Eur J Clin Pharmacol. 2022 Apr 28. doi: 10.1007/s00228-022-03325-y. Online ahead of print.

ABSTRACT

PURPOSE: To assess the impact of long-term use of different drugs commonly prescribed in Alzheimer's disease (AD) on its clinical course and to identify clinical and therapeutic factors associated with a delay in AD progression.

METHODS: We retrospectively enrolled 50 patients visited at the Neurology Unit, Careggi University Hospital (Florence), followed for at least 24 months. AD diagnosis was made according to clinical diagnostic criteria for probable/possible AD dementia, always supported at least by one biomarker. Clinical features, MMSE scores evaluated at diagnosis and every 6 months, and AD drugs used for at least 6 months, were recorded. Cox regression analysis was performed to estimate the hazard ratio (HR) for AD progression, assuming as the "final event," the progression to a more severe disease stage, defined as the achievement of an MMSE score less than 10.

RESULTS: At baseline, the median MMSE score was 22. During follow-up (median of 41 months), 56% of patients progressed to a more severe disease stage. The use of memantine, either alone (HR 0.24; 95% CI 0.09-0.60) or combined with acetylcholinesterase inhibitors (HR 0.35; 95% CI 0.14-0.88) and a higher MMSE score at baseline (HR 0.82; 95% CI 0.70-0.96) were associated with a significantly lower risk of AD progression.

CONCLUSION: Nowadays, effective disease-modifying therapy for AD is missing. Nevertheless, when the diagnosis is established, our results support the advantage of long-term use of available pharmacological treatments, especially in combination, in delaying AD progression to its more severe disease stage.

PMID:35484251 | DOI:10.1007/s00228-022-03325-y

Intern Emerg Med. 2022 Apr 12:1-10. doi: 10.1007/s11739-022-02976-0. Online ahead of print.

ABSTRACT

Given the increase in benzodiazepine (BZD) and Z-drug (ZD) use disorder, this study described the use of phenobarbital (PHB) as detoxification in clinical practice. A 15-year observational retrospective study was performed on medical records of BZD-ZD use disorder patients detoxified with PHB at the Toxicology Unit and Poison Centre, Careggi University Hospital, Florence (Italy). A multivariate logistic regression was used to estimate odd ratios (ORs) and related 95% confidence intervals (CI) of "treatment failure" considering demographic and pharmacological characteristics. "Hospitalisation length", "PHB discharge dose", and "BZD-ZD free status" at discharge were also calculated. During detoxification, out of 355 patients (57% of men), with a mean age of 42.92 years, only 20 (5.6%) treatment failures were recorded: 19 were discharged against medical advice or due to misbehaviour, and only one for PHB-related non-serious skin rash. Analysis showed a higher probability to be BZD-ZD free at discharge for subjects who reported to be employed (OR 2.29; CI 95% 1.00-5.24), for those who abused oral drops of BZD-ZD (OR 2.16, CI 1.30-3.59), and for those treated with trazodone (OR 2.86, CI 1.14-7.17) during hospital stay. A hospitalisation length of > 7 days was observed for patients with opioid maintenance therapy (OR 2.07, CI 1.20-3.58) for substance use disorder, and for those treated with more than 300 mg/day of PHB equivalents at hospital admission (OR 1.68, CI 1.03-2.72). Our results suggested that PHB can be considered a valuable detoxification option for different types of BZD and ZD use disorder patients.

PMID:35412225 | PMC:PMC9001824 | DOI:10.1007/s11739-022-02976-0

Pharmaceutics. 2022 Mar 11;14(3):619. doi: 10.3390/pharmaceutics14030619.

ABSTRACT

Moderate to severe cancer pain treatment in children is based on the use of weak and strong opioids. Pharmacogenetics play a central role in developing personalized pain therapies, as well as avoiding treatment failure and/or intolerable adverse drug reactions. This observational study aimed to investigate the association between IL-6, IL-8, and TNFα genetic single nucleotide polymorphisms (SNPs) and response to opioid therapy in a cohort of pediatric cancer patients. Pain intensity before treatment (PI_t0) significantly differed according to IL-6 rs1800797 SNP, with a higher PI for A/G and G/G individuals (p = 0.017), who required a higher dose of opioids (p = 0.047). Moreover, compared to G/G subjects, heterozygous or homozygous individuals for the A allele of IL-6 rs1800797 SNP had a lower risk of having a PI_t0 > 4. Dose_24h and Dose_tot were both higher in G/G individuals for TNFα rs1800629 (p = 0.010 and p = 0.031, respectively), while risk of having a PI_t0 > 4 and a ∆_VAS > 2 was higher for G/G subjects for IL-6 rs1800795 SNP compared to carriers of the C allele. No statistically significant association between genotypes and safety outcomes was found. Thus, IL-6 and TNFα SNPs could be potential markers of baseline pain intensity and opioid dose requirements in pediatric cancer patients.

PMID:35335997 | PMC:PMC8953705 | DOI:10.3390/pharmaceutics14030619

Pharmacoepidemiol Drug Saf. 2022 May;31(5):489-494. doi: 10.1002/pds.5420. Epub 2022 Feb 28.

NO ABSTRACT

PMID:35194891 | PMC:PMC9088595 | DOI:10.1002/pds.5420

Phytother Res. 2022 Mar;36(3):1093-1102. doi: 10.1002/ptr.7373. Epub 2022 Jan 17.

ABSTRACT

This systematic review and meta-analysis were conducted to determine the effects of anthraquinone (AQ) laxatives on colorectal cancer (CRC). We searched PubMed, Embase, Google Scholar, and CENTRAL from inception until March 2021, for randomized controlled trials (RCTs) and observational studies. Through the systematic review, we identified 8 observational studies evaluating AQ laxatives use as a risk factor for CRC development, and 5 studies on CRC risk were included in the meta-analysis using a random-effects model. Through the meta-analysis, we found that a history of AQ laxatives use compared with "other" and "no laxatives" use was associated with CRC development (OR: 1.41; 95% CI: 0.94-2.11), although not at a statistically significant level. The possible association persists even after removal of the outlier studies (OR: 1.51; 95% CI: 0.97-2.34). Selection of cases and controls was judged at low or unclear risk of bias across almost all studies, and the quality of evidence was from moderate to low. In conclusion, it is not possible to associate the use of AQ laxatives with the development of CRC. However, the trend toward an increased risk of CRC provides a strong indication for investigating this issue by performing further high-quality studies.

PMID:35040201 | DOI:10.1002/ptr.7373

Br J Clin Pharmacol. 2022 May;88(5):2441-2443. doi: 10.1111/bcp.15129. Epub 2021 Nov 7.

NO ABSTRACT

PMID:34747053 | DOI:10.1111/bcp.15129

Drug Saf. 2021 Dec;44(12):1247-1269. doi: 10.1007/s40264-021-01131-6. Epub 2021 Nov 5.

ABSTRACT

To date, four vaccines have been authorised for emergency use and under conditional approval by the European Medicines Agency to prevent COVID-19: Comirnaty, COVID-19 Vaccine Janssen, Spikevax (previously COVID-19 Vaccine Moderna) and Vaxzevria (previously COVID-19 Vaccine AstraZeneca). Although the benefit-risk profile of these vaccines was proven to be largely favourable in the general population, evidence in special cohorts initially excluded from the pivotal trials, such as pregnant and breastfeeding women, children/adolescents, immunocompromised people and persons with a history of allergy or previous SARS-CoV-2 infection, is still limited. In this narrative review, we critically overview pre- and post-marketing evidence on the potential benefits and risks of marketed COVID-19 vaccines in the above-mentioned special cohorts. In addition, we summarise the recommendations of the scientific societies and regulatory agencies about COVID-19 primary prevention in the same vaccinee categories.

PMID:34739716 | PMC:PMC8569292 | DOI:10.1007/s40264-021-01131-6

BioDrugs. 2021 Nov;35(6):749-764. doi: 10.1007/s40259-021-00498-3. Epub 2021 Oct 12.

ABSTRACT

BACKGROUND: Biological drugs have improved the management of immune-mediated inflammatory diseases (IMIDs) despite being associated with important safety issues such as immunogenicity, infections, and malignancies in real-world settings.

OBJECTIVE: The aim of this study was to explore the potential of a large Italian multi-database distributed network for use in the postmarketing surveillance of biological drugs, including biosimilars, in patients with IMID.

METHODS: A retrospective cohort study was conducted using 13 Italian regional claims databases during 2010-2019. A tailor-made R-based tool developed for distributed analysis of claims data using a study-specific common data model was customized for this study. We measured the yearly prevalence of biological drug users and the frequency of switches between originator and biosimilars for infliximab, etanercept, and adalimumab separately and stratified them by calendar year and region. We then calculated the cumulative number of users and person-years (PYs) of exposure to individual biological drugs approved for IMIDs. For a number of safety outcomes (e.g., severe acute respiratory syndrome coronavirus 2 [SARS-COV-2] infection), we conducted a sample power calculation to estimate the PYs of exposure required to investigate their association with individual biological drugs approved for IMIDs, considering different strengths of association.

RESULTS: From a total underlying population of almost 50 million inhabitants from 13 Italian regions, we identified 143,602 (0.3%) biological drug users, with a cumulative exposure of 507,745 PYs during the entire follow-up. The mean age ± standard deviation of biological drug users was 49.3 ± 16.3, with a female-to-male ratio of 1.2. The age-adjusted yearly prevalence of biological drug users increased threefold from 0.7 per 1000 in 2010 to 2.1 per 1000 in 2019. Overall, we identified 40,996 users of biosimilars of tumor necrosis factor (TNF)-α inhibitors (i.e., etanercept, adalimumab, and infliximab) in the years 2015-2019. Of these, 46% (N = 18,845) switched at any time between originator and biosimilars or vice versa. To investigate a moderate association (incidence rate ratio 2) between biological drugs approved for IMIDs and safety events of interest, such as optic neuritis (lowest background incidence rate 10.4/100,000 PYs) or severe infection (highest background incidence rate 4312/100,000 PYs), a total of 43,311 PYs and 104 PYs of exposure to individual biological drugs, respectively, would be required. As such, using this network, of 15 individual biological drugs approved for IMIDs, the association with those adverse events could be investigated for four (27%) and 14 (93%), respectively.

