Effectiveness of tailored talks between a cancer screening specialist and general practitioners to improve the uptake of colorectal cancer screening in Ancona (Italy) during the pandemic period.

BACKGROUND: Colorectal cancer (CRC) screening uptake in many countries has been low and further impacted by the COVID-19 pandemic. General Practitioners (GPs) are key facilitators, however research on their impact on organised CRC screening is still limited. OBJECTIVES: To evaluate the effectiveness of tailored talks with GPs to increase population uptake of the long-established CRC screening programme in Ancona province, Italy. METHODS: In this prospective cohort study, one-to-one tailored talks were organised in January 2020 between the GPs of one county of the province (with GPs from other counties as controls) and the screening programme physician-in-chief to discuss the deployment and effectiveness of organised screening. Data was extracted from the National Healthcare System datasets and linear regression was used to assess the potential predictors of CRC screening uptake. RESULTS: The mean CRC screening uptake remained stable from 39.9% in 2018-19 to 40.8% in 2020-21 in the 22 GPs of the intervention county, whereas it statistically significantly decreased from 38.7% to 34.7% in the 232 control GPs. In multivariate analyses, belonging to the intervention county was associated with an improved uptake compared to the control counties (+5.1%; 95% Confidence Intervals - CI: 2.0%; 8.1%). CONCLUSION: Persons cared for by GPs who received a tailored talk with a cancer screening specialist avoided a drop in CRC screening adherence, which characterised all other Italian screening programmes during the COVID-19 emergency. If future randomised trials confirm the impact of tailored talks, they may be incorporated into existing strategies to improve population CRC screening uptake.

Tailored talks on CRC screening were conducted between one cancer screening specialist and GPs.Even during the pandemic, CRC screening uptake was stable among persons cared for by GPs targeted by tailored talks.If confirmed by randomised trials, tailored talks may be employed to improve CRC screening uptake.

Impact of the Italian Healthcare Outcomes Program (PNE) on the Care Quality of the Poorest Performing Hospitals.

One of the main aims of the Italian National Healthcare Outcomes Program (Programma Nazionale Esiti, PNE) is the identification of the hospitals with the lowest performance, leading them to improve their quality. In order to evaluate PNE impact for a subset of outcome indicators, we evaluated whether the performance of the hospitals with the lowest scores in 2016 had significantly improved after five years. The eight indicators measured the risk-adjusted likelihood of the death of each patient (adjusted relative risk-RR) 30 days after the admission for acute myocardial infarction, congestive heart failure, stroke, chronic obstructive pulmonary disease, chronic kidney disease, femur fracture or lung and colon cancer. In 2016, the PNE identified 288 hospitals with a very low performance in at least one of the selected indicators. Overall, 51.0% (n = 147) of these hospitals showed some degree of improvement in 2021, and 27.4% of them improved so much that the death risk of their patients fell below the national mean value. In 34.7% of the hospitals, however, the patients still carried a mean risk of death >30% higher than the average Italian patient with the same disease. Only 38.5% of the hospitals in Southern Italy improved the scores of the selected indicators, versus 68.0% in Northern and Central Italy. Multivariate analyses, adjusting for the baseline performance in 2016, confirmed univariate results and showed a significantly lower likelihood of improvement with increasing hospital volume. Despite the overall methodological validity of the PNE system, current Italian policies and actions aimed at translating hospital quality scores into effective organizational changes need to be reinforced with a special focus on larger southern regions.

Risk of SARS-CoV-2 Reinfection 3 Years after the Start of the Pandemic: A Population-Level Observational Study.

