Pretreatment Alveolar Nitric Oxide Levels Predict Improvement of Pulmonary Function 1 Year Following Anti-Asthma Treatments in Patients with Inhaled Corticosteroid-Naïve Asthma

<b><i>Introduction:</i></b> Inhaled corticosteroids (ICS) are fundamental agents to subside airway inflammation and improve forced expiratory volume in 1 s (FEV₁) among asthmatics. Alveolar concentrations of nitric oxide (CANO), as well as the classical fraction of exhaled nitric oxide (FeNO50), are associated with the pathophysiology of asthma. However, the association between pretreatment CANO levels and response to anti-asthma treatments, including ICS, remains unknown. <b><i>Methods:</i></b> We retrospectively analyzed 107 patients newly diagnosed with asthma. ICS in combination with long-acting β₂-agonists (ICS/LABA) was initiated. FEV₁ and FeNO levels were evaluated at diagnosis and were followed up at 6 and 12 months after the treatment intervention. CANO levels were estimated using various expiratory flows of FeNO measurements. Factors associated with annual changes in FEV₁ (ΔFEV₁) were analyzed. Patients with a ΔFEV₁ &#x3c;–20 mL were defined as “poor-responders.” <b><i>Results:</i></b> FEV₁, FeNO50, and CANO levels significantly improved by anti-asthma treatments. The average ΔFEV₁ was 85 (176) mL. Eighty-two patients continuously took ICS/LABA treatment. Higher pretreatment CANO levels and continuous use of LABA were independent predictive factors for the improvement of FEV₁ on multivariate analysis. The decline in FeNO50 and CANO levels by the anti-asthma treatments was significantly greater in 81 responders than in 26 poor-responders. CANO, but not FeNO50, levels at 12 months were significantly higher in poor-responders than in responders (<i>p</i> = 0.009). <b><i>Conclusion:</i></b> Levels of CANO, but not FeNO50, predict changes in pulmonary function in ICS-naïve asthmatics. Meanwhile, persistently high levels of CANO may be related to poor responsiveness to treatments assessed by ΔFEV₁.

Enhancing Choices Regarding the Administration of Insulin Among Patients With Diabetes Requiring Insulin Across Countries and Implications for Future Care

There are a number of ongoing developments to improve the care of patients with diabetes across countries given its growing burden. Recent developments include new oral medicines to reduce cardiovascular events and death. They also include new modes to improve insulin administration to enhance adherence and subsequent patient management thereby reducing hypoglycaemia and improving long-term outcomes. In the case of insulins, this includes long-acting insulin analogues as well as continuous glucose monitoring (CGM) systems and continuous subcutaneous insulin infusion systems, combined with sensor-augmented pump therapy and potentially hybrid closed-loops. The benefits of such systems have been endorsed by endocrine societies and governments in patients with Type 1 diabetes whose HbA1c levels are not currently being optimised. However, there are concerns with the low use of such systems across higher-income countries, exacerbated by their higher costs, despite studies suggesting their cost-effectiveness ratios are within accepted limits. This is inconsistent in higher-income countries when compared with reimbursement and funding decisions for new high-priced medicines for cancer and orphan diseases, with often limited benefits, given the burden of multiple daily insulin injections coupled with the need for constant monitoring. This situation is different among patients and governments in low- and low-middle income countries struggling to fund standard insulins and the routine monitoring of HbA1c levels. The first priority in these countries is to address these priority issues before funding more expensive forms of insulin and associated devices. Greater patient involvement in treatment decisions, transparency in decision making, and evidence-based investment decisions should help to address such concerns in the future.

Implants for HIV prevention in young women: Provider perceptions and lessons learned from contraceptive implant provision

Preventing new HIV infections, especially amongst young women, is key to ending the HIV epidemic especially in sub-Saharan Africa. Potent antiretroviral (ARV) drugs used as pre-exposure prophylaxis (PrEP) are currently being formulated as long-acting implantable devices, or nanosuspension injectables that release drug at a sustained rate providing protection from acquiring HIV. PrEP as implants (PrEP Implants) offers an innovative and novel approach, expanding the HIV prevention toolbox. Feedback from providers and future users in the early clinical product development stages may identify modifiable characteristics which can improve acceptability and uptake of new technologies. Healthcare workers (HCWs) perspectives and lessons learned during the rollout of contraceptive implants will allow us to understand what factors may impact the roll-out of PrEP implants. We conducted eighteen interviews with HCWs (9 Nurses and 9 Community Healthcare Workers) in rural KwaZulu-Natal, South Africa. HCWs listed the long-acting nature of the contraceptive implant as a key benefit, helping to overcome healthcare system barriers like heavy workloads and understaffing. However, challenges like side effects, migration of the implant, stakeholder buy-in and inconsistent training on insertion and removal hampered the roll-out of the contraceptive implant. For PrEP implants, HCWs preferred long-acting products that were palpable and biodegradable. Our findings highlighted that the characteristics of PrEP implants that are perceived to be beneficial by HCWs may not align with that of potential users, potentially impacting the acceptability and uptake of PrEP implants. Further our data highlight the need for sustained and multi-pronged approaches to training HCWs and introducing new health technologies into communities. Finding a balance between the needs of HCWs that accommodate their heavy workloads, limited resources at points of delivery of care and the needs and preferences of potential users need to be carefully considered in the development of PrEP implants.

