 mumps cases with identical mumps virus sequences. Cases with symptom onset date between 1 October 2019 and 31 March 2020 reported through the National Notifiable Diseases Surveillance System were included. We described epidemiological and clinical characteristics of mumps cases. Sequence data was obtained from selected regions of mumps virus genomes (2270 nucleotides). Associations between epidemiological and molecular information were investigated. Results In total, 102 mumps cases were notified (90% laboratory-confirmed, 10% epidemiologically-linked). 71 out of 102 cases were identified as part of an epidemiological cluster and/or molecular group. Twenty-one (30%) of 71 cases were identified solely from epidemiological information, 25 (35%) solely from molecular surveillance, and 25 (35%) using both. Fourteen epidemiological clusters were identified containing a total of 46 (range: 2–12, median: 3) cases. Complete sequence data was obtained from 50 mumps genotype G viruses. Twelve molecular groups were identified containing 43 (range: 2–13) cases, dispersed geographically and timewise. Combined information grouped seven epidemiological clusters into two distinct molecular groups. The first lasting for 14 weeks, the other for 6. Additionally, one molecular group was detected, linked by geography and time but without an epidemiological-link. Conclusions Combined epidemiological and molecular information indicated ongoing mumps virus transmission from multiple introductions for extended time periods. Sequence analysis provided valuable insights into epidemiological clustering. If combined information is available in a timely manner, this would improve outbreak detection, generate further insight into mumps transmission, and guide necessary control measures.

Damoctocog alfa pegol (BAY 94-9027, Jivi ), is a site-specifically PEGylated, extended half-life recombinant factor VIII (FVIII) that is approved in several European and non-European countries for on-demand treatment and prophylaxis of bleeding in previously treated patients aged ≥ 12 years with hemophilia A. Reliable measurements can be obtained using most one-stage and chromogenic FVIII assays over a wide concentration range. The efficacy, safety and pharmacokinetics (PK) of damoctocog alfa pegol have been studied extensively in the PROTECT VIII clinical trials, and its long-term safety and effectiveness profile is continuing to build through observational and interventional real-world studies. The PK of damoctocog alfa pegol was shown to be improved as compared with that of sucrose-formulated rFVIII (rFVIII-FS, Kogenate ), and was also demonstrated to be non-inferior to and, for some variables, more favorable than rFVIII-Fc fusion protein, efmoroctocog alfa (Elocta ; NCT03364998), rurioctocog alfa pegol (BAX 855, Adynovate /Adynovi ; NCT04015492), and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM, Advate ; NCT02483208). Damoctocog alfa pegol was generally well tolerated and none of the patients in any of the clinical trials, including the PROTECT VIII clinical program, HEM-POWR, or ongoing single-center studies, developed FVIII inhibitors. Efficacy for perioperative hemostasis has been demonstrated. Low bleeding rates were achieved across the studies, with twice weekly, every 5-day and every 7-day prophylaxis offering patients ≥ 12 years and their clinicians the chance to tailor treatment to individual needs and lifestyles, while maintaining long-term protection from bleeds and their consequences.

A high proportion of active trachoma infection in children of Car-Nicobar Island was reported through the Trachoma Rapid Assessment survey conducted in year 2010 by the same researchers. Annual mass drug treatment with azithromycin was administered from years 2010-12 to all individuals residing in this island for reducing the burden of active trachoma infection. A cross-sectional prevalence survey was conducted in the year 2013 to assess the post-treatment burden of trachoma in this population. In the 15 randomly selected compact segments from each village of the island, children aged 1-9 years were examined for evidence of active trachoma infection and participants aged ten years and above were examined for trachomatous trichiasis and corneal opacity. A total of 809 children (1-9 years) and 2735 adults were examined. Coverage with azithromycin for all the three rounds was more than 80%. The prevalence of active trachoma infection in children aged 1-9 years old was 6.8% (95% CI 5.1, 8.5) and Trachomatous Trichiasis (TT) was 3.9% (95% CI 3.2, 4.6). The risk factors associated with active trachoma infection were older age and unclean faces. The risk factors associated with TT were older age and lower literacy level. Trachoma has not been eliminated from Car-Nicobar Island in accordance to 'Global Elimination of Trachoma, 2020' guidelines. Sustained efforts and continuous surveillance admixed with adequate programmatic response is imperative for elimination of trachoma in the island.

Granuloma Multiforme (GM) is a reactive skin disorder with annular lesion and focal necrobiosis. It was first described in Nigeria (Africa), since than it was mostly described from various regions of Africa where leprosy was endemic. Outside Africa, this disease is rarely reported. Till 2016 only five cases were reported from India. This is the second case report from Nepal. A fifty-nine-year-old female, farmer by occupation, presented with annular and polycyclic plaques with elevated beaded border for one year. It was distributed over upper trunk, lower back, and arms, and was mildly pruritic. Histopathologically, loss of elastic fibres at focal area of upper dermis, with elastic fibres engulfed histiocytes were noted. GM was mostly noted from leprosy endemic areas of Africa. Clinically, it is very difficult to distinguish from granuloma annulare. This report adds the number of GM occurrence in Asia especially from area where leprosy is still prevalent. This report also emphasizes in resource poor settings where most diagnosis is made clinically, the granuloma annulare should be looked for very carefully in order not to miss GM.