The risk of SARS-CoV-2 reinfections changes as new variants emerge, but the follow-up time for most of the available evidence is shorter than two years. This study evaluated SARS-CoV-2 reinfection rates in the total population of an Italian province up to three years since the pandemic's start. This retrospective cohort study used official National Healthcare System data on SARS-CoV-2 testing and vaccinations, demographics, and hospitalizations in the Province of Pescara, Italy, from 2 March 2020 to 31 December 2022. A total of 6541 (5.4%) reinfections and 33 severe and 18 lethal COVID-19 cases were recorded among the 121,412 subjects who recovered from a primary infection. There were no severe events following reinfection in the young population, whereas 1.1% of reinfected elderly died. A significantly higher reinfection risk was observed among females; unvaccinated individuals; adults (30-59 y); and subjects with hypertension, COPD, and kidney disease. Up to three years after a primary SARS-CoV-2 infection, the majority of the population did not experience a reinfection. The risk of severe COVID-19 following a reinfection was very low for young and adult individuals but still high for the elderly. The subjects with hybrid immunity showed a lower reinfection risk than the unvaccinated.

Predictors of SARS-CoV-2 Infection and Severe and Lethal COVID-19 after Three Years of Follow-Up: A Population-Wide Study.

In this cohort study, the general population of an Italian Province was followed for three years after the start of the pandemic, in order to identify the predictors of SARS-CoV-2 infection and severe or lethal COVID-19. All the National Healthcare System information on biographical records, vaccinations, SARS-CoV-2 swabs, COVID-19 cases, hospitalizations and co-pay exemptions were extracted from 25 February 2020 to 15 February 2023. Cox proportional hazard analysis was used to compute the relative hazards of infection and severe or lethal COVID-19, adjusting for age, gender, vaccine status, hypertension, diabetes, major cardiovascular diseases (CVD), chronic obstructive pulmonary disease (COPD), kidney disease or cancer. Among the 300,079 residents or domiciled citizens, 41.5% had ≥1 positive swabs during the follow-up (which lasted a mean of 932 days). A total of 3.67% of the infected individuals experienced severe COVID-19 (n = 4574) and 1.76% died (n = 2190). Females, the elderly and subjects with diabetes, CVD, COPD, kidney disease and cancer showed a significantly higher risk of SARS-CoV-2 infection. The likelihood of severe or lethal COVID-19 was >90% lower among the youngest, and all comorbidities were independently associated with a higher risk (ranging from +28% to +214%) of both outcomes. Two years after the start of the immunization campaign, the individuals who received ≥2 doses of COVID-19 vaccines still showed a significantly lower likelihood of severe or lethal disease, with the lowest risk observed among subjects who received at least one booster dose.

COVID-19 Vaccination Effectiveness in the General Population of an Italian Province: Two Years of Follow-Up.

We carried out a cohort study on the overall population of the province of Pescara, Italy, to assess the real-world effectiveness of SARS-CoV-2 vaccination against infection, severe, or lethal COVID-19, two years after the start of the vaccination campaign. We included all the resident or domiciled subjects, and extracted the official demographic, vaccination, COVID-19, hospital and co-pay exemption datasets from 1 January 2021, up to 15 February 2023. Cox proportional hazards analyses were adjusted for gender, age, diabetes, hypertension, COPD, major cardio- and cerebrovascular events, cancer, and kidney diseases. Throughout the follow-up (466 days on average), 186,676 subjects received greater than or equal to three vaccine doses (of ChAdOx1 nCoV-19, BNT162b2, mRNA-1273, NVX-CoV2373, or JNJ-78436735), 47,610 two doses, 11,452 one dose, and 44,989 none. Overall, 40.4% of subjects were infected with SARS-CoV-2. Of them, 2.74% had severe or lethal (1.30%) COVID-19. As compared to the unvaccinated, the individuals who received greater than or equal to one booster dose showed a ≥85% lower risk of severe or lethal COVID-19. A massive impact of vaccination was found among the elderly: 22.0% of the unvaccinated, infected individuals died, as opposed to less than 3% of those who received greater than or equal to three vaccine doses. No protection against infection was observed, although this finding was certainly influenced by the Italian restriction policies to control the pandemic. Importantly, during the Omicron predominance period, only the group who received at least a booster dose showed a reduced risk of COVID-19-related death.

