Clinical efficacy of inhaled corticosteroids in patients with coronavirus disease 2019: A living review and meta-analysis.

Inhaled corticosteroids are known to be relatively safe for long-term use in inflammatory respiratory diseases and it has been repurposed as one of the potential therapies for outpatients with coronavirus disease 2019 (COVID-19). However, inhaled corticosteroids have not been accepted for COVID-19 as a standard therapy because of its lack of proven benefits. Therefore, this study aimed to evaluate the effectiveness of inhaled corticosteroids in patients with COVID-19. Randomized controlled trials comparing the efficacy of inhaled corticosteroid treatment in patients with COVID-19 were identified through literature electronic database searches up to March 10, 2023. Meta-analyses were conducted for predefined outcomes, and the certainty of evidence was graded using the grading of recommendations, assessment, development, and evaluation approach. Overall, seven trials (eight articles) were included in this systematic review. Compared with usual care, inhaled corticosteroids was associated with significantly improved clinical recovery at 7 and 14 days in patients with COVID-19. In subgroup analysis, only budesonide showed significant efficacy in clinical recovery, whereas no significant benefit was observed for ciclesonide. Moreover, inhaled corticosteroids use was not significantly associated with all-cause hospitalization, all-cause mortality, admission to intensive care unit, or the use of mechanical ventilation. Our systematic review used evidence with very low to moderate certainty. Although based on limited evidence, our results suggest that inhaled corticosteroids treatment, especially budesonide, improves the clinical recovery of patients with COVID-19. More trials and meta-analyses are needed to assess the efficacy of inhaled corticosteroids for COVID-19 treatment.

Comparative Effects of Bivalent, Quadrivalent, and Nonavalent Human Papillomavirus Vaccines in The Prevention of Genotype-Specific Infection: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Human papillomavirus (HPV) infection is a major global disease burden and the main cause of cervical cancer. Certain HPV genotypes, with are the most common etiologic pathogens and cause a significant disease burden, are being targeted for vaccine development. However, few studies have focused on the comparative effectiveness of the bivalent HPV (2v-HPV), quadrivalent HPV (4v-HPV), and nonavalent HPV (9v-HPV) vaccines against HPV strain-specific infection. This study investigated the comparative effects of these vaccines against genotype-specific infection. MATERIALS AND METHODS: We conducted a pairwise and network meta-analysis of published randomized clinical trials of HPV vaccines according to sex and HPV infection status for nine HPV genotypes (HPV 6/11/16/18/31/33/45/52/58). RESULTS: Overall, 10 randomized controlled trials (12 articles) were included in this study. In the network meta-analysis, no statistically significant differences were observed in the prevention of carcinogenic HPV strains (16/18/31/33/45/52/58) between the 2v-HPV and 4v-HPV vaccines in female HPV infection-naïve populations. However, the 9v-HPV vaccine showed a significantly superior effect compared with 2v-HPV and 4v-HPV vaccines in preventing HPV 31/33/45/52/58 infections. Although 2v-HPV and 4v-HPV vaccines provided some cross-protection against HPV 31/33/45/52/58 infections, the effect was significant only on HPV 31 infection. For HPV 16 and 18, neither statistically significant nor small differences were found in the prevention of HPV infection among the 2v-HPV, 4v-HPV, and 9v-HPV vaccines. CONCLUSION: Our study complements previous understanding of how the effect of HPV vaccines differs according to the HPV genotype. This is important because HPV genotype prevalence varies among countries. We advocate for continued efforts in vaccinating against HPV, while public health agencies should consider the difference in the vaccine effect and HPV genotype prevalence when implementing HPV vaccination in public vaccination programs.

Clinical efficacy and safety of SARS-CoV-2-neutralizing monoclonal antibody in patients with COVID-19: A living systematic review and meta-analysis.

This study evaluated the efficacy and safety of neutralizing monoclonal antibodies (mAbs) with usual care in patients with coronavirus disease 2019 (COVID-19). Randomized controlled trials comparing the efficacy and safety of neutralizing mAb treatment in patients with COVID-19 were identified using electronic database searches through March 10, 2023. This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Overall, 13 trials (23 articles) involving 25,646 patients were included in this systematic review. Compared with usual care, neutralizing mAbs were associated with significantly reduced all-cause mortality in outpatients with COVID-19 (pooled risk ratios [RR], 0.41; 95% confidence interval (CI), 0.20-0.83; 12 studies), but not in inpatients. In the subgroup analysis, only outpatients infected prior to the emergence of Delta variant or those with mAb-VOC match had significantly reduced mortality, while no significant benefit was observed in patients infected with Delta and post-Delta variants or mAb-VOC mismatch. Moreover, the rate of hospitalization and number of hospital visits had significantly reduced only in outpatients infected prior to the emergence of the Delta variant and those with mAb-VOC match. Our systematic review used majority of the high-certainty evidence. Our study found neutralizing mAbs were beneficial for outpatients infected prior to Delta variant or mAb-VOC match. In the face of the continuous emergence of new COVID-19 variants, additional clinical data are needed to determine whether neutralizing mAb treatment will be effective for the newly emerging variants.

