BACKGROUND: Medication non-adherence is a significant problem in patients with Chronic Obstructive Pulmonary Disease (COPD). Efforts to address this issue are receiving increased attention. Simplifying treatment by prescribing single-inhaler triple therapy (SITT) as an alternative to multi-inhaler triple therapy (MITT) or with smart inhalers are often considered potential solutions. However, the actual impact of these innovations on adherence and clinical outcomes is unclear.
METHODS: To address this knowledge gap we first conducted a literature review focusing on two research questions: 1) the difference in adherence between SITT and MITT users in COPD, and 2) the effect of smart inhalers on adherence in COPD. Separate searches were conducted in PubMed and two authors independently assessed the articles. In addition, we present a protocol for a study to acquire knowledge for the gaps identified.
RESULTS: To address the first research question, 8 trials were selected for further review. All trials were observational, i.e. randomized controlled trials were lacking. Seven of these trials showed higher adherence and/or persistence in patients on SITT compared with patients on MITT. In addition, four studies showed a positive effect of SITT on various clinical outcomes. For the second research question, 11 trials were selected for review. While most of the studies showed a positive effect of smart inhalers on adherence, there was considerable variation in the results regarding their effect on other clinical outcomes. The TRICOLON (TRIple therapy COnvenience by the use of one or multipLe Inhalers and digital support in ChrONic Obstructive Pulmonary Disease) trial aims to improve understanding regarding the effectiveness of SITT and smart inhalers in enhancing adherence. This open-label, randomized, multi-center study will enroll COPD patients requiring triple therapy at ten participating hospitals. In total, 300 patients will be randomized into three groups: 1) MITT; 2) SITT; 3) SITT with digital support through a smart inhaler and an e-health platform. The follow-up period will be one year, during which three methods of measuring adherence will be used: smart inhaler data, self-reported data using the Test of Adherence to Inhalers (TAI) questionnaire, and drug analysis in scalp hair samples. Finally, differences in clinical outcomes between the study groups will be compared.
CONCLUSIONS: Our review suggests promising results concerning the effect of SITT, as opposed to MITT, and smart inhalers on adherence. However, the quality of evidence is limited due to the absence of randomized controlled trials and/or the short duration of follow-up in many studies. Moreover, its impact on clinical outcomes shows considerable variation. The TRICOLON trial aims to provide solid data on these frequently mentioned solutions to non-adherence in COPD. Collecting data in a well-designed randomized controlled trial is challenging, but the design of this trial addresses both the usefulness of SITT and smart inhalers while ensuring minimal interference in participants\' daily lives.
BACKGROUND: NCT05495698 (Clinicaltrials.gov), registered at 08-08-2022. Protocol version: version 5, date 27-02-2023.