Aspirin for prevention of preeclampsia and adverse perinatal outcome in twin pregnancies: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate the potential role of aspirin in reducing the risk of preeclampsia and adverse maternal and perinatal outcomes in twin pregnancies. DATA SOURCES: Medline, Embase, Google Scholar, Cochrane, and ClinicalTrial.gov databases were searched. STUDY ELIGIBILITY CRITERIA: The search and selection criteria were restricted to the English language. METHODS: The primary outcome was the incidence of preeclampsia. The secondary outcomes included gestational hypertension; fetal growth restriction; preterm birth, either spontaneous or iatrogenic, before 34 weeks of gestation; gestational age at birth; neonatal birthweight; and adverse events secondary to the administration of aspirin, including antepartum and postpartum hemorrhage. In addition, subgroup analyses according to chorionicity (dichorionic vs monochorionic), aspirin dose, and gestational age at administration of aspirin (<16 vs ≥16 weeks of gestation) and considering only studies with a daily aspirin dose of ≥100 mg/d were performed. Head-to-head meta-analyses reporting results as summary odds ratios and mean differences were used to analyze categorical and continuous variables, respectively. Quality assessment for randomized controlled trials was independently performed by 2 researchers based on the risk of bias that was assessed using the revised Cochrane risk-of-bias tool for randomized trials. The conclusion of the meta-analysis on the primary outcome was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation. RESULTS: Overall, 9 studies (2273 twin pregnancies) were included. When considering all studies, the risk of preeclampsia was lower in twin pregnancies treated with aspirin than in those not treated with aspirin (odds ratio, 0.64; 95% confidence interval, 0.48-0.85; P=.003), although there was no significant difference in the risk of gestational hypertension (P=.987), fetal growth restriction (P=.9), or adverse maternal and perinatal events (P=.9) in twin pregnancies treated with aspirin compared with those not treated with aspirin. There was no significant difference in the gestational age at birth (P=.2) and neonatal birthweight (P=.06) between women receiving aspirin and those not receiving aspirin. When considering only studies with an aspirin dose of >100 mg/d, the risk of preeclampsia (odds ratio, 0.45; 95% confidence interval, 0.23-0.86; P=.02) was significantly lower in pregnancies receiving aspirin than in those not receiving aspirin, Conversely, there was no significant difference in the risk of gestational hypertension (P=.20), fetal growth restriction (P=.1), gestational age at birth (P=.06), and neonatal weight (P=.05) between the 2 groups. Furthermore, there was no significant difference in the risk of preeclampsia when considering only studies with an aspirin dose of >80 mg/d (P=.611). The association between the administration of aspirin and preeclampsia persisted when considering an aspirin dose of >100 mg/day or when the medication was started before 16 weeks of gestation. The overall quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation assessment was low. CONCLUSION: The administration of aspirin in women with twin pregnancies reduced the risk of preeclampsia. The findings from this study highlighted the need for randomized controlled trials elucidating the actual role of aspirin in affecting maternal and perinatal outcomes in twin pregnancies.

COVID-19 vaccines reduce the risk of SARS-CoV-2 reinfection and hospitalization: Meta-analysis.

The addictive protection against SARS-CoV-2 reinfection conferred by vaccination, as compared to natural immunity alone, remains to be quantified. We thus carried out a meta-analysis to summarize the existing evidence on the association between SARS-CoV-2 vaccination and the risk of reinfection and disease. We searched MedLine, Scopus and preprint repositories up to July 31, 2022, to retrieve cohort or case-control studies comparing the risk of SARS-CoV-2 reinfection or severe/critical COVID-19 among vaccinated vs. unvaccinated subjects, recovered from a primary episode. Data were combined using a generic inverse-variance approach. Eighteen studies, enrolling 18,132,192 individuals, were included. As compared to the unvaccinated, vaccinated subjects showed a significantly lower likelihood of reinfection (summary Odds Ratio-OR: 0.47; 95% CI: 0.42-0.54). Notably, the results did not change up to 12 months of follow-up, by number of vaccine doses, in studies that adjusted for potential confounders, adopting different reinfection definitions, and with different predominant strains. Once reinfected, vaccinated subjects were also significantly less likely to develop a severe disease (OR: 0.45; 95% CI: 0.38-0.54). Although further studies on the long-term persistence of protection, under the challenge of the new circulating variants, are clearly needed, the present meta-analysis provides solid evidence of a stronger protection of hybrid vs. natural immunity, which may persist during Omicron waves and up to 12 months.

