UNASSIGNED: Cabozantinib use in everyday clinical practice for advanced or metastatic renal cell carcinoma (RCC) is relatively recent, and real-world data on treatment persistence, adherence and sequencing are still limited.
UNASSIGNED: We conducted an analysis based on an integrated administrative database, covering around 6.9 million health-assisted Italian individuals, to explore the use of cabozantinib for RCC. Patients with at least one prescription for cabozantinib during 2017-2020 were searched. These were characterized during all available period (i.e. from 2010 onwards) before the index date and were observed after inclusion.
UNASSIGNED: A total of 113 patients treated with cabozantinib in second or subsequent line were included, and their demographic, clinical and treatment characteristics were described. About half of these RCC patients were aged >65 years (47.8%). Sixty patients (53.1%) were highly adherent to cabozantinib therapy, and the median cabozantinib treatment duration of use was 8.7 months (95% confidence interval: 5.8-11.1). During the first year of follow-up, the average total cost per patient was €32,508.
UNASSIGNED: We described second or subsequent line cabozantinib treatment for RCC in a real-world setting and the economic burden of disease in Italy, taking advantage of large, integrated administrative databases.

OBJECTIVE: To estimate the incremental medical cost of diabetes mellitus using information from administrative databases in Colombia.
METHODS: We carried out a retrospective cohort study with administrative health databases from Colombian population affiliated in the contributory health insurance scheme. We used an operative definition to select the cohort with diabetes. Incremental cost and cost ratio of diabetes were estimated using an inverse probability weighting of treatment approach to find the causal effect of having the disease. Weights were calculated by a propensity score method using a Random Forest model. The flexibility of this machine learning algorithm allows to have a better specification and bias reduction. Additionally, we reported incremental costs and cost ratios with confidence intervals using bootstrapping and analyzed costs by age groups and complications associated with diabetes.
RESULTS: The estimated prevalence of diabetes was 2834 per 100 000 cases, in 2018. The group with diabetes was comprised 634 015 people and the control group 1 524 808. The calculated annual direct medical cost was $860, for which the incremental cost was $493 and the cost ratio 2.34. The incremental annual cost for some type of complication ranges from $1239 to $2043, renal complication being the most expensive. Incremental cost by age groups ranges from $347 to $878, being higher in younger people.
CONCLUSIONS: Although the cost of diabetes in Colombia ranges among the global averages and is similar to other Latin-American countries, a greater incremental cost was found in patients with renal, circulatory, and neurologic complications.

BACKGROUND: The diagnosis of peripheral arterial disease (PAD) is commonly applied for symptoms related to atherosclerotic obstructions in the lower extremity, though its clinical manifestations range from an abnormal ankle-brachial index to critical limb ischemia. Subsequently, management and prognosis of PAD vary widely with the disease stage. A critical aspect is how this variation is addressed in administrative database-based studies that rely on diagnosis codes for case identification. The objective of this scoping review is to inventory the identification strategies used in studies on PAD that rely on administrative databases, to map the pros and cons of the International Classification of Diseases (ICD) codes applied, and to propose a first outline for a consensus framework for case identification in administrative databases.
METHODS: Registry-based reports published between 2010 and 2021 were identified through a systematic PubMed search. Studies were subcategorized on the basis of the expressed study focus: claudication, critical limb ischemia, or general peripheral arterial disease, and the ICD code(s) applied for case identification mapped.
RESULTS: Ninety studies were identified, of which 36 (40%) did not specify the grade of PAD studied. Forty-nine (54%) articles specified PAD grade studied. Five (6%) articles specified different PAD subgroups in methods and baseline demographics, but not in further analyses. Mapping of the ICD codes applied for case identification for studies that specified the PAD grade studied indicated a remarkable heterogeneity, overlap, and inconsistency.
CONCLUSIONS: A large proportion of registry-based studies on PAD fail to define the study focus. In addition, inconsistent strategies are used for PAD case identification in studies that report a focus. These findings challenge study validity and interfere with inter-study comparison. This scoping review provides a first initiative for a consensus framework for standardized case selection in administrative studies on PAD. It is anticipated that more uniform coding will improve study validity and facilitate inter-study comparisons.

