Dengue Fever in Italy: The “Eternal Return” of an Emerging Arboviral Disease

Enhanced surveillance for dengue virus (DENV) infections in Italy has been implemented since 2012, with annual reports from the National Health Institute. In this study, we summarize available evidence on the epidemiology of officially notified DENV infections from 2010–2021. In total, 1043 DENV infection cases were diagnosed, and most of them occurred in travelers, with only 11 autochthonous cases. The annual incidence rates of DENV infections peaked during 2019 with 0.277 cases per 100,000 (95% confidence interval [95% CI] 0.187–0.267), (age-adjusted incidence rate: 0.328, 95% CI 0.314–0.314). Cases of DENV were clustered during the summer months of July (11.4%), August (19.3%), and September (12.7%). The areas characterized by higher notification rates were north-western (29.0%), and mostly north-eastern Italy (41.3%). The risk for DENV infection in travelers increased in the time period 2015–2019 (risk ratio [RR] 1.808, 95% CI 1.594–2.051) and even during 2020–2021 (RR 1.771, 95% CI 1.238–2.543). Higher risk for DENV was additionally reported in male subjects compared with females subjects, and aged 25 to 44 years, and in individuals from northern and central Italy compared to southern regions and islands. In a multivariable Poisson regression model, the increased number of travelers per 100 inhabitants (incidence rate ratio [IRR] 1.065, 95% CI 1.036–1.096), the incidence in other countries (IRR 1.323, 95% CI 1.165–1.481), the share of individuals aged 25 to 44 years (IRR 1.622, 95% CI 1.338–1.968), and foreign-born residents (IRR 2.717, 95% CI 1.555–3.881), were identified as effectors of annual incidence. In summary, although the circulation of DENV remains clustered among travelers, enhanced surveillance is vital for the early detection of human cases and the prompt implementation of response measures.

Retrospective analysis of arterial occlusive events in the PACE trial by an independent adjudication committee

Background The phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial of ponatinib showed robust long-term benefit in relapsed Philadelphia chromosome-positive (Ph+) leukemia; arterial occlusive events (AOEs) occurred in ≥ 25% of patients based on investigator reporting. However, AOE rates vary depending on the definitions and reporting approach used. Methods To better understand clinically relevant AOEs with ponatinib, an independent cardiovascular adjudication committee reviewed 5-year AOE data from the PACE trial according to a charter-defined process and standardized event definitions. Results A total of 449 patients with chronic myeloid leukemia (CML) or Ph+ acute lymphoblastic leukemia (ALL) received ponatinib (median age 59 y; 47% female; 93% ≥ 2 prior tyrosine kinase inhibitors (TKIs); median follow-up, 37.3 months). The adjudicated AOE rate (17%) was lower than the non-adjudicated rate (i.e., rate before adjudication; 25%). The only adjudicated AOE in > 2% of patients was peripheral arterial occlusive disease (4%). Exposure-adjusted incidence of newly occurring adjudicated AOEs decreased over time. Patients with multiple baseline cardiovascular risk factors had higher adjudicated AOE rates than those without risk factors. Conclusions This independent adjudication study identified lower AOE rates than previously reported, suggesting earlier overestimation that may inaccurately reflect AOE risk with ponatinib. This trial was registered under ClinicalTrials.gov identifier NCT01207440 on September 23, 2010 (https://clinicaltrials.gov/ct2/show/NCT01207440).

Proximal humeral fractures in Finland

Aims Proximal humeral fractures (PHFs) are common. There is increasing evidence that most of these fractures should be treated conservatively. However, recent studies have shown an increase in use of operative treatment. The aim of this study was to identify the trends in the incidence and methods of treatment of PHFs in Finland. Methods The study included all Finnish inhabitants aged ≥ 16 years between 1997 and 2019. All records, including diagnostic codes for PHFs and all surgical procedure codes for these fractures, were identified from two national registers. Data exclusion criteria were implemented in order to identify only acute PHFs, and the operations performed to treat them. Results During the 23-year study period, 79,676 PHFs were identified, and 14,941 operations were performed to treat them. The incidence of PHFs steadily increased. In 2019, the overall incidence was 105 per 100,000 person-years (105). The sex-adjusted incidence for females was 147.1 per 105, and the age-adjusted incidence for patients aged ≥ 80 years was 407.1 per 105. The incidence of operative treatment for PHFs rose during the first half of the study period and decreased during the second half. The use of plate osteosynthesis in particular decreased. In 2019, the incidence of operative treatment for PHFs was 13.2 per 105, with 604 operations. Conclusion Although the incidence of PHFs is steadily increasing, particularly in elderly females, the incidence of operative treatment is now decreasing, which is in line with current literature regarding their treatment. Cite this article: Bone Joint J 2022;104-B(1):150–156.

