Therapeutic vaccines for advanced non-small cell lung cancer.

BACKGROUND: New strategies in immunotherapy with specific antigens that trigger an anti-tumour immune response in people with lung cancer open the possibility of developing therapeutic vaccines aimed at boosting the adaptive immune response against cancer cells. OBJECTIVES: To evaluate the effectiveness and safety of different types of therapeutic vaccines for people with advanced non-small cell lung cancer. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Wanfang Data, and China Journal Net (CNKI) up to 22 August 2023. SELECTION CRITERIA: We included parallel-group, randomised controlled trials evaluating a therapeutic cancer vaccine, alone or in combination with other treatments, in adults (> 18 years) with advanced non-small cell lung cancer (NSCLC), whatever the line of treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were overall survival, progression-free survival, and serious adverse events; secondary outcomes were three- and five-year survival rates and health-related quality of life. MAIN RESULTS: We included 10 studies with 2177 participants. The outcome analyses included only 2045 participants (1401 men and 644 women). The certainty of the evidence varied by vaccine and outcome, and ranged from moderate to very low. We report only the results for primary outcomes here. TG4010 The addition of the vector-based vaccine, TG4010, to chemotherapy, compared with chemotherapy alone in first-line treatment, may result in little to no difference in overall survival (hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.65 to 1.05; 2 studies, 370 participants; low-certainty evidence). It may increase progression-free survival slightly (HR 0.74, 95% CI 0.55 to 0.99; 1 study, 222 participants; low-certainty evidence). It may result in little to no difference in the proportion of participants with at least one serious treatment-related adverse event, but the evidence is very uncertain (risk ratio (RR) 0.70, 95% CI 0.23 to 2.19; 2 studies, 362 participants; very low-certainty evidence). Epidermal growth factor vaccine Epidermal growth factor vaccine, compared to best supportive care as switch maintenance treatment after first-line chemotherapy, may result in little to no difference in overall survival (HR 0.82, 95% CI 0.66 to 1.02; 1 study, 378 participants; low-certainty evidence), and in the proportion of participants with at least one serious treatment-related adverse event (RR 1.32, 95% CI 0.88 to 1.98; 2 studies, 458 participants; low-certainty evidence). hTERT (vx-001) The hTERT (vx-001) vaccine compared to placebo as maintenance treatment after first-line chemotherapy may result in little to no difference in overall survival (HR 0.97, 95% CI 0.70 to 1.34; 1 study, 190 participants). Racotumomab Racotumomab compared to placebo as a switch maintenance treatment post-chemotherapy was assessed in one study with 176 participants. It may increase overall survival (HR 0.63, 95% CI 0.46 to 0.87). It may make little to no difference in progression-free survival (HR 0.73, 95% CI 0.53 to 1.00) and in the proportion of people with at least one serious treatment-related adverse event (RR 1.03, 95% CI 0.15 to 7.18). Racotumomab versus docetaxel as switch maintenance therapy post-chemotherapy was assessed in one study with 145 participants. The study did not report hazard rates on overall survival or progression-free survival time, but the difference in median survival times was very small - less than one month. Racotumomab may result in little to no difference in the proportion of people with at least one serious treatment-related adverse event compared with docetaxel (RR 0.89, 95% CI 0.44 to 1.83). Personalised peptide vaccine Personalised peptide vaccine plus docetaxel compared to docetaxel plus placebo post-chemotherapy treatment may result in little to no difference in overall survival (HR 0.80, 95% CI 0.42 to 1.52) and progression-free survival (HR 0.78, 95% CI 0.43 to 1.42). OSE2101 The OSE2101 vaccine compared with chemotherapy, after chemotherapy or immunotherapy, was assessed in one study with 219 participants. It may result in little to no difference in overall survival (HR 0.86, 95% CI 0.62 to 1.19). It may result in a small difference in the proportion of people with at least one serious treatment-related adverse event (RR 0.95, 95% CI 0.91 to 0.99). SRL172 The SRL172 vaccine of killed Mycobacterium vaccae, added to chemotherapy, compared to chemotherapy alone, may result in no difference in overall survival, and may increase the proportion of people with at least one serious treatment-related adverse event (RR 2.07, 95% CI 1.76 to 2.43; 351 participants). AUTHORS' CONCLUSIONS: Adding a vaccine resulted in no differences in overall survival, except for racotumomab, which showed some improvement compared to placebo, but the difference in median survival time was very small (1.4 months) and the study only included 176 participants. Regarding progression-free survival, we observed no differences between the compared treatments, except for TG4010, which may increase progression-free survival slightly. There were no differences between the compared treatments in serious treatment-related adverse events, except for SRL172 (killed Mycobacterium vaccae) added to chemotherapy, which was associated with an increase in the proportion of participants with at least one serious treatment-related adverse event, and OSE2101, which may decrease slightly the proportion of people having at least one serious treatment-related adverse event. These conclusions should be interpreted cautiously, as the very low- to moderate-certainty evidence prevents drawing solid conclusions: many vaccines were evaluated in a single study with small numbers of participants and events.