CONCLUSION: The VALORE project multi-database network has access to data on more than 140,000 biological drug users (and > 0.5 million PYs) from 13 Italian regions during the years 2010-2019, which will be further expanded with the inclusion of data from other regions and more recent calendar years. Overall, the cumulated amount of person-time of exposure to biological drugs approved for IMIDs provides enough statistical power to investigate weak/moderate associations of almost all individual compounds and the most relevant safety outcomes. Moreover, this network may offer the opportunity to investigate the interchangeability of originator and biosimilars of several TNFα inhibitors in different therapeutic areas in real-world settings.

PMID:34637126 | PMC:PMC8507511 | DOI:10.1007/s40259-021-00498-3

Pharmaceuticals (Basel). 2021 Jul 15;14(7):678. doi: 10.3390/ph14070678.

ABSTRACT

This post hoc analysis of an Italian active pharmacovigilance study describes pharmacological differences of ADEs leading to emergency department (ED) visits and hospitalization in women and men. During the study period (January 2007-December 2018), 61,855 reports of ADEs leading to ED visits were collected. Overall, 30.6% of ADEs resulted in hospitalization (30% in women and 31% in men). Multivariate logistic regression showed that, among women, drug classes significantly associated with an increased risk of hospitalization were heparins (ROR 1.41, CI 1.13-176), antidepressants (ROR 1.12, CI 1.03-1.23) and antidiabetics (ROR 1.13, CI 1.02-1.24). Among men, only vitamin K antagonists (ROR 1.28, CI 1.09-1.50), opioids (ROR 1.30, CI 1.06-1.60) and digitalis glycosides (ROR 1.32, CI 1.09-1.59) were associated with a higher risk of hospitalization. Overall, older age, multiple suspected drugs and the presence of comorbidities were significantly associated with a higher risk of hospitalization. A significantly reduced risk of hospitalization was observed in both women and men experiencing an adverse event following immunization (ROR 0.36, CI 0.27-0.48 and 0.83, 0.42-0.74, respectively) compared to drugs. Results obtained from this real-world analysis highlight important aspects of drug safety between sexes.

PMID:34358104 | PMC:PMC8308702 | DOI:10.3390/ph14070678

Rheumatology (Oxford). 2022 Apr 11;61(4):1518-1528. doi: 10.1093/rheumatology/keab572.

ABSTRACT

OBJECTIVES: Limited data about use of biosimilars (BIOs) are available in children with JIA. This study therefore aimed to evaluate long-term efficacy and safety of switching from etanercept (ETA) and adalimumab (ADA) originators to their biosimilars (BIOs), in children with JIA, in a real-world setting.

METHODS: This is a retro-prospective non-interventional multicentre Italian comparative cohort study. Medical charts of JIA children treated with biosimilars of ETA or ADA were included. Efficacy and safety of TNF-inhibitors therapy was evaluated at last follow-up during originator and at 3, 6 and 12 months following the switch to biosimilar.

RESULTS: A total of 59 children (42 female, median age at onset 88 months) were treated with biosimilar of ETA (21) and ADA (38). Forty-five switched from the originator to the BIO (17 ETA, 28 ADA). At time of switch, 12/17 patients on ETA and 18/28 on ADA were in remission. No significant difference has been found at 3, 6 and 12 months after the switch. Ten patients discontinued biosimilars due to disease remission (4 ETA, 3 ADA), family willing (1 ETA), occurrence of burning at injection site (1 ETA) and persistent activity (1 ADA). No statistically significant difference was observed between originator and BIOs, nor between originator and BIOs, and between ADA and ETA in time to disease remission achievement, time to relapse and number of patients who experienced adverse event (AE).

CONCLUSION: Our real-life results seem to confirm the efficacy and safety profile of switching from originator of ADA and ETA to their respective BIOs, also in paediatric patients with JIA.

PMID:34273158 | DOI:10.1093/rheumatology/keab572

PLoS One. 2021 Jun 15;16(6):e0252836. doi: 10.1371/journal.pone.0252836. eCollection 2021.

ABSTRACT

Influenza vaccine effectiveness (IVE) assessment is increasingly stratified by vaccine type or brand, such as done by the European network of DRIVE. In 2019/2020, eleven influenza vaccines were licensed in Europe. If more than one vaccine type is recommended or if more than one vaccine brand is available for a specific risk group, it is not clear which factors affect the choice of a specific vaccine (type or brand) by a health practitioner for individual patients. This is important for IVE assessment. A survey tailored to the 2019/20 local vaccine recommendations was conducted among GPs in four European countries (Austria, Italy, Spain, UK) to understand how influenza vaccine is offered to recommended risk groups and, if GPs have a choice between 2 or more vaccines, what factors influence their vaccine choice for patients. Overall, 360 GPs participated. In Austria, Italy and Spain GPs indicated that influenza vaccines are commonly offered when patients present for consultation, whereas in the UK all GPs indicated that all relevant patients are contacted by letter. In Austria and Italy, roughly 80% of GPs had only one vaccine type available for patients <65y. The use of any specific vaccine type in this age group is mostly determined by the availability of specific vaccine type(s) at the clinic. GPs frequently reported availability of more than one vaccine type for patients ≥65y in Austria (45%), Italy (70%) and Spain (79%). In this group, patient characteristics played a role in choice of vaccine, notably older age and presence of (multiple) comorbidities. Knowing that a non-patient related factor usually determines the vaccine type a patient receives in settings where more than one vaccine type is recommended for risk groups <65y, simplifies IVE assessment in this age group. However, patient characteristics need careful consideration when assessing IVE in those ≥65y.

PMID:34129638 | PMC:PMC8205138 | DOI:10.1371/journal.pone.0252836

Intern Emerg Med. 2022 Mar;17(2):535-540. doi: 10.1007/s11739-021-02774-0. Epub 2021 Jun 6.

ABSTRACT

Data on cleaner and disinfectant exposure and misuse-related acute intoxications in Italy during SARS-CoV-2 pandemic are still lacking. The aim of the present study was to analyse and describe cleaner and disinfectant-related intoxications during SARS-CoV-2 pandemic in an Italian poison control centre. Data were obtained from the toxicological consultations requested to the Toxicology Unit and Poison Centre, Careggi University Hospital, Florence (Italy). We compared data from January 1st to April 30th of 2019 and 2020. Data concerning probable or acute intoxication from any causative agent in the general population (all age groups), from private individuals or from Regional and National health structures, were included in the analysis. A toxicological evaluation was also performed to calculate the Poisoning Severity Score.In 2019, 451 phone counselling sessions were performed and compared to a total of 410 calls received during the same period of 2020. In both periods, the majority of events occurred in paediatric (0-17 years) and adult (18-65 years) patients, who were mainly exposed to one toxic agent, and intoxications took place principally at home due to domestic accidents. The oral route of intoxication was the most frequently observed one, followed by inhalation of toxic agents, which increased by 4.7% in 2020. In 2020, sanitizers and cleaners were reported in 21.6% of cases compared to 12.5% in 2019. This is the first study describing cleaner and disinfectant-related intoxications in Italy. Our results suggested a possible misuse of these products during the SARS-CoV-2 pandemic, underling the effects of home isolation on mental health and unintentional toxic exposures.

PMID:34091841 | PMC:PMC8180185 | DOI:10.1007/s11739-021-02774-0

Clin Toxicol (Phila). 2022 Feb;60(2):175-183. doi: 10.1080/15563650.2021.1919693. Epub 2021 May 28.

ABSTRACT

INTRODUCTION: Exposure of the embryo or fetus to ionizing radiations is a potential danger since it may induce clinically relevant fetal and/or neonatal damages. The aim of the present study was to examine fetal and neonatal outcomes after maternal exposure to radio-diagnostic procedures during first trimester of pregnancy, and to evaluate whether these effects might be related to the fetal absorbed dose of ionizing radiations.

METHODS: A 10-year prospective cohort study was performed on 1979 pregnant women who underwent a radio-diagnostic procedure within the first trimester of pregnancy. Women were divided into two groups: those exposed to abdominal or lumbar radio-diagnostic procedure (Cohort A, n = 130), and those exposed to radio-diagnostic procedures in any other body regions (Cohort B, n = 415). Health physicists performed tailored fetal radiation dose calculation. Multivariate logistic regression model was used to estimate the risk of adverse pregnancy outcomes.

RESULTS: The tailored fetal radiation dose was calculated for a total of 97 women (range 0.05-92 mSv). Major congenital malformations were detected in four infants in Cohort A, six infants in Cohort B, and 24 infants in controls (p = 0.445). Multivariate analysis confirmed the negative association between age and adverse pregnancy outcomes (OR 1.08 [1.06-1.11]), and the protective role of folic acid. A higher rate of small for gestational age seems to be present in women who underwent radio-diagnostic procedures that involve maternal thyroid.

CONCLUSION: Despite several limitations, our study confirms that exposure to radio-diagnostic procedures that may involve uterus at doses below 100 mSv does not increase the risk of embryo-fetal toxicity. The relationship between maternal thyroid irradiation and small for gestational age needs to be further investigated.

PMID:34047628 | DOI:10.1080/15563650.2021.1919693

Eur Respir J. 2021 May 6;57(5):2004158. doi: 10.1183/13993003.04158-2020. Print 2021 May.