SPATIAL ANALYSIS OF CERVICAL CANCER INCIDENCE IN IRAQ DURING 2010-2015

Cervical cancer is the most common cancer in Iraq. This study aimed to examine the spatial pattern and high-risk clusters of cervical cancer in different areas of Iraq (except the Kurdish region) during the period 2010-2015. The age-adjusted incidence rates (AAIRs), age-specific incidence rates (ASIRs), and annual percent changes (APCs) were calculated for 2010–2015. We used three techniques of spatial statistical analysis which are Global spatial autocorrelation, Getis-Ord Gi* statistic, and Anselin Local Moran’s statistic to investigate spatial clustering and outliers. Over the period 2000-2015, 1037 cases were diagnosed with AAIR of incidence of (3.521 per 100,000). Depending on AAIRs, we found cervical cancer incidence was highest (8.212 per 100,000) in the age group of 60-69 years old. The APC of cervical cancer age-specific rates has significantly risen for the age groups 60-69 only. We identified spatial high-risk clusters for incidence. The cluster was mainly located in the center of Iraq (Baghdad, Najaf, Kerbala, and Babil provinces), the central-eastern part of Iraq (Diyala province), and the southern part of Iraq (Basrah province). While the provinces in the northern and northeastern parts of Iraq, as well as the western province, had relatively lower AAIRs from cervical cancer. A spatial cluster pattern for the incidence of cervical cancer in Iraq was revealed, which will be valuable for improving the allocation of health resources in Iraq.

Incidence and Prognostic Nomogram for Resected Non-small Cell Neuroendocrine Tumor: A Population-Based Respective Study in China and the SEER Database

Background: Pulmonary neuroendocrine tumors, including small cell lung cancer (SCLC) and non-small cell neuroendocrine tumor (NSCLC-NET), have obvious heterogeneity. The comparison between SCLC and NSCLC-NET, and prognostic nomogram of resected NSCLC-NET have not been performed.Methods: We retrieved patients’ information with pulmonary neuroendocrine tumors from SEER database. Age-adjusted incidence and prognostic impacts of histological subtypes, surgery strategies and smoking were compared between SCLC and NSCLC-NET. Independent prognostic factors, screened by Cox regression, were enrolled for prognostic nomogram of resected NSCLC-NET. The nomogram were evaluated and compared to the 8th AJCC TNM staging system. A Chinese cohort was used for external validation.Results: Age-adjusted incidence of SCLC declined after 1991 but the incidence of NSCLC-NET continuously rose. Patients with typical carcinoid had the best prognosis in both overall survival and lung cancer specific survival after operation. Sleeve and segmental resection were more recommended in NSCLC-NET and SCLC, respectively. High-smoking index was associated with worse prognosis in both SCLC and NSCLC-NET. Histological subtype, age, surgery type, N, M stage and chemotherapy were independent prognostic factors and used to construct prognostic nomogram of resected NSCLC-NET. The nomogram performed well with good discrimination, calibration and clinical usefulness, which was validated by Chinese cohort (1, 3, 5-year AUC: SEER cohort 0.873, 0.901, 0.875; Chinese cohort 0.867, 0.892, 0.874). Compared to 8th staging system, the nomogram had higher C-index (0.87 vs 0.728, P < 0.001), clinical usefulness, increasing AUC value over time and improved 68%. The online server can be accessed at https://nsclc-net-prognostic-prediction.shinyapps.io/DynNomapp/. Conclusion: NSCLC-NET had increasing incidence over the past decades. The nomogram had high discrimination, calibration and clinical usefulness and performed better than 8th staging system. It may have certain value in risk stratification and survival prediction of patients with resected NSCLC-NET and help clinicians to take measures for high-risk patients in advance.

Excess Mortality Attributable to COVID-19 Among Assisted Living Residents

This study examines the excess mortality attributable to COVID-19 among a national cohort of assisted living (AL) residents. To do this, we compare the weekly rate of all-cause mortality during 1/1/20-8/11/20 with the same weeks in 2019 and calculated adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs). All-cause mortality rates, nationally, were 14% higher in 2020 compared with 2019 (mean, 2.309 vs. 2.020, respectively, per 1000 residents per week; adjusted IRR, 1.169; 95% CI 1.165-1.173). Among the 10 states with the highest community spread, the excess mortality attributable to COVID-19 was 24% higher, with 2.388 deaths per 1000 residents per week in 2020 during January-August vs 1.928 in 2019 (adjusted IRR, 1.241; 95% CI 1.233-1.250). These results suggest that AL residents suffered excess mortality due to COVID-19.