Has the Copayment Ceiling Improved Financial Protection in the Korean National Health Insurance System? Evidence From the 2009 Policy Change.

OBJECTIVES: To relieve the financial burden faced by households, the Korean National Health Insurance (NHI) system introduced a "copayment ceiling," which evolved into a differential ceiling in 2009, with the copayment ceiling depending on patients' income. This study aimed to examine the effect of the differential copayment ceiling on financial protection and healthcare utilization, particularly focusing on whether its effects varied across different income groups. METHODS: This study obtained data from the Korea Health Panel. The number of households included in the analysis was 6555 in 2008, 5859 in 2009, 5539 in 2010, and 5372 in 2011. To assess the effects of the differential copayment ceiling on utilization, out-of-pocket (OOP) payments, and catastrophic payments, various random-effects models were applied. Utilization was measured as treatment days, while catastrophic payments were defined as OOP payments exceeding 10% of household income. Among the right-hand side variables were the interaction terms of the new policy with income levels, as well as a set of household characteristics. RESULTS: The differential copayment ceiling contributed to increased utilization regardless of income levels both in all patients and in cancer patients. However, the new policy did not seem to reduce significantly the incidence of catastrophic payments among cancer patients, and even increased the incidence among all patients. CONCLUSIONS: The limited effect of the differential ceiling can be attributed to a high proportion of direct payments for services not covered by the NHI, as well as the relatively small number of households benefiting from the differential ceilings; these considerations warrant a better policy design.

In-gap discounts in Medicare Part D and specialty drug use.

OBJECTIVES: Specialty drugs can bring significant benefits to patients, but they can be expensive. Medicare Part D plans charge relatively high cost-sharing costs for specialty drugs. A provision in the Affordable Care Act reduced cost sharing in the Part D coverage gap phase in an attempt to mitigate the financial burden of beneficiaries with high drug spending. We examined the early impact of the Part D in-gap discount on specialty cancer drug use and patients' out-of-pocket (OOP) spending. STUDY DESIGN: Natural experimental design. METHODS: We compared changes in outcomes before and after the in-gap discount among beneficiaries with and without low-income subsidies (LIS). Beneficiaries with LIS, who were not affected by the in-gap discount, made up the control group. We studied a random sample of elderly standalone prescription drug plan enrollees with relatively uncommon cancers (eg, leukemia, skin, pancreas, kidney, sarcomas, and non-Hodgkin lymphoma) between 2009 and 2013. We constructed 4 outcome variables annually: 1) use of any specialty cancer drug, 2) the number of specialty cancer drug fills, 3) total specialty drug spending, and 4) OOP spending for specialty cancer drugs. RESULTS: The in-gap discount did not influence specialty cancer drug use, but reduced annual OOP spending for specialty cancer drugs among users without LIS by $1108. CONCLUSIONS: In-gap discounts in Part D decreased patients' financial burden to some extent, but resulted in no change in specialty drug use. As demand for specialty drugs increases, it will be important to ensure patients' access to needed drugs, while simultaneously reducing their financial burden.

Coverage for hepatitis C drugs in Medicare Part D.

OBJECTIVES: The recent arrival of new hepatitis C virus (HCV) drugs has brought fiscal pressures onto Medicare Part D; spending on HCV drugs in Part D jumped from $283 million in 2013 to $4.5 billion in 2014. We examined the current benefit designs for HCV drugs in Part D plans and analyzed patients' financial burden for those drugs. STUDY DESIGN: A cross-sectional analysis of CMS' July 2015 Part D Plan Formulary File and the Wolters Kluwer Health Medi-Span Electronic Drug File v.2. METHODS: We analyzed the type and amount of cost sharing for HCV drugs and the extent to which plans apply utilization management tools. We then estimated total out-of-pocket spending for beneficiaries to complete a course of treatment. RESULTS: All Part D plans covered at least 1 recently introduced HCV drug, as of July 2015. Nearly all plans charged relatively high coinsurance and required prior authorization for new HCV drugs. For enrollees with no subsidy, the mean out-of-pocket spending needed to complete a course of treatment is substantial, ranging from $6297 to $10,889. For enrollees with a low-income subsidy, out-of-pocket spending varies between $10.80 and $1191. CONCLUSIONS: Under the current Part D benefits, HCV drug users with no subsidy face sizable financial burdens, even with catastrophic coverage and the recent in-gap discount for brand name drugs. As baby boomers-the group most likely to have HCV-join Medicare, efforts should be made to ensure patient access to these needed drugs.

Prevalence and healthcare utilization of herpes zoster and postherpetic neuralgia in South Korea: disparity among patients with different immune statuses.