NO ABSTRACT

PMID:33833031 | DOI:10.1183/13993003.04158-2020

Front Psychol. 2021 Mar 18;12:615699. doi: 10.3389/fpsyg.2021.615699. eCollection 2021.

ABSTRACT

Background: When infertility is diagnosed, physicians have the difficult task to break bad news. Their communication skills play a central role in improving patients' coping abilities and adherence to infertility treatments. However, specific guidelines and training courses on this topic are still lacking. The aim of the present study is to provide some practical advice for improving breaking bad news in infertility diagnosis through a systematic literature review of qualitative and quantitative studies. Methods: Electronic searches were performed in the MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Psychology and Behavioral Sciences Collection databases. All articles focusing on the communication of the diagnosis of infertility were included. The main findings of each included article were then summarized. Results: Literature search identified 11,838 references that were screened for eligibility. Full texts of 81 articles were retrieved, and their analysis led to the inclusion of 4 articles, which treated the theme of communication of infertility only partially. The main addressed aspects concerning the communication of the infertility diagnosis were the following: (i) the value that patients give to healthcare professionals' communication skills; (ii) the importance of giving clear information on diagnostic procedures and treatments in order to decrease patients' anxiety; and (iii) the importance of involving both partners. Conclusions: This review pointed out that the communication of the infertility diagnosis is still underinvestigated. Specific guidelines are currently not available, but other protocols could be used. Taking into account the principal aspects of communication highlighted with this review, in this study, we suggested an adaptation of the original SPIKES protocol that could be used by healthcare professionals for the communication of the infertility status.

PMID:33815202 | PMC:PMC8015870 | DOI:10.3389/fpsyg.2021.615699

Birth. 2021 Sep;48(3):366-374. doi: 10.1111/birt.12546. Epub 2021 Mar 18.

ABSTRACT

BACKGROUND: Stillbirth, the death of a baby before birth, is associated with significant psychological and social consequences that can be mitigated by respectful and supportive bereavement care. The absence of high-level evidence to support the broad scope of perinatal bereavement practices means that offering a range of options identified as valued by parents has become an important indicator of care quality. This study aimed to describe bereavement care practices offered to parents across different high-income and middle-income countries.

METHODS: An online survey of parents of stillborn babies was conducted between December 2014 and February 2015. Frequencies of nine practices were compared between high-income and middle-income countries. Differences in proportions of reported practices and their associated odds ratios were calculated to compare high-income and middle-income countries.

RESULTS: Over three thousand parents (3041) with a self-reported stillbirth in the preceding five years from 40 countries responded. Fifteen countries had atleast 40 responses. Significant differences in the prevalence of offering nine bereavement care practices were reported by women in high-income countries (HICs) compared with women in middle-income countries (MICs). All nine practices were reported to occur significantly more frequently by women in HICs, including opportunity to see and hold their baby (OR = 4.8, 95% CI 4.0-5.9). The widespread occurrence of all nine practices was reported only for The Netherlands.

CONCLUSIONS: Bereavement care after stillbirth varies between countries. Future research should look at why these differences occur, their impact on parents, and whether differences should be addressed, particularly how to support effective communication, decision-making, and follow-up care.

PMID:33738843 | DOI:10.1111/birt.12546

Epilepsy Behav. 2021 Apr;117:107876. doi: 10.1016/j.yebeh.2021.107876. Epub 2021 Mar 11.

ABSTRACT

PURPOSE: To assess patterns of use of antiseizure medications (ASMs) and to compare the safety of generic versus branded formulations in terms of admission to hospital or to emergency department (ED).

METHODS: We conducted a drug utilization study with a propensity score-matched design using the administrative databases of the Italian Tuscany region. New users of ASMs during 2015 with no history of neoplasia were considered and their first prescription was classified as: available only as branded (only-B-ASM); branded with generic available (B-ASM); and generic (G-ASM). Patients with G-ASM first prescription were matched with four patients with B-ASM prescription. Participants were followed up for one year or until the date of death or diagnosis of neoplasia. Cox regression models were fitted to estimate the risk of admission to hospital or ED.

RESULTS: We identified 36,601 ASM new-users, including 2094 (6.4%) with only-B-ASM as first prescription, 24,588 (74.9%) with B-ASM, and 5788 (17.6%) with G-ASM. We found no differences in the risk of admission to hospital or ED (Hazard Ratio (HR), 0.92; 95% Confidence Interval (CI), 0.85-1.02) among users of generic ASMs compared to those using branded ASMs.

CONCLUSIONS: In our study population, generic ASMs were used less than branded ones. The similarity in the safety of branded and generic formulations suggests that generic ASMs could be the preferred formulation in current clinical practice resulting in a substantial decrease in the cost of treatment.

PMID:33714929 | DOI:10.1016/j.yebeh.2021.107876

Front Pharmacol. 2021 Jan 29;11:611102. doi: 10.3389/fphar.2020.611102. eCollection 2020.

ABSTRACT

Background: There is a significant gap in knowledge addressing cardiovascular (CV) medications safety in elderly. In this context, our purposes were to define clinical and pharmacological characteristics of outpatients' adverse drug events (ADEs) related to CV medications leading to emergency department (ED) visits in the elderly Italian patients according to different age groups, and to evaluate the risk of hospitalization associated to ADEs in this population. Methods: A multicentre, retrospective study was performed on reports of suspected ADEs collected between 2007-2018 in 94 EDs involved in the MEREAFaPS Study. Elderly patients who experienced one or more CV medications-related ADEs leading to ED visit were selected. Patients' characteristics, suspected (ATC classes B and C) and concomitant drugs, and ADE description were collected. Elderly patients were stratified into three age groups (65-74, 75-84, and ≥85 years) and compared to adults (18-64 years). Logistic regression analyses were used to estimate the reporting odds ratios (RORs) with 95% confidence intervals (CIs) of ADE-related hospitalization adjusting for sex, presence of two or more suspected drugs, concomitant drugs, and one or more comorbidities. Results: Among elderly, 16,926 reports of suspected ADE related to CV medications were collected, and 6,694 (39.5%) resulted in hospitalization. Patients were mostly female, Caucasians, and middle-old (75-84). 78.9% of patients were treated with only one suspected drug, and 71.9% and 47.1% reported concomitant medications and comorbidities, respectively. Compared to adults, risk of hospitalization was significantly higher for middle-old and oldest-old patients exposed to vitamin K antagonists (1.29 [1.09-1.52] and 1.56 [1.30-187]), direct thrombin inhibitors (3.41 [1.44-8.08] and 4.12 [1.67-10.17]), antiplatelets (1.51 [1.26-1.81] and 2.09 [1.71-2.57]), and beta-blockers (1.89 [1.38-2.59 and 2.31 [1.60-3.35]). Overall, a higher risk of hospitalization was observed for renin-angiotensin system inhibitors (1.32 [1.04-1.68], 1.65 [1.32-2.06], and 2.20 [1.70-2.85]), presence of two or more concomitant drugs, and concomitant conditions. Conclusion: Our real-world findings underline relevant safety aspects of CV medications in the elderly Italian population. ED clinicians must always consider the higher risk of hospitalization related to the use of CV drugs in elderly, particularly in oldest-old ones, for antiarrhythmics, beta-blocking agents, renin-angiotensin system inhibitors, antiplatelets, and anticoagulants.

PMID:33708120 | PMC:PMC7941274 | DOI:10.3389/fphar.2020.611102

Intern Emerg Med. 2021 Apr;16(3):799-800. doi: 10.1007/s11739-021-02677-0. Epub 2021 Feb 26.

NO ABSTRACT

PMID:33635496 | PMC:PMC7908935 | DOI:10.1007/s11739-021-02677-0

Women Birth. 2022 Feb;35(1):48-58. doi: 10.1016/j.wombi.2021.01.003. Epub 2021 Jan 26.

ABSTRACT

BACKGROUND: Respectful care of bereaved parents after stillbirth plays a pivotal role in enabling the grieving process and reducing the traumatic impact of this life-changing event. Unfortunately, professionals and midwives, in particular, are often emotionally unprepared and frequently left alone when dealing with these stressful events.

AIM: The BLOSSoM (Burnout after perinatal LOSS in Midwifery) study aims to address the levels of professional burnout in Italian midwives and evaluate the psychological impact of bereavement care on professionals.

METHODS: Web-based cross-sectional study, including socio-demographic questionnaire, survey on the knowledge of guidelines for stillbirth management and two psychometric tests: Maslach Burnout Inventory (MBI) and Impact of Event Scale - Revised (IES-R).

FINDINGS: Of 445 female midwives, mean age 35.1 (SD 9.9), working years 11.2 (SD 10.2), 149 (33.4%) reported specific training on stillbirth and 420 (94.6%) highlighted the need for further training and support. Medium to high levels of burnout (Emotional Exhaustion) were present in 65 midwives (15.9%) with a high prevalence of Reduced Personal Accomplishment (292, 64.2%). 'Communicating the diagnosis of death' was considered the hardest task, followed by 'assisting the meeting with the baby'; 109 midwives (24.5%) reported high IES-R scores (>30), suggesting symptoms of PTSD related to stillbirth events; a good level of knowledge of guidelines favoured Personal Accomplishment (OR 0.3 [0.1 - 0.6]). The number of stillbirths assisted by midwives was not associated with burnout levels.

CONCLUSION: Midwives are particularly at risk of developing professional burnout, as early as after five years of work, with a significant association with the psychological impact exerted by stressful events (stillbirth).

PMID:33509735 | DOI:10.1016/j.wombi.2021.01.003

Intern Emerg Med. 2021 Aug;16(5):1357-1367. doi: 10.1007/s11739-020-02609-4. Epub 2021 Jan 21.