Incidence of COVID-19 in patients treated with infliximab compared with patients treated with rituximab

ObjectiveTo determine whether patients with inflammatory autoimmune diseases treated with rituximab (RTX) have more severe forms of COVID-19 compared with patients treated with anticytokine therapies, such as Tumour Necrosis Factor (TNF) inhibitors.MethodsWe included all patients who were on either RTX or infliximab (IFX) in two Swiss cantons during the first wave of the COVID-19 pandemic. We collected self-reported symptoms compatible with COVID-19, PCR-confirmed diagnoses of COVID-19 and the evolution of COVID-19 infections. We computed the raw and propensity score-adjusted incidence of COVID-19 by treatment group.Results190 patients were enrolled, of whom 121 (64%) were in the RTX group and 69 (36%) were in the IFX group. Twenty-one patients (11%) reported symptoms compatible with COVID-19 (RTX: 10, IFX: 11, p=0.14). Among patients with COVID-19 symptoms, four developed severe forms of the disease, with life-threatening pulmonary manifestations requiring intensive mechanical ventilation (RTX: 4 of 10, IFX: 0 of 11, Fisher’s exact test p=0.04). The incidence rate of COVID-19 symptoms was 0.73 (95% CI 0.39 to 1.37) cases per 1000 patient-days on RTX vs 1.52 (95% CI 0.82 to 2.85) cases per 1000 patient-days on IFX (crude p=0.10, adjusted p=0.07). The incidence rate of severe COVID-19 was 0.28 (95% CI 0.08 to 0.7.2) cases per 1000 patient-days on RTX compared with null on IFX (95% CI 0.0 to 0.44) (p=0.13). A replication in an independent validation cohort confirmed these findings, with consistent results in the Swiss Clinical Quality Management registry.ConclusionWhile the incidence of symptoms compatible with COVID-19 was overall similar in patients receiving RTX or IFX, the incidence of severe COVID-19 tended to be higher in the RTX group.

Accelerometer-Measured Daily Steps, Physical Function, and Subsequent Fall Risk in Older Women: The OPACH Study

We sought to investigate the association between steps per day (steps/d) and incident fall risk while also assessing the role of physical functioning on this association. Steps/d were measured by accelerometer for 7 days in 5,545 women aged 63 to 97 years between 2012 - 2014. Falls were ascertained from daily fall calendars for 13 months. Median steps/d were 3,216. There were 5,473 falls recorded over 61,564 fall calendar months. The adjusted incidence rate ratio comparing women in the highest vs. lowest step quartiles was 0.71 (95% confidence interval, 0.54 - 0.95; P-trend across quartiles of steps/d = 0.01). After further adjustment for physical function using the Short Physical Performance Battery, the rate ratio was 0.86 (0.64-1.16; P-trend = 0.27). Mediation analysis estimated that 66.7% to 70.2% of the association of steps/d and fall risk may be mediated by physical function. In conclusion, higher steps/d were related to lower incident falls primarily through their beneficial association with physical functioning. Interventions that improve physical function, including those that involve stepping, could reduce falls in older adults.

Marked reduction in antibiotic usage following intensive malaria control in a cohort of Ugandan children

Background Intensive malaria control may have additional benefits beyond reducing the incidence of symptomatic malaria. We compared antibiotic treatment of children before and after the implementation of highly effective malaria control interventions in Tororo, a historically high transmission area of Uganda. Methods Two successive cohorts of children, aged 0.5 to 10 years, were followed from September 2011 to October 2019 in a dedicated study clinic. Universal distribution of long-lasting insecticidal nets was conducted in 2013 and 2017. Sustained indoor residual spraying of insecticide (IRS) was initiated in December 2014. Generalized linear mixed-effects models were used to compare the incidence of antimalarial and antibiotic treatments before and after vector control measures were implemented. Results Comparing the period prior to the implementation of IRS to the period after IRS had been sustained for 4–5 years, the adjusted incidence of malaria treatments decreased from 2.68 to 0.05 per person-year (incidence rate ratio [IRR] = 0.02, 95% CI 0.01–0.03, p < 0.001), and the adjusted incidence of antibiotic treatments decreased from 4.14 to 1.26 per person-year (IRR = 0.30, 95% CI 0.27–0.34, p < 0.001). The reduction in antibiotic usage was primarily associated with fewer episodes of symptomatic malaria and fewer episodes of fever with sub-microscopic parasitemia, both of which were frequently treated with antibiotics. Conclusions In a historically high transmission setting, the implementation of highly effective vector control interventions was followed by a marked reduction in antibiotic treatment of children. This added benefit of malaria control could have important implications for antibiotic prescribing practices, efforts to curtail antimicrobial resistance, and health system costs.