Excess risk of subsequent malignant neoplasms in adolescent and young adult cancer survivors: Results from the first Italian population-based cohort.

BACKGROUND: Evidence about late effects in adolescent and young adult (AYA) cancer survivors is scarce. This study assessed the risk of subsequent malignant neoplasms (SMNs) to identify the most common SMNs to be considered in follow-up care. METHODS: Population-based cancer registries retrospectively identified first primary tumors (between 1976 and 2013) and SMNs in AYAs (15-39 years old at their cancer diagnosis). AYA cancer survivors were those alive at least 5 years after their first cancer diagnosis. The excess risk of SMNs was measured as standardized incidence ratios (SIRs) and absolute excess risk together with the cumulative incidence of SMNs. RESULTS: The cohort included 67,692 AYA cancer survivors. The excess risk of developing any SMN (SIR, 1.6; 95% confidence interval, 1.5-1.7) was 60%. The excess risk of SMNs was significantly high for survivors of lymphomas; cancers of the breast, thyroid, female genital tract, digestive organs, gonads, and urinary tract; and melanomas. The cumulative incidence of all SMNs in AYA cancer survivors within 25 years of their first cancer diagnosis was approximately 10%. Subsequent tumors contributing to approximately 60% of all SMNs were breast cancer, colorectal cancer, corpus uteri cancer, and ovarian cancer in females and colorectal cancer, bladder cancer, prostate cancer, lung cancer, and lymphomas in males. CONCLUSIONS: These results highlight the need to personalize follow-up strategies for AYA cancer survivors.

Effectiveness of treatments for acute and subacute mechanical non-specific low back pain: a systematic review with network meta-analysis.

OBJECTIVE: To assess the effectiveness of interventions for acute and subacute non-specific low back pain (NS-LBP) based on pain and disability outcomes. DESIGN: A systematic review of the literature with network meta-analysis. DATA SOURCES: Medline, Embase and CENTRAL databases were searched from inception until 17 October 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised clinical trials (RCTs) involving adults with NS-LBP who experienced pain for less than 6 weeks (acute) or between 6 and 12 weeks (subacute). RESULTS: Forty-six RCTs (n=8765) were included; risk of bias was low in 9 trials (19.6%), unclear in 20 (43.5%), and high in 17 (36.9%). At immediate-term follow-up, for pain decrease, the most efficacious treatments against an inert therapy were: exercise (standardised mean difference (SMD) -1.40; 95% confidence interval (CI) -2.41 to -0.40), heat wrap (SMD -1.38; 95% CI -2.60 to -0.17), opioids (SMD -0.86; 95% CI -1.62 to -0.10), manual therapy (SMD -0.72; 95% CI -1.40 to -0.04) and non-steroidal anti-inflammatory drugs (NSAIDs) (SMD -0.53; 95% CI -0.97 to -0.09). Similar findings were confirmed for disability reduction in non-pharmacological and pharmacological networks, including muscle relaxants (SMD -0.24; 95% CI -0.43 to -0.04). Mild or moderate adverse events were reported in the opioids (65.7%), NSAIDs (54.3%) and steroids (46.9%) trial arms. CONCLUSION: With uncertainty of evidence, NS-LBP should be managed with non-pharmacological treatments which seem to mitigate pain and disability at immediate-term. Among pharmacological interventions, NSAIDs and muscle relaxants appear to offer the best harm-benefit balance.

The relationship between frailty and delirium: insights from the 2017 Delirium Day study.

BACKGROUND: although frailty and delirium are among the most frequent and burdensome geriatric syndromes, little is known about their association and impact on short-term mortality. OBJECTIVE: to examine, in hospitalized older persons, whether frailty is associated with delirium, and whether these two conditions, alone or in combination, affect these patients' 30-day survival. DESIGN: observational study nested in the Delirium Day project, with 30-day follow-up. SETTING: acute medical wards (n = 118) and rehabilitation wards (n = 46) in Italy. SUBJECTS: a total of 2,065 individuals aged 65+ years hospitalized in acute medical (1,484 patients, 71.9%) or rehabilitation (581 patients, 28.1%) wards. METHODS: a 25-item Frailty Index (FI) was created. Delirium was assessed using the 4AT test. Vital status was ascertained at 30 days. RESULTS: overall, 469 (22.7%) patients experienced delirium on the index day and 82 (4.0%) died during follow-up. After adjustment for potential confounders, each FI score increase of 0.1 significantly increased the odds of delirium (odds ratio, OR: 1.66 [95% CI: 1.45-1.90]), with no difference between the acute (OR: 1.65 [95% CI: 1.41-1.93]) and rehabilitation ward patients (OR: 1.71 [95% CI: 1.27-2.30]). The risk of dying during follow-up also increased significantly for every FI increase of 0.1 in the overall population (OR: 1.65 [95% CI: 1.33-2.05]) and in the acute medical ward patients (OR: 1.61 [95% CI: 1.28-2.04]), but not in the rehabilitation patients. Delirium was not significantly associated with 30-day mortality in either hospital setting. CONCLUSIONS: in hospitalized older patients, frailty is associated with delirium and with an increased risk of short-term mortality.