OBJECTIVES: Despite the clinical and epidemiological importance of herpes zoster (HZ) and postherpetic neuralgia (PHN), their disease and economic burden related to immune status has not been studied in South Korea. Our aim was to calculate the prevalence and rate of healthcare utilization related to HZ and PHN among Korean patients stratified by immune status. METHODS: This retrospective study used the Health Insurance Review and Assessment Service National Patients Sample (HIRA K-NPS) database, which includes all medical claims from January to December 2009 on a representative sample of the Korean population. HZ and PHN patients aged ≥ 50 years were categorized into three groups by immune status: severely immunocompromised group, moderately compromised group, and non-compromised group. The prevalence, disease-related healthcare utilization, and medical costs were compared across the three groups. RESULTS: We estimated that there were 312,136 HZ patients and 48,461 PHN patients ≥ 50 years in South Korea. The prevalence of HZ and PHN was 18.54 and 2.88 per 1,000 persons, respectively, and increased with deteriorating immune status. The number of outpatient visits and hospitalization rate among HZ patients were highest in the severely immunocompromised group (4.38% and 7.52%, respectively) and lowest in the non-compromised group (3.82% and 4.08%, respectively). The average medical cost per patient in the severe group was the highest (240 US dollars) and that of the non-compromised group was the lowest (161 US dollars). No parameters were significantly different among patients with PHN by immunity. CONCLUSIONS: HZ patients with severe immunodeficiency had a higher prevalence of HZ, more outpatient visits and hospitalizations, longer hospitalizations, and higher medical costs than their counterparts did. Efforts should be made to reduce the HZ-related burden of severely immunocompromised patients.

Prevalence and factors affecting glucosamine use in Korea: a survey-based study.

Glucosamine and chondroitin are widely used as pharmaceutical and dietary supplements. However, there is a lack of information regarding consumer consumption of glucosamine and chondroitin in the Republic of Korea. We investigated the prevalence and factors affecting the use of glucosamine products in the general population aged 40 years and older in the Republic of Korea. We conducted this descriptive and exploratory study using a telephone-based survey with a structured questionnaire. We randomly selected subjects using a proportional allocation method based on age, gender, and region. We started the survey on September 19, 2009, and continued the survey until we obtained 1,000 respondents who were currently taking glucosamine or chondroitin, which occured on September 30, 2009. Among the 8,135 people approached, the response rate was 29.6%. A total of 12.2% of respondents (n = 991) were current users of glucosamine, while only 0.1% (n = 9) were current users of chondroitin. Two-fifths of current glucosamine users were not diagnosed with osteoarthritis by a doctor nor did they experience arthritis pain. These participants used glucosamine to maintain and promote joint health. Information on glucosamine was mainly obtained through advertisements on television or the Internet. Seventy percent of current users indicated that they did not know the composition of the glucosamine they took. Appropriate information and guides concerning glucosamine or chondroitin usage should be provided by expert clinicians because of the accessibility of both these cartilage derivatives as supplements and medical drugs in the Republic of Korea.

Patient adherence and reimbursement amount for antidiabetic fixed-dose combination products compared with dual therapy among Texas Medicaid recipients.

BACKGROUND: Little is known about the potential for improved adherence with and cost savings of fixed-dose combination therapy (FDCT) products compared with analogous dual therapy for type 2 diabetes mellitus. OBJECTIVES: The objectives of this study were as follows: (1) to describe patient adherence to various oral antidiabetic regimens (ie, dual therapy and FDCT); (2) to determine whether there is a difference in medication adherence between FDCT users and analogous dual-therapy users; and (3) to assess whether there is a difference in reimbursement amounts between an FDCT product and its individual components. METHODS: This study was a retrospective cohort analysis using the Texas Medicaid prescription claims database. The study subjects included those who used antidiabetic FDCT or dual therapy from August 1, 2000, to July 31, 2004. The identification period of study subjects was between August 1, 2000, and July 31, 2004, including 12 months before and after the index date, so that the overall time frame was from August 1, 1999, through July 31, 2005. Prescription claims were analyzed over a 12-month preindex and 12-month postindex period. Adherence was measured using medication possession ratio (MPR), and regimen costs per tablet were assessed utilizing the index prescription. RESULTS: Overall, 7570 FDCT users and 14,762 dual-therapy users were identified. Regarding the postindex period, FDCT users had 1.8% higher MPR compared with dual-therapy users (78.6% vs 77.2%). Patients who switched from monotherapy to FDCT had a 1.5% decrease in adherence (from 79.7% to 78.5%), whereas those who switched from monotherapy to dual therapy had a 10.0% decrease in adherence (from 83.0% to 74.7%). Those who switched from dual therapy to FDCT had a 12.4% increase in adherence (from 72.7% to 81.7%). Multivariate logistic regression analyses revealed that among preindex monotherapy users, FDCT users were significantly more likely to have higher adherence than dual-therapy users (odds ratio [OR] = 1.867; 95% CI, 1.716-2.032) after controlling for covariates, and the results were similar among preindex dual-therapy users (OR = 1.551; 95% CI, 1.204-1.999). From the perspective of the third-party payer, all FDCT products were significantly less expensive than their equivalent individual components (P < 0.001). CONCLUSIONS: Among these Texas Medicaid beneficiaries, antidiabetic FDCT users were more adherent to their regimen than dual-therapy users, and FDCT was less expensive than the analogous dual therapy. Because multiple agents are often required to achieve adequate glycemic control, it may be clinically and economically beneficial to treat eligible patients with FDCT products.