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy.

Importance: Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. Objective: To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. Design, Setting, and Participants: This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. Exposures: Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. Main Outcomes and Measures: The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. Results: A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95% CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95% CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95% CI, 1.01-1.31; P = .03). Conclusions and Relevance: This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients.

Genotype prevalence and age distribution of human papillomavirus from infection to cervical cancer in Japanese women: A systematic review and meta-analysis.

BACKGROUND: National HPV vaccination coverage in Japan is less than one percent of the eligible population and cervical cancer incidence and mortality are increasing. This systematic review and meta-analysis aimed to provide a comprehensive estimate of HPV genotype prevalence for Japan. METHODS: English and Japanese databases were searched to March 2021 for research reporting HPV genotypes in cytology and histology samples from Japanese women. Summary estimates were calculated by disease stage from cytology only assessment - Normal, ASCUS, LSIL, HSIL and from histological assessment - CIN1, CIN2, CIN3/AIS, ICC (ICC-SCC, and ICC-ADC), and other. A random-effects meta-analysis was used to calculate summary prevalence estimates of any-HPV, high-risk (HR) and low-risk (LR) vaccine types, and vaccine genotypes (bivalent, quadrivalent, or nonavalent). This study was registered with PROSPERO: CRD42018117596. RESULTS: A total of 57759 women with normal cytology, 1766 ASCUS, 3764 LSIL, 2017 HSIL, 3130 CIN1, 1219 CIN2, 869 CIN3/AIS, and 4306 ICC (which included 1032 ICC-SCC, and 638 ICC-ADC) were tested for HPV. The summary estimate of any-HPV genotype in women with normal cytology was 15·6% (95% CI: 12·3-19·4) and in invasive cervical cancer (ICC) was 85·6% (80·7-89·8). The prevalence of HR-HPV was 86·0% (95% CI: 73·9-94·9) for cytological cases of HSIL, 76·9% (52·1-94·7) for histological cases of CIN3/AIS, and 75·7% (68·0-82·6) for ICC. In women with ICC, the summary prevalence of bivalent vaccine genotypes was 58·5% (95% CI: 52·1-64·9), for quadrivalent genotypes was 58·6% (52·2-64·9) and for nonavalent genotypes was 71·5% (64·9-77·6), and of ICC cases that were HPV positive over 90% of infections are nonavalent vaccine preventable. There was considerable heterogeneity in all HPV summary estimates and for ICC, this heterogeneity was not explained by variability in study design, sample type, HPV assay type, or HPV DNA detection method, although studies published in the 1990s had lower prevalence estimates of any-HPV and HR HPV genotypes. INTERPRETATIONS: HPV prevalence is high among Japanese women. The nonavalent vaccine is likely to have the greatest impact on reducing cervical cancer incidence and mortality in Japan.

Inhaled CO2 Concentration While Wearing Face Masks: A Pilot Study Using Capnography.