ABSTRACT

Women with criteria and non-criteria obstetric antiphospholipid syndrome (APS) carry an increased risk of pregnancy complications, including fetal growth restriction (FGR). The management of obstetric APS traditionally involves clinicians, obstetricians and gynaecologists; however, the most appropriate prophylactic treatment strategy for FGR prevention in APS is still debated. We performed a systematic review and network meta-analysis (NetMA) to summarize current evidence on pharmacological treatments for the prevention of FGR in APS. We searched PubMed and Embase from inception until July 2020, for randomized controlled trials and prospective studies on pregnant women with criteria or non-criteria obstetric APS. NetMA using a frequentist framework were conducted for the primary outcome (FGR) and for secondary outcomes (fetal or neonatal death and preterm birth). Adverse events were narratively summarised. Out of 1124 citations, we included eight studies on 395 pregnant patients with obstetric APS treated with low-dose aspirin (LDA) + unfractionated heparin (UFH) (n = 132 patients), LDA (n = 115), LDA + low molecular weight heparin (n = 100), LDA + corticosteroids (n = 29), LDA + UFH + intravenous immunoglobulin (n = 7), or untreated (n = 12). No difference among treatments emerged in terms of FGR prevention, but estimates were largely imprecise, and most studies were at high/unclear risk of bias. An increased risk of fetal or neonatal death was found for LDA monotherapy as compared to LDA + heparin, and for no treatment as compared to LDA + corticosteroids. The risk of preterm birth was higher for LDA + UFH + IVIg as compared to LDA or LDA + heparin, and for LDA + corticosteroids as compared to LDA or LDA + LMWH. No treatment was associated with an increased risk of bleeding, thrombocytopenia or osteopenia.

PMID:33475972 | PMC:PMC8310508 | DOI:10.1007/s11739-020-02609-4

Clin Pharmacol Ther. 2021 Jul;110(1):189-199. doi: 10.1002/cpt.2164. Epub 2021 Feb 26.

ABSTRACT

The prevention of fetal growth restriction (FGR) is challenging in clinical practice. To date, no meta-analysis summarized evidence on the relative benefits and harms of pharmacological interventions for FGR prevention. We performed a systematic review and network meta-analysis (NetMA), searching PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception until November 2019. We included clinical trials and observational studies on singleton gestating women evaluating antiplatelet, anticoagulant, or other treatments, compared between each other or with controls (placebo or no treatment), and considering the pregnancy outcome FGR (primary outcome of the NetMA). Secondary efficacy outcomes included preterm birth, placental abruption, and fetal or neonatal death. Safety outcomes included bleeding and thrombocytopenia. Network meta-analyses using a frequentist framework were conducted to derive odds ratios (ORs) and 95% confidence intervals (CIs). Of 18,780 citations, we included 30 studies on 4,326 patients. Low molecular weight heparin (LMWH), alone or associated with low-dose aspirin (LDA), appeared more efficacious than controls in preventing FGR (OR 2.00, 95% CI 1.27-3.16 and OR 2.67, 95% CI 1.21-5.89 for controls vs. LMWH and LDA + LMWH, respectively). No difference between active treatments emerged in terms of FGR prevention, but estimates for treatments other than LMWH +/- LDA were imprecise. Only the confidence in the evidence regarding LMWH vs. controls was judged as moderate, according to the Confidence in Network Meta-Analysis framework. No treatment was associated with an increased risk of bleeding, although estimates were precise enough only for LMWH. These results should inform clinicians on the benefits of active pharmacological prophylaxis for FGR prevention.

PMID:33423282 | DOI:10.1002/cpt.2164

Int J Clin Pharm. 2021 Aug;43(4):1045-1054. doi: 10.1007/s11096-020-01215-w. Epub 2021 Jan 7.

ABSTRACT

Background General practitioners often deal with patients suffering acute musculoskeletal disorders. Paracetamol, non-steroidal anti-inflammatory drugs, and opioids are the most prescribed medications, according to pain intensity and patient's features. Combinations of different analgesics can be adopted to enhance pain relief, but only one fixed-dose combination has been recently launched to treat acute musculoskeletal pain. Objective This study aimed to investigate the effectiveness of ibuprofen plus paracetamol (fixed-dose) combination compared to other analgesics in preventing musculoskeletal pain persistence. Setting Italian outpatients' data extracted from a national general practice database. Method A retrospective cohort study was conducted on the Health Search Database. Patients prescribed with analgesics for acute musculoskeletal painful conditions were considered (i.e., non-chronic painful conditions, identified using a query validated by two expert General Practitioners (GPs)). For each patient, the first prescription of an analgesic was defined as index date. A new GP's visit related to musculoskeletal disorders in the first 3 months following the index date was defined as "pain persistence". Main outcome measure Risk of pain persistence among users of the ibuprofen plus paracetamol combination compared to other systemic analgesics. Results Overall, 102,216 patients were treated with systemic analgesics for acute musculoskeletal disorders. Most patients were middle-aged or elderly women. 939 (0.92%) patients were prescribed with the fixed-dose ibuprofen plus paracetamol combination for a mean duration of 7.23 ± 2.68 days, mainly for low back pain and cervicalgia. Musculoskeletal pain persistence was found in 22,125 (21.65%) patients. Compared to other systemic analgesics, the ibuprofen plus paracetamol combination resulted significantly more effective in preventing pain persistence (adjusted hazard ratio 0.72, 95% confidence interval 0.61-0.85). Conclusion These findings suggest that the fixed-dose ibuprofen plus paracetamol combination might be effective in controlling musculoskeletal pain persistence.

PMID:33411104 | DOI:10.1007/s11096-020-01215-w

Intern Emerg Med. 2021 Apr;16(3):741-748. doi: 10.1007/s11739-020-02521-x. Epub 2021 Jan 4.

ABSTRACT

Fatal Adverse Events (FADEs) are a major public health problem, and some FADEs could be preventable. The aim of the present study is to describe the frequency, the drugs involved and the preventability in the FADEs collected through the MEREAFaPS Study between 2012 and 2018. All cases including the outcome "death" have been examined. We excluded cases with vaccine-related ADEs, overdose or suicide, and ADEs occurred during the hospitalisation. Two trained assessors evaluated all cases fulfilling the inclusion criteria. ADEs' preventability was evaluated applying the Schumock and Thornton algorithm. During the study period, we observed 429 cases of death, 92 of which were excluded. The remaining 337 cases involved 187 women and 150 men, with a mean age of 79 and of 77 years, respectively. For each report, the suspected drugs and concomitant ones were 1.26 and 4.20, respectively. Anticoagulants and antiplatelet agents account for more than 40% of FADE cases and the most frequent reactions are haemorrhages (37.5%). The 25% of the FADEs were preventable. This study confirms that FADEs are still a relevant clinical occurrence, and are often caused by widely used old drugs associated with adverse events. The death of one in four patients was preventable. Further efforts should be done to improve the appropriateness of the therapy, especially in older patients who are treated with anticoagulants.

PMID:33392971 | DOI:10.1007/s11739-020-02521-x

Intern Emerg Med. 2021 Apr;16(3):697-710. doi: 10.1007/s11739-020-02586-8. Epub 2020 Dec 23.

ABSTRACT

Due to the need of early and emergency effective treatments for COVID-19, less attention may have been paid to their safety during the global emergency. In addition, characteristics of drug-drug interaction (DDI)-related adverse drug reactions (ADRs) in COVID-19 patients have not yet been studied in depth. The aim of the present case-series study is to describe clinical and pharmacological characteristics of SARS-CoV-2 hospitalised patients, focusing on ADRs, particularly those related to DDIs. We evaluated all reports of COVID-19 medication-related ADRs collected within the COVID-19 Units of Careggi University Hospital, Florence (Italy), between January 1st and 31st May 2020. Information regarding COVID-19 medications, patients' demographic and clinical characteristics, concomitant drugs, ADRs description and outcome, were collected. Each case was evaluated for the causality assessment and to identify the presence of DDIs. During the study period, 23 Caucasian patients (56.5% males, mean age 76.1 years) experienced one or more ADRs. The majority of them were exposed to polypharmacy and 17.4% presented comorbidities. ADRs were referred to cardiovascular, psychiatric and gastrointestinal disorders. The most frequently reported preferred term was QT prolongation (mean QT interval 496.1 ms). ADRs improved or resolved completely in 60.8% of cases. For all patients, a case-by-case evaluation revealed the presence of one or more DDIs, especially those related to pharmacokinetic interactions. Despite the small number of patients, our evidence underline the clinical burden of DDIs in SARS-CoV-2 hospitalised patients and the risk of unexpected and uncommon psychiatric ADRs.

PMID:33355896 | PMC:PMC7755981 | DOI:10.1007/s11739-020-02586-8

Lancet Glob Health. 2021 Jan;9(1):e17. doi: 10.1016/S2214-109X(20)30462-9.

NO ABSTRACT

PMID:33338452 | DOI:10.1016/S2214-109X(20)30462-9

Arch Womens Ment Health. 2020 Dec;23(6):783-786. doi: 10.1007/s00737-020-01086-0. Epub 2020 Nov 20.

