Interventions aimed to increase average 24-h systolic blood pressure reduce blood pressure drops in patients with reflex syncope and orthostatic intolerance.

AIMS: Systolic blood pressure (SBP) drops recorded by 24-h ambulatory blood pressure (BP) monitoring (ABPM) identify patients with susceptibility to reflex syncope and orthostatic intolerance. We tested the hypothesis that treatments aimed to increase BP (reassurance, education, and lifestyle measures plus pharmacological strategies) can reduce SBP drops. METHODS AND RESULTS: This was a multicentre, observational proof-of-concept study performed in patients with reflex syncope and/or orthostatic intolerance and with SBP drops on a screening ABPM. Among 144 eligible patients, 111 underwent a second ABPM on average 2.5 months after start of treatment. Overall, mean 24-h SBP increased from 114.1 ± 12.1 to 121.4 ± 14.5 mmHg (P < 0.0001). The number of SBP drops <90 and <100 mmHg decreased by 61%, 46% during daytime, and by 48% and 37% during 24-h period, respectively (P < 0.0001 for all). The dose-response relationship between difference in 24-h average SBP increase and reduction in number of SBP drops reached a plateau around ∼15 mmHg increase of 24-h SBP. The reduction in SBP drop rate was consistent and significant in patients who underwent deprescription of hypotensive medications (n = 44) and in patients who received BP-rising drugs (n = 67). CONCLUSION: In patients with reflex syncope and/or orthostatic intolerance, an increase in average 24-h SBP, regardless of the implemented strategy, significantly reduced the number of SBP drops and symptom burden. A 13 mmHg increase in 24-h SBP appears to represent the optimal goal for aborting the maximal number of SBP drops, representing a possible target for future interventions. ClincalTrials.gov identifier: NCT05729724.

Detection of impending reflex syncope by means of an integrated multisensor patch-type recorder.

We assessed the capability of an integrated multisensory patch-type monitor (RootiRx®) in detecting episodes of reflex (pre)syncope induced by tilt table test (TTT). Firstly, we performed an intrapatient comparison of cuffless systolic blood pressure (SBP), R-R interval (RRI) and variability (power spectrum analysis) obtained by means of the RootiRx® with those obtained with conventional methods (CONV) with validated finger pressure devices at baseline in supine position and repeatedly during TTT in 32 patients affected by likely reflex syncope. Secondly, the LF/HF values obtained with RootiRx® during TTT were analyzed in 50 syncope patients. Compared with baseline supine recordings, during TTT a decrement of median SBP was observed with CONV (-53.5 mmHg) but not with RootiRx® ®(-1 mmHg). Conversely, RRI reduction (CONV: 102 ms; RootiRx®: 127 ms) and RRI Low Frequency/High Frequency powers ratio (LF/HF) increase (CONV: 1.6; RootiRx®: 2.5) were similar. The concordance was good for RRI (0.97 [95% CI 0.96-0.98]) and fair for LF/HF ratio (0.69 [95% CI 0.46-0.83]). During the first 5 min of TTT the LF/HF ratio was higher in patients who later developed syncope than in no-syncope patients. This ratio was significantly different among patients with syncope, presyncope or without symptoms at the time of syncope (p value = 0.02). In conclusion, cuffless RootiRx® was unable to detect rapid drops of SBP occurring during impending reflex syncope and thus cannot be used as a diagnostic tool for hypotensive syncope. On the other hand, RRI mean values and LF/HF power ratios obtained with RootiRx® were consistent with those simultaneously obtained using conventional methods.

Towards an individualized management of pubertal induction in girls with hypogonadism: insight into the best replacement outcomes from a large multicentre registry.