Background: Face masks are recommended based on the assumption that they protect against SARS-CoV-2 transmission, however studies on their potential side effects are still lacking. We aimed to evaluate the inhaled air carbon dioxide (CO2) concentration, when wearing masks. Methods: We measured end-tidal CO2 using professional side-stream capnography, with water-removing tubing, (1) without masks, (2) wearing a surgical mask, and (3) wearing a FFP2 respirator (for 5 minutes each while seated after 10 minutes of rest), in 146 healthy volunteers aged 10 to 90 years, from the general population of Ferrara, Italy. The inhaled air CO2 concentration was computed as: ([mask volume × end-tidal CO2] + [tidal volume - mask volume] × ambient air CO2)/tidal volume. Results: With surgical masks, the mean CO2 concentration was 7091 ± 2491 ppm in children, 4835 ± 869 in adults, and 4379 ± 978 in the elderly. With FFP2 respirators, this concentration was 13 665 ± 3655 in children, 8502 ± 1859 in adults, and 9027 ± 1882 in the elderly. The proportion showing a CO2 concentration higher than the 5000 ppm (8-hour average) acceptable threshold for workers was 41.1% with surgical masks, and 99.3% with FFP2 respirators. Adjusting for age, gender, BMI, and smoking, the inhaled air CO2 concentration significantly increased with increasing respiratory rate (mean 10 837 ±3712 ppm among participants ⩾18 breaths/minute, with FFP2 respirators), and among the minors. Conclusion: If these results are confirmed, the current guidelines on mask-wearing should be reevaluated.

Risk of reinfection and disease after SARS-CoV-2 primary infection: Meta-analysis.

INTRODUCTION: A precise estimate of the frequency and severity of SARS-CoV-2 reinfections would be critical to optimize restriction and vaccination policies for the hundreds of millions previously infected subjects. We performed a meta-analysis to evaluate the risk of reinfection and COVID-19 following primary infection. METHODS: We searched MedLine, Scopus and preprint repositories for cohort studies evaluating the onset of new infections among baseline SARS-CoV-2-positive subjects. Random-effect meta-analyses of proportions were stratified by gender, exposure risk, vaccination status, viral strain, time between episodes, and reinfection definition. RESULTS: Ninety-one studies, enrolling 15,034,624 subjects, were included. Overall, 158,478 reinfections were recorded, corresponding to a pooled rate of 0.97% (95% CI: 0.71%-1.27%), with no substantial differences by definition criteria, exposure risk or gender. Reinfection rates were still 0.66% after ≥12 months from first infection, and the risk was substantially lower among vaccinated subjects (0.32% vs. 0.74% for unvaccinated individuals). During the first 3 months of Omicron wave, the reinfection rates reached 3.31%. Overall rates of severe/lethal COVID-19 were very low (2-7 per 10,000 subjects according to definition criteria) and were not affected by strain predominance. CONCLUSIONS: A strong natural immunity follows the primary infection and may last for more than one year, suggesting that the risk and health care needs of recovered subjects might be limited. Although the reinfection rates considerably increased during the Omicron wave, the risk of a secondary severe or lethal disease remained very low. The risk-benefit profile of multiple vaccine doses for this subset of population needs to be carefully evaluated.

Effectiveness of COVID-19 Vaccines in the General Population of an Italian Region before and during the Omicron Wave.

We performed a cohort analysis of the entire population of Abruzzo, Italy, to evaluate the real-world effectiveness of SARS-CoV-2 vaccines against infection, COVID-19 hospitalization or death, over time and during the Omicron wave. All resident or domiciled subjects were included, and official vaccination, COVID-19, demographic, hospital and co-pay exemption datasets were extracted up to 18 February 2022. Multivariable analyses were adjusted for age, gender, hypertension, diabetes, major cardio- and cerebrovascular events, COPD, kidney diseases, and cancer. During the follow-up (average 244 days), 252,365 subjects received three vaccine doses (of BNT162b2, ChAdOx1 nCoV-19, mRNA-1273 or JNJ-78436735), 684,860 two doses, 29,401 one dose, and 313,068 no dose. Overall, 13.4% of the individuals were infected with SARS-CoV-2 (n = 170,761); 1.1% of them had severe COVID-19, and 0.6% died. Compared with the unvaccinated, those receiving two or three vaccine doses showed an 80% to 90% lower risk of COVID-19 hospitalization or death. Protection decreased during the Omicron wave and six months after the last dose, but it remained substantial. Lethal disease was uncommon during the Omicron wave and in the young population, even among the unvaccinated. Some of the current policies may need a re-evaluation in light of these findings. The results from the Omicron wave will inevitably require confirmation.

