Lamotrigine efficacy, safety, and tolerability for women of childbearing age with bipolar I disorder: Meta-analysis from four randomized, placebo-controlled maintenance studies.

This meta-analysis investigated the efficacy, safety, and tolerability of lamotrigine versus placebo in preventing relapse and recurrence of mood episodes in women of childbearing age with bipolar I disorder. Following up to 16 weeks' open-label lamotrigine treatment, responders were randomized to double-blind treatment, including lamotrigine 100-400 mg/day or placebo, in four trials of up to 76 weeks. Women aged 18-45 years who received ≥ 1 dose of study treatment and had ≥ 1 efficacy assessment in the double-blind phase were pooled for efficacy analysis. The primary outcome was median time to intervention for any mood episode (TIME). Of 717 eligible women in the open-label phase, 287 responded and were randomized to lamotrigine (n = 153) or placebo (n = 134). The randomized group had a mean (SD) of 2.0(2.02) manic and 2.5(2.02) depressive episodes in the 3 years before screening. Median TIME was 323 days with lamotrigine and 127 days with placebo (HR 0.69; 95% CI 0.49, 0.96; p = 0.030). Lamotrigine delayed time to intervention for any depressive episode (HR 0.59; 95% CI 0.39, 0.90; p = 0.014) with no treatment difference for manic episodes (HR 0.91; 95% CI 0.52, 1.58; p = 0.732). 2/717 (< 1%) participants experienced serious rash-related adverse events (AEs) during the open-label phase, and 52/717 (7%) had non-serious rash-related events leading to study withdrawal. Incidence of AEs and AEs leading to withdrawal were similar between lamotrigine and placebo groups. Lamotrigine delayed relapse and recurrence of mood episodes, largely by preventing depressive episodes, and was well tolerated in women of childbearing age.

Meta-analysis and cost-effectiveness analysis of intranasal corticosteroid treatment in allergic rhinitis with ocular symptoms.

BACKGROUND: Intranasal corticosteroid (INCS) has a beneficial effect on ocular symptoms in allergic rhinitis (AR). To our knowledge, the cost-effectiveness of available INCS for AR with ocular symptoms is yet to be demonstrated. OBJECTIVE: To evaluate the cost-effectiveness of INCSs including Budesonide (BANS), Mometasone furoate (MFNS), Triamcinolone (TANS), and Fluticasone furoate (FFNS) on ocular symptoms associated with AR in the Thai context. METHODS: The percentage of effectiveness in improving total ocular symptoms score (TOSS) was derived from the result of a meta-analysis that estimated the SMD of each INCS treatment compared to placebo as clinical input parameters. A cost-effectiveness analysis based on a decision-tree model to assess one-year costs and outcomes from a Thai societal perspective. The outcomes were to compare incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analyses (PSA) were also conducted to capture parameter uncertainties. RESULTS: 13 eligible RCTs with a total of 3,722 patients with SAR were included in the analysis. The percentage of effectiveness of FFNS, MFNS, TANS, and BANS was 59.89%, 45.60%, 24.89%, and 16.00%, respectively. The ICER of FFNS, MFNS, and TANS is THB-6,539.92, 4,593.83, and 1,401.24 compared to BANS. CECA result showed the probability of using FFNS is considered cost-effective in 87.50% of cases from zero value followed by MFNS (0.80%), TANS (5.40%), and BANS (6.30%). With a threshold greater than THB20,000, FFNS is considered a cost-effective strategy. CONCLUSIONS: FFNS is a cost-effective option compared to alternative INCSs in Thailand for treating AR with ocular symptoms.

SABAs as Reliever Medications in Asthma Management: Evidence-Based Science.

The role of as-needed inhaled short-acting ß2-agonists (SABAs) in the management of asthma has become a subject of debate due to differing opinions in the professional community relating to the use of SABAs. In this article, we summarize the current position of SABAs when used as reliever medications and examine the challenges to appropriate use including a critique of the data that have led to the condemnation of SABA used as a reliever. We consider the evidence for the appropriate use of SABA as a reliever together with practical solutions to ensure such use, including identifying patients at risk of misusing their SABA relievers and managing issues of inhaler technique and treatment adherence. We conclude that inhaled corticosteroid (ICS)-based maintenance treatment with SABA used as-needed as a reliever is an effective and safe treatment for patients with asthma, with no scientific evidence of a causal link between SABA use as a reliever and mortality or serious adverse events (including exacerbations). Increased SABA use warns of a deterioration in asthma control, and patients at risk of misusing their ICS and SABA medication should be rapidly identified to ensure they are receiving adequate ICS-based controller therapy. Appropriate use of ICS-based controller therapy and as-needed SABA should be encouraged and promoted with educational activities.