UNASSIGNED: Dementia is prevalent among the elderly, also representing a risk for seizures/epilepsy. Estimations of epilepsy risk in dementia patients are not widely available.
UNASSIGNED: Our research aims to ascertain the incidence of epilepsy and its associated risk factors in subjects with dementia in the Umbria region, based on data from healthcare databases.
UNASSIGNED: In this retrospective study based on the healthcare administrative database of Umbria, we identified all patients diagnosed with dementia from 2013 to 2017, based on ICD-9-CM codes. For epilepsy ascertainment, we used a validated algorithm that required an EEG and the prescription of one or more anti-seizure medications post-dementia diagnosis. A case-control analysis was conducted, matching five non-dementia subjects by gender and age to each dementia patient. Cox proportional hazards models were then utilized in the analysis.
UNASSIGNED: We identified 7,314 dementia cases, also including 35,280 age- and sex-matched control subjects. Out of patients with dementia, 148 individuals (2.02%) were diagnosed with epilepsy. We observed a progressive increase in the cumulative incidence of seizures over time, registering 1.45% in the first year following the diagnosis, and rising to 1.96% after three years. Analysis using Cox regression revealed a significant association between the development of epilepsy and dementia (HR = 4.58, 95% CI = 3.67-5.72). Additional risk factors were male gender (HR = 1.35, 95% CI = 1.07-1.69) and a younger age at dementia onset (HR = 1.03, 95% CI=1.02-1.04).
UNASSIGNED: Dementia increases epilepsy risk, especially with early onset and male gender. Clinicians should have a low threshold to suspect seizures in dementia cases.

UNASSIGNED: In spring 2022, a series of reports from the United Kingdom and the United States identified an increase in the incidence of acute severe hepatitis in children. The Public Health Agency of Canada (PHAC) collaborated with provincial/territorial health partners to investigate in Canada. Clinical hepatitis, or inflammation of the liver, is not reportable in Canada, so to determine if an increase was occurring above historical levels, the baseline incidence in Canada was estimated. This article estimates the pre-existing baseline incidence of acute severe hepatitis of unknown origin in children in Canada using administrative databases. It further summarizes the outbreak investigation using information from the national case report forms.
UNASSIGNED: A committee with representatives from PHAC and provincial/territorial health partners was established to investigate current cases in Canada. A national probable case definition and case report form were developed, and intentionally created to be highly sensitive to capture all potential cases for etiological investigations. To estimate a nationally representative baseline incidence, hospitalization data were extracted from the Discharge Abstract Database and was combined with data from Québec from the Ministère de la Santé et des Services sociaux.
UNASSIGNED: Twenty-eight probable cases of acute severe hepatitis of unknown origin in children were reported between October 1, 2021, to September 23, 2022, by six provinces: British Columbia=1; Alberta=5; Saskatchewan=1; Manitoba=3; Ontario=14; and Québec=4. The estimated national baseline incidence was an average of 70 cases annually, or 5.8 cases per month.
UNASSIGNED: There was no apparent increase above the estimated historical baseline levels.

This study evaluated the economic burden of metastatic non-small cell lung cancer patients before and after the availability of an immuno-oncology (IO) regimen as a first-line (1L) treatment. Patients from 2014 to 2020 were categorized according to mutational status into mutation-positive and negative/unknown groups, which were further divided into pre-1L IO and post-1L IO sub-groups depending on the availability of pembrolizumab monotherapy in 1L. Healthcare costs and HCRU for a 1L treatment and overall follow-up were reported as the mean total and per-month cost per patient by groups. Of 644 patients, 125were mutation-positive and 519 negative/unknown (229 and 290 in pre- and post-1L IO, respectively). The mean total per-patient cost in 1L was lower in pre- (EUR 7804) and post-1L IO (EUR 19,301) than the mutation-positive group (EUR 45,247), persisting throughout overall disease follow-up. However, this difference was less when analyzing monthly costs. Therapy costs were the primary driver in 1L, while hospitalization costs rose during follow-up. In both mutation-positive and post-IO 1L groups, the 1L costs represented a significant portion (70.1% and 66.3%, respectively) of the total costs in the overall follow-up. Pembrolizumab introduction increased expenses but improved survival. Higher hospitalisation and emergency room occupation rates during follow-up reflected worsening clinical conditions of the negative/unknown group than the mutation-positive population.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease. Riluzole may increase survival and delay the need for mechanical ventilation. The CAESAR project (\'Comparative evaluation of the efficacy and safety of drugs used in rare neuromuscular and neurodegenerative diseases\', FV AIFA project 2012-2013-2014) involves evaluating prescribing patterns, and analysing effectiveness and comparative safety of drugs, in patients with neurodegenerative diseases. The aim of this study is to evaluate adherence to riluzole in patients with ALS during the first year of use, identifying adherence clusters.
METHODS: A retrospective cohort study was conducted using administrative data from Latium, Tuscany, and Umbria. We identified subjects with a new diagnosis of ALS between 2014 and 2019, with the first dispensation of riluzole within 180 days of diagnosis. We considered a two-year look-back period for the characterization of patients, and we followed them from the date of first dispensing of riluzole for 1 year. We calculated 12 monthly adherence measures, through a modified version of the Medication Possession Ratio, estimating drug coverage with Defined Daily Dose. Adherence trajectories were identified using a three-step method: (1) calculation of statistical measures; (2) principal component analysis; (3) cluster analysis. Patient characteristics at baseline and during follow-up were described and compared between adherence groups identified.
RESULTS: We included 264 ALS patients as new users of riluzole in Latium, 344 in Tuscany, and 63 in Umbria. We observed a higher frequency of males (56.2%) and a mean age of 67.4 (standard deviation, SD, 10.4) in the overall population. We identified two clusters in all regions: one more numerous, including adherent patients (60%, 74%, 88%, respectively), and another one including patients who discontinued therapy (40%, 26%, 12%, respectively). In Tuscany patients discontinuing riluzole more frequently died (28.6% vs. 15.4%, p-value <0.01). Additionally, low-adherers had a higher frequency of central nervous system disorders (69.0% vs. 52.5%, p-value 0.01), and a greater use of non-pharmacological treatments (p-values ≤0.01 for invasive ventilation and tracheostomy). We did not observe any differences in Lazio, whereas in Umbria we observed a higher use of drugs for dementia-related psychiatric problems among low-adherers (57.1% vs. 7.8%, respectively, p-value <0.01), although with small numbers.
CONCLUSIONS: Most ALS patients who start riluzole adhere to therapy during the first year. Patients who discontinue therapy early show greater fragility and mortality.