Risk of SARS-CoV-2 Reinfection 18 Months After Primary Infection: Population-Level Observational Study.

Current data suggest that SARS-CoV-2 reinfections are rare. Uncertainties remain, however, on the duration of the natural immunity, its protection against Omicron variant, and on the impact of vaccination to reduce reinfection rates. In this retrospective cohort analysis of the entire population of an Italian region, we followed 1,293,941 subjects from the beginning of the pandemic to the current scenario of Omicron predominance (up to mid-February 2022). After an average of 277 days, we recorded 729 reinfections among 119,266 previously infected subjects (overall rate: 6.1‰), eight COVID-19-related hospitalizations (7/100,000), and two deaths. Importantly, the incidence of reinfection did not vary substantially over time: after 18-22 months from the primary infection, the reinfection rate was still 6.7‰, suggesting that protection conferred by natural immunity may last beyond 12 months. The risk of reinfection was significantly higher among females, unvaccinated subjects, and during the Omicron wave.

Impact of a Human Papillomavirus Vaccination Program within Organized Cervical Cancer Screening: Cohort Study.

BACKGROUND: We assessed the effectiveness of an HPV (human papillomavirus) vaccination program in lowering cervical abnormality risk, and conferring herd protection. METHODS: Retrospective cohort study using linked screening and vaccination administrative health data of the general population of Ancona Province, Italy. We included all female residents born in 1990-1993, eligible for catch-up HPV vaccination up to age 25 years, and adhering to organized screening in 2015-2020 (n = 4,665). Cervical abnormalities rates were compared between: Vaccinated and unvaccinated women, and cohorts with high and low vaccination uptake. Analyses were adjusted for age, country of birth, screening tests number, laboratory, and municipality average income. Main outcomes were ASC-US+ or LSIL+ Pap smears, and CIN1+ or CIN2+ histology. RESULTS: Mean screening age was 26.6±1.5 years, and 1,118 screened women (24.0%) were vaccinated (mean vaccination age 19.2±1.5 years). The diagnosed cervical abnormalities were: 107 LSIL+ (2.3%), 70 CIN1+ (1.5%), and 35 CIN2+ (0.8%). The adjusted odds ratios of LSIL+, CIN1+, and CIN2+ among vaccinated versus unvaccinated women were, respectively: 0.55 [(95% confidence interval (CI), 0.33-0.91)], 0.43 (95% CI, 0.22-0.86), and 0.31 (95% CI, 0.11-0.91). Among the unvaccinated, those in the highest-uptake (45.3%) 1993 cohort, versus the last pre-vaccination 1990 cohort, showed AORs of LSIL+ and CIN1+ of 0.23 (95% CI, 0.10-0.50), and 0.22 (95% CI, 0.07-0.69), respectively. CONCLUSIONS: In the first evaluation from Central Italy, catch-up HPV vaccination considerably reduced the risk of all cervical abnormalities diagnosed within organized screening, and conferred an elevated degree of herd protection among unvaccinated women. IMPACT: The high protection conferred by HPV vaccination suggests the need to update cervical screening.

Repetitive transcranial magnetic stimulation in treatment-seeking subjects with cocaine use disorder: A randomized, double-blind, sham-controlled trial.