UNASSIGNED: Current guidelines recommend triple therapy maintenance inhalers for patients with recurrent exacerbations of chronic obstructive pulmonary disease (COPD); however, these maintenance therapies are underutilized. This study aimed to understand how physicians make COPD treatment decisions, and how combination maintenance therapies are utilized in a real-world setting.
UNASSIGNED: This exploratory, hypothesis-generating, non-interventional study used a cross-sectional online survey that was administered to a sample of practicing physicians in the United States. The survey included five fictitious vignettes detailing common symptoms experienced by patients with COPD. Survey questions included factors physicians consider in their decisions, and perceived barriers to prescribing treatments. Repeated measures multivariable analyses were conducted to evaluate how likely physicians were to switch to triple therapy versus no change to patient\'s current maintenance therapy or change to another maintenance therapy.
UNASSIGNED: In total, 200 physicians completed the survey. Cost of treatment and patient access to treatment were reported as the most common barriers physicians consider in their prescribing decisions. Physicians were more likely to switch a patient\'s maintenance inhaler to triple therapy versus no change to maintenance inhaler if they considered the patient\'s history of new symptoms, insurance status, and clinical guidelines in their decision. Physicians with more experience treating patients with COPD, and those who treat more patients with COPD per week, were more likely to switch to triple therapy versus no change to maintenance inhaler.
UNASSIGNED: This study demonstrates the complexity of factors that can influence physicians\' decisions when prescribing treatments for patients with COPD, including considerations of treatment cost, patient access and adherence, patient comorbidities, efficacy of current treatment, clinical guidelines, and provider\'s level of experience treating COPD. Further research may help elucidate the relative importance of the factors influencing physicians\' decisions and inform what types of decision-support tools would be most beneficial.
Chronic obstructive pulmonary disease (COPD) symptoms can be effectively managed with maintenance therapies, which are treatments that are taken routinely to help improve symptoms. A combination of three different therapies (triple therapy maintenance) has been shown to be more effective than a combination of two different therapies (dual therapy maintenance) in patients with moderate-to-severe COPD. However, maintenance therapies, including triple therapy, are underutilized. This study aimed to explore how physicians make their treatment decisions for patients with COPD, and how combination maintenance therapies are utilized. To do so, we administered a survey to a sample of practicing physicians in the United States. The survey included five clinically based, fictitious profiles, or vignettes, of patients with COPD, with common symptoms and patient characteristics being described. Physicians were then asked to answer questions about what treatment they would prescribe for each patient, and any factors they considered when deciding on a treatment for a patient. We found that cost of treatment and patient access to treatment were the most common barriers that physicians considered when choosing a treatment. Physicians were also more likely to switch a patient’s maintenance inhaler to a triple therapy maintenance inhaler if they considered the patient’s history of new symptoms, patient’s insurance status, and clinical guidelines when making their decisions. Our study shows that there are many complex factors that influence physicians’ decisions when deciding on a treatment for patients with COPD.

UNASSIGNED: Helicobacter pylori infection is a common gastrointestinal infection that affects around 50% of the global population. This infection can lead to various health conditions such as peptic ulcer disease, dyspepsia, gastric carcinoma, and mucosa-associated lymphoid tissue lymphoma. The triple therapy which consists of proton-pump inhibitors, clarithromycin, and amoxicillin or metronidazole for 14 days is considered the first-line treatment for H. pylori and its eradication, especially in areas where clarithromycin sensitivity is still high. However, recent research shows that the efficacy of this treatment is decreasing due to antibiotic resistance.
UNASSIGNED: This was a retrospective study that took place at Al-Hayat Jazan Hospital in Jazan, Saudi Arabia. The study analyzed the medical records of 186 patients with H. pylori who had undergone the standard triple therapy. The objectives of this study were to determine the eradication rate of H. pylori by using the standard triple therapy, and to highlight the influence of some demographic characteristics such as age, gender, diabetes mellitus, and smoking on the eradication rate, in Jazan region, Saudi Arabia.
UNASSIGNED: The medical records of 186 patients were included in the study. The overall rate of successful eradication was found to be 77.4%. The results of the study showed that the decline in the eradication rate was significantly associated with the presence of diabetes and smoking status (with p-values of <0.001 and <0.004, respectively).
UNASSIGNED: This study finds that the standard triple therapy for H. pylori eradication is less effective than optimal standards, as per literature and guidelines. Given its declining efficacy globally, alternative first-line treatments may be necessary. Further research is needed to assess its effectiveness in various regional contexts.