The role of modeling studies in asthma management and clinical decision-making: a Delphi survey of physician knowledge and perceptions.

OBJECTIVE: To investigate the knowledge and perceptions of physicians on the role of modeling studies in asthma, using a modified Delphi procedure. METHODS: Group opinions among a panel of respiratory experts were obtained using two online questionnaires and a virtual scientific workshop. A consensus was pre-defined as agreement by >75% of participants. RESULTS: From 26 experts who agreed to participate, 22 completed both surveys. At the end of the process, the panel rated their own understanding of modeling as good (77%) but that among physicians in general as poor (77%). Participants agreed that data from modeling studies should be used, at least sometimes, to inform treatment guidelines (91%) and could be useful for guiding clinical decisions (100%). Perceived barriers to using modeling studies were 'A lack of understanding' (81%) and 'A lack of standardized methodology' (82%). Based on data from two modeling studies, no consensus was reached on physicians recommending regular inhaled corticosteroids (ICS) versus as-needed therapy for patients with mild asthma, whereas 77% agreed that they would recommend regular ICS over maintenance and reliever therapy for ≥80% of their patients with moderate asthma. No consensus was reached on the value of modeling data in relation to empirical data. CONCLUSION: There is overall support among respiratory experts for the usefulness of modeling data to guide asthma treatment guidelines and clinical decision making. More publications on modeling data using robust models and accessible terminology will aid the understanding of physicians in general and help clarify the evidence-based value of modeling studies.

Safety of SABA Monotherapy in Asthma Management: a Systematic Review and Meta-analysis.

INTRODUCTION: Short-acting ß2-agonist (SABA) reliever overuse is common in asthma, despite availability of inhaled corticosteroid (ICS)-based maintenance therapies, and may be associated with increased risk of adverse events (AEs). This systematic literature review (SLR) and meta-analysis aimed to investigate the safety and tolerability of SABA reliever monotherapy for adults and adolescents with asthma, through analysis of randomized controlled trials (RCTs) and real-world evidence. METHODS: An SLR of English-language publications between January 1996 and December 2021 included RCTs and observational studies of patients aged ≥ 12 years treated with inhaled SABA reliever monotherapy (fixed dose or as needed) for ≥ 4 weeks. Studies of terbutaline and fenoterol were excluded. Meta-analysis feasibility was dependent on cross-trial data comparability. A random-effects model estimated rates of mortality, serious AEs (SAEs), and discontinuation due to AEs (DAEs) for as-needed and fixed-dose SABA treatment groups. ICS monotherapy and SABA therapy were compared using a fixed-effects model. RESULTS: Forty-two studies were identified by the SLR for assessment of feasibility. Final meta-analysis included 24 RCTs. Too few observational studies (n = 2) were available for inclusion in the meta-analysis. One death unrelated to treatment was reported in each of the ICS, ICS + LABA, and fixed-dose SABA groups. No other treatment-related deaths were reported. SAE and DAE rates were < 4%. DAEs were reported more frequently in the SABA treatment groups than with ICS, potentially owing to worsening asthma symptoms being classified as an AE. SAE risk was comparable between SABA and ICS treatments. CONCLUSIONS: Meta-analysis of data from RCTs showed that deaths were rare with SABA reliever monotherapy, and rates of SAEs and DAEs were comparable between SABA reliever and ICS treatment groups. When used appropriately within prescribed limits as reliever therapy, SABA does not contribute to excess rates of mortality, SAEs, or DAEs.

Impact of inhaled fluticasone propionate/salmeterol on health-related quality of life in asthma: A network meta-analysis.