OBJECTIVE: An evidence-based pubertal induction scheme in hypogonadal girls is still to be established. Interestingly, literature data report a suboptimal uterine longitudinal diameter (ULD) in >50% of treated hypogonadal women, negatively influencing their pregnancy outcomes. This study aims to investigate auxological and uterine outcomes of pubertal induction in girls in the light of underlying diagnosis and therapeutic schemes used. DESIGN: Retrospective analysis of longitudinal data from a multicentric registry. METHODS: Auxological, biochemical, and radiological data were collected at baseline and during follow-up in 95 hypogonadal girls (chronological age > 10.9 years, Tanner stage ≤ 2) treated with transdermal 17ß-oestradiol patches for at least 1 year. Induction was started at a median dose of 0.14 mcg/kg/day with a 6-monthly increase and was considered completed for 49/95 patients who started progesterone with a concomitant oestrogen adult dose. RESULTS: At the end of induction, the achievement of the complete breast maturation was associated with a 17ß-oestradiol dose at progesterone introduction. ULD showed a significant correlation with a 17ß-oestradiol dosage. Final ULD was >65 mm in only 17/45 girls. At multiple regression analysis, pelvic irradiation represented the major determinant of reduced final ULD. After correction for uterine irradiation, ULD was associated with the 17ß-oestradiol dose at progesterone introduction. Final ULD was not significantly different from the one assessed after progesterone introduction. CONCLUSIONS: Our results provide evidence that progestins, hampering further changes in uterine volume and breast development, should be introduced only in the presence of a concomitant adequate 17ß-oestradiol dose and an appropriate clinical response.

Feasibility of Blood Pressure Measurement With a Wearable (Watch-Type) Monitor During Impending Syncopal Episodes.

Background We assessed the reliability and feasibility of blood pressure (BP) measurements by means of a new wearable watch-type BP monitor (HeartGuide) in detecting episodes of hypotensive (pre)syncope induced by tilt table test. Methods and Results An intrapatient comparison between systolic BP (SBP) measured by means of the HeartGuide device and noninvasive finger beat-to-beat BP monitoring was undertaken both at baseline in supine position and repeatedly during tilt table test in patients evaluated for reflex syncope. Intrapatient fall of systolic BP from baseline was measured. Eighty-one patients (mean age, 61±19 years; 46 women) were included. Overall, HeartGuide was able to yield BP values at the time of BP nadir in 58 (72%) patients (average HeartGuide SBP 102±18 mm Hg, versus finger SBP 101±19 mm Hg). Compared with baseline, the maximum SBP decrease was on average -28.5±27.8 and -30.3±33.9 mm Hg respectively (Lin's concordance correlation coefficient=0.78, r=0.79, P=0.001). In the subgroup of 38 patients with tilt table test induced (pre)syncope, the average HeartGuide SBP during symptoms was 97±16 mm Hg, and the finger SBP was 94±18 mm Hg. Compared with baseline, the maximum SBP decrease was on average -35.2±29.3 and -43.3±31.8 mm Hg, respectively (Lin's concordance correlation coefficient=0.83, r=0.87, P=0.001). Conclusions Our data indicate that the HeartGuide BP monitor can detect low BP during presyncope and that its measure of SBP change is consistent with that simultaneously obtained through continuous BP monitoring, despite some intrapatient variability. Thus, this device might be useful in determining the hypotensive nature of spontaneous (pre)syncopal symptoms, a possibility that should be verified by field studies.

Psychological complications in patients with acromegaly: relationships with sex, arthropathy, and quality of life.

PURPOSE: Current treatment of acromegaly restores a normal life expectancy in most cases. So, the study of persistent complications affecting patients' quality of life (QoL) is of paramount importance, especially motor disability and depression. In a large cohort of acromegalic patients we aimed at establishing the prevalence of depression, to look for clinical and sociodemographic factors associated with it, and to investigate the respective roles (and interactions) of depression and arthropathy in influencing QoL. METHODS: One hundred and seventy-one acromegalic patients (95 women and 76 men, aged 20-85 years) among those recruited in a cross-sectional Italian multicentric study were investigated. Each patient filled in three validated questionnaires: AcroQoL, WOMAC (measuring articular pain, stiffness and functionality), and AIMS (evaluating articular symptoms and depression). RESULTS: A very high (up to 28%) depression rate was detected in acromegalic subjects. Two patients showing pathological AIMS depression scores, committed suicide during the three years observational period. In our population poor psychological status was significantly associated with female sex. Furthermore, a significant strong correlation was found between AIMS depression score and WOMAC score. Both depression and arthropathy-related motor disability turned out to independently contribute with similar strength to the impairment of QoL. CONCLUSIONS: We report a high prevalence of depression in acromegaly, which is associated with female sex and arthropathy. Both depression and arthropathy strongly and independently contribute to the impaired QoL of patients. Our study shows that assessment and monitoring of psychological status is mandatory in acromegaly, also suggesting an inexpensive tool for this assessment.

