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Bonifacio et al provide an overview of the management of gender dysphoria in postpubertal adolescents, including practical advice on approaches to social and medical transitioning, aimed at supporting primary care practitioners in supporting youth with gender dysphoria in their practices. They use the current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria when referring to gender dysphoria. Youth may present to either primary care or mental health care providers stating overtly that they are \"transgender\" and requesting a gender assessment, or they may present less overtly with a mood disorder, anxiety or depressive traits, or caregiver concern about social problems such as a change in academic performance or school truancy. An increasing number of adolescents seeking care for gender dysphoria suggests that more primary care providers will encounter such youth in clinical practice and should be familiar with the key aspects of their management.

Noroviruses are a leading cause of acute gastroenteritis (AGE) among adults and children worldwide. NoroSurv is a global network for norovirus strain surveillance among children <5 years of age with AGE. Participants in 16 countries across 6 continents used standardized protocols for dual typing (genotype and polymerase type) and uploaded 1,325 dual-typed sequences to the NoroSurv web portal during 2016-2020. More than 50% of submitted sequences were GII.4 Sydney[P16] or GII.4 Sydney[P31] strains. Other common strains included GII.2[P16], GII.3[P12], GII.6[P7], and GI.3[P3] viruses. In total, 22 genotypes and 36 dual types, including GII.3 and GII.20 viruses with rarely reported polymerase types, were detected, reflecting high strain diversity. Surveillance data captured in NoroSurv enables the monitoring of trends in norovirus strains associated childhood AGE throughout the world on a near real-time basis.

We report a new norovirus GII.4 variant, GII.4 Hong Kong, with low-level circulation in 4 Eurasia countries since mid-2017. Amino acid substitutions in key residues on the virus capsid associated with the emergence of pandemic noroviruses suggest that GII.4 Hong Kong has the potential to become the next pandemic variant.

Correspondence to Dr Jillian Margaret Baker; jillian.baker@unityhealth.to Introduction Transition clinics have been introduced as a way to address the needs of adolescents and young adults (AYA) with a chronic condition requiring ongoing care.1 Poor clinical attendance in this population due to social, economic and personal issues are known, however solutions to address this have been limited.2 3 Miscommunication and forgetfulness were cited as some of the reasons for missed appointments.4 5 Studies have shown using short message service (SMS), also known as text messages, to remind patients of clinical appointments can reduce missed appointments and improve young patients’ engagement in the management of their chronic disease.4 6 7 However further high quality research is required in AYA to determine the feasibility and effectiveness of SMS reminders.4 The primary objective of this study was to determine the effect of SMS appointment reminders to patients on uninformed no-show rates. Table 1 summarises demographic characteristics of survey participants.Table 1 Demographic characteristics of 26 patients in benign haematology transition clinic with text-message reminders Characteristics Number (%) Gender  Male 4 (15.4)  Female 22 (84.6) Age, years  16–18 7 (26.9)  19–21 14 (53.8)  22–24 3 (11.5)  25+ 2 (7.7) Educational and/or work status  Currently in school 16 (61.5)  Currently working 6 (23.1)  Taking time off 1 (3.8)  Prefer not to answer 3 (11.5) Health condition  Anaemia 7 (26.9)  Idiopathic Thrombocytopenic Purpura 3 (11.5)  Hereditary spherocytosis 2 (7.7)  Autosomal dominant thrombocytopenia 1 (3.8)  Kikuchi 1 (3.8)  Other blood count related issues (ie, low platelets) 2 (7.7)  Unsure 7 (26.9)  No answer 3 (11.5) Prior to intervention From April 2013 to August 2015 a total of 51 clinical days with 236 appointments occurred since the start of the AYA clinic. SMS reminders significantly improved the uninformed no-show rates by encouraging communication between the clinic and patient which in turn also improved overall clinical productivity.4 8 When patients miss appointments, not only does it impact their diagnostic evaluation and timely initiation of required treatment, it also places a monetary burden on health systems.9 The most commonly reported reason for missing an appointment was forgetfulness9 and SMS reminders could be simple and efficient way to remind patients about their appointments. [...]this study did not address the complex reasons why AYA patients missed appointments.