Factors associated with salbutamol overuse in bronchiolitis.

Numerous studies have shown that quality improvement methods can reduce the use of medications in the management of bronchiolitis. Our objective is to identify factors related to the overuse of salbutamol in the treatment of bronchiolitis before and after an improvement initiative. Observational study of sociodemographic and clinical factors associated with the use of salbutamol in children diagnosed with bronchiolitis. This was a secondary analysis of a prospective cohort study conducted at 135 primary care (PC) centers and eight pediatric emergency departments (ED) in the Osakidetza/Basque Health Service (Spain) in two epidemic seasons between which a bronchiolitis integrated care pathway (BICP) had been implemented: pre-intervention season from October 2018 to March 2019 and post-intervention season from October 2019 to March 2020. Generalized linear mixed models were used to estimate association of studied variables on use of salbutamol over the two seasons. Four thousand one hundred thirty-four ED attendances and 8573 PC visits were included, of which 1936 (46.8%). And 4067 (47.4%) occurred in the post-intervention period respectively. Six independent risk factors were associated with overuse of salbutamol in both seasons: age ≥ 1 year, aOR 2.32 (2.01 to 2.68) in PC centers, and aOR 6.84 (4.98 to 9.39) in EDs; being seen in the last third of the bronchiolitis season, aOR 1.82 (1.51 to 2.18) in PC centers and aOR 1.78 (1.19 to 2.64) in EDs; making more than one visit to the PC center, aOR 4.18 (3.32 to 5.27) or the ED, aOR 2.06 (1.59 to 2.66); being seen by a general practitioner, aOR 1.97 (1.58 to 2.46) in PC centers; and having a more severe episode, aOR 3.01 (1.89 to 4.79) in EDs.     Conclusion:There are factors associated with salbutamol overuse in children diagnosed with bronchiolitis in PC and emergency settings that persist after the deployment of quality improvement initiatives. What is Known: • Quality improvement initiatives have been shown to decrease the use of non-evidence-based treatments and testing in bronchiolitis. • The magnitude and pattern of change in the use of medications linked to the quality improvement initiatives are not uniform across the same health service. What is New: • Children diagnosed with bronchiolitis ≥ 1 year of age, seen in the last third of the bronchiolitis season, attending more than once, treated by a general practitioner, and/or with more severe episodes are more likely to be treated with salbutamol. • These factors may remain present despite the implementation of improvement initiatives focused on reducing the use of medications in the management of bronchiolitis.