Postoperative and mid-term hemodynamic changes after replacement of the ascending aorta.

OBJECTIVES: To evaluate aortic distensibility and pulse waveform patterns associated with the ascending aortic aneurysm, and to analyze the postoperative and mid-term hemodynamic changes induced by prosthetic replacement of the ascending aorta. METHODS: Central blood pressure waves were recorded at the carotid artery level by means of a validated transcutaneous arterial tonometer in 30 patients undergoing prosthetic replacement of ascending aortic aneurysm and in 30 control patients. Measurements were obtained the day before surgery and 5 to 7 days and 16 to 20 months after surgery. RESULTS: The ascending aortic aneurysm was associated with a less steep slope of early systolic phase of the pressure curve (pulsus tardus) compared with a control group (0.54 ± 0.18 mm Hg/ms vs 0.69 ± 0.26 mm Hg/ms; P = .011). Replacing the ascending aorta with a noncompliant vascular prosthesis steepened the pulse pressure slope during the early systolic phase in the postoperative period (0.77 ± .29 mm Hg/ms), providing values comparable with those of the control group in the mid-term (0.67 ± .20 mm Hg/ms). No change in aortic stiffness was found either postoperatively or in the mid-term after ascending aorta surgical replacement (carotid-femoral pulse wave velocity: preoperative, 9.0 ± 2.6 m/s; postoperative, 9.0 ± 2.9 m/s; mid-term postoperative, 9.3 ± 2.8 m/s). CONCLUSIONS: This study does not confirm the assumption that substitution of the viscoelastic ascending aorta with a rigid prosthesis can cause serious hemodynamic alterations downstream, because we did not observe a worsening of global aortic distensibility after insertion of a rigid prosthetic aorta. The ascending aortic aneurysm is associated with a pulsus tardus.

Neuroinflammation, body temperature and behavioural changes in CD1 male mice undergoing acute restraint stress: An exploratory study.

BACKGROUND: Animal models used to study pathologies requiring rehabilitation therapy, such as cardiovascular and neurologic disorders or oncologic disease, must be as refined and translationally relevant as possible. Sometimes, however, experimental procedures such as those involving restraint may generate undesired effects which may act as a source of bias. However, the extent to which potentially confounding effects derive from such routine procedures is currently unknown. Our study was therefore aimed at exploring possible undesirable effects of acute restraint stress, whereby animals were exposed to a brightly lit enclosed chamber (R&L) similar to those that are commonly used for substance injection. We hypothesised that this would induce a range of unwanted physiological alterations [such as neuroinflammatory response and changes in body weight and in brown adipose tissue (BAT)] and behavioural modification, and that these might be mitigated via the use of non-aversive handling methods: Tunnel Handling (NAH-T) and Mechanoceptive Handling (NAH-M)) as compared to standard Tail Handling (TH). METHODS: Two indicators of physiological alterations and three potentially stress sensitive behavioural parameters were assessed. Physiological alterations were recorded via body weight changes and assessing the temperature of Brown Adipose Tissue (BAT) using infra-red thermography (IRT), and at the end of the experiment we determined the concentration of cytokines CXCL12 and CCL2 in bone marrow (BM) and activated microglia in the brain. Nest complexity scoring, automated home-cage behaviour analysis (HCS) and Elevated Plus Maze testing (EPM) were used to detect any behavioural alterations. Recordings were made before and after a 15-minute period of R&L in groups of mice handled via TH, NAH-T or NAH-M. RESULTS: BAT temperature significantly decreased in all handling groups following R&L regardless of handling method. There was a difference, at the limit of significance (p = 0.06), in CXCL12 BM content among groups. CXCL12 content in BM of NAH-T animals was similar to that found in Sentinels, the less stressed group of animals. After R&L, mice undergoing NAH-T and NAH-M showed improved body-weight maintenance compared to those exposed to TH. Mice handled via NAH-M spent a significantly longer time on the open arms of the EPM. The HCS results showed that in all mice, regardless of handling method, R&L resulted in a significant reduction in walking and rearing, but not in total distance travelled. All mice also groomed more. No difference among the groups was found in Nest Score, in CCL2 BM content or in brain activated microglia. CONCLUSIONS: Stress induced by a common restraint procedure caused metabolic and behavioural changes that might increase the risk of unexpected bias. In particular, the significant decrease in BAT temperature could affect the important metabolic pathways controlled by this tissue. R&L lowered the normal frequency of walking and rearing, increased grooming and probably carried a risk of low-grade neuro-inflammation. Some of the observed alterations can be mitigated by Non-aversive handlings.

Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy.

BACKGROUND: Vitamin D deficiency has been suggested to favor a poorer outcome of Coronavirus disease-19 (COVID-19). We aimed to assess if 25-hydroxyvitamin-D (25OHD) levels are associated with interleukin 6 (IL-6) levels and with disease severity and mortality in COVID-19. METHODS: We prospectively studied 103 in-patients admitted to a Northern-Italian hospital (age 66.1 ± 14.1 years, 70 males) for severely-symptomatic COVID-19. Fifty-two subjects with SARS-CoV-2 infection but mild COVID-19 symptoms (mildly-symptomatic COVID-19 patients) and 206 subjects without SARS-CoV-2 infection were controls. We measured 25OHD and IL-6 levels at admission and focused on respiratory outcome during hospitalization. RESULTS: Severely-symptomatic COVID-19 patients had lower 25OHD levels (18.2 ± 11.4 ng/mL) than mildly-symptomatic COVID-19 patients and non-SARS-CoV-2-infected controls (30.3 ± 8.5 ng/mL and 25.4 ± 9.4 ng/mL, respectively, p < 0.0001 for both comparisons). 25OHD and IL-6 levels were respectively lower and higher in severely-symptomatic COVID-19 patients admitted to intensive care Unit [(ICU), 14.4 ± 8.6 ng/mL and 43.0 (19.0-56.0) pg/mL, respectively], than in those not requiring ICU admission [22.4 ± 1.4 ng/mL, p = 0.0001 and 16.0 (8.0-32.0) pg/mL, p = 0.0002, respectively]. Similar differences were found when comparing COVID-19 patients who died in hospital [13.2 ± 6.4 ng/mL and 45.0 (28.0-99.0) pg/mL] with survivors [19.3 ± 12.0 ng/mL, p = 0.035 and 21.0 (10.5-45.9) pg/mL, p = 0.018, respectively). 25OHD levels inversely correlated with: i) IL-6 levels (ρ - 0.284, p = 0.004); ii) the subsequent need of the ICU admission [relative risk, RR 0.99, 95% confidence interval (95%CI) 0.98-1.00, p = 0.011] regardless of age, gender, presence of at least 1 comorbidity among obesity, diabetes, arterial hypertension, creatinine, IL-6 and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count; iii) mortality (RR 0.97, 95%CI, 0.95-0.99, p = 0.011) regardless of age, gender, presence of diabetes, IL-6 and C-reactive protein and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count. CONCLUSION: In our COVID-19 patients, low 25OHD levels were inversely correlated with high IL-6 levels and were independent predictors of COVID-19 severity and mortality.

Determinants of the Lifestyle Changes during COVID-19 Pandemic in the Residents of Northern Italy.