Kinesio taping for rotator cuff disease.

BACKGROUND: Kinesio Taping (KT) is one of the conservative treatments proposed for rotator cuff disease. KT is an elastic, adhesive, latex-free taping made from cotton, without active pharmacological agents. Clinicians have adopted it in the rehabilitation treatment of painful conditions, however, there is no firm evidence on its benefits. OBJECTIVES: To determine the benefits and harms of KT in adults with rotator cuff disease. SEARCH METHODS: We searched the Cochrane Library, MEDLINE, Embase, PEDro, CINAHL, Clinicaltrials.gov and WHO ICRTP registry to July 27 2020, unrestricted by date and language. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials (RCTs) including adults with rotator cuff disease. Major outcomes were overall pain, function, pain on motion, active range of motion, global assessment of treatment success, quality of life, and adverse events. DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane. MAIN RESULTS: We included 23 trials with 1054 participants. Nine studies (312 participants) assessed the effectiveness of KT versus sham therapy and fourteen studies (742 participants) assessed the effectiveness of KT versus conservative treatment. Most participants were aged between 18 and 50 years. Females comprised 52% of the sample. For the meta-analysis, we considered the last available measurement within 30 days from the end of the intervention. All trials were at risk of performance, selection, reporting, attrition, and other biases.  Comparison with sham taping Due to very low-certainty evidence, we are uncertain whether KT improves overall pain, function, pain on motion and active range of motion compared with sham taping. Mean overall pain (0 to 10 scale, 0 no pain) was 2.96 points with sham taping and 3.03 points with KT (3 RCTs,106 participants), with an absolute difference of 0.7% worse, (95% CI 7.7% better to 9% worse) and a relative difference of 2% worse (95% CI 21% better to 24% worse) at four weeks. Mean function (0 to 100 scale, 0 better function) was 47.1 points with sham taping and 39.05 points with KT (6 RCTs, 214 participants), with an absolute improvement of 8% (95% CI 21% better to 5% worse)and a relative improvement of 15% (95% CI 40% better to 9% worse) at four weeks. Mean pain on motion (0 to 10 scale, 0 no pain) was 4.39 points with sham taping and 2.91 points with KT even though not clinically important (4 RCTs, 153 participants), with an absolute improvement of 14.8% (95% CI 22.5% better to 7.1% better) and a relative improvement of 30% (95% CI 45% better to 14% better) at four weeks. Mean active range of motion (shoulder abduction) without pain was 174.2 degrees with sham taping and 184.43 degrees with KT (2 RCTs, 68 participants), with an absolute improvement of 5.7% (95% CI 8.9% worse to 20.3% better) and a relative improvement of 6% (95% CI 10% worse to 22% better) at two weeks. No studies reported global assessment of treatment success. Quality of life was reported by one study but data were disaggregated in subscales. No reliable estimates for adverse events (4 studies; very low-certainty) could be provided due to the heterogeneous description of events in the sample. Comparison with conservative treatments Due to very low-certainty evidence, we are uncertain if KT improves overall pain, function, pain on motion and active range of motion compared with conservative treatments. However, KT may improve quality of life (low certainty of evidence).  Mean overall pain (0 to 10 scale, 0 no pain) was 0.9 points with conservative treatment and 0.46 points with KT (5 RCTs, 266 participants), with an absolute improvement of 4.4% (95% CI 13% better to 4.6% worse) and a relative improvement of 15% (95% CI 46% better to 16% worse) at six weeks. Mean function (0 to 100 scale, 0 better function) was 46.6 points with conservative treatment and 33.47 points with KT (14 RCTs, 499 participants), with an absolute improvement of 13% (95% CI 24% better to 2% better) and a relative improvement of 18% (95% CI 32% better to 3% better) at four weeks. Mean pain on motion (0 to 10 scale, 0 no pain) was 4 points with conservative treatment and 3.94 points with KT (6 RCTs, 225 participants), with an absolute improvement of 0.6% (95% CI 7% better to 8% worse) and a relative improvement of 1% (95% CI 12% better to 10% worse) at four weeks. Mean active range of motion (shoulder abduction) without pain was 156.6 degrees with conservative treatment and 159.64 degrees with KT (3 RCTs, 143 participants), with an absolute improvement of 3% (95% CI 11% worse to 17 % better) and a relative improvement of 3% (95% CI 9% worse to 14% better) at six weeks.  Mean of quality of life (0 to 100, 100 better quality of life) was 37.94 points with conservative treatment and 56.64 points with KT (1 RCTs, 30 participants), with an absolute improvement of 18.7% (95% CI 14.48% better to 22.92% better) and a relative improvement of 53% (95% CI 41% better to 65% better) at four weeks.  No studies were found for global assessment of treatment success. No reliable estimates for adverse events (7 studies, very low certainty of evidence) could be provided due to the heterogeneous description of events in the whole sample. AUTHORS' CONCLUSIONS: Kinesio taping for rotator cuff disease has uncertain effects in terms of self-reported pain, function, pain on motion and active range of motion when compared to sham taping or other conservative treatments as the certainty of evidence was very low. Low-certainty evidence shows that kinesio taping may improve quality of life when compared to conservative treatment. We downgraded the evidence for indirectness due to differences among co-interventions, imprecision due to small number of participants across trials as well as selection bias, performance and detection bias. Evidence on adverse events was scarce and uncertain. Based upon the data in this review, the evidence for the efficacy of KT seems to demonstrate little or no benefit.