BACKGROUND: This cost-utility analysis assessed the long-term clinical and economic benefits of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy vs FF/VI or UMEC/VI from a Quebec societal perspective in patients with chronic obstructive pulmonary disease (COPD) with ≥1 moderate/severe exacerbation in the previous year.
METHODS: The validated GALAXY disease progression model was utilized, with parameters set to baseline and efficacy data from IMPACT. Treatment costs (2017 Canadian dollars [C$]) were estimated using Quebec-specific unit costs. Costs and health outcomes were discounted at 1.5 %/year. A willingness-to-pay threshold of C$50,000/quality-adjusted life year (QALY) was considered cost-effective. Outcomes modeled were exacerbation rates, QALYs, life years (LYs), costs and incremental cost-effectiveness ratios (ICERs). Subgroup analyses were performed according to prior treatment, exacerbation history in the previous year, and baseline lung function.
RESULTS: Over a lifetime horizon, FF/UMEC/VI resulted in more QALYs and LYs gained, at a small incremental cost compared with FF/VI and UMEC/VI. From a societal perspective, the estimated ICER for the base case was C$18,152/QALY vs FF/VI, and C$15,847/QALY vs UMEC/VI. For the subgroup analyses (FF/UMEC/VI compared with FF/VI and UMEC/VI), ICERs ranged from: C$17,412-25,664/QALY and C$16,493-18,663/QALY (prior treatment); C$15,247-19,924/QALY and C$15,444-28,859/QALY (exacerbation history); C$14,025-34,154/QALY and C$16,083-17,509/QALY (baseline lung function).
CONCLUSIONS: FF/UMEC/VI was predicted to improve outcomes and be cost-effective vs both comparators in the base case and all subgroup analyses, and based on this analysis would be an appropriate investment of health service funds in Quebec.
BACKGROUND: IMPACT trial NCT02164513.

UNASSIGNED: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti-PD-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT.
UNASSIGNED: This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles.
UNASSIGNED: During a median follow-up of 11.23 months (range, 3.07-34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The two-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively.
UNASSIGNED: Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.

Background Helicobacter pylori infection has been identified to cause constantly recurring inflammation, leading to gastrointestinal tract disorders, including carcinoma. The standard triple therapy (STT), used to eradicate H. pylori, includes two antimicrobials and a proton pump inhibitor for two weeks. Other drug regimens have also been developed since H. pylori exhibits antimicrobial resistance. These regimens, including probiotics, have been shown to lower adverse drug reactions (ADR), improve drug adherence, exert bacteriostatic effect, and reduce inflammation. Objective This study intended to explore probiotic intervention for improving eradication rates and mitigating adverse effects while administrating STT.  Methods This prospective study was conducted from May to December, 2021, in the Department of Gastroenterology of Ship International Hospital, Dhaka, Bangladesh, to observe the effects of probiotics inclusion along with STT on H. pylori eradication. A total of 100 patients aged ≥18 years who tested positive for H. pylori were included. The experimental group (n=50) was given STT and probiotics, and the control group (n=50) was given only STT without probiotics for 14 days. Necessary follow-up was done six weeks after treatment. An independent sample t-test, chi-square test, and multiple regression analysis were used for statistical analysis. Result The odds of getting rapid urease test (RUT) negative results from positive were 2.06 times higher (95%CI= 0.95, 3.22, p=0.054) in the experimental group. ADRs were crucially towering in the control group (p=0.045) compared to the probiotics group. The probiotics group had a lower risk of having adverse effects by 0.54 times (95%CI=0.19, 0.84, p=0.032) than the control group. Conclusion Using probiotics and STT together to eradicate H. pylori may lower ADR and improve treatment adherence. It may also help terminate H. pylori infection more effectively. More research is required as H. pylori is very contagious and can ultimately cause life-threatening gastric cancer.

BACKGROUND: Helicobacter pylori (H. pylori) is strongly associated with peptic ulcer disease and gastric cancer. We evaluated two triple therapy regimens comprising esomeprazole, high dose bismuth, and different doses of amoxicillin for first-line H. pylori eradication.
METHODS: Two hundred patients with dyspepsia and naive H. pylori infection were randomly assigned into two groups (n = 100). Both groups were treated for 14 days similarly with esomeprazole (40 mg, twice daily) and bismuth subcitrate (240 mg, three times daily), but the dose of amoxicillin was varied between Groups A (750 mg) and B (1000 mg) three times daily. Treatment compliance and side effect were evaluated following the therapies and after 8 weeks, a negative test of stool H. pylori antigen confirmed eradication.
RESULTS: The two groups were comparable with respect to sex and age. According to intention to treat analysis, eradication rates were 80% (95% CI: 77.2%-82.8%) and 90% (95% CI: 84.1%-95.9%) in A and B groups, respectively (p = 0.22). Per-protocol eradication rates were 87% (95% CI: 80.4%-93.6%) and 92.8% (95% CI: 87.7%-97.9%), respectively (p = 0.23). Severe adverse effects were 3% and 2%, respectively (p = 0.34).
CONCLUSIONS: High dose esomeprazole, amoxicillin and bismuth achieved 92.8% cure rates per protocol in a country with a high background rate of resistance. Additional studies are needed to ascertain whether this therapy can be further improved. Until then, it can be recommended as a first-line H. pylori eradication in north of Iran.