BACKGROUND: The confinement recommended during COVID-19 pandemic could affect behavior and health. METHODS: We conducted a self-reported survey in northern Italy to observe the lockdown effects on lifestyle changes and to assess their determinants. Prevalence Odds Ratio and Prevalence Risk Ratio were determined. RESULTS: 490 adults (84% female) completed the survey: 13% and 43% reported improved and unchanged sleep quality, respectively, while 43% had insomnia symptoms. Among the 272 active subjects in pre-lockdown, 14% continued habitual exercising, 18% increased it and 68% reduced it; 27% of sedentary subjects started physical exercise; 34% reported an improvement in diet quality; 42% increased food intake and 13% decreased it; and 38% of the smokers increased cigarette consumption. Age and the pre-lockdown habit of regular physical exercising were the mainly determinants of lifestyle changes whereas BMI, gender, and the presence of chronic diseases did not. Living with other people increased the likelihood of increasing the food intake (p = 0.002). CONCLUSIONS: More than a third of people were able to positively reorganize their lives during the forced home confinement. It is worth to disseminate information to preserve a healthy lifestyle even when confined at home.

Periodic limb movements during sleep and blood pressure changes in sleep apnoea: Data from the European Sleep Apnoea Database.

BACKGROUND AND OBJECTIVE: OSA and PLMS are known to induce acute BP swings during sleep. Our current study aimed to address the independent effect of PLMS on BP in an unselected OSA patient cohort. METHODS: This cross-sectional analysis included 1487 patients (1110 males, no previous hypertension diagnosis or treatment, mean age: 52.5 years, mean BMI: 30.5 kg/m2 ) with significant OSA (defined as AHI ≥ 10) recruited from the European Sleep Apnoea Cohort. Patients underwent overnight PSG. Patients were stratified into two groups: patients with significant PLMS (PLMSI > 25 events/hour of sleep) and patients without significant PLMS (PLMSI < 25 events/hour of sleep). SBP, DBP and PP were the variables of interest. For each of these, a multivariate regression linear model was fitted to evaluate the relationship between PLMS and outcome adjusting for sociodemographic and clinical covariates (gender, age, BMI, AHI, ESS, diabetes, smoking and sleep efficiency). RESULTS: The univariate analysis of SBP showed an increment of BP equal to 4.70 mm Hg (P < 0.001) in patients with significant PLMS compared to patients without significant PLMS. This increment remained significant after implementing a multivariate regression model (2.64 mm Hg, P = 0.044). No significant increment of BP was observed for DBP and PP. CONCLUSION: PLMS is associated with a rise in SBP regardless of AHI, independent of clinical and sociodemographic confounders. A PLMS phenotype may carry an increased risk for cardiovascular disease in OSA patients.

Impact of Mutation Density and Heterogeneity on Papillary Thyroid Cancer Clinical Features and Remission Probability.

BACKGROUND: The need to integrate the classification of cancer with information on the genetic pattern has emerged in recent years for several tumors. METHODS: The genomic background of a large series of 208 papillary thyroid cancers (PTC) followed at a single center was analyzed by a custom MassARRAY genotyping platform, which allows the simultaneous detection of 19 common genetic alterations, including point mutations and fusions. RESULTS: Of the PTCs investigated, 71% were found to have pathognomonic genetic findings, with BRAFV600E and TERT promoter mutations being the most frequent monoallelic alterations (42% and 23.5%, respectively), followed by RET/PTC fusions. In 19.2% of cases, two or more point mutations were found, and the co-occurrence of a fusion with one or more point mutation(s) was also observed. Coexisting BRAFV600E and TERT promoter mutations were detected in a subgroup of aggressive PTCs (12%). A correlation between several aggressive features and mutation density was found, regardless of the type of association (i.e., only point mutations, or point mutations and fusions). Importantly, Kaplan-Meier curves demonstrated that mutation density significantly correlated with a higher risk of persistent disease. In most cases, the evaluation of the allelic frequencies normalized for the cancer cell content indicated the presence of the monoallelic mutation in virtually all tumor cells. A minority of cases was found to harbor low allelic frequencies, consistent with the presence of the mutations in a small subset of cancer cells, thus indicating tumor heterogeneity. Consistently, the presence of coexisting genetic alterations with different allelic frequencies in some tumors suggests that PTC can be formed by clones/subclones with different mutational profiles. CONCLUSIONS: A large mono-institutional series of PTCs was fully genotyped by means of a cost- and time-effective customized panel, revealing a strong impact of mutation density and genetic heterogeneity on the clinical features and on disease outcomes, indicating that an accurate risk stratification of thyroid cancer cannot rely on the analysis of a single genetic event. Finally, the heterogeneity found in some tumors warrants attention, since the occurrence of this phenomenon is likely to affect response to targeted therapies.