Metabolic syndrome and risk of COVID-19-related hospitalization: a large, population-based cohort study carried out during the first European outbreak of SARS-CoV-2 infection in the Metropolitan area of Milan (Lombardy Region, Northern Italy).

BACKGROUND: since the beginning of the COVID-19 pandemic, specific characteristics of the infected subjects appeared to be associated with a severe disease, leading to hospitalization or death. OBJECTIVES: to evaluate the association between three components of the metabolic syndrome (diabetes mellitus, dyslipidaemia, and hypertension), alone and in combination, and risk of hospitalization in subjects with nasopharyngeal swab-confirmed COVID-19. DESIGN: cohort study. SETTING AND PARTICIPANTS: the study subjects were all COVID-19 cases diagnosed in the area of the Agency for Health Protection of the Metropolitan Area of Milan (Lombardy Region, Northern Italy) between 10.02.2020 and 25.04.2020, whose data were gathered with an ad hoc information system developed at the beginning of the pandemic. MAIN OUTCOME MEASURES: the association between metabolic syndrome components (alone and in combination) and hospitalization (both in any ward and in intensive care unit) was measured by means of cause-specific Cox models with gender, age, and comorbidities as potential confounders. RESULTS: the cohort included 15,162 subjects followed from diagnosis up to 20.07.2020. Adjusted hazard ratios (HRs) of hospitalization in any ward estimated by the Cox model were 1.26 for uncomplicated diabetes mellitus (95%CI 1.18-1.34); 1.21 for complicated diabetes mellitus (95%CI 1.05-1.39); 1.07 for dyslipidaemia (95%CI 1.00-1.14); and 1.11 for hypertension (95%CI 1.05-1.17). When all components coexisted in the same subject, the HR was 1.46 (95%CI 1.31-1.62). A significant increase in risk of hospitalization in intensive care unit was found for uncomplicated diabetes mellitus (HR 1.38; 95%CI 1.15-1.66). CONCLUSIONS: this population-based study confirms that metabolic syndrome components increase the risk of hospitalization for COVID-19. The HR increases in an additive manner when the three components are simultaneously present.

Development of a multivariable model predicting mortality risk from comorbidities in an Italian cohort of 18,286 confirmed COVID-19 cases aged 40 years or older.

OBJECTIVES: to develop a risk prediction model for 30-day mortality from COVID­19 in an Italian cohort aged 40 years or older. DESIGN: a population-based retrospective cohort study on prospectively collected data was conducted. SETTING AND PARTICIPANTS: the cohort included all swab positive cases aged 40 years older (No. 18,286) among residents in the territory of the Milan's Agency for Health Protection (ATS-MI) up to 27.04.2020. Data on comorbidities were obtained from the ATS administrative database of chronic conditions. MAIN OUTCOME MEASURES: to predict 30-day mortality risk, a multivariable logistic regression model, including age, gender, and the selected conditions, was developed following the TRIPOD guidelines. Discrimination and calibration of the model were assessed. RESULTS: after age and gender, the most important predictors of 30-day mortality were diabetes, tumour in first-line treatment, chronic heart failure, and complicated diabetes. The bootstrap-validated c-index was 0.78, which suggests that this model is useful in predicting death after COVID-19 infection in swab positive cases. The model had good discrimination (Brier score 0.13) and was well calibrated (Index of prediction accuracy of 14.8%). CONCLUSIONS: a risk prediction model for 30-day mortality in a large COVID-19 cohort aged 40 years or older was developed. In a new epidemic wave, it would help to define groups at different risk and to identify high-risk subjects to target for specific prevention and therapeutic strategies.

Emergency attendance for acute hyper- and hypoglycaemia in the adult diabetic population of the metropolitan area of Milan: quantifying the phenomenon and studying its predictors.

