The prevalence and incidence of thrombotic primary antiphospholipid syndrome in adults aged 18-49 years: A population-based study in a mountain community in northern Italy.

OBJECTIVE: To estimate prevalence and incidence of thrombotic Primary Antiphospholipid Syndrome (PAPS) in the general population aged 18-49 years. METHODS: The study was carried out in Valtrompia, a valley in northern Italy, in 2011-2015. The identification of PAPS cases leveraged three integrated sources: 1) Rheumatology Unit at the University Hospital; 2) General Practitioners; 3) hospital discharge codes of patients admitted for thrombotic events. RESULTS: Prevalence and incidence were estimated as 22.9 (95% C.I. 11.4-41.0) and 5.0 (2.6-8.7) cases per 100,000 individuals, respectively. The estimates were 28.3 and 4.8, and 17.2 and 5.1 in males and females, respectively. The type of disease onset was mainly of arterial type in men and venous in women. CONCLUSIONS: Thrombotic PAPS was found to be a rare disease in this population-based study. Prevalence and incidence were not significantly different between males and females aged 18-49 years, but a different type of onset was observed.

Impact of a diagnostic therapeutic educational pathway program for asthma management in preschool children.

BACKGROUND: Preschool children with clinically-diagnosed asthma have a higher rate of emergency department visits and consume more resources for management than older children. However, no clinical trials have yet been performed measuring the impact of a combined diagnostic, therapeutic and educational pathway regimen for evaluation of wheezing control in children aged less than 6 years. The purpose of the present study was to assess the impact of a pediatric program developed in Italy, the Diagnostic Therapeutic Educational Pathway (DTEP), for asthma management in children less than 6 years old attending an asthma referral center. METHODS: This is a retrospective population-based cohort study performed in children with asthma aged 0-5 years, attending at "Io e l'Asma center", Brescia, Italy between September 2007 and December 2014. The incidence rates (IRs) of hospitalization, emergency room visits, use of outpatient services and drug usage for dyspnea, wheezing, or respiratory symptoms were evaluated for time periods prior to and after DTEP intervention. RESULTS: A total of 741 patients, aged 0-5 years completed the DTEP, including 391 and 350 children aged 0-2 and 3-5 years, respectively. The percentage of children aged 0-2 and 3-5 years showing improved control of wheezing symptoms during the 1st to 3rd visit interval as a result of the DTEP intervention increased from 39.5 to 60.9% and from 25.5 to 75.5%, respectively. During these periods, the IRs showed a significant decrease for all outcomes, from-8.6% to - 80.4%. Although specific IRs for drug prescriptions declined, particularly for LABA plus corticosteroids, antibiotics, and systemic corticosteroids, they increased for SABA, inhaled corticosteroid and leukotriene receptor antagonist usage. CONCLUSIONS: The results suggest that a real-world assessment of the integrated DTEP program for preschool children provides evidence for improved wheezing control and reduction of adverse therapeutic related outcomes.

Neoplastic and inflammatory skin disorders and serum levels of polychlorinated biphenyls in a population living in a highly polluted area.

BACKGROUND: Although polychlorinated biphenyls (PCBs) have been classified as human carcinogens for their association with melanoma, few data are available for other skin lesions. OBJECTIVES: To investigate the prevalence of skin disorders in a highly PCB polluted area in northern Italy, with locally produced food as the main source of human contamination, and evaluate the association between skin lesions and PCB serum levels, taking account of possible confounders. MATERIALS & METHODS: Thirty-three PCB congeners were quantitatively assessed and a total of 189 subjects were equally divided into three groups using the tertiles of total PCB serum concentrations. All subjects underwent a clinical examination and were interviewed on their risk factors and history of skin diseases. RESULTS: No statistically significant difference was found in the prevalence of skin cancer, nevi, pigmentary disorders as well as inflammatory and infectious skin diseases among the three PCB exposure groups. It should be noted that the use of questionnaires to assess subjects' past sun exposure and photoprotection is intrinsically flawed due to random error. CONCLUSION: Our study does not support the hypothesis that chronic PCB exposure, through the ingestion of contaminated food, determines an increased risk of developing skin diseases.