ABSTRACT

Italy was the first COVID-19 pandemic epicenter among European countries and established a period of full "lockdown", consisting of travel bans, mandatory staying at home, and temporary closure of nonessential businesses. Similar measures are known risk factors for psychological disturbances in the general population; still, little is known about their impact on pregnant women's mental health during COVID-19 pandemic. The cross-sectional, web-based, national survey "COVID-19 related Anxiety and StreSs in prEgnancy, poSt-partum and breaStfeeding" (COVID-ASSESS) was conducted during the first month of full "lockdown" in Italy. Participants were recruited via social networks with a snowball technique. The questionnaire was specifically developed to examine COVID-19 concerns and included the psychometric tests National Stressful Events Survey (NSESSS) for posttraumatic stress disorder (PTSD) and State-Trait Anxiety Inventory. A multivariable logistic regression model was fitted to explore the association of the concern, anxiety and PTSD symptoms with age, gestational weeks, parity, days of "lockdown", assisted reproductive technology use, psychopathological history, and previous perinatal losses. Out of 1015 pregnant women reached, 737 (72.6%) fully answered the questionnaire; no woman reported a COVID-19 infection. Median age was 34.4 years [quartiles 31.7, 37.2], median days in "lockdown" were 13.1 [11.0, 17.0], median gestational weeks were 27.8 [19.8, 34.0]. Clinically significant PTSD symptoms were present in 75 women (10.2%, NSESSS cutoff 24) and clinically significant anxiety symptoms were present in 160 women (21.7%, STAI-Y1 cutoff 50). Women were particularly worried about the health of their baby and of their elderly relatives, as well as of the possible impact of pandemic in the future of society. Previous anxiety predicted higher concern and PTSD symptoms; previous depression and anxiety were independently associated with current PTSD symptoms.

PMID:33215247 | PMC:PMC7677012 | DOI:10.1007/s00737-020-01086-0

J Matern Fetal Neonatal Med. 2020 Nov 18:1-5. doi: 10.1080/14767058.2020.1849120. Online ahead of print.

ABSTRACT

Aim: Coffee intake is common during pregnancy. However, the influence of coffee and caffeine on pregnancy has not yet been fully determined. Some studies show that high coffee intake could cause miscarriage, preterm birth or reduction of fetal growth, but other studies do not support these findings. The aim of the present study was to analyze data collected from a database focusing on coffee intake during pregnancy, which was specifically created for multicenter studies carried out in the maternity units of Italian general hospitals. Principal outcomes of pregnancy during pregnancy were considered. Methods: Data of 5405 pregnancies were collected by a direct questionnaire supplemented with data from patients'clinical records during the survey named PHYTO.VIG.GEST. Results: We observed that 42.3% of the total sample had consumed at least one coffee a day during pregnancy. Analysis of a dose-response relationship showed that, in pregnant women starting from the consumption of three coffees a day (6% of pregnant women consuming coffee), there is a statistically significant association between number of coffees and reduction of babies birth weight (< 2500 g). Coclusion: Even though high coffee intake is known to influence negatively birth weight, our results indicate that a significant percentage of pregnant women maintain this habit.

PMID:33207986 | DOI:10.1080/14767058.2020.1849120

Data Brief. 2020 Dec;33:106440. doi: 10.1016/j.dib.2020.106440. Epub 2020 Oct 20.

ABSTRACT

The COVID-ASSESS questionnaire (COVID-19 related Anxiety and StreSs in prEgnancy, poSt-partum and breaStfeeding) was developed and distributed by CiaoLapo Foundation, an Italian charity for healthy pregnancy and perinatal loss support. Data were collected during phase 1 and phase 2 of COVID-19 lockdown in Italy (March, April and May 2020). The final dataset consists of 2448 women, of whom 1307 during pregnancy and 1141 women during post-partum or breastfeeding period. Variables collected for each subject are: sociodemographic and clinical information (previous losses, history of psychological disorders), birth expectations before and after COVID-19, concerns regarding pandemic consequences, perception of media and health professionals' information and communication on COVID-19, psychopathological assessment (anxiety, post-traumatic stress and general psychopathology).

PMID:33102644 | PMC:PMC7573634 | DOI:10.1016/j.dib.2020.106440

Women Birth. 2021 Jul;34(4):335-343. doi: 10.1016/j.wombi.2020.07.002. Epub 2020 Jul 13.

ABSTRACT

BACKGROUND: In March 2020, COVID-19 was declared to be a pandemic. While data suggests that COVID-19 is not associated with significant adverse health outcomes for pregnant women and newborns, the psychological impact on pregnant women is likely to be high.

AIM: The aim was to explore the psychological impact of the COVID-19 pandemic on Italian pregnant women, especially regarding concerns and birth expectations.

METHODS: A cross-sectional online survey of pregnant women in Italy was conducted. Responses were analysed for all women and segregated into two groups depending on previous experience of pregnancy loss. Analysis of open text responses examined expectations and concerns before and after the onset of the pandemic.

FINDINGS: Two hundred pregnant women responded to the first wave of the survey. Most (n=157, 78.5%) had other children and 100 (50.0%) had a previous history of perinatal loss. 'Joy' was the most prevalent emotion expressed before COVID-19 (126, 63.0% before vs 34, 17.0% after; p<0.05); fear was the most prevalent after (15, 7.5% before vs 98, 49.0% after; p<0.05). Positive constructs were prevalent before COVID-19, while negative ones were dominant after (p<0.05). Across the country, women were concerned about COVID-19 and a history of psychological disorders was significantly associated with higher concerns (p<0.05). A previous pregnancy loss did not influence women's concerns.

CONCLUSIONS: Women's expectations and concerns regarding childbirth changed significantly as a result of the COVID-19 pandemic in Italy. Women with a history of psychological disorders need particular attention as they seem to experience higher levels of concern.

PMID:32684343 | PMC:PMC7357495 | DOI:10.1016/j.wombi.2020.07.002

Autoimmun Rev. 2020 Sep;19(9):102620. doi: 10.1016/j.autrev.2020.102620. Epub 2020 Jul 16.

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of intravenous immunoglobulin (IVIg) in secondary prevention of pregnancy complications for patients with obstetric antiphospholipid syndrome (APS) and history of stillbirth.

METHODS: We described three cases of obstetric APS patients with history of stillbirth treated with IVIg in four pregnancies. In addition, we conducted a systematic literature review on the use of IVIg in obstetric APS with history of stillbirth.

RESULTS: Three patients with obstetric APS and history of stillbirth were treated with prophylactic IVIg, in addition to standard treatment (hydroxychloroquine, low-dose aspirin, low molecular weight heparin, and prednisone), in four pregnancies (three singleton and one twin). All pregnancies resulted in live healthy newborns. Long-term follow-up re-evaluations (24-53 months) did not shown any sign or symptom of active systemic disease, and the children were healthy. The systematic literature review retrieved only three cases of use of IVIg in obstetric APS patients with history of stillbirth. All three cases resulted in live healthy newborns. Only in one case, mild thrombocytopenia occurred during treatment, although this event was unlikely to be related to IVIg.

CONCLUSION: Our experience suggests that IVIg as secondary prevention of APS-related stillbirth is associated with good pregnancy and long-term outcomes, with no relevant safety concerns. However, the literature evidence on this topic is limited to few isolated cases, and further studies are needed to clarify which obstetric APS patients may benefit the most from IVIg.

PMID:32682986 | DOI:10.1016/j.autrev.2020.102620

Br J Clin Pharmacol. 2021 Mar;87(3):741-753. doi: 10.1111/bcp.14460. Epub 2020 Jul 20.

ABSTRACT

AIMS: Several cases of acute non-infectious cholestatic hepatitis recently appeared in Italy following consumption of Curcuma longa-containing dietary supplements. The aim of this research was to describe the Tuscan (Italy) cases of acute hepatitis and to compare them with similar cases of hepatotoxicity published in the literature by performing a systematic review.

METHODS: Records of Tuscan cases of acute hepatitis were obtained from the Italian Phytovigilance system. Each spontaneous report was analysed in order to collect all relevant clinical information of patients and information concerning the Curcuma longa-containing dietary supplement. Moreover, both the RUCAM and WHO-UMC systems were used to evaluate the causal relationship between the use of dietary supplement and acute hepatitis. A systematic literature review was performed in MEDLINE and Embase and all case-reports and case-series published in English were included.

RESULTS: Seven cases of acute hepatitis occurring in Tuscany up to September 2019 are described. In all cases, hepatotoxicity was associated with Curcuma longa formulations with high bioavailability and high dosage of curcumin/curcuminoids. The causal relationship was also supported by the positive dechallenge observed in most cases. In the 23 cases identified through the systematic review, the majority of patients were concomitantly exposed to at least one other medication and 16 of them experienced a positive dechallenge.

CONCLUSIONS: Within the frame of poorly controlled and regulated products, such as dietary supplements, the evaluation of Italian cases of Curcuma longa-induced acute hepatitis and the systematic review of literature confirmed the association between Curcuma longa and liver injury.

PMID:32656820 | DOI:10.1111/bcp.14460

Cancers (Basel). 2020 Jun 6;12(6):1485. doi: 10.3390/cancers12061485.

ABSTRACT

Radiotherapy (RT) and transoral laser microsurgery (TLM) represent the main treatment modalities for early glottic carcinoma. Local failure is notoriously more frequent in T1b glottic cancer in comparison to T1a and T2 tumors. In this scenario, the role of anterior commissure (AC) involvement is still controversial. The aim of the present study was therefore to determine its potential prognostic power in worsening patients' survival and outcomes. We categorized different tumor glottic fold locations with respect to the involvement of one (T1a) or both vocal cords, with or without AC involvement. We analyzed a retrospective cohort of 74 patients affected by Stage I glottic cancer, treated between 2011 and 2018 by TLM or RT at a single academic institution. There were 22 T1a (30%) and 52 T1b (70%) cases. The median follow-up period was 30 months (mean, 32.09 ± 18.738 months; range, 12-79). Three-year overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and laryngectomy-free survival (LFS) were compared according to tumor location, extension, and cT category. According to both uni- and multivariate analyses, an increased risk for recurrence in T1b with AC involvement and T1a tumors was 7.31 and 9.45 times, respectively (p-values of 0.054 and 0.030, respectively). Among the 17 recurrences, T1b with AC involvement experienced 15 tumor relapses (88.2%), thus significantly affecting both the RFS and LFS in comparison to the other two tumor subcategories (T1a, p = 0.028 and T1b without AC involvement, p = 0.043). The deteriorating prognosis in the presence of AC involvement likely reflects the need to power the hazard consistency and discrimination of the T1b category when associated with such a risk factor, thus deserving an independent T category.