BACKGROUND: We quantified, among diabetic adults, the frequency, costs, and factors associated with visits to the emergency department (EDs) and subsequent hospitalizations for acute hypoglycaemic and hyperglycaemic events. METHODS: We included adults with diabetes residing in the Milan Agency for Health Protection between 2015 and 2017. From healthcare databases, we identified demographic variables, comorbidities, type of treatment, insulin treatment duration, previous ED attendances for acute glycaemic events, and two indicators of glycaemic monitoring. Using a validated ICD-9-CM coding algorithm, we identified all ED attendances for acute glycaemic events from the ED database and calculated their incidence. We computed the direct costs from health databases and presented them as average annual mean costs for those having had at least an ED attendance. The analysis of the association between the number of ED attendances and potential determinants was performed using zero-inflated negative binomial regression models. These two-part models concomitantly estimate two sets of parameters: the odds-ratios (ORs) of having no attendances and the incidence rate ratios (IRRs) of attendance. RESULTS: The cohort included 168,285 subjects, 70% of subjects were older than 64 years, 56% were males, and 26% were treated with insulin. The incidence of acute glycaemic events for those attending the ED was 7.0 per 1000 patient-years, followed by hospitalization 26.0% of the time. The total annual direct cost for ED attendances due to acute glycaemic events was 174,000 €. Type of antidiabetic treatment had the strongest association with ED attendances for hypoglycaemia. Patients assuming insulin only had a lower probability of having no attendances (OR compared to those who assumed non-insulin antidiabetic drugs =0.01, 95% CI = 0.00-0.02). These patients also had the highest rate of hyperglycaemic episodes (IRR = 7.7, 95% CI = 5.1-11.7 for insulin only vs. non-insulin antidiabetic drugs). Subjects having had a previous episode of the same type leading to an ED visit had a higher rate of subsequent attendances (IRR for hypoglycaemia = 5.3, 95% CI = 3.9-7.3 and IRR for hyperglycaemia = 3.7, 95% CI = 1.3-10.2). CONCLUSION: Insulin treatment and having had a prior acute glycaemic event leading to an ED visit were major predictors of ED attendance for hyper and hypoglycaemia in a population of adults with diabetes.

Association between uric acid and pulse wave velocity in hypertensive patients and in the general population: a systematic review and meta-analysis.

Purpose: The association between serum uric acid (SUA) and pulse wave velocity (PWV), has been extensively evaluated but with some discrepancies in results. A further limitation refers to the fact that only few data were analyzed taking into account the possible effects of gender. The purpose of this study was to estimate the association between SUA and arterial stiffness in general population and hypertensive patients, as a whole population and as divided by gender, by pooling results from existing studies.Materials and methods: Carotid-femoral and brachial-ankle PWV (cf- and ba-PWV) have been analyzed separately and subgroup analyses by gender are reported. Among 692 potentially relevant works, 24 articles were analyzed.Results: Seven studies referred to cf-PWV in the general population with an overall positive association at adjusted analysis for both males and females (beta regression coefficient (ß): 0.07; 95%CI: 0.03; 0.11 and ß: 0.06; 95%CI: 0.03; 0.09, respectively). Twelve studies referred to ba-PWV in the general population with the finding of a positive association at adjusted analysis for females (ß: 0.04; 95% confidence interval (CI): 0.01;0.07), but not for males (ß: 0.13; 95%CI: -0.09; 0.34). In hypertensive patients only four studies evaluated cf-PWV and one ba-PWV with only one study (with cf-PWV) finding positive association.Conclusion: The association between SUA and cf-PWV resulted significant in general population in both males and females while it was only significant for female regarding ba-PWV. Furthermore, the few available studies found no significant relationship between SUA and both cf- and ba-PWV in hypertensive subjects.

Three-year National report from the Gruppo Italiano di Ortogeriatria (GIOG) in the management of hip-fractured patients.

BACKGROUND: Hip fractures (HF) are a major issue worldwide. We aimed at evaluating the practices in delivering care to patients with HF among several Italian Orthogeriatric centers. METHODS: The study took place from February 2016 to July 2018. Seven performance indicators (pre-surgical cognitive assessment, surgery performed ≤ 48 h from fracture, removal of urinary catheter/absence of delirium/start of physiotherapy on the first post-operative day, prescription of bone protection at discharge, and discharge toward rehabilitation) were collected. RESULTS: The 14 participating hospitals totally recruited 3.017 patients. Patients were old (median age 86 years; Inter Quartile Range [IQR] 80-90), mostly females (77%). Nearly 55% of them were already impaired in mobility and about 10% were nursing home residents. Median time-to-surgery was 41 h (IQR 23-62). Models of care greatly varied among centers, only 49.3% of patients being co-managed by geriatricians and orthopedics. There was high variability across centers in four indicators ("pre-surgical cognitive assessment", "bone protection prescription", "use of urinary catheter" and "start of physiotherapy"), moderate in two indicators ("surgery performed ≤ 48 h from fracture" and "discharge toward rehabilitation" and low in one ("absence of delirium on day following surgery"). Comparison with international studies suggests very different ways of providing care to HF Italian patients. CONCLUSIONS: The study results suggest high inter-center variability in the key-performance indicators, and different approaches in providing care to our HF patients in comparison to other countries. A National debate on the topic is required in Italy to harmonize practices of orthogeriatric care.