Evaluation of influenza vaccination efficacy in reducing influenza-related complications and excess mortality in Northern Italy (2014-2017).

OBJECTIVE: The main objective of this study was to estimate the efficacy of influenza vaccination in reducing influenza-attributable hospitalization and emergency room (ER) admission for severe complications and influenza-attributable excess mortality in individuals ≥65 years of age. METHODS: We analyzed the ≥65 years-old community (n = 952,822) afferent to the Brescia (Northern Italy) Health Protection Agency, considered an Italian population reference, to evaluate the efficacy of influenza vaccination (seasons 2014-17) in reducing deaths, ER-admissions, and hospitalizations for influenza-related complications in the elderly. RESULTS: A protective effect of influenza vaccination emerged in reducing hospitalization and ER admission for diseases of the respiratory system and for death from all causes in people ≥65 years. The major effect of influenza vaccination was the reduction in risk of death from all causes, increasing with age and comorbidity. CONCLUSION: Influenza vaccination has reduced the number of ER admissions and hospitalizations caused by influenza-related complications and has prevented death among high-risk groups in elderly ≥65 years, resulting in social and public health cost savings. Stronger or new vaccination strategies are needed to improve vaccination rates among the elderly.

Guggulu and Triphala for the Treatment of Hypercholesterolaemia: A Placebo-Controlled, Double-Blind, Randomised Trial.

BACKGROUND: Several herbs are used for lowering high blood cholesterol levels in traditional medicines including Indian Medicine (Ayurveda). We aimed to assess the short-term effects of the combination of Guggulu (Commiphora mukul) and Triphala (Terminalia chebula, Terminalia belerica, and Phyllanthus emblica) on serum cholesterol in healthy subjects with hypercholesterolaemia. PATIENTS AND METHODS: This was a parallel randomised double-blind controlled trial that included 90 individuals at low-moderate cardiovascular risk. The main outcome measures were serum levels of total and low- and high-density lipoprotein cholesterol (LDL-C, HDL-C). Secondary outcome measures included BMI, waist circumference, and adverse events. Subjects were administered either Guggulu and Triphala or placebo three times daily for 3 months, with 3 months of follow-up after the end of treatment. RESULTS: At intention-to-treat analysis, from baseline to 3 months, total serum cholesterol decreased by 1.9% in the placebo (n = 44) and 3.3% (p = 0.01) in the intervention (n = 46) group. Serum LDL-C decreased by 4.9% (p = 0.03) and 4.8% (p = 0.02) in the placebo and intervention group, respectively, without differences between them. Two participants in the intervention group developed hypersensitivity rash (4.3%) as compared with none in the placebo group. CONCLUSIONS: Three months of treatment with Guggulu and Triphala did not show better effects than placebo on serum levels of total and LDL cholesterol, BMI, and waist circumference.

Evaluation of a Diagnostic Therapeutic Educational Pathway for Asthma Management in Children and Adolescents.

Background: Limited evidence exists for the effectiveness of educational programs that improve pediatric asthma control in real-world settings. We aimed to assess the impact of a diagnostic, therapeutic, and educational pathway (DTEP) for asthma management in children and adolescents attending an asthma referral center. Methods: This is a retrospective population-based cohort study, including two groups of patients with asthma, aged 6-17 years and residing in the Local Health Authority (LHA) of Brescia, Italy: (a) the children who followed a DTEP (intervention group) and (b) all the children residing in the LHA who did not follow DTEP (control group). The incidence rates (IRs) of hospitalization, emergency room visit, use of outpatient services, and drug prescription for dyspnea, wheezing, or respiratory symptoms were computed for time before and after attending DTEP in the intervention group and for "early" and "late" time since asthma diagnosis in the control group. Results: There were 9,191 patients included in the study, 804 of whom followed DTEP. In the before-DTEP/early time, the intervention and control groups showed similar IRs for all the outcomes apart from emergency room visits (IRs of 138.6 and 60.3 per 1,000 person-years, respectively). The IRs decreased from before to after DTEP and from early to late time in both groups. The IR decrease for emergency room visits was significantly higher in the intervention than in the control group (-51.3 and -28.2%, respectively; IRR = 0.61, P = 0.001). Conclusion: The DTEP can increase patients' capability in managing asthma and preventing asthma attacks.

