Is phased implementation of HPV testing and triage with dual staining the way to transform organized cytology screening?

OBJECTIVE: The substantial material and legislative investments in establishing and maintaining cytological screening in the Czech Republic represent barriers to a direct transition to primary HPV screening. Therefore, the LIBUSE project was implemented to test the efficacy of phasing in HPV DNA testing as a co-test to cytology in routine screening of women >30 years of age. METHODS: Women aged 30 to 60 years who underwent regular annual Pap smears were co-tested for HPV DNA with selective 16/18 genotyping at 3-year intervals. All HPV 16/18-positive cases and/or cases with a severe abnormality in cytology were sent for colposcopy; HPV non-16/18-positive cases and LSILs were graded using p16/Ki67 dual-stain cytology, and positive cases were sent for colposcopy. RESULTS: Overall, 2409 patients were included. After the first combined screening (year 'zero') visit, 7.4% of women were HPV-positive and 2.0% were HPV16/18-positive; only 8 women had severe Pap smear abnormalities. Triage by dual staining was positive in 21.9% of cases (28/128). Biopsy confirmed 34 high-grade precancer lesions. At the second combined visit (year 'three'), the frequency of HPV infection (5.3% vs. 7.4%) frequency of HPV16/18 (1.1% vs. 2.0%), referrals for colposcopy (35 vs. 83), and biopsy verified high-grade lesions (5 vs. 34) were significantly lower (all P  ≤ 0.001). CONCLUSION: The addition of HPV DNA testing with selective genotyping of HPV16/18 to existing cytology screening significantly increased the safety of the program. The gradual introduction of HPV testing was well received by healthcare professionals and patients, and can facilitate transformation of the cytology-based screening. ClinicalTrials.gov Identifier: NCT05578833.

Lifestyle Walking Intervention for Patients With Heart Failure With Reduced Ejection Fraction: The WATCHFUL Trial.

BACKGROUND: Physical activity is pivotal in managing heart failure with reduced ejection fraction, and walking integrated into daily life is an especially suitable form of physical activity. This study aimed to determine whether a 6-month lifestyle walking intervention combining self-monitoring and regular telephone counseling improves functional capacity assessed by the 6-minute walk test (6MWT) in patients with stable heart failure with reduced ejection fraction compared with usual care. METHODS: The WATCHFUL trial (Pedometer-Based Walking Intervention in Patients With Chronic Heart Failure With Reduced Ejection Fraction) was a 6-month multicenter, parallel-group randomized controlled trial recruiting patients with heart failure with reduced ejection fraction from 6 cardiovascular centers in the Czech Republic. Eligible participants were ≥18 years of age, had left ventricular ejection fraction <40%, and had New York Heart Association class II or III symptoms on guidelines-recommended medication. Individuals exceeding 450 meters on the baseline 6MWT were excluded. Patients in the intervention group were equipped with a Garmin vívofit activity tracker and received monthly telephone counseling from research nurses who encouraged them to use behavior change techniques such as self-monitoring, goal-setting, and action planning to increase their daily step count. The patients in the control group continued usual care. The primary outcome was the between-group difference in the distance walked during the 6MWT at 6 months. Secondary outcomes included daily step count and minutes of moderate to vigorous physical activity as measured by the hip-worn Actigraph wGT3X-BT accelerometer, NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity C-reactive protein biomarkers, ejection fraction, anthropometric measures, depression score, self-efficacy, quality of life, and survival risk score. The primary analysis was conducted by intention to treat. RESULTS: Of 218 screened patients, 202 were randomized (mean age, 65 years; 22.8% female; 90.6% New York Heart Association class II; median left ventricular ejection fraction, 32.5%; median 6MWT, 385 meters; average 5071 steps/day; average 10.9 minutes of moderate to vigorous physical activity per day). At 6 months, no between-group differences were detected in the 6MWT (mean 7.4 meters [95% CI, -8.0 to 22.7]; P=0.345, n=186). The intervention group increased their average daily step count by 1420 (95% CI, 749 to 2091) and daily minutes of moderate to vigorous physical activity by 8.2 (95% CI, 3.0 to 13.3) over the control group. No between-group differences were detected for any other secondary outcomes. CONCLUSIONS: Whereas the lifestyle intervention in patients with heart failure with reduced ejection fraction improved daily steps by about 25%, it failed to demonstrate a corresponding improvement in functional capacity. Further research is needed to understand the lack of association between increased physical activity and functional outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03041610.

Trunk muscle dysfunction in patients with myotonic dystrophy type 2 and its contribution to chronic low back pain.