Is ellipsoid zone integrity essential for visual recovery in myopic neovascularization after anti-VEGF therapy?

PURPOSE: To evaluate functional prognostic factors and neuroretinal changes after anti-vascular endothelial growth factor (VEGF) treatment in patients with naïve, recent myopic neovascularization (mCNV), as assessed by spectral-domain optical coherence tomography (SD-OCT). METHODS: Specific changes in tomographic features between baseline and final follow-up were retrospectively evaluated by two examiners independently. Imaging was obtained by a multi-modal imaging system which combines fluorescein angiography and SD-OCT. RESULTS: Twenty-two eyes (male, six; female, 16; mean age, 65 ± 14 years) were considered. Mean follow-up was 21.5 ± 14 months. Best-corrected visual acuity (BCVA) improved from 0.38 ± 0.26 to 0.16 ± 0.20 logMAR (p < 0.001). The ellipsoid zone and the external limiting membrane (ELM) were disrupted in 21 (95.5%) and 15 (68.2%) eyes at baseline, and in 16 (72.7%) and nine (40.9%) eyes after therapy respectively. The ellipsoid zone and ELM were typically intact at lesion margins in 13 (59.1%) and 19 eyes (86.5%) respectively at baseline. The inner retina was intact in 20 eyes (91%). Six eyes (27.3%) exhibited complete regression without fibrosis. Absence of hemorrhage and integrity of lesion-adjacent ELM and of lesion-adjacent ellipsoid zone at baseline were factors for better final BCVA (p ≤ 0.05) CONCLUSION: Vision gain might occur despite ellipsoid zone or ELM restoration. Hemorrhage could be considered a negative prognostic factor, integrity of lesion-adjacent ELM and of lesion-adjacent ellipsoid zone as positive prognostic factors. Myopic CNV can also resolve completely without fibrosis.

Intraoperative Retrograde Perfusion Sphincterometry to Evaluate Efficacy of Autologous Vas Deferens 6-Branch Suburethral Sling to Properly Restore Sphincteric Apparatus During Robot-Assisted Radical Prostatectomy.

OBJECTIVE: The aim of this study is to describe (urodynamically) the effect of the use of a 6-branch autologous suburethral sling, made with absorbable sutures and vas deferens, to support the bladder neck and urethra during robot-assisted laparoscopic prostatectomy (RALP) to improve early urinary continence (EUC) recovery. MATERIALS AND METHODS: Retrograde leak point pressure (RLPP) was intraoperatively evaluated, by means of retrograde perfusion sphincterometry (RPS), in 77 patients (mean age ± standard deviation [SD]: 65.64 ± 7.23 years, mean body mass index ± SD: 26.69 ± 3.89) scheduled to undergo RALP at our institution. RLPP was evaluated before (RLPPb) and after pneumoperitoneum induction (RLPPp). RLPP was then evaluated after urethrovesical anastomosis (RLPPa) and after proper sling tensioning (RLPPs), with the aim to obtain the same pressure as after pneumoperitoneum induction. EUC recovery, defined as the use of no pad, was assessed 10 days, 30 days, and 6 months after catheter removal. RESULTS: RPS and proper autologous 6-branch sling positioning were feasible in all patients, without perioperative complications and negligible impact on overall operative time. Pneumoperitoneum induction increased, similarly, RLPP in all patients. An important decrease of sphincteric capability was evident after prostate removal and the following urethrovesical anastomosis, while proper sling tensioning allowed for restoration of sphincteric apparatus capability to its presurgical status (mean RLPPs 40.84 cmH2O vs RLPPp 40.39 cmH2O, p = 0.942). EUC recovery within 10 days after catheter removal was achieved in 59 (77%) patients and progressively improved over time. CONCLUSIONS: RPS, intraoperatively performed during RALP, allows for precise evaluation of the impact of the surgical procedure on sphincteric apparatus competence. Moreover, the use of the 6-branch suburethral sling, in association with RPS, allows for restoration of the proper supporting system to the urethral sphincter, similar to the preoperative condition, offering the basis for EUC recovery after radical prostate surgery.