BACKGROUND: Due to the progressive decline in β-cell function, it is often necessary to utilize multiple agents with complementary mechanisms of action to address various facets and achieve glycemic control. Thus, this study aimed to evaluate the efficacy and safety of a fixed-dose combination (FDC) of metformin/sitagliptin/pioglitazone (MSP) therapy vs. metformin/sitagliptin (MS) in type 2 diabetes mellitus (T2DM).
METHODS: In this phase 3, multicenter, double-blind study, patients with T2DM who exhibited inadequate glycemic control with HbA1c of 8.0-11.0% while taking ≥1500 mg/day metformin for at least 6 weeks were randomized to receive either FDC of MSP (1000/100/15 mg) or MS (1000/100 mg) per day for 24 weeks. The primary outcome measure was the change in HbA1c, and secondary outcomes included changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and body weight from baseline to 24 weeks along with safety and tolerability.
RESULTS: Among the 236 patients randomized, 207 (87.71%) successfully completed the study. All baseline characteristics were comparable between the FDC of MSP and MS groups. There was a subsequent significant reduction of HbA1c in FDC of MSP (- 1.64) vs. MS (- 1.32); between groups was [- 0.32% (95% CI, - 0.59, - 0.05)], P = 0.0208. Similar reductions were found in FPG [- 13.2 mg/dL (95% CI, - 22.86, - 3.71)], P = 0.0068, and PPG [- 20.83 mg/dL (95% CI, - 34.11, - 7.55)], P = 0.0023. There were no significant changes in body weight. A total of 27 adverse effects (AEs) and one severe AE were reported, none of which were related to the study drug.
CONCLUSIONS: The FDC of MSP demonstrated significant efficacy in managing glycemic indices and could serve as a valuable tool for physicians in the management of Indian patients with T2DM.
BACKGROUND: Clinical Trials Registry of India, CTRI/2021/10/037461.

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BACKGROUND: Adding LAMA to LABA/ICS is recommended to improve control in patients with persistent asthma.
METHODS: This observational, retrospective, before-and-after study considered patients diagnosed with asthma who started LABA/ICS + LAMA treatment (triple therapy, TT) between 1 January 2017 and 31 December 2018 and had been treated with LABA/ICS (dual therapy, DT) in the year before. Changes in lung function and exacerbation rates, healthcare resource utilization, and healthcare and non-healthcare costs (€2019) were estimated in patients with asthma in clinical practices in Spain. Data from computerized medical records from seven Spanish regions were collected ±1 year of LAMA addition.
RESULTS: 4740 patients (64.1 years old [SD: 16.3]) were included. TT reduced the incidence of exacerbations by 16.7% (p < 0.044) and the number of patients with exacerbations by 8.5% (p < 0.001) compared to previous DT. The rate of patients with severe exacerbations requiring systemic corticosteroids and their hospitalization rates significantly decreased by 22.5% and 29.5%. TT significantly improved FEV1, FVC, and FEV1/FVC, saving €571/patient for society. Younger patients with asthma (18-44 years old) and patients with severe asthma (FEV1 < 60%) performed better upon the initiation of TT.
CONCLUSIONS: TT reduced asthma exacerbations, improved lung function and reduced healthcare costs vs. DT, particularly in patients requiring systemic corticosteroids to treat severe exacerbations.