The National Violent Death Reporting System (NVDRS) is a Centers for Disease Control and Prevention (CDC) restricted-access database detailing precipitating circumstances to U.S. violent deaths. In 2013 and 2015, the CDC added codes denoting sexual orientation and gender identity (SOGI) and sex of partner. In the past decade, researchers have leveraged NVDRS data to document SOGI-related patterns and characteristics of violent death including suicide. Yet, there are substantial limitations to NVDRS SOGI information that should be considered in responsible reporting by researchers and informed assessment by reviewers. In this perspective, we summarize some of these challenges and offer recommendations for using NVDRS SOGI data responsibly.

Chronic stress and depression are potential risk factors for mild cognitive impairment and dementia, including Alzheimer disease. The aim was to investigate whether any such risk is additive.
Cohort study including 1 362 548 people (665 997 women, 696 551 men) with records in the Region Stockholm administrative healthcare database (VAL). Exposure was a recorded ICD-10 diagnosis of chronic stress, depression, or both, recorded in 2012 or 2013. Outcome was a diagnosis of Alzheimer disease, other dementia, or mild cognitive impairment recorded from 2014 through 2022. Odds ratios with 99% confidence intervals (CI) adjusted for age, sex, neighborhood socioeconomic status, diabetes, and cardiovascular disorders were calculated.
During the exposure period, 4 346 patients were diagnosed with chronic stress, 40 101 with depression, and 1 898 with both. The average age at baseline was around 40 years in all groups. In the fully adjusted model, the odds ratio of Alzheimer disease was 2.45 (99% CI 1.22-4.91) in patients with chronic stress, 2.32 (99% CI 1.85-2.90) in patients with depression, and 4.00 (99% CI 1.67-9.58) in patients with chronic stress and depression. The odds ratio of mild cognitive impairment was 1.87 (99% CI 1.20-2.91) in patients with chronic stress, 2.85 (99% CI 2.53-3.22) in patients with depression, and 3.87 (99% CI 2.39-6.27) in patients with both. When other dementia was analyzed, the odds ratio was significant only in patients with depression, 2.39 (99% CI 1.92-2.96).
Documented chronic stress increased the risk of mild cognitive impairment and Alzheimer disease. The same was seen with depression. The novel finding is the potential additive effect of chronic stress to depression, on risk of MCI and AD.

Miscarriage is one of the most frequent adverse events that occurs during pregnancy. This retrospective study aimed to verify if the environmental and socioeconomic conditions related to geographical areas where women live, and the socio-demographic and clinical factors play a role in the risk of spontaneous abortion (SA). The analyses were conducted by hospital discharge records (HDRs) from public and private hospitals in Apulia from 1 January 2021 to 31 December 2021. Women with an age over 40 years old had a major risk of SA compared with women under 18 years (OR 2.30, IC95%1.16-4.54). A reduction in the risk of SA was found for women with an endocrinological or metabolic disease (OR 0.28, 95% CI 0.19-0.41), while genetic disease greatly increases the risk (OR 9.63, IC95% 1.98-46.86). The greatest risk of spontaneous abortion was found in the province of Taranto compared to the province of Foggia (OR 2.01, 95% CI 1.52-2.64). The provinces with a higher risk of SA in the multiple comparisons were Taranto, Brindisi, and BAT. Municipalities with socioeconomic disadvantages classified as very low, low, and medium had a higher risk of SA compared to the municipalities with a high disadvantage. In conclusion, our study indicates the possible association between SA rate and environmental conditions. Additionally, the socioeconomic, clinical, and demographic factors were related to the risk of SAs.