Current therapeutical strategies for allergic rhinitis

Introduction: Allergic rhinitis is a common condition with increasing prevalence and is associated with several comorbid disorders such as bronchial asthma and atopic dermatitis. If allergen avoidance is not possible, allergen-specific immunotherapy is the only causal treatment option.

Areas covered: This review focuses on current treatments and the future outlook for allergic rhinitis. Pharmacotherapy includes mast cell stabilizers, antihistamines, glucocorticosteroids (GCSs), leukotriene receptor antagonists, and nasal decongestants. Nasal GCSs are currently regarded as the most effective treatment and are considered first-line therapy together with non-sedating antihistamines. The new formulation MP29-02 combines the nasal GCS fluticasone propionate with azelastine in one single spray and has achieved greater improvements than those under monotherapy with modern GCSs or antihistamines. Furthermore, this review discusses allergen immunotherapy alone and in combination with modern monoclonal antibodies.

Expert opinion: Despite the variety of medications for allergic rhinitis, ranging from general symptomatic agents like GCSs or decongestants, to more specific ones like histamine receptor or leukotriene blockers, to causal therapy like immunotherapy, many patients still experience treatment failures or unsatisfactory results. The ultimate goal may be to endotype every downstream pathway separately in order to offer patients individualized, targeted therapy with specific antibodies against the respective pathway.     

Trabecular Bone Score Reference Values for Children and Adolescents According to Age,Sex, and Ancestry

Trabecular bone score (TBS) is used for fracture prediction in adults, but its utility in children is limited by absence of appropriate reference values. We aimed to develop reference ranges for TBS by age, sex, and population ancestry for youth ages 5 to 20 years. We also investigated the association between height, body mass index (BMI), and TBS, agreement between TBS and lumbar spine areal bone mineral density (aBMD) and bone mineral apparent density (BMAD) Z-scores, tracking of TBS Z-scores over time, and precision of TBS measurements. We performed secondary analysis of spine dual-energy X-ray absorptiometry (DXA) scans from the Bone Mineral Density in Childhood Study (BMDCS), a mixed longitudinal cohort of healthy children (n = 2014) evaluated at five US centers. TBS was derived using a dedicated TBS algorithm accounting for tissue thickness rather than BMI. TBS increased only during ages corresponding to pubertal development with an earlier increase in females than males. There were no differences in TBS between African Americans and non-African Americans. We provide sex-specific TBS reference ranges and LMS values for calculation of TBS Z-scores by age and means and SD for calculation of Z-scores by pubertal stage. TBS Z-scores were positively associated with height Z-scores at some ages. TBS Z-scores explained only 27% and 17% of the variance of spine aBMD and BMAD Z-scores. Tracking of TBS Z-scores over 6 years was lower (r = 0.47) than for aBMD or BMAD Z-scores (r = 0.74 to 0.79), and precision error of TBS (2.87%) was greater than for aBMD (0.85%) and BMAD (1.22%). In sum, TBS Z-scores provide information distinct from spine aBMD and BMAD Z-scores. Our robust reference ranges for TBS in a well-characterized pediatric cohort and precision error estimates provide essential tools for clinical assessment using TBS and determination of its value in predicting bone fragility in childhood and adolescence. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Association Between Patient and Physician Sex and Physician-Estimated Stroke and Bleeding Risks in Atrial Fibrillation

Background

Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain.

Fibrous dysplasia of the jaws: Integrating molecular pathogenesis with clinical,radiological, and histopathological features

Fibrous dysplasia is a non‐neoplastic developmental process that affects the craniofacial bones, characterized by painless enlargement as a result of bone substitution by abnormal fibrous tissue. Postzygotic somatic activating mutations in the GNAS1 gene cause fibrous dysplasia and have been extensively investigated, as well as being helpful in the differential diagnosis of the disease. Fibrous dysplasia may involve one (monostotic) or multiple bones (polyostotic), sporadically or in association with McCune‐Albright syndrome, Jeffe‐Lichenstein syndrome, or Mazabreud syndrome. This review summarizes the current knowledge on fibrous dysplasia, emphasizing the value of integrating the understanding of its molecular pathogenesis with the clinical, radiological, and histopathological features. In addition, we address important aspects related to the differential diagnosis and patient management.     