PMID:32517265 | PMC:PMC7352716 | DOI:10.3390/cancers12061485

Eur Arch Otorhinolaryngol. 2020 Dec;277(12):3459-3467. doi: 10.1007/s00405-020-06084-7. Epub 2020 Jun 3.

ABSTRACT

PURPOSE: All kinds of ear, nose, and throat and maxillofacial surgery (ENT/MFS) procedures are being increasingly performed in the elderly although old age is a major risk factor for increased postoperative complications. With only scarce evidence on the topic, surgeons are asked to critically evaluate their procedures' indications and outcomes to balance the treatment risks and benefits. Our primary aim was to identify predictive factors for surgical outcomes in this setting and to create a predictive model for a tailored risk assessment.

METHODS: We analyzed a case series of 435 patients from an institutional clinical database at our academic tertiary care center. Multivariate logistic regression was used to identify all possible covariates and nomograms using stepwise backward method were generated. The performance was assessed by calibration curves and c-index.

RESULTS: Overall complication rate was 18.3% within the first 30 days and the need for re-intervention was 5.9%. For those under general anesthesia, we identified specific risk factors and developed three risk-predicting models of overall, early, and late complications. All of the nomograms showed satisfactory accuracy with a c-index of 0.83, 0.75, 0.86, and 0.82, respectively.

CONCLUSION: Using clinical preoperative variables, we constructed a model for predicting major adverse events in ENT/MFS patients. In our experience, patients over 65 showed a non-negligible risk for postoperative complications depending on several factors. Such tools might help in decision-making, by increasing the risk-awareness of clinicians, to better address peri-operative and post-operative care of these patients.

PMID:32494949 | DOI:10.1007/s00405-020-06084-7

Expert Opin Drug Saf. 2020 Jun;19(6):661-671. doi: 10.1080/14740338.2020.1763300. Epub 2020 May 14.

ABSTRACT

INTRODUCTION: Childhood rheumatic diseases (CRD) are chronic inflammatory conditions, often leading to severe functional impairment and disability. They produce high direct and indirect costs for patients, their families and society overall. Biologic treatment, adalimumab of note, has drastically changed the disease management, significantly decreasing morbidity, over childhood, and eventually lifelong. After 12 years of pediatric experience with adalimumab, safety data resulted of great interest.

AREAS COVERED: This review summarizes published knowledge about safety of adalimumab in clinical trials and real-life setting studies. Infections and site injection reactions are considered the most frequent adverse events, but the occurrence of second autoimmune diseases as well as malignancy development are the two major concerns of the medical community and families.

EXPERT OPINION: Adalimumab has revolutionized treatment and prognosis of most of CRD, resulting in good outcomes with highly acceptable safety profile. Number and type of entered adverse events differ from clinical trials and registries, these latter mirroring clinical real life. Different temporal observations and sample cohorts mainly account of this discrepancy. Both randomized clinical trials and real-world data are complementary. Clinical trials coupled with long-term registries will help to improve the evidence-based safety for children with CRD.

PMID:32406768 | DOI:10.1080/14740338.2020.1763300

Rheumatology (Oxford). 2020 Dec 1;59(12):3709-3716. doi: 10.1093/rheumatology/keaa116.

ABSTRACT

OBJECTIVES: The persistent positivity of aPLs, either isolated or associated with thrombotic and/or obstetric events (APS), has been associated with the increase of intima-media thickness (IMT) and carotid plaques. Despite the fact that aPLs can promote both thrombotic and obstetric complications, some pathogenic differences have been documented between the two entities. This study aimed to evaluate whether the atherosclerotic risk differs between subjects with obstetric and thrombotic APS.

METHODS: A total of 167 APS women (36 obstetric and 131 thrombotic) were compared with 250 aPLs negative controls. IMT of the common carotid artery (CCA) and of the bulb and the prevalence of carotid plaques were assessed.

RESULTS: CCA- and bulb-IMT were significantly higher in women with thrombotic APS, while being similar between the obstetric APS and the controls [CCA-IMT: mean (s.d.) 0.97 (0.49), 0.78 (0.22) and 0.81 (0.12) mm for the thrombotic, obstetric and control groups, respectively, P < 0.001 between thrombotic and controls, P = 0.002 between thrombotic and obstetric; bulb-IMT: mean (s.d.) 1.38 (0.79), 0.96 (0.27) and 0.96 (0.51) mm for the thrombotic, obstetric and control groups, P < 0.001]. Women with thrombotic APS had significantly increased risk of presenting carotid plaques. This risk was significantly lower in obstetric APS.

CONCLUSION: Unlike thrombotic APS, obstetric APS is not associated with an increase of markers of subclinical atherosclerosis. If confirmed on wider populations, these results could suggest different pathogenetic role of aPLs in promoting atherosclerosis in vascular and obstetric APS, and raise questions on the risk-benefit profile of thromboprophylaxis in obstetric APS outside pregnancy periods.

PMID:32388557 | DOI:10.1093/rheumatology/keaa116

Intern Emerg Med. 2020 Oct;15(7):1291-1302. doi: 10.1007/s11739-020-02339-7. Epub 2020 Apr 24.

ABSTRACT

Benzodiazepines (BZD) and z-drugs (ZD) are a widely prescribed group of medicines. They are often used inappropriately, and this is associated with adverse events (AEs), which may cause emergency department (ED) visits. The present study aimed to describe the characteristics of BZD and ZD related AEs leading to emergency department (ED) visit and hospitalisation in Italy, considering their plasma half-life. Ninety-two Italian EDs were monitored between 2007 and 2018. Rates of ED visit and hospitalisation were calculated. Multivariate logistic regression was used to estimate the reporting odds ratios (RORs) of hospitalisation. Univariate linear regression was performed to evaluate the ROR of hospitalisation according the plasma half-life of the suspected agents. A total of 3203 AE reports were collected. Overall, multivariate logistic regression showed that the risk of hospitalisation was higher for prazepam (3.26 [1.31-8.11]), flurazepam (1.62 [1.15-2.27]), and lorazepam (1.36 [1.15-1.61]). In the elderly, this risk was higher for prazepam (3.98 [1.03-15.3]), and lorazepam (1.58 [1.19-2.11]). Parenteral and rectal formulations were associated with a lower risk of hospitalisation compared to oral formulations. Our findings underlined the dangers in the use of BZD and ZD in Italy, particularly in women and older adults. ED clinicians must always take into account that the higher risk in terms of hospitalisation related to the use of BZD and ZD can be observed in patients treated with oral formulations, in those exposed to more than one sedative-hypnotics, and in patients exposed to compounds with intermediate or long plasma half-life.

PMID:32333265 | DOI:10.1007/s11739-020-02339-7

Front Pharmacol. 2020 Apr 6;11:412. doi: 10.3389/fphar.2020.00412. eCollection 2020.

ABSTRACT

BACKGROUND: Adverse drug event (ADEs) are a significant cause of emergency department (ED) visits and consequent hospitalization. Preventing ADEs and their related ED visits in outpatients remains a public health safety challenge. In this context, the aims of the present study were to describe the frequency, seriousness and preventability of outpatients' ADE-related ED visits and hospitalizations in the Italian general population, and to identify the presence of potential predictors of ADE-related hospitalization.

METHODS: We performed a nationwide, multicentre, observational, retrospective study based on reports of suspected ADEs collected between January 1, 2007 and December 31, 2018 in 94 EDs involved in the MEREAFaPS project. Patients' demographic characteristics, their clinical status, suspected and concomitant drugs, ADE description, and its degree of seriousness, were collected. Causality and preventability were assessed using validated algorithms, and logistic regression analyses were used to estimate the reporting odds ratios (RORs) with 95% confidence intervals (CIs) of ADE-related hospitalization, considering the following covariates: age, sex, ethnicity, number of implicated medications, parenteral administration, presence of interaction, therapeutic error, and/or complementary and alternative medicines (CAM).

RESULTS: Within 12 years, 61,855 reports of suspected ADE were collected, of which 18,918 (30.6%) resulted in hospitalization (ADE defined as serious). Patients were mostly female (56.6%) and Caucasians (87.7%), with a mean age of 57.5 ± 25.0 years. 58% of patients were treated with more than two drugs, and 47% of ADEs leading to hospitalization were preventable. Anticoagulants, antibiotics, and nonsteroidal anti-inflammatory drugs (NSAIDs) were the most frequently implicated agents for ED visits and/or hospitalization, which included clinically significant ADEs, such as haemorrhage for anticoagulants, moderate to severe allergic reactions for antibiotics, and dermatologic reactions and gastrointestinal disturbances for NSAIDs. Older age (1.54 [1.48-1.60]), higher number of concomitantly taken drugs (2.22 [2.14-2.31]), the presence of drug-drug interactions (1.52 [1.28-1.81]), and therapeutic error (1.54 [1.34-1.78]), were significantly associated with an increased risk of hospitalization.

CONCLUSION: Our long-term active pharmacovigilance study in ED provided a valid estimation of ADE-related hospitalization in a representative sample of the Italian general population and can suggest further focus on medication safety in outpatients, in order to early recognise and prevent ADEs.

PMID:32327995 | PMC:PMC7153477 | DOI:10.3389/fphar.2020.00412

Aging Clin Exp Res. 2020 Oct;32(10):2057-2064. doi: 10.1007/s40520-020-01534-y. Epub 2020 Mar 30.

ABSTRACT

BACKGROUND: Optimal blood pressure (BP) control can prevent major adverse health events, but target values are still controversial, especially in older patients with comorbidities, frailty and disability.