OBJECTIVE: This network meta-analysis (NMA) compared fixed-dose, twice daily fluticasone propionate/salmeterol (FP/Sal) vs. inhaled corticosteroid (ICS) and other ICS/long-acting beta-agonists (LABA) treatments, including when administered using maintenance and reliever therapy (MART) regimens, in terms of improvements in health-related quality of life (HRQoL). The relationship between changes in asthma control and HRQoL was assessed. METHODS: Articles published between 2001 and 2021, reporting change from baseline (CFB) in Asthma Quality of Life Questionnaire (AQLQ) in patients with moderate-to-severe asthma, were identified by a systematic review. Random effects Bayesian NMAs derived estimates of the mean difference in CFB in AQLQ vs. other interventions connected to the network (included 15 studies). Sensitivity analyses explored the impacts of differences in follow-up duration, baseline asthma control, the inclusion of observational studies, adjusting for baseline FEV1, and low-medium ICS dose arms only. Linear regression analysis compared CFBs in AQLQ and Asthma Control Questionnaire (ACQ) score. RESULTS: Mean CFB in AQLQ with FP/Sal vs. comparators demonstrated expected ranked effects: mean difference 0.65 [95% credible interval: 0.54, 0.78] versus placebo, 0.58 [ 0.33, 0.84] versus LABA, 0.21 [ 0.13, 0.31] versus ICS alone, 0.06 [-0.04, 0.19] versus other ICS/LABA, and 0.00 [-0.13, 0.14] versus ICS/formoterol MART. Sensitivity analyses largely showed consistent results. Improvements in AQLQ and ACQ were strongly correlated (R = 0.94). CONCLUSIONS: This NMA demonstrates that HRQoL is responsive to treatment, is strongly related to asthma control and that it can be well-managed in patients with moderate-to-severe asthma using regular treatment with inhaled FP/Sal.

A randomised, double-blind, placebo-controlled study to evaluate the safety and efficacy of lamotrigine in the maintenance treatment of Chinese adult patients with bipolar I disorder.

BACKGROUND: Lamotrigine is approved as a maintenance therapy for bipolar I disorder in many countries, including China in 2021. This study evaluated the efficacy and safety of lamotrigine in controlling relapse and/or recurrence of mood episodes in Chinese patients with bipolar I disorder. METHODS: Patients aged ≥ 18 years with bipolar I disorder who met response criteria (Clinical Global Impression-Severity [CGI-S] score of ≤ 3 for ≥ 4 consecutive weeks) during treatment with lamotrigine in a 6-16 week open-label (OL) phase, and who were maintained for ≥ 1 week on lamotrigine 200 mg/day monotherapy, were randomised (1:1) to continue receiving lamotrigine 200 mg/day or switch to placebo in a 36-week randomised double-blind (RD) phase. The primary efficacy outcome measure was time from entry into the RD phase to intervention for relapse and/or recurrence of a mood episode (TIME). Post hoc analyses assessed the impact of OL baseline mood severity on TIME. Safety assessments were conducted throughout the study. RESULTS: Of 420 patients treated in the OL phase, 264 were randomised to receive lamotrigine (n = 131) or placebo (n = 133). Overall, 112 patients had an intervention for relapse and/or recurrence of a mood episode (lamotrigine, n = 50/130 [38.5%]; placebo, n = 62/133 [46.6%]), with no significant difference in TIME between groups (adjusted hazard ratio [95% confidence interval (CI)] 0.93 [0.64, 1.35]; p = 0.701). Post hoc analyses indicated a significant difference in TIME, favouring lamotrigine over placebo, for patients with baseline CGI-S score ≥ 4 (hazard ratio [95% CI] 0.52 [0.30, 0.89]; p = 0.018) and with baseline Hamilton Depression Rating Scale ≥ 18 or Young Mania Rating Scale ≥ 10 (0.44 [hazard ratio [95% CI] 0.25, 0.78]; p = 0.005). Lamotrigine was well tolerated with no new safety signals. CONCLUSIONS: Lamotrigine was not significantly superior to placebo in preventing relapse and/or recurrence of mood episodes in this study of Chinese patients with bipolar I disorder but post hoc analyses suggested a therapeutic benefit in patients with moderate/severe mood symptoms at baseline. The discrepancy between these findings and the positive findings of the pivotal studies may be attributable to the symptom severity of the bipolar patients recruited, a high dropout rate, and the comparatively short duration of the RD phase rather than race/ethnicity differences. Clinical trial registration ClinicalTrial.gov Identifier NCT01602510; 21st May 2012; https://clinicaltrials.gov/ct2/show/NCT01602510 .