Elderly people: propensity to be vaccinated for seasonal influenza in Italy.

Seasonal influenza continues to be a major cause of illness and death. Vaccination is the most cost-effective prophylaxis to prevent the disease and it is particularly important for people who are at high risk of serious complications derived from influenza, especially for people ≥65 years. In Italy, the influenza vaccination program has been unsuccessful with low rates of uptake in people ≥65 years. We analyzed all the community ≥65 years of the Health Promoting Agency (HPA) of Brescia (northern Italy) to evaluate the propensity attitudes toward influenza vaccination among people ≥65 years in four consecutive seasonal influenza campaigns (from 2014/2015 to 2017/2018). Information about subjects were retrieved from administrative databases. Data from 952,822 records were analyzed. The prevalence of vaccinated subjects in the four campaigns was 38.6%, 33.7%, 37.7%, and 40.1%, respectively. Among vaccinated people, the frequencies of individuals aged 65-69.9 years were lower than the frequencies of those in the other age classes, with highest frequencies of vaccinated people in the 75-79.9 years age-class. Overall, males showed a slightly higher propensity to be vaccinated and the propensity toward vaccination increased with age in both genders. Suffering from a chronic disease increased the propensity to vaccination; hypertension had the highest impact on the propensity whereas suffering from vasculopathy has the opposite effect. The value of this study is the possibility to know the factors that might indicate a propensity to get an influenza vaccination and to consider a different approach to people ≥65 years with the characteristics indicating a lower propensity to vaccination.

Serum levels of polychlorinated biphenyls and risk of non-Hodgkin lymphoma: A hospital-based case-control study.

Polychlorinated biphenyls (PCB) have been classified by the International Agency for Research on Cancer (IARC) in Group 1 as carcinogenic to human, based on sufficient evidence in humans of an increased risk of cutaneous malignant melanoma and limited evidence for non-Hodgkin lymphoma (NHL). However present findings on the association of PCB exposure and NHL are still controversial. This study examined the relationship between PCB serum levels and risk of NHL in a Northern Italy area (Brescia province), where a chemical factory produced PCBs from 1938 to 1984, causing human contamination. A case-control study of 215 NHL patients and 215 control subjects was conducted. Cases and controls were assayed for serum levels of 33 PCB congeners. No associations were found between risk of NHL and serum levels of total PCBs (OR = 0.51; 95% CI: 0.25-1.04 for highest vs lowest quartile) or specific PCB congeners. The study confirmed a strong association of NHL with HCV infection (OR = 3.60; 95% CI: 1.30-10.02). This case-control study does not support the hypothesis of an association between current serum levels of PCBs and NHL development in the general population.

Polychlorinated biphenyl serum levels, thyroid hormones and endocrine and metabolic diseases in people living in a highly polluted area in North Italy: A population-based study.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants produced until the 1980s, which they are still present worldwide. They have been associated with metabolic and endocrine diseases and hypertension in humans, but definite evidence is lacking. A chemical factory producing PCBs caused a heavy pollution in an urban area in Northern Italy. We aimed to evaluate present PCBs serum levels according to demographic and lifestyle variables and their associations with endocrine and metabolic diseases and hypertension in the resident general population. A random sample of 816 adults aged 20-79 years (mean ± SD: 49.1 ± 16.5 years) was enrolled in a cross-sectional population-based study. The participants provided a fasting blood sample for laboratory analysis and were face-to-face interviewed about the presence of chronic diseases. The serum level of total PCBs was computed as the sum of 33 PCB congeners. The median serum level of lipid-adjusted total PCBs was 435.2 and 95th centile was 2154.9 ng/g lipid. Medium and high chlorinated PCBs with immunotoxic and endocrine disrupting activity contributed most to total PCB serum levels, particularly PCBs 138, 153, 170, 180 and 194. The serum levels of total PCBs and of PCB functional groups were positively associated with age and negatively with female gender, education, smoking habit and BMI, and not associated with serum levels of thyroid hormones and TSH and glycaemia and with presence of endocrine diseases, diabetes and hypertension by multivariable analysis. Subgroup analyses according to gender, age and BMI provided similar results. In conclusion, this study shows a long-term persistence of past exposure to PCBs and does not support the hypothesis of an association between PCB exposure and prevalence of endocrine and metabolic diseases and hypertension.