•Starting in 2012, RVV was introduced in public health clinics of Agusan del Sur province.•Declines in diarrheal hospitalizations and consults were seen following RVV introduction.•No declines in diarrheal admissions were observed in a province where RVV was not introduced.•This is the first evidence of the public health impact of RVV in a middle income country Asia. Monovalent rotavirus (RV) vaccine was introduced in the Philippines in a phased manner beginning in 2012. To assess the impact of RV vaccine, we conducted a retrospective review of diarrheal admissions in two hospitals. Records of physician-diagnosed diarrheal admissions were reviewed in D.O. Plaza Hospital (DOPH) from 2009 to 2016 in Agusan del Sur where RV vaccine was introduced in the immunization program; and in Cotabato Regional Medical Center (CRMC) from 2011 to 2016 in a region where the vaccine was not introduced. Reports from consultations in public health clinics in Agusan Del Sur and RV vaccine coverage were obtained. All-cause diarrheal admissions among children <5 years old in DOPH declined from 2013 to 2016 following RV vaccine introduction in 2012. Using the 2009–2011 mean number of hospitalizations as baseline (X‾ = 1,141), the reductions were 28% (n = 821), 56% (n = 507), 63% (n = 417) and 59% (n = 466) in 2013, 2014, 2015 and 2016, respectively. In comparison, no substantial declines in diarrheal hospitalizations were seen in CRMC from 2011 to 2016. A declining trend was also seen in outpatient consultations in Agusan del Sur following RV vaccine introduction with declines of 27% (n = 2,333), 33% (n = 2,143), 45% (n = 1,764) and 67% (n = 1,059) in 2013, 2014, 2015 and 2016. From September 2012 to December 2016, the 1 and 2-dose RV vaccine coverage gradually increased from 5% and 4% in 2012 to 92% and 88% in 2015, but decreased in 2016 to 53% and 52%, respectively. RV vaccine introduction was associated with a substantial decline in diarrheal hospitalizations and outpatient consultations for diarrhea in Agusan del Sur, Philippines.

Rotavirus (RV) is an important cause of diarrheal disease particularly in children aged under 5 years. Monovalent RV vaccine (RVV) was selectively introduced in 2012 in the Philippines and in July 2014 was introduced in the public health program of a province. Two RVV doses are recommended at 6 and 10 weeks of age. We conducted a test negative case-control evaluation to assess the effectiveness of RVV when given in a routine public health program in the Philippines. From September 2014 to August 2017, 967 children aged <5 years were hospitalized with diarrhea and of these, we enrolled 600 who were eligible to have received RVV and provided stool specimens for testing. Among children ≥8 months of age who were age-eligible to have received RVV, at least one dose of RVV had an adjusted vaccine effectiveness (VE) against RV hospitalization of 60% (95% confidence interval, CI: 24%, 79%), and against severe rotavirus diarrhea, VE was 64% (95% CI: 11%, 85%). These findings support the introduction of RVV into routine public health use in the Philippines. However, other factors such as costs, cost-effectiveness and operational issues must be considered prior to adoption of the vaccine into the countries’ public immunization program.

With the availability of new and existing rotavirus vaccines, credible and reliable data on burden of rotavirus-associated disease are needed to enable evidence-based decision making regarding the introduction of rotavirus vaccines. The national rotavirus surveillance program in the Philippines, a sentinel-based surveillance, was established in 2012 to determine the proportion of laboratory-confirmed rotavirus cases among children under five years with acute gastroenteritis and to describe the geographic distribution and molecular epidemiology of rotavirus in the country. During 2013 to 2015, rotavirus infection was the cause of acute gastroenteritis among children under five years admitted to hospitals or evaluated in emergency rooms, constituting more than one-third of gastroenteritis hospitalizations at the sentinel site hospitals. The predominant genotype observed was G1P[8]. Although a rotavirus surveillance network has been established, findings suggest the need to strengthen the network in the country and to continue monitoring prevalent rotavirus strains to help identify the possible emergence of new strains.

A new ethical medical dilemma concerns the use of hormone-blockers or medications that put puberty on hold in the care of transgender/transsexual (TG/TS) adolescents. These medications are taken until she is old enough to legally consent to cross-sex hormones. Such individuals are often “invisible” in clinical medicine because of a lack of knowledge and research concerning TG/TS. Using Emmanuel and Emmanuel's preferred decision-making patient-physician relationship, I critique clinical medicine‘s (1) inadequacy of clinical knowledge regarding TG/TS and hormone-blocker therapy, (2) misunderstanding of the health-related values of the TG/TS adolescent, and (3) lack of appreciation of her autonomy. Despite a problematic relationship, I argue that hormone-blockers are an ethical and viable option in TG/TS care and their use can be grounded through the ethical considerations of trust, privacy, and self-determination. Clinical guidelines are recommended through the incorporation of hormone-blocker therapy in the management of TG/TS adolescents. Such suggestions are in hopes of providing greater access to transgender care so that TG/TS adolescents are finally seen and no longer “invisible”.