BACKGROUND: Cocaine use disorder (CUD) is a chronic and relapsing brain disorder with no approved treatments. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in open label and single-blind studies, reducing cocaine craving and consumption. Although, large randomized, double-blind, controlled trials are still missing. OBJECTIVE: This multi-center, randomized, double-blind, sham-controlled study was designed to evaluate the safety and efficacy of multiple sessions of active rTMS compared to sham stimulation in patients with CUD. METHODS: rTMS (15 Hz, 2 daily sessions for 5 days/week,for a total of 20 stimulation sessions) was delivered over the left DLPFC for two weeks of continuous treatment followed by 12 weeks of maintenance (1 day/week, twice a day), in a double-blind, randomized sham-controlled design. Our primary outcomes included self-reported cue-induced craving and cocaine consumption, as measured by percentage of negative urine tests. Our secondary outcomes included: 1) changes in depressive symptoms; 2) changes in cocaine withdrawal symptoms; and 3) changes in self-reported days of cocaine use. RESULTS: Forty-two outpatients with CUD were enrolled in the active rTMS group and 38 patients in the sham group. We observed a significant decrease in self-reported cue-induced cocaine craving and consumption in both the active rTMS and sham, whereas no main effect of treatment was found. However, the active rTMS group showed greater changes in depressive symptoms. The improvement on depressive symptomatology was particularly marked among patients receiving a total number of rTMS sessions greater than 40 and those reporting more severe depressive symptoms at baseline. CONCLUSIONS: A significant improvement of CUD symptoms during active rTMS treatment was observed. However, we did not observe significant differences in cocaine craving and consumption between treatment groups, highlighting the complexity of factors contributing to CUD maintenance. A significant improvement in depressive symptoms was observed in favour of the active group. Clinical trial registration details:clinicaltrials.govidentifierNCT03333460.

Sutureless "Contact Lens Sandwich" Technique for Amniotic Membrane Therapy of Central Corneal Ulcers.

PURPOSE: To describe a new technique for sutureless and glue-free amniotic membrane transplantation (AMT) and to investigate its effectiveness to treat corneal persistent epithelial defects (PEDs), compared to bandage contact lens (BCL) application alone. METHODS: We performed AMT with "contact lens sandwich technique" (CLS-AMT) in 8 consecutive patients with central/para-central (up to 4.00 mm from the geometrical centre) PED/ulceration and we retrospectively compared the results with 11 BCL procedures. RESULTS: The procedures were performed successfully with no complications.CLS-AMT showed significantly shorter healing time than BCL (24.0 ± 19.1 vs 42.9 ± 14.6 days; P < 0.05, Mann-Whitney test). Recurrence rates were 12% and 27% for CLS-AMT and BCL, respectively. CONCLUSION: CLS-AMT technique, based on the suction effect due to the superposition of a bandage contact lens on the AM-ring complex, represents a quick, low cost, easy to perform and nearly non-invasive AMT technique. This approach is able to provide adequate fixation of AM, and it seems to be a safe and effective treatment for patients with PEDs.

Wide variability in colorectal cancer screening uptake by general practitioner: Cross-sectional study.

OBJECTIVES: Despite several interventions, colorectal cancer (CRC) screening uptake remains below acceptable levels in Italy. Among the potential determinants of screening uptake, only a few studies analysed the role of general practitioners (GPs). The aim was to evaluate the variation in screening uptake of the clusters of subjects assisted by single GPs. SETTING: Ancona province, Central Italy. METHODS: Cross-sectional study, including all residents aged 50-69 years, who were offered the public screening programme with biannual faecal immunochemical tests. Demographic (of all GPs) and screening data (of all eligible residents) for years 2018-2019 were collected from the official electronic datasets of the Ancona Local Health Unit. The potential predictors of acceptable screening uptake, including GP's gender, age, and number of registered subjects, were evaluated using random-effect logistic regression, with geographical area as the cluster unit. RESULTS: The final sample consisted of 332 GP clusters, including 120,178 eligible subjects. The overall province uptake was 38.0% ± 10.7%. The uptake was lower than 30% in one-fifth of the GP clusters, and higher than 45% in another fifth. At multivariable analysis, the significant predictors of uptake were younger GP age (p = 0.010) and lower number of registered subjects (p < 0.001). None of the GP clusters with 500 subjects or more showed an uptake ≥45%. CONCLUSIONS: The wide variation across GPs suggests they might substantially influence screening uptake, highlighting a potential need to increase their commitment to CRC screening. Further research is needed to confirm the role of the number of registered subjects.