Describing the epidemic trends of COVID-19 in the area covered by Agency for Health Protection of the Metropolitan Area of Milan.

OBJECTIVES: to describe the epidemic trends of COVID-19 over time and by area in the territory covered by Milan's Agency for Health Protection (ATS-MI) from February to May 2020. DESIGN: descriptive study of COVID-19 cases. SETTING AND PARTICIPANTS: a new information system was developed to record COVID-19 cases with positive nasopharyngeal swab. Patients resident in the area covered by ATS-MI with symptom onset between February and May 2020 were selected. Different epidemic periods were considered based on the timeline of the various regional and national containment measures. MAIN OUTCOME MEASURES: case fatality ratios, incidence rates, and reproduction number by epidemic period and sub-area of ATS-MI. RESULTS: a total of 27,017 swab-positive COVID-19 cases were included. Mean age was 65 years and males were 45%. Incidence in the ATS-MI area was 776 per 100,000 population. The number of deaths was 4,660, the crude case fatality ratio was 17.3%, higher in males (21.2%) than in females (14.0%). The estimated reproduction number registered its peak (3.0) in the early stages of the epidemic and subsequently decreased. Territorial differences were observed in the epidemic spread, with a higher incidence in the Lodi area. CONCLUSIONS: estimated incidence and case fatality ratios were higher than national estimates for Italy. Each ATS-MI area had different epidemic spread patterns.

Assessment of the Overall Mortality during the COVID-19 Outbreak in the Provinces of Milan and Lodi (Lombardy Region, Northern Italy).

OBJECTIVES: to describe the overall mortality increase in the provinces of Milan and Lodi - area covered by the Agency for Health Protection of Milan - during the COVID-19 epidemic in the first four months of 2020, compare it with the same time period in the years 2016-2019, and evaluate to what extent the mortality can be directly attributed to the outbreak. DESIGN: cohort study. SETTING AND PARTICIPANTS: using a new information system developed during the pandemic, we gathered data on the number of daily deaths in the population residing in the provinces of Milan and Lodi by Local Health Unit (ASST) and age groups. To describe the case fatality of COVID-19, we performed a record linkage with a database specially constructed during the epidemic to identify deaths that occurred in confirmed cases. MAIN OUTCOME MEASURES: mortality and excess mortality were analysed by comparing the number of observed deaths in the first 4 months of 2020 with the average deaths of the years 2016-2019 in the same calendar period and with expected deaths, estimated using a Poisson model. Furthermore, a measure of relative risk was calculated as observed/expected ratio with a 95% confidence interval. RESULTS: the increase in mortality for all causes occurring in the study population in the first 4 months of 2020 was 48.8%, 30.8% for ages between 60 and 69, 43.9% for ages between 70 and 79, and 56.7% for subjects above 80 years of age. Focusing on the epidemic period, from 1 March to 30 April, the excess is quantifiable as more than 2-fold and mainly concerns the population over 60 years of age. The excess mortality was observed in all local health units (ASSTs). The highest increments were in the province of Lodi and the North-East of Milan (ASST Nord). In the ASSTs of Lodi and Melegnano-Martesana the mortality excess was detectable from March 15th, while for the other ASSTs the increase began in the first week of April. CONCLUSIONS: evaluation of overall mortality in the provinces of Milan and Lodi during the first wave of the Covid-19 epidemic showed a significant excess compared to the first 4 months of the years 2016-2019, mainly in the population over 60 years of age. However, this excess cannot be completely attributed directly to COVID-19 itself. This phenomenon was more intense in the Lodi ASST, with daily deaths up to 5 times higher than expected.

Multidisciplinary biopsychosocial rehabilitation for chronic low back pain: the need to present minimal important differences units in meta-analyses.

BACKGROUND: The results of meta-analyses are all too often elusive, making it difficult to interpret their relevance for clinical practice. Reporting them in minimal important difference (MID) units could improve the interpretation of evidence in meta-analyses. The aim of this study was to compare, via calculation of MID units, outcomes after multidisciplinary biopsychosocial rehabilitation (MBR) versus usual care for pain relief in chronic low back pain (LBP). METHODS: We re-analyzed the data of a published Cochrane review on MBR. To attribute a MID to each pain instrument, we first searched the literature for MIDs. The MID was imputed for instruments without an established MID. We compared outcomes after MBR versus usual care for chronic LBP in the short (< 3 months), mid (> 3 and < 12 months), and long (≥12 months) term. The results of the meta-analyses are reported in MID units and interpreted as follows: if the overall effect size was greater than 1, many patients gained clinically important benefits, if it lay between 0.5 and 1.0, an appreciable number benefited, and if it fell below 0.5 few did. RESULTS: Improvement in back pain was observed in an appreciable number of patients in the short- and medium-term after MBR: the MID was lower but still close to 1 (0.75 and 0.86 MID units, respectively). MBR probably had little or no benefit for the majority of patients in the long-term, where the MID approached 0 (0.27 MID units, confidence interval 0.07-0.48). CONCLUSIONS: Meta-analyses expressed in MID units may offer better insight into the clinical relevance of MBR: the intervention is highly recommended for reducing pain in the short- and medium-term but cannot be recommended for long-term pain reduction since the benefit decays rapidly.