Myofunctional therapy (oropharyngeal exercises) for obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is a syndrome characterised by episodes of apnoea (complete cessation of breathing) or hypopnoea (insufficient breathing) during sleep. Classical symptoms of the disease - such as snoring, unsatisfactory rest and daytime sleepiness - are experienced mainly by men; women report more unspecific symptoms such as low energy or fatigue, tiredness, initial insomnia and morning headaches. OSA is associated with an increased risk of occupational injuries, metabolic diseases, cardiovascular diseases, mortality, and being involved in traffic accidents. Continuous positive airway pressure (CPAP) - delivered by a machine which uses a hose and mask or nosepiece to deliver constant and steady air pressure- is considered the first treatment option for most people with OSA. However, adherence to treatment is often suboptimal. Myofunctional therapy could be an alternative for many patients. Myofunctional therapy consists of combinations of oropharyngeal exercises - i.e. mouth and throat exercises. These combinations typically include both isotonic and isometric exercises involving several muscles and areas of the mouth, pharynx and upper respiratory tract, to work on functions such as speaking, breathing, blowing, sucking, chewing and swallowing. OBJECTIVES: To evaluate the benefits and harms of myofunctional therapy (oropharyngeal exercises) for the treatment of obstructive sleep apnoea. SEARCH METHODS: We identified randomised controlled trials (RCTs) from the Cochrane Airways Trials Register (date of last search 1 May 2020). We found other trials at web-based clinical trials registers. SELECTION CRITERIA: We included RCTs that recruited adults and children with a diagnosis of OSA. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We assessed our confidence in the evidence by using GRADE recommendations. Primary outcomes were daytime sleepiness, morbidity and mortality. MAIN RESULTS: We found nine studies eligible for inclusion in this review and nine ongoing studies. The nine included RCTs analysed a total of 347 participants, 69 of them women and 13 children. The adults' mean ages ranged from 46 to 51, daytime sleepiness scores from eight to 14, and severity of the condition from mild to severe OSA. The studies' duration ranged from two to four months. None of the studies assessed accidents, cardiovascular diseases or mortality outcomes. We sought data about adverse events, but none of the included studies reported these. In adults, compared to sham therapy, myofunctional therapy: probably reduces daytime sleepiness (Epworth Sleepiness Scale (ESS), MD (mean difference) -4.52 points, 95% Confidence Interval (CI) -6.67 to -2.36; two studies, 82 participants; moderate-certainty evidence); may increase sleep quality (MD -3.90 points, 95% CI -6.31 to -1.49; one study, 31 participants; low-certainty evidence); may result in a large reduction in Apnoea-Hypopnoea Index (AHI, MD -13.20 points, 95% CI -18.48 to -7.93; two studies, 82 participants; low-certainty evidence); may have little to no effect in reduction of snoring frequency but the evidence is very uncertain (Standardised Mean Difference (SMD) -0.53 points, 95% CI -1.03 to -0.03; two studies, 67 participants; very low-certainty evidence); and probably reduces subjective snoring intensity slightly (MD -1.9 points, 95% CI -3.69 to -0.11 one study, 51 participants; moderate-certainty evidence). Compared to waiting list, myofunctional therapy may: reduce daytime sleepiness (ESS, change from baseline MD -3.00 points, 95% CI -5.47 to -0.53; one study, 25 participants; low-certainty evidence); result in little to no difference in sleep quality (MD -0.70 points, 95% CI -2.01 to 0.61; one study, 25 participants; low-certainty evidence); and reduce AHI (MD -6.20 points, 95% CI -11.94 to -0.46; one study, 25 participants; low-certainty evidence). Compared to CPAP, myofunctional therapy may result in little to no difference in daytime sleepiness (MD 0.30 points, 95% CI -1.65 to 2.25; one study, 54 participants; low-certainty evidence); and may increase AHI (MD 9.60 points, 95% CI 2.46 to 16.74; one study, 54 participants; low-certainty evidence). Compared to CPAP plus myofunctional therapy, myofunctional therapy alone may result in little to no difference in daytime sleepiness (MD 0.20 points, 95% CI -2.56 to 2.96; one study, 49 participants; low-certainty evidence) and may increase AHI (MD 10.50 points, 95% CI 3.43 to 17.57; one study, 49 participants; low-certainty evidence). Compared to respiratory exercises plus nasal dilator strip, myofunctional therapy may result in little to no difference in daytime sleepiness (MD 0.20 points, 95% CI -2.46 to 2.86; one study, 58 participants; low-certainty evidence); probably increases sleep quality slightly (-1.94 points, 95% CI -3.17 to -0.72; two studies, 97 participants; moderate-certainty evidence); and may result in little to no difference in AHI (MD -3.80 points, 95% CI -9.05 to 1.45; one study, 58 participants; low-certainty evidence). Compared to standard medical treatment, myofunctional therapy may reduce daytime sleepiness (MD -6.40 points, 95% CI -9.82 to -2.98; one study, 26 participants; low-certainty evidence) and may increase sleep quality (MD -3.10 points, 95% CI -5.12 to -1.08; one study, 26 participants; low-certainty evidence). In children, compared to nasal washing alone, myofunctional therapy and nasal washing may result in little to no difference in AHI (MD 3.00, 95% CI -0.26 to 6.26; one study, 13 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Compared to sham therapy, myofunctional therapy probably reduces daytime sleepiness and may increase sleep quality in the short term. The certainty of the evidence for all comparisons ranges from moderate to very low, mainly due to lack of blinding of the assessors of subjective outcomes, incomplete outcome data and imprecision. More studies are needed. In future studies, outcome assessors should be blinded. New trials should recruit more participants, including more women and children, and have longer treatment and follow-up periods.