Aims/hypothesisOral administration of antigen can induce immunological tolerance. Insulin is a key autoantigen in childhood type 1 diabetes. Here, oral insulin was given as antigen-specific immunotherapy before the onset of autoimmunity in children from age 6 months to assess its safety and immune response actions on immunity and the gut microbiome.MethodsA phase I/II randomised controlled trial was performed in a single clinical study centre in Germany. Participants were 44 islet autoantibody-negative children aged 6 months to 2.99 years who had a first-degree relative with type 1 diabetes and a susceptible HLA DR4-DQ8-containing genotype. Children were randomised 1:1 to daily oral insulin (7.5 mg with dose escalation to 67.5 mg) or placebo for 12 months using a web-based computer system. The primary outcome was immune efficacy pre-specified as induction of antibody or T cell responses to insulin and measured in a central treatment-blinded laboratory.ResultsRandomisation was performed in 44 children. One child in the placebo group was withdrawn after the first study visit and data from 22 insulin-treated and 21 placebo-treated children were analysed. Oral insulin was well tolerated with no changes in metabolic variables. Immune responses to insulin were observed in children who received both insulin (54.5%) and placebo (66.7%), and the trial did not demonstrate an effect on its primary outcome (p = 0.54). In exploratory analyses, there was preliminary evidence that the immune response and gut microbiome were modified by the INS genotype Among children with the type 1 diabetes-susceptible INS genotype (n = 22), antibody responses to insulin were more frequent in insulin-treated (72.7%) as compared with placebo-treated children (18.2%; p = 0.03). T cell responses to insulin were modified by treatment-independent inflammatory episodes.Conclusions/interpretationThe study demonstrated that oral insulin immunotherapy in young genetically at-risk children was safe, but was not associated with an immune response as predefined in the trial primary outcome. Exploratory analyses suggested that antibody responses to oral insulin may occur in children with a susceptible INS genotype, and that inflammatory episodes may promote the activation of insulin-responsive T cells.Trial registrationClinicaltrials.gov NCT02547519FundingThe main funding source was the German Center for Diabetes Research (DZD e.V.)

Objectives The aim of this study was to assess the cost effectiveness of midostaurin + cytarabine + daunorubicin (midostaurin arm) versus placebo + cytarabine + daunorubicin (placebo arm) in the treatment of adult patients with newly diagnosed FLT3 -mutated acute myeloid leukemia (AML) who are eligible for standard cytarabine + daunorubicin chemotherapy, from a US third-party payer perspective. Methods A lifetime partitioned survival model with four health states (active disease, complete remission [CR], relapse, and death) was constructed. Efficacy inputs (time to CR or death, time to relapse or death, and overall survival) were estimated using data from the RATIFY trial (NCT00651261). Costs (inflated to 2016 US dollars) included treatment, drug monitoring, stem cell transplantation (SCT), adverse events costs, and medical costs associated with health states. Incremental costs per quality-adjusted life-year (QALY) and life-year (LY) gained were estimated. Deterministic (DSA) and probabilistic sensitivity analyses (and PSA) were performed to assess model robustness. Results In the base case, patients in the midostaurin arm incurred higher total direct costs over a lifetime compared with the placebo arm ($4,043,470 vs. $3,959,741), resulting in an incremental cost of $83,729; however, the midostaurin arm had better effectiveness, with 1.59 more LYs and 1.37 more QALYs. These led to a base-case incremental cost-effectiveness ratio (ICER) of $52,596 per LY, or $61,167 per QALY. Results were robust in the DSA. In the PSA, the probability of the midostaurin arm being cost-effective compared with the placebo arm was 65.9%, at a willingness to pay of $150,000/QALY. Conclusions This analysis suggests that midostaurin is a cost-effective treatment for adult patients with newly diagnosed FLT3 -mutated AML, from a US third-party payer perspective.