Polychlorinated biphenyls (PCBs) exposure and cardiovascular, endocrine and metabolic diseases: A population-based cohort study in a North Italian highly polluted area.

BACKGROUND AND AIMS: Exposure to polychlorinated biphenyls (PCBs) has been linked to the onset of cardiovascular, endocrine, and metabolic diseases, but no conclusive evidence has been provided so far. A chemical factory produced PCBs from 1938 to 1984 in Brescia (North Italy) resulting in environmental contamination and human exposure. We aimed to evaluate the association between PCB serum levels and subsequent incidence of chronic diseases through a prospective cohort study design. METHODS: Based on surveys conducted in Brescia province between 2001 and 2013, a cohort of 1331 subjects with at least one measure of PCB serum levels during the period was selected and followed longitudinally. Serum concentration of total PCBs was computed summing up the levels of 24 PCB congeners determined by gas chromatography. The data on incidence of hypertension, cardiovascular diseases, and endocrine and metabolic chronic diseases were retrieved from the Brescia Health Protection Agency database. Poisson regression models adjusted for age, level of education, BMI, cholesterol level, tobacco smoking and alcohol drinking were employed to calculate rate ratios (RRs). RESULTS: 1331 subjects were enrolled (45.7% males, mean age 50.6 years) contributing to 10,006 person-years of follow-up. A dose-response relationship was observed between PCB serum levels and the onset of hypertension (RR for 2nd and 3rd tertiles of serum PCB distribution: 2.07, 95% CI 1.18-3.63, and 2.41, 1.30-4.47, respectively). A possible, though not statistically significant, increase of the risk of cardiovascular disease was also found (RR for 2nd and 3rd tertiles of serum PCB distribution: 1.61, 0.72-3.64, and 1.96, 0.86-4.48, respectively). The results based on lipid-standardized PCBs were slightly attenuated. No association was found between PCB serum levels and occurrence of diabetes and endocrine disorders. Stratified analysis by body mass index showed an increased risk of hypertension in subjects at 2nd and 3rd tertile of serum PCB distribution in overweight/obese subjects only. CONCLUSIONS: These results suggest that PCBs might play a role in the development of hypertension and possibly cardiovascular disease, though alternative explanations are to be considered too.

Plasma levels of polychlorinated biphenyls and risk of cutaneous malignant melanoma: A hospital-based case-control study.

Polychlorinated biphenyls (PCB) have been classified by the International Agency for Research on Cancer (IARC) in Group 1 as carcinogenic to human, based on sufficient evidence in humans of an increased risk of cutaneous malignant melanoma (CMM), however few studies have been done in the general population. This study examined the relationship between PCB plasma levels and risk of CMM adjusting for sun sensitivity and sun exposure in a province of Northern Italy (Brescia), where a chemical factory produced PCBs from 1938 to 1984 causing human contamination. A case-control study of 205 CMM patients and 205 control subjects was conducted. Cases and controls were assayed for plasma levels of 33 PCB congeners. No associations was found between risk of CMM and plasma levels of total PCB (OR = 0.81; 95% CI: 0.34-1.96 for highest vs lowest quartile) or specific congeners. The study confirmed the association with light skin colour (OR = 3.00; 95% CI: 1.91-4.73), cumulative lifetime UV exposure (OR = 2.56; 95% CI: 1.35-4.85) and high level of education (OR = 1.45; 95% CI: 1.03-2.05). This case-control study does not support the hypothesis of an association between current plasma levels of PCBs and CMM development in the general population.