Case Report: Eosinophilic Bronchiolitis With Eosinophil ETosis in Mucus Plugs Successfully Treated With Benralizumab

Eosinophilic bronchiolitis is a rare allergic disorder caused by eosinophilic inflammation in the bronchioles of the lungs. An effective treatment strategy is needed in cases resistant to steroids. However, its pathophysiology remains unclear owing to the limited number of cases. We herein present the case of a 31-year-old man who experienced eosinophilic bronchiolitis with eosinophil ETosis (EETosis) in the mucus plugs. The patient was diagnosed with asthma. His respiratory symptoms worsened with eosinophilia when treated with the standard asthma regimen, including inhaled corticosteroids, long-acting β2-agonist, long-acting muscarinic antagonist, and leukotriene receptor antagonist. Chest computed tomography revealed bronchial wall thickening and centrilobular nodules in the lower lobes of both lungs. Bronchoscopy showed obstruction of the subsegmental bronchus with mucus plugs. Histological analysis demonstrated abundant eosinophils in the mucus plugs. Cytolytic eosinophils together with Charcot–Leyden crystal formations and deposition of major basic proteins were also observed, indicating the occurrence of EETosis. Introduction of benralizumab, an anti-interleukin-5 receptor α antibody, successfully controlled the patient’s condition and reduced the amount of systemic corticosteroids administered. Our findings confirm that this antibody strongly decreases airway eosinophils in patients with severe asthma. Thus, benralizumab might be an optimal therapeutic agent for the treatment of mucus plug-forming and/or EETosis-occurring eosinophilic lung diseases, including eosinophilic bronchiolitis.

Respiratory Syncytial Virus (RSV) Diseases

The respiratory syncytial virus (RSV) is an RNA virus that causes annual ARI outbreaks during winter with mild URTI in the general population, but with severe LRTI particularly among young children (bronchiolitis), patients with underlying diseases and people >65 years of age. RSV does not induce a long-lasting protective immunity and repeated infections throughout life are the norm. Basically, all children have been infected by 2 years of age and of those hospitalized, >50% are <3 months and 75% are <6 months of age. The overall CFR is 1/500. For adults ≥65 years, RSV hospitalization rates are 90–250/105. There is no specific therapy, general preventive measures include general hygiene and isolation/separation of patients. A monoclonal anti-F-protein antibody is available for passive immunization of selected high-risk children. It requires monthly injections, comes at a high cost and has limited efficacy (50% against RSV hospitalization). Active immunization failed in the past, probably as the post-fusion conformation of the F-protein was used. Long-acting monoclonal antibodies (for infants) as well as stabilized pre-fusion F-protein vaccines (for immunization of pregnant women, children, older adults) produced on various platforms are in late stages of clinical development.

The combined oral contraceptive pill

The combined oral contraceptive pill (COCP) has been a popular choice of contraception since it was first introduced in 1961. There are numerous varieties of COCP and tailored regimes allow patients more choice and opportunities to adapt contraception to suit individual needs. The pandemic has made it more difficult for patients to access long-acting reversible contraception support and many have been using interim methods of contraception, including the COCP. In this article we explore which pill to prescribe, developments in tailored regimes, guidance about changing pills when side effects arise, health risks and benefits, as well as best practice for remote assessments and prescribing.

Role of Insulin: Perspectives

The pancreas in a non-diabetic patient invariably produces a lesser quantum of insulin (basal production). Insulin furnishes glucose homeostasis by keeping the plasma glucose worth in an optimum class throughout the day. It assists transport blood glucose into the body cells where the glucose is metabolized to generate energy. Regular insulin is inserted pre-meal to abrupt the postprandial ascend in glucose levels. It figures hexamers after insertion into the subcutaneous space sluggishing its absorption. Ultra-fast acting commences to act 4-7 minutes before regular apidra and lasts for around 3 hours. The absorption rate of lente insulin is downgraded by the extension of zinc to the insulin preparation. Long-acting insulins furnish basal insulin coverage. Atrophy of subcutaneous fat owing to applicability of further greater accumulated insulin preparations of neutral potenz hydrogen.

Understanding Medication Adherence in Patients with Limited English Proficiency

Introduction. Approximately 41.6% of the US population who speak a language other than English (20% over all) and have limited English proficiency (LEP) status.1 Health outcomes for patients with LEP status or who are language discordant (speak a different language than their clinicians) have been studied in several settings, including the hospital and outpatient, with results widely demonstrating that these patients have worse outcomes when a professional interpreter is not used consistently. 2,3 The aim of this study was to investigate the impact of preferred language and language discordance on medication adherence. Methods. Data were collected via review of pharmacy-acquired medication profiles for three primary language cohorts: Nepali, Spanish, and English. Total Days of Adherence, Adherence Ratio, and Maximum Days Non-adherent were calculated and compared between language groups. We examined these statistics for regular and long-acting insulin, metformin and ACE inhibitors, testing for differences between language groups and those who experienced greater vs less than the median value for language concordant clinical encounters. Results. The most adherent group over all (highest adherence-ratio) were the Nepali-speaking, but the results showed high variability across outcomes and medications. Conclusions. After adjustment and stratification for greater vs lesser language concordant patient visit experience, we found that language-spoken plays an important role in the clinical encounter, and that LEP patients could have improved outcomes in their adherence to medications by having providers who speak their language or use an interpreter.