AIMS: To evaluate mortality according to BP values in a cohort of older adults enrolled in the Fiesole Misurata Study, after a 6-year follow-up.

METHODS: Living status as of December 31, 2016 was obtained in 385 subjects participating in the Fiesole Misurata Study. Patients' characteristics were analysed to detect predictors of mortality. At baseline, all participants had undergone office BP measurement and a comprehensive geriatric assessment.

RESULTS: After a 6-year follow-up, 97 participants had died (25.2%). After adjustment for comorbidities and comprehensive geriatric assessment, mortality was significantly lower for SBP 140-159 mmHg as compared with 120-139 mmHg (HR 0.54, 95% CI 0.33-0.89). This result was also confirmed in patients aged 75 + (HR 0.49, 95% CI 0.29-0.85), and in those with disability (HR 0.36, 95% CI 0.15-0.86) or taking antihypertensive medications (HR 0.49, 95% CI 0.28-0.86).

DISCUSSION: An intensive BP control may lead to greater harm than benefit in older adults. Indeed, the European guidelines recommend caution in BP lowering in older patients, especially if functionally compromised, to minimize the risk of hypotension-related adverse events.

CONCLUSIONS: After a 6-year follow-up, mortality risk was lower in participants with SBP 140-159 mmHg as compared with SBP 120-139 mmHg, in the overall population and in the subgroups of subjects aged 75 + , with a disability or taking anti-hypertensive medications.

PMID:32227283 | DOI:10.1007/s40520-020-01534-y

Am J Cardiol. 2020 May 1;125(9):1429-1435. doi: 10.1016/j.amjcard.2020.01.036. Epub 2020 Feb 7.

ABSTRACT

Combination therapies are often needed to modify the concomitant risk factors for cardiovascular disease. Nonadherence to cardiovascular medications is a relevant concern, especially in polytherapy. We conducted a population-based, cohort study with the aim of quantifying the level of adherence and its related determinants in patients exposed to free 3-drug combination therapies, namely concurrent use of angiotensin-converting-enzyme inhibitor (ACEi), calcium channel blocker (CCB), and statin or of ACEi, statin, and low-dose aspirin. Within Health Search Database, we selected a cohort of adult patients concurrently prescribed with ACEi, CCB, and statin, as well as those prescribed with ACEi, statin and low-dose aspirin, from the January 1, 2002 to the December 31, 2014. Adherent patients were concurrent users of triple free pill regimen with a proportion of days covered ≥80% during 1-year follow-up; demographics and clinical determinants of 1-year adherence were identified by multivariate logistic regression. We found that more than half of patients prescribed with triple free drug combination therapy with ACEi plus CCB plus statin or ACEi plus statin plus low-dose aspirin, were found to be nonadherent to these treatments. Males and patients at high/very-high cardiovascular risk were more likely to be adherent, whereas depression and atrial fibrillation were associated with nonadherence. Our findings indicate that sex, cardiovascular risk, presence of atrial fibrillation, and depression can influence adherence to polytherapy. In conclusion, given that patients suffering from multiple cardiovascular risk factors are at higher risk of fatal events, strategies are needed to improve medication adherence to combination therapies.

PMID:32156412 | DOI:10.1016/j.amjcard.2020.01.036

J Clin Psychopharmacol. 2020 Mar/Apr;40(2):112-121. doi: 10.1097/JCP.0000000000001189.

ABSTRACT

PURPOSE: The purpose of this study was to assess the possible relation between use of antidepressant (AD) drugs, that is, tricyclic ADs, selective serotonin reuptake inhibitors (SSRIs), and atypical ADs (AAs), and the risk of hospitalization for cardiovascular (CV) events among older patients with previous CV diseases.

METHODS: A nested case-control study was carried out among patients aged 65 years and older from 5 Italian health care territorial units who were discharged for CV disease during 2008 to 2010. The cohort was composed by 344,747 individuals, and of these, 97,739 (28%) experienced hospital admission for CV events (myocardial infarction, arrhythmia, stroke, heart failure) during follow-up (until 2014) and were included as cases. Up to 5 controls were randomly selected and matched to each. A conditional logistic regression was fitted to estimate the risk of CV events associated with ADs past or current use. A within-patient comparison was performed by the case-crossover design to account the effect of depression.

FINDINGS: Current users of SSRIs and AAs were at increased risk of CV events with odds ratios of 1.25 (95% confidence interval, 1.21-1.29) and 1.31 (1.25-1.37), respectively. An increased risk of arrhythmia and stroke was associated with current use of SSRIs and AAs, whereas an increased risk of heart failure was detected with current use of any ADs. The results were confirmed by the case-crossover approach.

IMPLICATIONS: Evidence that AD use is associated with an increased risk of CV events in accordance with specific mechanisms of action among older people with CV disease was added by this study.

PMID:32134848 | DOI:10.1097/JCP.0000000000001189

Syst Rev. 2020 Jan 24;9(1):19. doi: 10.1186/s13643-020-1280-5.

ABSTRACT

INTRODUCTION: Products containing anthraquinones (AQ) are mainly used as laxatives and have several biological effects. Long-term use of AQ laxatives is associated with an increased risk of serious adverse events (AEs), such as colorectal cancer (CRC). We will systematically synthesize the evidence on the potential association between the use of AQ laxatives and the risk of CRC.

METHODS AND ANALYSIS: We will search MEDLINE, Embase, Scopus, the Cochrane Library, Google Scholar, and Clinicaltrials.gov. To avoid missing any relevant studies, we will search the bibliographies of retrieved papers and recent reviews in the field. Interventions will include products containing oral AQ laxatives, in particular, those derived from rhubarb, senna, cascara, buckhorn, and aloe. Two review authors will independently screen title, abstract, and full texts and will independently extract data from included studies. The primary outcome is the number of participants diagnosed with CRC, while the secondary outcome will be cases of melanosis coli. We will also consider all other AEs reported in the included studies, in particular, intestinal bleeding, alterations of gastrointestinal motility, and potential for dependence. When possible and appropriate, for each outcome, a meta-analysis will be performed.

DISCUSSION: This protocol is prepared in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. The protocol gives an insight into the scope and parameters for the systematic review to be carried out.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019125414.

PMID:31980030 | PMC:PMC6979293 | DOI:10.1186/s13643-020-1280-5

Scand J Caring Sci. 2020 Sep;34(3):684-689. doi: 10.1111/scs.12772. Epub 2019 Oct 30.

ABSTRACT

AIMS: The short version of the Perinatal Grief Scale (PGS) has 33 items of Likert type whose answers vary from 1 (strongly agree) to 5 (strongly disagree), and is used to assess the grief after perinatal loss and to identify women at major need of specific support. This is the first attempt to validate an Italian version of PGS.

MATERIALS AND METHODS: The English version of PGS by Potvin et al. was translated into Italian by a professional mother tongue English translator. The survey was administered at 3 different times (translated Italian version; original English version after 10 days; and same Italian version after other 10 days) to 16 Italian/English bilingual women who had experienced a perinatal loss. The reproducibility among the three administrations and concordance were assessed using Cronbach's alpha and Cohen's kappa, respectively.

RESULTS: Considering the PGS, median score ranged from 74.5 (58.5-94.5) to 78 (64-95), with no significant difference among the three questionnaire administrations (p = 0.616). No significant difference emerged among the three administered questionnaires for subscales (p = 0.095, 0.410 and 0.410 for 'active grief' AG, 'difficulty in coping' DC and 'despair' D scores, respectively). Concordance varied from good to very good among all questionnaire administrations.

CONCLUSIONS: This Italian version of the PGS can be used by clinicians to assess Italian women's responses to stillbirth and perinatal loss, as well as by researchers for research purposes.

PMID:31667868 | DOI:10.1111/scs.12772

Br J Clin Pharmacol. 2020 Jan;86(1):106-120. doi: 10.1111/bcp.14140. Epub 2020 Jan 3.

ABSTRACT

AIMS: Despite a significant increase in using cannabis for medical purposes, current evidence on its safety in real-world clinical practice is still poorly characterised. By a case-by-case analysis of spontaneous reports of suspected adverse events (AEs) collected in Tuscany within the Italian Phytovigilance database, the aim of the present study was to describe AEs occurred in patients exposed to medical cannabis.

METHODS: We evaluated all reports of cannabis-related suspected AEs collected within the Phytovigilance database up to December 2018. Information regarding cannabis therapy, patient's demographic and clinical characteristics, concomitant medications, AE description according to the Medical Dictionary for Regulatory Activities (MedDRA) classification, AE seriousness and AE outcome, were collected. The causality assessment was performed following World Health Organisation-Uppsala Monitoring Centre criteria.

RESULTS: Fifty-three cannabis-related AE reports were analysed. The majority of patients were females (77.3%), with a mean age of 61.9 years. Thirty-nine (73.6%) cases were defined as nonserious and the majority of them (86.9%) showed a complete resolution or improvement. Forty-six (86.8%) cases were judged as probably related to cannabis consumption. The most frequently reported system organ class was psychiatric and nervous system disorders, and a potential drug-drug interaction was present in 16 cases.

CONCLUSION: Cannabis was generally well tolerated and the majority of AEs were mild and transient. Our analysis highlighted important safety issues for clinical practice, in particular the need for an accurate prescription monitoring during the titration phase, particularly in the presence of concomitant medications.

PMID:31656045 | PMC:PMC6983517 | DOI:10.1111/bcp.14140

Front Pharmacol. 2019 Aug 30;10:948. doi: 10.3389/fphar.2019.00948. eCollection 2019.