How Accurate Is a Single Cutpoint to Identify High Blood Pressure in Adolescents?

In 2007 the International Diabetes Federation (IDF) proposed single blood pressure (BP) cutpoints (systolic: ≥130 mm Hg and diastolic: ≥85 mm Hg) for the diagnosis of high blood pressure (HBP) in adolescents. Before this proposal, HBP had been defined as BP at or above the 95th percentile for age, sex, and height percentile (reference standard). In this study, we evaluated the risk for misclassification when using the IDF single-cutpoints criteria. We first applied the IDF criteria to a reconstructed population with the same age, sex, and height distribution as the population used to develop the reference standard. The proposed single cutpoints corresponded to percentiles from the 81.6th to 99.9th for systolic BP and from the 92.9th to 98.9th for diastolic BP in the reconstructed population. Using IDF criteria, there were high false-negative fractions for both systolic and diastolic BP (from 54% to 93%) in 10- to 12-year-olds and a false-positive fraction up to 35% in older subjects. We then applied the IDF criteria to 1,162 overweight/obese adolescents recruited during 1998-2000 from pediatric clinical centers in Milano, Varese, and Modena in Italy and in Zaragoza, Spain. Overall false-negative and false-positive fractions were 22% and 2%, respectively; negative predictive values were especially low for 10- to 12-year-old subjects. The use of IDF's single cutpoints carries a high risk of misclassification, mostly due to false negatives in younger subjects. The effort to simplify diagnosis could be overcome by the risk of undiagnosed HBP.

Adherence to guidelines and breast cancer patients survival: a population-based cohort study analyzed with a causal inference approach.

PURPOSE: There is a lack of real-world studies evaluating the impact on survival of an evidence-based pathway of care in breast cancer. The aim of this work is to investigate the effect of adherence to guidelines on long-term survival for a cohort of Italian breast cancer patients. METHODS: The cohort included incident female breast cancer cases (2007-12), from the registry of the Milan province (Italy), not metastatic at diagnosis and receiving primary surgery. We selected sets of indicators, according to patient and tumor characteristics. We then defined the pathway of care as adherent to guidelines if it fulfilled at least 80% of the indicators. Indicators were measured using different administrative health databases linked on a unique key. A causal inference approach was used, drawing a directed acyclic graph and fitting an inverse probability weighted marginal structural model, accounting for patient's demographic, socioeconomic and tumor characteristics. RESULTS: The analysis included 6333 patients, 69% of them were classified as having an adherent care. Mean age was 61 years (standard deviation, 13.6 years) and half of the patients were in Stage I (50%) at diagnosis. Median follow-up time was 5.6 years. Overall, 5-year survival was 90% (95% CI, 89-91%). The estimated risk of death was 30% lower for patients with adherent than nonadherent care (hazard ratio [HR], 0.66; 95% CI, 0.55-0.77). CONCLUSIONS: Our study confirms, in real-world care, the impact on survival of receiving a care pathway adherent to guidelines in non-metastatic breast cancer patients.

Measures of single arm outcome in meta-analyses of rare events in the presence of competing risks.

When performing single arm meta-analyses of rare events in small populations, if the outcome of interest is incidence, it is not uncommon to have at least one study with zero events, especially in the presence of competing risks. In this paper, we address the problem of how to include studies with zero events in inverse variance meta-analyses when individual patient data are not available, going beyond the naïve approach of not including the study or the use of a continuity correction. The proposed solution is the arcsine transformation of the crude cumulative incidence as its approximate variance, which is inversely proportional to the sample size, can be calculated also for studies with a zero estimate. As an alternative, generalized linear mixed models (GLMM) can be used. Simulations were performed to compare the results from inverse variance method meta-analyses of the arcsine transformed cumulative incidence to those obtained from meta-analyses of the cumulative incidence itself and of the logit transformation of the cumulative incidence. The comparisons have been carried out for different scenarios of heterogeneity, incidence, and censoring and for competing and not competing risks. The arcsine transformation showed the smallest bias and the highest coverage among models assuming within study normality. At the same time, the GLMM model had the best performance at very low incidences. The proposed method was applied to the clinical context that motivated this work, i.e. a meta-analysis of 5-year crude cumulative incidence of central nervous system recurrences in children treated for acute lymphoblastic leukemia.