Statin use and risk of cataract: A nested case-control study within a healthcare database.

BACKGROUND AND AIMS: We aimed to assess the association between exposure to statins and hospitalization for cataract. METHODS: A population-based, nested case-control study was performed on a cohort of 134,441 patients from Lombardy (Italy), newly treated with statins between 2005 and 2007. Cases were patients hospitalized for cataract or lens extraction surgery after initial statin prescription until December 31, 2012. For each case patient, up to 5 controls were randomly selected from the cohort and matched by gender, age at cohort entry, and date of index prescription. Logistic regression was used to model the outcome risk associated with low (proportion of days covered, PDC 25-49%), intermediate (PDC 50-74%), and high (PDC ≥ 75%) adherence compared with very-low adherence (PDC < 25%). RESULTS: 1334 case patients were matched to 6601 controls. Mean age (SD) of cases and controls was about 70 years (9 years) and 51% of them were men. There was a slight but continuous trend toward an increased risk of cataract as adherence to statin therapy increased in the adjusted risk models, with a significant odds ratio of 1.19 (95% CI 1.01-1.40%) for PDC 50-74% and 1.20 (95% CI 1.02-1.40) for PDC ≥ 75% vs. PDC < 25%, respectively. There was no statistical evidence that the effect of statins on cataract risk differed according to statin potency at starting therapy. CONCLUSIONS: Statin therapy was associated with a modestly increased risk of cataract surgery. Nevertheless, in view of the overwhelming benefit of statins for reduction of CV events, clinical practice for statins therapy does not need to change.

Statins use and the risk of all and subtype hematological malignancies: a meta-analysis of observational studies.

In order to quantify the association between use of statins and the risk of all hematological malignancies and of subtypes, we performed a meta-analysis of observational studies. We achieved a MEDLINE/EMBASE comprehensive search for studies published up to August 2014 investigating the association between use of statins and the risk of hematological malignancies, including Hodgkin- and non-Hodgkin lymphoma, leukemia, and myeloma. Fixed- and random-effect models were fitted to estimate the summary relative risk (RR) based on adjusted study-specific results. Between-study heterogeneity was assessed using the Q and I(2) statistics and the sources of heterogeneity were investigated using Deeks' test. Moreover, an influence analysis was performed. Finally, publication bias was evaluated using funnel plot and Egger's regression asymmetry test. Fourteen studies (10 case-control and four cohort studies) contributed to the analysis. Statin use, compared to nonuse of statins, was negatively associated with all hematological malignancies taken together (summary RR 0.86; 95% CI: 0.77-0.96), with leukemia (0.83; 0.74-0.92), and non-Hodgkin lymphoma (0.81; 0.68 to 0.96), but it was not related to the risk of myeloma (0.89; 0.53-1.51). Long-term users of statins showed a statistically significant reduction in the risk of all hematological malignancies taken together (0.78; 0.71-0.87). Statistically significant between-studies heterogeneity was observed for all outcome except for leukemia. Heterogeneity was caused by differences confounding-adjustment level of the included studies only for Myeloma. No significant evidence of publication bias was found.

Factors involved in the discontinuation of antihypertensive drug therapy: an analysis from real life data.