BAY 81-8973 (Kovaltry) is an unmodified full-length recombinant factor VIII (rFVIII) for treatment of hemophilia A. The BAY 81-8973 manufacturing process results in a product of enhanced purity with a consistently high degree of branching and sialylation of N-linked glycans. This study evaluated whether a relationship exists between N-linked glycosylation patterns of BAY 81-8973 and two other rFVIII (sucrose-formulated rFVIII [rFVIII-FS; Kogenate FS]) and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM; Advate) and their pharmacokinetic (PK) characteristics. N-linked glycans or terminal carbohydrates were enzymatically removed from immobilized BAY 81-8973, rFVIII-FS, and rAHF-PFM proteins and analyzed using high-performance liquid chromatography to determine the percentage of individual N-linked glycan structures and degree of sialylation of each structure. PK data were available from two separate phase 1 crossover studies in which the PK profile of BAY 81-8973 was compared with that of rFVIII-FS (n=26) and rAHF-PFM (n=18) in patients with severe hemophilia A who received a single 50 IU/kg dose of each product. BAY 81-8973 and rFVIII-FS had increased N-linked glycan branching with higher levels of sialylation compared with rAHF-PFM. Levels of trisialylated glycans were 29.0% for BAY 81-8973 vs 11.5% for rFVIII-FS and 4.8%-5.5% for rAHF-PFM; tetrasialylated glycans were 12.0% vs 2.8% and 0.6%, respectively. Degree of sialylation was 96% for BAY 81-8973, 94% for rFVIII-FS, and 78%-81% for rAHF-PFM. Based on chromogenic assay results from the single-dose phase 1 PK studies, BAY 81-8973 half-life was 15% longer than that for rFVIII-FS and 16% longer than rAHF-PFM. Increased N-glycan branching and sialylation were seen for BAY 81-8973 vs rFVIII-FS and rAHF-PFM. Improved PK for BAY 81-8973 relative to rFVIII-FS and rAHF-PFM as seen in single-dose crossover PK studies might be related to this greater level of branching and sialylation, which can prolong the time BAY 81-8973 remains in the circulation.

BackgroundVitamin B12 deficiency is common in populations with limited animal-source foods and has been linked to delayed infant neurodevelopment and adverse pregnancy outcomes. Evidence on the benefits of maternal B12 supplementation for improving infant neurodevelopment remains mixed, particularly in low-income and middle-income countries where deficiency is prevalent.MethodsThis double-blind, randomised controlled trial was conducted in two tertiary maternity care centres in India and Nepal. Pregnant women in their first trimester, following a vegetarian diet, were enrolled and randomised to receive either a daily oral supplement of 250 µg (group A) or 50 µg (group B) of methyl-cobalamin from enrolment to 6 months post partum. The primary outcomes were infant neurodevelopment assessed at 9–12 months using the Development Assessment Scale of Indian Infants and biochemical B12 status in mothers and infants measured through blood tests.Results531 mothers completed the study (group A n=255; group B n=276). There were no significant differences in baseline characteristics between mothers at both centres or in groups A and B. Mental developmental quotients (DQs) were higher in the infants of group A: 103.7 (7.7) than group B: 101.7 (8.8); p=0.008). This corresponds to a mean difference of 7.8 centiles (p=0.007). Mean motor DQs were not significantly different between the groups. Maternal vitamin B12 levels rose from the first to third trimester in both groups, with a larger increase in group A (104.9 pg/mL (SD 159.1)) than group B (47.5 pg/mL (SD 118.0)), p<0.001. Holotranscobalamin levels improved similarly (p<0.001). All infant levels of vitamin B12 were within the normal range. Newborn anthropometry, APGAR scores and morbidity profiles were similar in both groups (p>0.05). Serum ferritin, vitamin D and folate were similar (p>0.05).ConclusionsDaily supplementation with 250 µg of vitamin B12 during pregnancy in vegetarian mothers significantly improved infant mental DQ and maternal B12 status compared with a 50 µg dose.

Process mapping is a systems thinking approach used to understand, analyse and optimise processes within complex systems. We aim to demonstrate how this methodology can be applied during disease outbreaks to strengthen response and health systems. Process mapping exercises were conducted during three unique emerging disease outbreak contexts with different: mode of transmission, size, and health system infrastructure. System functioning improved considerably in each country. In Sierra Leone, laboratory testing was accelerated from 6 days to within 24 hours. In the Democratic Republic of Congo, time to suspected case notification reduced from 7 to 3 days. In Nigeria, key data reached the national level in 48 hours instead of 5 days. Our research shows that despite the chaos and complexities associated with emerging pathogen outbreaks, the implementation of a process mapping exercise can address immediate response priorities while simultaneously strengthening components of a health system.