Evaluation of a diagnostic therapeutic educational pathway for asthma management in youth.

BACKGROUND: In spite of some evidence for positive effects of patient's education to asthma self-management by randomized clinical trials, there are few studies on the impact of patient' s educational programs in the real world. We aimed to assess the impact of a diagnostic therapeutic educational pathway (DTEP) on asthma control of children and adolescents by comparing frequency of outcomes indicative of asthma control before and after attending the pathway. METHODS: This is a retrospective cohort study including all patients aged 6-11 and 12-17 years who attended the DTEP in 2007-2014. The DTEP includes 3 specialist's evaluations at 8- to 12-week intervals and two follow-up visits. Patients and their parents receive an educational course concerning prevention measures, early recognition of symptoms, and appropriate use of drugs and devices. The rates of hospitalizations, outpatient services, emergency room visits, and drug prescriptions were considered as outcomes and computed as number of events divided by person-time. RESULTS: A total of 806 patients were enrolled. A statistically significant decrease in rates from before to after DTEP was observed for almost all outcomes, in both age groups, with relative risks ranging from 0.12 to 0.60. The rates of drug prescription showed a statistically significant decrease, from before to after DTEP, for each type of medicine for asthma, in both age groups, from percent difference of -66% to -24.3%. CONCLUSIONS: The positive impact of this program on the outcomes indicative of asthma control in both children and adolescents suggests that it may be valuable for asthma management.

Optimization of PAM-4 transmitters based on lumped silicon photonic MZMs for high-speed short-reach optical links.

We demonstrate how to optimize the performance of PAM-4 transmitters based on lumped Silicon Photonic Mach-Zehnder Modulators (MZMs) for short-reach optical links. Firstly, we analyze the trade-off that occurs between extinction ratio and modulation loss when driving an MZM with a voltage swing less than the MZM's Vπ. This is important when driver circuits are realized in deep submicron CMOS process nodes. Next, a driving scheme based upon a switched capacitor approach is proposed to maximize the achievable bandwidth of the combined lumped MZM and CMOS driver chip. This scheme allows the use of lumped MZM for high speed optical links with reduced RF driver power consumption compared to the conventional approach of driving MZMs (with transmission line based electrodes) with a power amplifier. This is critical for upcoming short-reach link standards such as 400Gb/s 802.3 Ethernet. The driver chip was fabricated using a 65nm CMOS technology and flip-chipped on top of the Silicon Photonic chip (fabricated using IMEC's ISIPP25G technology) that contains the MZM. Open eyes with 4dB extinction ratio for a 36Gb/s (18Gbaud) PAM-4 signal are experimentally demonstrated. The electronic driver chip has a core area of only 0.11mm2 and consumes 236mW from 1.2V and 2.4V supply voltages. This corresponds to an energy efficiency of 6.55pJ/bit including Gray encoder and retiming, or 5.37pJ/bit for the driver circuit only.

Temporal trends of polychlorinated biphenyls serum levels in subjects living in a highly polluted area from 2003 to 2015: a follow-up study.