OBJECTIVES: We have previously shown that in Italian region of Lombardy (about 10 million citizens), adherence to antihypertensive treatment is low, and that this is associated with a greater risk of hospitalization for cardiovascular events. In this study, we used a healthcare database to study the factors involved in discontinuation of antihypertensive drug prescriptions in real life. METHODS AND RESULTS: The analysis was restricted to 493 623 new users of antihypertensive drugs (no prescriptions in the previous 3 years) recruited in 2003, 2006 and 2009. Discontinuation was defined as lack of prescription renewal for at least 3 months. Each patient was followed at most for 1 year. The adjusted risk of treatment discontinuation depended on the type of initial antihypertensive treatment (diuretic monotherapy associated with higher risk) and it was lower in men (-17%) and older (-21 to -29%) patients, in patients with co-treatment with antidiabetic drugs, or hospitalization for cardiovascular or renal disease (-12 to -27%), but greater in patients under co-treatment with antidepressant drugs or hospitalization for concomitant pulmonary, rheumatic, neoplastic or neurological diseases (+9 to +32%). An unexpected relationship between discontinuation of treatment and density of the population of patient's residence, with a much greater discontinuation in metropolitan areas, was observed. CONCLUSIONS: In a real life setting, discontinuation of antihypertensive treatment is affected in an opposite direction by a large number of factors: type of antihypertensive treatment, co-treatments, clinical conditions and even demographic characteristics of the geographical area where the patient lives. Knowledge of these factors may help the effort to reduce this phenomenon.

Statins and primary liver cancer: a meta-analysis of observational studies.

Statins are among the most commonly prescribed drugs used to manage dyslipidemia. Hepatocellular carcinoma is the third leading cause of cancer mortality and its rates have recently been increasing in central and northern Europe and USA. To quantify the association between statin use and risk for HCC, we performed a meta-analysis of published studies. We conducted a MEDLINE search for observational studies reporting the association between exposure to statins and risk for incident liver cancer until March 2012. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Moreover, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Five observational studies (two case-control and three cohort studies) based on 2574 cases of HCC were included. Statin treatment, compared with no treatment, was inversely related to HCC (summary RR=0.58; 95% CI 0.46-0.74). Between-study heterogeneity was significant (P<0.001) and numerically relevant (I=65%). When only longest statin use was considered, the RR was 0.66 (95% CI 0.55-0.80). Influence analysis on the overall estimate showed that heterogeneity was largely because of one study; when omitting it, the I dropped to 27% (P=0.240), whereas the summary RR was only marginally modified (RR=0.52; 95% CI 0.44-0.62). There was no evidence of publication bias. This meta-analysis suggests a favorable effect of statins on HCC, in the absence, however, of a duration-risk relationship.

Cancer risk associated with use of metformin and sulfonylurea in type 2 diabetes: a meta-analysis.

OBJECTIVE: Oral antidiabetic drugs (including metformin and sulfonylurea) may play a role in the relationship between type 2 diabetes and cancer. To quantify the association between metformin and sulfonylurea and the risk of cancer, we performed a meta-analysis of available studies on the issue. MATERIALS AND METHODS: We performed a MEDLINE search for observational studies that investigated the risk of all cancers and specific cancer sites in relation to use of metformin and/or sulfonylurea among patients with type 2 diabetes mellitus. Fixed- and random-effect models were fitted to estimate the summary relative risk (RR). Between-study heterogeneity was tested using χ(2) statistics and measured with the I(2) statistic. Publication bias was evaluated using funnel plot and Egger's regression asymmetry test. RESULTS: Seventeen studies satisfying inclusion criteria and including 37,632 cancers were evaluated after reviewing 401 citations. Use of metformin was associated with significantly decreased RR of all cancers (summary RR 0.61, 95% confidence interval [CI] 0.54-0.70), colorectal cancer (0.64, 95% CI 0.54-0.76), and pancreatic cancer (0.38, 95% CI 0.14-0.91). With the exception of colorectal cancer, significant between-study heterogeneity was observed. Evidence of publication bias for metformin-cancer association was also observed. There was no evidence that metformin affects the risk of breast and prostate cancers, nor that sulfonylurea affects the risk of cancer at any site. CONCLUSIONS: Metformin, but not sulfonylurea, appears to reduce subsequent cancer risk. This has relevant implications in light of the exploding global epidemic of diabetes.