Introduction: Myotonic dystrophy type 2 (MD2) presents with a varied manifestation. Even though the myopathy in these patients is more widespread, axial musculature involvement is one of the most prominent conditions. MD2 patients also often report chronic low back pain (CLBP). The purpose of this study was to evaluate trunk muscle function, including respiratory muscles, in patients with MD2 and to compare it with healthy controls, to determine the occurrence of CLBP in patients with MD2, and to assess whether trunk muscle dysfunction increases the risk of CLBP in these patients. Methods: We enrolled 40 MD2 patients (age range 23 to 76 years, 26 women). A comprehensive battery of tests was used to evaluate trunk muscle function. The tests consisted of quantitative muscle strength testing of low back extensor muscles and respiratory muscles and the assessment of trunk muscle endurance. A neurological evaluation contained procedures assessing the distribution of muscle weakness, myotonia, and pain, and used questionnaires focused on these items and on disability, depression, and physical activity. Results: The results of this study suggest that patients with MD2 show significant dysfunction of the trunk muscles, including the respiratory muscles, expressed by decreased muscle strength and endurance. The prevalence of CLBP in patients with MD2 was 52.5%. Based on our analysis, the only independent significant risk factor for CLBP in these patients was maximal isometric lower back extensor strength in a prone position ≤ 15.8 kg (OR = 37.3). Other possible risk factors were severity of myotonia and reduced physical activity. Conclusion: Outcomes of this study highlighted the presence of axial muscle dysfunction, respiratory muscle weakness, and frequent occurrence of CLBP together with its risk factors in patients with MD2. We believe that the findings of this study may help in management and prevention programs for patients with MD2.

Effectiveness of first-line anticancer treatment may predict treatment response in further lines in stage III/IV patients with non-small cell lung cancer.

PURPOSE: The aim of our study was to evaluate if therapeutic success in the first-line of anticancer treatments in patients with NSCLC may predict treatment success in the following lines. METHODS: We analyzed the data of patients with NSCLC stage III/IV from the TULUNG registry separately for chemotherapy, TKIs, ALK inhibitors, and immunotherapy in the first line during the years 2011-2019. "Succesful treatment " was defined as PFS ≥ 6 months, a "good responder " was a patient with ˃50% of "successful treatment " lines. Treatment responses were analyzed separately for each drug group. Descriptive statistics, Fisher exact test, Pearson Chi-Squared test, log-rank test, and univariate/multivariate logistic regression models were used. RESULTS: The first-line TKI therapy was successful in 66.2%, while good responders accounted for 50.7% of the cohort and their rates were similar for all types of TKIs. First-line platinum-based chemotherapy was successful in 43.1% and 48.6% for combinations with pemetrexed and bevacizumab, respectively. Good responders accounted for 29.5% and 25.9%, respectively. In the group of ALK inhibitors, we observed treatment success in 52.3% of cases, while alectinib showed the highest effectiveness (up to 70%). Good responders constituted 50% of the group. In the first-line immunotherapy group, survival benefit was observed in 52.3%, and good responders constituted 52.3% of the cohort. CONCLUSION: We concluded that the treatment success in first-line therapies in patients with NSCLC may predict survival benefits in the subsequent lines, particularly in EGFR- or ALK-positive disease and immunotherapy-treated patients.

Serious Immune-related Adverse Events Are Associated With Greater Efficacy of Nivolumab Therapy Against Non-small Cell Lung Cancer.

BACKGROUND/AIM: The aim of this study was to investigate possible association between adverse events of nivolumab therapy and the effectiveness of treatment in patients with non-small cell lung cancer (NSCLC). Focusing on serious adverse events (i.e., those of grade ≥3), we evaluated overall survival (OS), progression-free survival (PFS), as well as objective response rate (ORR) to treatment. PATIENTS AND METHODS: We retrospectively analyzed a set of patients from the TULUNG database of NSCLC treated with nivolumab in eight oncology centers. We evaluated OS data based upon this set. To reduce possible bias, we further evaluated a subgroup of patients treated at the University Hospital in Pilsen, where the occurrence of adverse events, PFS, and ORR were independently examined by two experienced physicians. Survival statistics were evaluated using the Kaplan-Meier method and Cox analysis. RESULTS: We observed significantly greater OS, PFS, and ORR in the group of patients experiencing adverse events upon nivolumab treatment versus in those patients without such events. Although the univariable model analyzing the data set of all patients demonstrated higher OS in patients with serious adverse events, only a nonsignificant trend was observed in the Cox multivariable model. In a subgroup of patients with PFS and ORR evaluation, we did observe significant, favorable effects for patients having had serious adverse effects. CONCLUSION: Patients experiencing severe adverse events show a tendency toward better OS, PFS, and ORR compared to patients without or having only mild adverse events with nivolumab treatment.