INTRODUCTION: A chemical factory located in Brescia, an industrialized town in North Italy, produced polychlorinated biphenyls (PCBs) since the 1930s to the 1980s, determining a relevant pollution of soil, food and people. Since 2001, following a survey carried out in the general population living in the town, the individuals with PCB serum levels higher than the reference entered a follow-up study. METHODS: We performed a prospective cohort study including subjects with at least three PCB measures during the period 2003-2015. We evaluated the temporal trends of total PCB serum levels, the most common PCB congeners (PCB 138,153, 170, 180, 194 and 209), and toxic equivalency of dioxin-like PCBs using univariate and multivariate mixed models with and without a cubic-spline term for time. RESULTS: A total of 128 subjects were enrolled (46.1% males, mean age at enrolment 57.7 years). The geometric mean of PCBs decreased from 35.4ng/ml at 0-3 years to 29.3ng/ml at 4-8 years and to 23.0ng/ml at 9-12 years. A 3.8% reduction of total PCB serum levels per year was estimated using both univariate and multivariate mixed models adjusted for age; a similar reduction was found for the most common PCB congeners and for toxic equivalency. Total PCB serum levels decreased over time for each age group: -3.9%, -4.0% and -3.4% for subjects aged ≤55 years, 56-65 and ≥66 years, respectively. CONCLUSION: A significant decrease of serum concentrations of PCBs was observed in subjects with high serum levels of these chemicals at enrolment over a twelve year period. The decrease was evident for each PCB congener and age group.

The burden of chronic diseases and cost-of-care in subjects with HIV infection in a Health District of Northern Italy over a 12-year period compared to that of the general population.

BACKGROUND: The increase in life expectancy of HIV-infected patients has driven increased costs due to life-long HIV treatment and concurrent age-related comorbidities. This population-based study aimed to investigate the burden of chronic diseases and health costs for HIV+ subjects compared to the general population living in Brescia Local health Agency (LHA) over a 12-year period. METHODS: LHA database recorded diagnoses, deaths, drug prescriptions and health resource utilization for all residents during 2003-2014. We estimated HIV prevalence and incidence, HIV-related mortality as well as prevalence of chronic diseases in HIV+ subjects. Observed/expected ratio of chronic diseases was calculated by indirect standardization with the general population as reference. Direct cost of HIV care and determinants were estimates across the period. RESULTS: HIV prevalence increased from 220 to 307 per 100 000 person-years while incidence decreased from 16.1 to 10.8 per 100 000 person-years from 2003 to 2014. Prevalence of most comorbidities increased over time but it reduced significantly (annual mean change - 0.7 %) when adjusting for age and gender. Observed to expected ratio for each chronic disease in HIV+ subjects decreased over time. Cost of HIV+ cures increased (+25 %) mainly due to cost for drugs (+50 %) but it stabilized in recent years. CD4+ cell count at the time of diagnosis was an important predictor of cost for HIV management. CONCLUSIONS: Expenditures for HIV-infection are driven mainly by drugs cost and they have increased overtime. However, our findings suggest that spending on public health for HIV care can improve prognosis of HIV-infected patients, reduce transmission of HIV infection and reduce the global burden of chronic diseases, leading to a reduction of HIV global cost in the medium-long time.

Towards correcting atmospheric beam wander via pump beam control in a down conversion process.

Correlated photon pairs produced by a spontaneous parametric down conversion (SPDC) process can be used for secure quantum communication over long distances including free space transmission over a link through turbulent atmosphere. We experimentally investigate the possibility to utilize the intrinsic strong correlation between the pump and output photon spatial modes to mitigate the negative targeting effects of atmospheric beam wander. Our approach is based on a demonstration observing the deflection of the beam on a spatially resolved array of single photon avalanche diodes (SPAD-array).

Substantial decline of polychlorinated biphenyls serum levels 10years after public health interventions in a population living near a contaminated site in Northern Italy.