MR diffusion imaging for preoperative staging of myometrial invasion in patients with endometrial cancer: a systematic review and meta-analysis.

OBJECTIVES: To compare the diagnostic accuracy of dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) MR imaging in detecting deep myometrial invasion in endometrial cancer, using surgical-pathological staging as reference standard. METHODS: After searching a wide range of electronic databases and screening titles/abstracts, we obtained full papers for potentially eligible studies and evaluated according to predefined inclusion criteria. Quality assessment was conducted by adapting the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) checklist. From each study, we extracted information on diagnostic performance of DW and DCE sequences. After exploring heterogeneity, we adopted a bivariate generalized linear mixed model to compare the effect of the two MR sequences jointly on sensitivity and specificity. RESULTS: Nine studies (442 patients) were considered. Significant evidence of heterogeneity was found only for specificity, both in DW and DCE imaging (I (2) = 70.8 % and 70.6 %). Pooled sensitivity of DW and DCE was 0.86 and specificity did not significantly differ (p = 0.16) between the two sequences (DW = 0.86 and DCE = 0.82). No difference was found between 3-T and 1.5-T MR. There was no evidence of publication bias. CONCLUSIONS: MR diagnostic accuracy in presurgical detection of deep myometrial infiltration in endometrial cancer is high. DCE and DW imaging do not differ in sensitivity and specificity. KEY POINTS: Myometrial invasion is the most important morphological prognostic feature of endometrial cancer. MR diagnostic accuracy in presurgical detection of deep myometrial infiltration is high. MR examination including T2 and DCE imaging is considered the reference standard. DW imaging has been increasingly employed with heterogeneous results. This meta-analysis shows that DCE and DW do not differ in diagnostic accuracy.

Percutaneous microwave ablation of hepatic tumors: prospective evaluation of postablation syndrome and postprocedural pain.

PURPOSE: To prospectively investigate the frequency and severity of postablation syndrome (PAS) and postprocedural pain in a cohort of patients undergoing hepatic microwave ablation. MATERIALS AND METHODS: From March 2009 to November 2011, 54 consecutive patients undergoing microwave ablation for liver tumors were enrolled. A questionnaire was administered to investigate PAS and pain at 1, 7, and 40 days after ablation. Four patients did not complete all three questionnaires and were excluded from the analysis. Additionally, laboratory tests with results known to significantly increase or decrease after ablation were performed, and ablation parameters were recorded. Potential predictors of PAS and pain at 1 and 7 days were evaluated by a logistic regression model. RESULTS: Fifty patients underwent a single microwave ablation session, 33 for hepatocellular carcinoma (HCC) and 17 for liver metastasis. Median ablation volumes on computed tomography were 31 cm(3) for HCC and 42 cm(3) for metastasis. Sixty percent of patients experienced PAS in the first week. Aspartate aminotransferase (AST) levels after ablation were significantly associated with PAS during postprocedure days 1-7. Median visual analog scale scores for pain at the puncture site were 1 and 0.24 at 1 and 7 days, respectively. The risk of having at least moderate pain in the first week was significantly related to ablation volume and time and postablation increase in AST level. CONCLUSIONS: The incidence and severity of PAS with hepatic microwave ablation is similar to that reported for radiofrequency ablation, with the best predictive factor being postablation AST level elevation. Postablation pain was best predicted by total ablation volume and AST level.

[A set of indicators to monitor the adherence to the guidelines for the diagnosis and treatment of breast cancer]. / Indicatori per il monitoraggio dei percorsi diagnostico-terapeutici del tumore della mammella.

OBJECTIVES: to present a set of indicators developed from six Local Health Authorities of the Lombardy Region to monitor the diagnostic and therapeutic pathway of breast cancer patients, applied to 2007-2009 incident cases. DESIGN: retrospective cohort study. SETTING AND PARTICIPANTS: all subjects with primary breast cancer, incident in the period 2007-2009, and collected by cancer registries of Milano 1, Bergamo, Cremona, Milano, Milano 2 and Monza-Brianza (5,320,272 inhabitants) were included. MAIN OUTCOME MEASURES: through the use of combined current health databases (health registry, hospitalizations, outpatient, pharmaceutical prescription and specific database for anticancer drugs), for each incident case 34 different indicators have been developed to measure the appropriateness of the procedures provided for diagnosis, treatment (surgical and medical) and follow-up. For each indicator, we analyzed the relationship with age, stage, deprivation index, type of treatment, volume of the specific procedure of the hospital where primary surgery was performed. Estimates were adjusted using multilevel regression models. RESULTS: 12,988 incident cases, without metastatic diseases and other cancers, were included in the cohort: 62% were localized to the breast, 33% to the axillary lymph-nodes, 3% metastatic ab initio, and 2% with unknown stage. Deviations from the expected value of different magnitude depending on the type of indicator were observed: the most important differences were detected for the follow-up indicators. There was, in fact, an excess of several procedures in the first year of follow-up: 75% of the cases performed a dosage of a tumor marker, 67% an ecography or a CT scan or an MR, and 37% a bone scan. On the other hand, the access to neoadjuvant and adjuvant treatments in older women was far below the expected values. CONCLUSIONS: the study presents data derived from a large cohort of population cases; the set of indicators was validated by a board of oncologists. The use of indicators calculated by linking the cancer registries (that provide staging) and administrative databases allows the assessment of compliance to the guidelines for diagnosis and treatment of tumours. This experience shows that it is possible to develop a methodology, shared with clinicians, to define indicators that measure the distance between guidelines and current clinical practice in order to decrease variability, to limit inappropriateness, and to reduce unnecessary diagnostic tests for patients (and, consequently, hospitals organizational overload). In order to be sustainable and equitable, a health care system must be able to ensure implementation of protocols/procedures based exclusively on the best available scientific evidences.