Airway Diseases Education and Expertise (ADEX ) in Pediatrics: Adaptation for Clinical Practice in India.

JUSTIFICATION: Asthma and allergic rhinitis together are part of the concept of one airway, one disease or united airway disease. The management of allergic airway diseases should address this united concept and manage the issue by educating the patients and their parents and health care providers, along with environmental control measures, pharmacotherapy and immunotherapy. Here, we present recommendations from the module of Airway Diseases Education and Expertise (ADEX) that focused on allergic rhinitis, asthma and sleep disorder breathing as a single entity or Allergic Airway Disease. PROCESS: A working committee was formed by the collaboration of Pediatric Allergy Association of India (PAAI) and Indian Academy of Pediatrics (IAP) Allergy and Applied Immunology chapter to develop a training module on united airway disease. OBJECTIVE: To increase awareness, understanding and acceptance of the concept of United Airway disease and to educate the primary health care providers for children and public health officials, in the management of united airway diseases. RECOMMENDATIONS: Recommendations for diagnosis, management and follow-up of Allergic airway disease are presented in this document. A better compliance by linking education of child, parent, grandparents and other health care providers, and scientific progress by collaboration between practitioners, academicians, researchers and pharmaceutical companies is suggested.

Cross-Sectional Study for Prevalence of Non-Steroidal Anti-Inflammatory Drug-Induced Gastrointestinal, Cardiac and Renal Complications in India: Interim Report.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common therapeutic products used for the management of inflammation and pain. However, their use is associated with gastrointestinal (GI), cardiovascular and renal complications. Although prevalence data regarding NSAID-induced complications are available worldwide, but none of the study has assessed the prevalence of GI, cardiac and renal complications in India. This study aimed to assess the point prevalence of GI, cardiac and renal complications associated with the use of NSAIDs in India. The study also aimed to evaluate the association between the risk factors and GI, renal and cardiac complications in patients using NSAIDs. METHODS: This prospective, cross-sectional, multi-centric study was conducted in eight medical colleges across India (North, East, West, South and Central India). Data related to GI complications including gastric, duodenal and gastroduodenal erosions/ulcers/gastritis, renal complications including acute and chronic renal failure or cardiac complications including acute coronary syndrome (ACS), acute myocardial infarction (AMI) and cardiac failure, were collected from patients. RESULTS: The cut-off date for interim data analysis was July 7, 2014. A total of 2,140 patients out of 3,600 were enrolled from eight centers at the time of interim analysis. The NSAID-associated point prevalence of GI complications was 30.08%; cardiac complication was 42.77%; and renal complication was 27.88%. CONCLUSIONS: Results of the present interim analysis show that the prevalence of GI, cardiac and renal complications among patients is high due to exaggerated usage; however, the final analysis would provide the overall prevalence of these complications.

Prevalence of chronic pain, impact on daily life, and treatment practices in India.

OBJECTIVE: Chronic pain is of concern to health professionals, patients, society, and negatively impacts quality of life (QoL). The present epidemiologic study identified point prevalence of chronic pain in India, impact on individual's QoL, unveiling current pain treatment practices, and levels of satisfaction with treatment. METHODS: This epidemiological telephonic survey consisted of two questionnaires: screening questionnaire that assessed prevalence of pain, its frequency during the past week, intensity during last episode, sites of pain, and main causes, and in-depth questionnaire that evaluated demography, frequency, duration, and intensity of pain; impact of pain on QoL; respondent's perception regarding the attitude of their family, friends, and doctors toward their pain. RESULTS: A total of 5004 respondents were included from eight cities across India. The overall point prevalence of chronic pain was 13%, and the mean intensity of pain on NRS scale was 6.93. Respondents with chronic moderate and chronic severe pain were 37% and 63%, respectively. Pain in knees (32%), legs (28%), and joints (22%) was most prevalent. Respondents with chronic pain were no longer able to exercise, sleep, maintain relationships with friends and family, and maintain an independent lifestyle. About 32% of patients lost ≥4 hours of work in the past 3 months. Majority (68%) of respondents were treated for pain with over the counter (OTC) drugs, and most were taking NSAIDs (95%). CONCLUSION: A significant population of India suffers from chronic pain, and their QoL is affected leading to disability. A proportion of respondents receiving pain treatment were taking nonprescription medications with a majority of respondents on NSAIDs. A very few were consulting pain management specialists.