INTRODUCTION: Polychlorinated biphenyls (PCBs) are persistent pollutants classified among endocrine disruptors and human carcinogens. In an urban area in Northern Italy (Brescia), a chemical factory producing PCBs from 1938 to 1984 caused soil and food pollution. Since the discovering of the environmental pollution in the area in 2001, various public health interventions have been implemented to avoid human contamination. METHODS: Two independent surveys were carried out in 2003 and 2013 using the same study design and methods. A random sample of the adult general population living in four areas of the town with different soil contamination level was enrolled in both surveys. Investigation included serum levels of 24 PCB congeners and of other common clinical-chemical parameters and questions about residential and occupational history as well as current and past diet and consumption of locally produced food. 537 subjects were tested in the 2003 and 488 in the 2013 survey. RESULTS: Total PCB serum levels showed a strong correlation with age (Spearman r=0.71 in 2003 and r=0.80 in 2013), but not with gender. Consumers of food produced in the most polluted area had higher total PCB serum levels (median 15.6 and 4.7ng/ml in 2003 and 2013, respectively) than non-consumers (4.1 and 2.3ng/ml) and consumers of food produced in non-polluted areas (6.5 and 1.9ng/ml), with increasing trend of PCB serum levels with cumulative local food intake. PCB serum levels from 2003 to 2013 survey declined by around half in all age groups, especially among the youngest people. The total PCB reduction was found to be due to a combination of a birth cohort effect (-41% every 10years) and survey period effect (-18% in 2013 versus 2003), with medium chlorinated CB congeners showing the most relevant reduction (-30%) between the two surveys. High chlorinated CBs were more strongly associated with birth cohort (-46% every 10years): in the 2013 survey they represented 58% of total PCBs in 60-79years old while they were 37% among the under 40s with a median value 20 times higher in the oldest than in the youngest (3.1 versus 0.16ng/ml). CONCLUSIONS: PCBs serum levels declined from the 2003 to 2013 survey though they are still high in the elderly mainly because of past intake of locally produced contaminated food. Present findings suggest that PCBs food chain contamination and human absorption have been interrupted successfully in the area since discovery of the pollution in 2001.

Flip-chip integration of tilted VCSELs onto a silicon photonic integrated circuit.

In this article we describe a cost-effective approach for hybrid laser integration, in which vertical cavity surface emitting lasers (VCSELs) are passively-aligned and flip-chip bonded to a Si photonic integrated circuit (PIC), with a tilt-angle optimized for optical-insertion into standard grating-couplers. A tilt-angle of 10° is achieved by controlling the reflow of the solder ball deposition used for the electrical-contacting and mechanical-bonding of the VCSEL to the PIC. After flip-chip integration, the VCSEL-to-PIC insertion loss is -11.8 dB, indicating an excess coupling penalty of -5.9 dB, compared to Fibre-to-PIC coupling. Finite difference time domain simulations indicate that the penalty arises from the relatively poor match between the VCSEL mode and the grating-coupler.

Incidence of cardiovascular events in HIV-positive patients compared to general population over the last decade: a population-based study from 2000 to 2012.

Cardiovascular diseases are currently a main cause of death among people living with HIV. This population-based study aimed to investigate the incidence of cardiovascular events (CVEs) in HIV-positive people and factors associated with CVEs. We performed a retrospective cohort study of the HIV-infected patients residing in the Local Health Authority of Brescia, northern Italy, from 2000 to 2012. Incidence of CVEs events in HIV-positive patients was compared with that expected in general population living in the same area, computing standardized incidence ratios (SIRs). CVEs-associated risk factors were assessed using Cox regression analysis and competing risk model of death. About 3766 HIV-infected patients were included in the study. Over the 12-year-period, we recorded 134 CVEs: 83 (61.9%) acute myocardial infarctions (CVE type-1), and 51 (38.1%) strokes (CVE type-2). A twofold increased risk (SIR = 2.02) of CVEs was found in HIV-infected patients compared to the general population. Notably, within male patients: for CVE type-1, SIR = 1.89, for CVE type-2 SIR = 2.25; within female patients: for CVE type-1, SIR = 2.91, for CVE type-2 SIR = 2.07. Age >45 years, male gender, diabetes, and total blood cholesterol >200 mg/dl were significantly associated with CVEs incidence (for all, p < .05). These results were confirmed using the competing risk model. Our cohort study confirmed the higher incidence of CVEs in HIV-positive patients, and put emphasis on the importance of traditional cardiovascular risk factors. Overall CVE risk in HIV-positive patients was twice as high as CVE risk in general population. We found a peculiar gender distribution, with a relative risk for CVE type-1 higher in HIV-positive females, and a higher CVE type-2 risk in male patients. More studies are needed in order to support these findings and to further highlight possible gender differences in the risk of developing CVEs in HIV-positive patients.