ABSTRACT

Background: The concern for adverse events following immunization (AEFI) and anti-vaccination movements that lacked scientific evidence-based supports may reduce vaccine uptake in the general population. Thus, the aims of the present study were to characterize AEFI in general population (all age groups), in terms of frequency, preventability, and seriousness and to define predictors of their seriousness in children. Methods: A retrospective study was performed on suspected AEFI reports for children and adults who received any form of vaccinations, collected in Tuscany, Italy, between 1 January and 31 December 2017. Patients' characteristics, suspected vaccines, and AEFI description were collected. Causality and preventability were assessed using WHO and Schumock and Thornton algorithms, respectively. Logistic regression was used to estimate the reporting odds ratios of potential predictors of AEFI seriousness in children. Results: A total of 223 suspected AEFI reports were collected, and the majority of them were defined as non-serious (76.7%). Reports were mostly related to one vaccine, and to a median of two to five strains/toxoids. The total number of simultaneously administered strains/toxoids and the presence of allergens did not correlate with AEFI seriousness. Considering vaccines with a high number of administered doses (≥60,000 doses), the rates estimated for serious AEFI reports were always very low, ranging between 0.01 and 0.2/1,000 doses. Twenty-four vaccines (8,993 doses) were not related to any AEFI. Conclusion: Results of present study showed that AEFI were very rare; the vast majority of them was non-serious and, despite the claims of anti-vaccination movements, the simultaneous administration of vaccines was safe and did not influence the risk of reporting a serious AEFI, particularly in children.

PMID:31543816 | PMC:PMC6728926 | DOI:10.3389/fphar.2019.00948

Pharmacol Res. 2019 Oct;148:104418. doi: 10.1016/j.phrs.2019.104418. Epub 2019 Aug 31.

ABSTRACT

Efficacy and safety profiles of different pharmacological interventions used to treat patent ductus arteriosus (PDA) are relatively unexplored. Integrating the findings of randomized clinical trials (RCTs) with those from observational studies may provide key evidence on this important issue. We aimed at estimating the relative likelihood of failure to close the PDA, need for surgical closure, and occurrence of adverse events among preterm and full-term infants treated with indomethacin, ibuprofen, or acetaminophen, placebo, or no treatment including both RCTs and observational studies. We searched PubMed, Embase, and the Register of Controlled Trials from inception to October 30, 2018. We first estimated proportions of subjects with failure to close the PDA, subjects in whom surgical closure was performed after pharmacological treatment, death, and subjects with selected adverse events (AEs). These estimates were obtained using frequentist random-effect meta-analysis of arm-specific proportions. We then compared active drugs with each other and with control (either placebo or no treatment) by summarizing results at the end of treatment reported in the papers, regardless of number of administration(s), dose, route and type of administration, and study design and quality. We also summarized primary outcome results separately at first, second and third cycles of treatment. These estimates were obtained using Bayesian random-effects network meta-analysis for mixed comparisons, and frequentist random-effect pairwise meta-analysis for direct comparisons. We included 64 RCTs and 24 observational studies including 14,568 subjects (5339 in RCTs and 9229 in observational studies, 8292 subjects received indomethacin, 4761 ibuprofen, 574 acetaminophen, and 941 control (including placebo or no intervention).The proportion of subjects with failure to close the PDA was 0.24 (95% Confidence Interval, CI: 0.20, 0.29) for indomethacin, 0.18 (0.14, 0.22) for ibuprofen, 0.19 (0.09, 0.30) for acetaminophen, and 0.59 (0.48, 0.69) for control. At end of treatment, compared to control, we found inverse associations between all active drugs and failure to close PDA (for indomethacin Odds Ratio, OR, was 0.17 [95% Credible Interval, CrI: 0.11-0.24], ibuprofen 0.19 [0.12-0.28], and acetaminophen 0.15 [0.09-0.26]), without differences among active drugs. We showed inverse associations between effective drugs and need for surgical closure, as compared to control (for indomethacin OR was 0.28 [0.15-0.50], ibuprofen 0.30 [0.16-0.54], and acetaminophen 0.19 [0.07-0.46]), without differences among drugs. Indomethacin was directly associated with intraventricular hemorrhage (IVH) (1.27; 1.00, 1.62) compared to ibuprofen, and to oliguria as compared to ibuprofen (3.92; 1.69, 9.82) or acetaminophen (10.8; 1.86, 93.1). In conclusion, active pharmacological treatment, with indomethacin, ibuprofen, or acetaminophen, is inversely associated with failure to close the PDA compared to non-treatment. Ibuprofen should be preferred to indomethacin to avoid occurrence of IVH or oliguria, acetaminophen should be preferred to indomethacin to avoid oliguria.

PMID:31479749 | DOI:10.1016/j.phrs.2019.104418

BMJ Open. 2019 Jul 26;9(7):e029467. doi: 10.1136/bmjopen-2019-029467.

ABSTRACT

INTRODUCTION: Fetal growth restriction (FGR) includes different conditions in which a fetus fails to reach the own full growth, and accounts for 28%-45% of non-anomalous stillbirths. The management of FGR is based on the prolongation of pregnancy long enough for fetal organs to mature while preventing starvation. As for pharmacological management, most guidelines recommend treatment with low-dose aspirin and/or with heparin, although this approach is still controversial and innovative promising therapies are under investigation. As no firm evidence exists to guide clinicians towards the most effective therapeutic intervention, this protocol describes methods for a systematic review and network meta-analysis (NetMA) of pharmacological treatments for FGR prevention.

METHODS AND ANALYSIS: We will search MEDLINE and Embase for clinical trials and observational studies performed on gestating women with clinically diagnosed risk of FGR. Experimental interventions will include heparin and low-molecular-weight heparin, acetylsalicylic acid, antiplatelet agents, phosphodiesterase type 3 and 5 inhibitors, maternal vascular endothelial growth factor gene therapy, nanoparticles, microRNA, statins, nitric oxide donors, hydrogen sulphide, proton pump inhibitors, melatonin, creatine and N-acetylcysteine, and insulin-like growth factors, compared between each other or to placebo or no treatment. Primary efficacy outcome is FGR. Secondary efficacy outcomes will be preterm birth, fetal or neonatal death and neonatal complications. For the safety outcome, all adverse events reported in included studies and experienced by either mothers, fetuses or newborns will be considered. Two review authors will independently screen title, abstract and full paper text, and will independently extract data from included studies. Where possible and appropriate, for primary and secondary efficacy outcomes, a NetMA will be performed using a random-effects model within a frequentist framework. Adverse events will be narratively described.

ETHICS AND DISSEMINATION: Results will be disseminated through a peer-reviewed scientific journal, and by scientific congresses and meetings.

PROSPERO REGISTRATION NUMBER: CRD42019122831.

PMID:31350249 | PMC:PMC6661573 | DOI:10.1136/bmjopen-2019-029467

Eur Arch Otorhinolaryngol. 2019 Jul 25. doi: 10.1007/s00405-019-05556-9. Online ahead of print.

ABSTRACT

PURPOSE: Malignant parotid tumours are rare and multiple prognostic factors exist.

METHODS: Through a retrospective study we aimed to identify nomograms predicting recurrence and mortality rates in 228 primary parotid cancers. Patients clinical, treatment and tumour characteristics were retrospectively collected between 1980 and 2005 at our Institution. Factors predictive of disease-free-specific-survival (DSS) and overall survival (OS) were calculated by univariate and multivariate analysis. Nomograms were then constructed.

RESULTS: The 5- and 10-year DSS rates were 73% and 71.4%, and nomogram was drawn based on five parameters where perineural invasion showed the most significant predicting influence (p < 0.001). The median follow-up was of 95 months and the 5- and 10-year OS rates were 68.7% and 53.1%; six predictive variables (age, histological grade, perineural invasion, pathological lymph node status, resection margins and distant metastasis) were used to create nomogram.

CONCLUSIONS: Our nomograms provide a tailored outcome to a patient affected by malignant parotid tumour and give him/her a risk assessment for recurrence and mortality based on individual factors by a concordance index > 0.8.

PMID:31346721 | DOI:10.1007/s00405-019-05556-9

Phytother Res. 2019 Sep;33(9):2465-2469. doi: 10.1002/ptr.6437. Epub 2019 Jul 22.

NO ABSTRACT

PMID:31328315 | DOI:10.1002/ptr.6437

J Matern Fetal Neonatal Med. 2021 Mar;34(6):952-959. doi: 10.1080/14767058.2019.1622675. Epub 2019 Jun 5.

ABSTRACT

BACKGROUND: Stillbirths affect more than 2.5 million pregnancies worldwide every year and the progress in reducing stillbirth rates is slower than that required by World Health Organization. The aim of the present study was to investigate which factors were associated with stillbirths in a University Hospital in the North of Italy, over a time span of 30 years. The goal was to identify which factors are potentially modifiable to reduce stillbirth rate.

METHODS: Retrospective case-control study (358 stillbirths, 716 livebirths) subdivided into two study periods (1987-2006 and 2007-2017).

RESULTS: The prevalence of conception obtained by assisted reproductive technologies, pregnancy at advanced maternal age, and complications of pregnancy such as preeclampsia, fetal growth restriction (FGR), and other fetal diseases (abnormal fetal conditions including fetal anemia, fetal hydrops, TORCH infections) increased through the years of the study. Despite a rising prevalence, the last 10 years showed a significant reduction in stillbirths associated with preeclampsia and FGR. Similarly, the risk of stillbirth related to abnormal fetal conditions decreased in the second study period and a history of previous stillbirth becomes a nonsignificant risk factor.

CONCLUSIONS: Altogether these results suggest that in pregnancies perceived as "high risk" (i.e. previous stillbirth, preeclampsia, FGR, abnormal fetal conditions) appropriate care and follow-up can indeed lower stillbirth rates. In conclusion, the road to stillbirth prevention passes inevitably through awareness and recognition of risk factors.

PMID:31113267 | DOI:10.1080/14767058.2019.1622675