Inhibitors of the Hepatitis C Virus Polymerase; Mode of Action and Resistance

The hepatitis C virus (HCV) is a pandemic human pathogen posing a substantial health and economic burden in both developing and developed countries. Controlling the spread of HCV through behavioural prevention strategies has met with limited success and vaccine development remains slow. The development of antiviral therapeutic agents has also been challenging, primarily due to the lack of efficient cell culture and animal models for all HCV genotypes, as well as the large genetic diversity between HCV strains. On the other hand, the use of interferon-α-based treatments in combination with the guanosine analogue, ribavirin, achieved limited success, and widespread use of these therapies has been hampered by prevalent side effects. For more than a decade, the HCV RNA-dependent RNA polymerase (RdRp) has been targeted for antiviral development. Direct acting antivirals (DAA) have been identified which bind to one of at least six RdRp inhibitor-binding sites, and are now becoming a mainstay of highly effective and well tolerated antiviral treatment for HCV infection. Here we review the different classes of RdRp inhibitors and their mode of action against HCV. Furthermore, the mechanism of antiviral resistance to each class is described, including naturally occurring resistance-associated variants (RAVs) in different viral strains and genotypes. Finally, we review the impact of these RAVs on treatment outcomes with the newly developed regimens.     

Prevalence and Correlates of Mental Health Problems in Norwegian Peacekeepers 18–38 Years Postdeployment

Peacekeeping missions involve experiences that may impact the mental health of participating soldiers. However, research on the long-term mental health consequences of peacekeeping is sparse. The present study aimed to find the prevalence of mental health problems (MHPs), possible MHP predictors, and associations between predictors and MHPs in Norwegian peacekeepers 18–38 years after deployment to a United Nations peacekeeping mission. We used data from a cross-sectional, postdeployment survey of Norwegian peacekeepers who served in Lebanon between 1978 and 1998 (N = 10,605). Participants were assessed for posttraumatic stress disorder (PTSD); anxiety; depression; insomnia; alcohol misuse; drug misuse; and exposure to pre-, peri-, and postdeployment stressors. Logistic regressions were executed to explore key variables associated with MHPs. Total MHP prevalence was 15.1%, 95% CI [14.4, 15.8]. The estimates for specific disorders were 0.1% for drug misuse, 3.4% for alcohol misuse, 4.0% for depression, 6.2% for PTSD, 6.4% for anxiety, and 9.3% for insomnia. Postdeployment stressors, OR = 1.91, 95% CI [1.79, 2.04]; employment status, OR = 1.41, 95% CI [1.33, 1.48]; and traumatic exposure during deployment, OR = 1.11, 95% CI [1.09, 1.12], were positively related to PTSD, χ2(17, N = 8,568) = 1,791.299, p < .001. Similar patterns were found for the other MHPs. Considering that most participants (84.9%) reported low symptom levels, our findings challenge the widespread public perception that most peacekeepers have MHPs. Moreover, our results indicate that future peacekeepers should be prepared for challenges they may face not only during deployment but also in the years following their homecoming.     

Leveraging strong social ties among young men in Dar es Salaam: A pilot intervention of microfinance and peer leadership for HIV and gender-based violence prevention

Gender inequality is at the core of the HIV patterns that are evident in sub-Saharan Africa. Gender-based violence (GBV) and lack of economic opportunity are important structural determinants of HIV risk. We piloted a microfinance and health promotion intervention among social networks of primarily young men in Dar es Salaam. Twenty-two individuals participated in the microfinance component and 30 peer leaders were recruited and trained in the peer health leadership component. We collected and analysed observational data from trainings, monitoring data on loan repayment, and reports of peer conversations to assess the feasibility and acceptability of the intervention. Eighteen of the loan recipients (82%) paid back their loans, and of these 15 (83%) received a second, larger loan. Among the loan defaulters, one died, one had chronic health problems, and two disappeared, one of whom was imprisoned for theft. The majority of conversations reported by peer health leaders focused on condoms, sexual partner selection, and HIV testing. Few peer leaders reported conversations about GBV. We demonstrated the feasibility and acceptability of this innovative HIV and GBV prevention intervention. The lessons learned from this pilot have informed the implementation of a cluster-randomised trial of the microfinance and peer health leadership intervention.