Hospital-Acquired Anemia in Patients with Acute Coronary Syndrome: Epidemiology and Potential Impact on Long-Term Outcome.

BACKGROUND: Anemia (either pre-existing or hospital-acquired) is considered an independent predictor of mortality in acute coronary syndromes. However, it is still not clear whether anemia should be considered as a marker of worse health status or a therapeutic target. We sought to investigate the relationship between hospital-acquired anemia and clinical and laboratory findings and to assess the association with mortality and major cardiovascular events at long-term follow-up. METHODS: Patients consecutively admitted at Niguarda Hospital between February 2014 and November 2020 for an acute coronary syndrome were included in this cohort analysis and classified as anemic at admission (group A), with normal hemoglobin at admission but developing anemia during hospitalization (hospital-acquired anemia) (group B); and with normal hemoglobin levels throughout admission (group C). RESULTS: Among 1294 patients included, group A included 353 (27%) patients, group B 468 (36%), and group C 473 patients (37%). In terms of cardiovascular burden and incidence of death, major cardiovascular events and bleeding at 4.9-year median follow-up, group B had an intermediate risk profile as compared with A and C. Baseline anemia was an independent predictor of death (hazard ratio 1.51; 95% confidence interval, 1.02-2.25; P = .04) along with frailty, Charlson comorbidity Index, estimated glomerular filtration rate, previous myocardial infarction, and left ventricular ejection fraction. Conversely, hospital-acquired anemia was not associated with increased mortality (hazard ratio 1.18; 95% confidence interval, 0.8-1.75; P = .4). CONCLUSIONS: Hospital-acquired anemia affects one-third of patients hospitalized for acute coronary syndrome and is associated with age, frailty, and comorbidity burden, but was not found to be an independent predictor of long-term mortality.

High-powered microwave ablation with a small-gauge, gas-cooled antenna: initial ex vivo and in vivo results.

PURPOSE: To evaluate the performance of a gas-cooled, high-powered microwave system. MATERIALS AND METHODS: Investigators performed 54 ablations in ex vivo bovine livers using three devices-a single 17-gauge cooled radiofrequency(RF) electrode; a cluster RF electrode; and a single 17-gauge, gas-cooled microwave (MW) antenna-at three time points (n = 6 at 4 minutes, 12 minutes, and 16 minutes). RF power was applied using impedance-based pulsing with maximum 200 W generator output. MW power of 135 W at 2.45 GHz was delivered continuously. An approved in vivo study was performed using 13 domestic pigs. Hepatic ablations were performed using single applicators and the above-mentioned MW and RF generator systems at treatment times of 2 minutes (n = 7 MW, n = 6 RF), 5 minutes (n = 23 MW, n = 8 RF), 7 minutes (n = 11 MW, n = 6 RF), and 10 minutes (n = 7 MW, n = 9 RF). Mean transverse diameter and length of the ablation zones were compared using analysis of variance (ANOVA) with post-hoc t tests and Wilcoxon rank-sum tests. RESULTS: Single ex vivo MW ablations were larger than single RF ablations at all time points (MW mean diameter range 3.5-4.8 cm 4-16 minutes; RF mean diameter range 2.6-3.1 cm 4-16 minutes) (P < .05). There was no difference in mean diameter between cluster RF and MW ablations (RF 3.3-4.4 cm 4-16 minutes; P = .4-.9). In vivo lesion diameters for MW (and RF) were as follows: 2.6 cm ± 0.72 (RF 1.5 cm ± 0.14), 3.6 cm ± 0.89 (RF 2.0 cm ± 0.4), 3.4 cm ± 0.87 (RF 1.8 cm ± 0.23), and 3.8 cm ± 0.74 (RF 2.1 cm ± 0.3) at 2 minutes, 5 minutes, 7 minutes, and 10 minutes (P < .05 all time points). CONCLUSIONS: Gas-cooled, high-powered MW ablation allows the generation of large ablation zones in short times.