A nonlinear dynamic factor model of health and medical treatment.

Quantitative assessments of the relationship between health and medical treatment are of great importance to policy makers. To overcome endogeneity problems we formulate and estimate a tractable dynamic factor model where observed health outcomes are driven by the individual's latent health. The dynamics of latent health reflects both exogenous health deterioration and endogenous health investments. Our model allows us to investigate the effect of medical treatment on current health, as well as on future medical treatment and health outcomes. We estimate the model by maximum simulated likelihood and minimum distance methods using a rich longitudinal data set from Italy obtained by merging a number of administrative archives. These data contain detailed information on medical drug purchase, hospitalization, and mortality for a representative sample of elderly hypertensive patients. Our findings show that the observed autocorrelation in medical treatment reflects both permanent and time-varying observed and unobserved heterogeneity. They also show that medical drug purchase significantly maintains future health levels and prevents transitions to worse health. This suggests that policies aimed at increasing the awareness and the compliance of hypertensive patients help reduce cardiovascular risks and consequent hospitalization and mortality.

Prevalence of interstitial pneumonia suggestive of COVID-19 at 18F-FDG PET/CT in oncological asymptomatic patients in a high prevalence country during pandemic period: a national multi-centric retrospective study.

PURPOSE: To assess the presence and pattern of incidental interstitial lung alterations suspicious of COVID-19 on fluorine-18-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) ([18F]FDG PET/CT) in asymptomatic oncological patients during the period of active COVID-19 in a country with high prevalence of the virus. METHODS: This is a multi-center retrospective observational study involving 59 Italian centers. We retrospectively reviewed the prevalence of interstitial pneumonia detected during the COVID period (between March 16 and 27, 2020) and compared to a pre-COVID period (January-February 2020) and a control time (in 2019). The diagnosis of interstitial pneumonia was done considering lung alterations of CT of PET. RESULTS: Overall, [18F]FDG PET/CT was performed on 4008 patients in the COVID period, 19,267 in the pre-COVID period, and 5513 in the control period. The rate of interstitial pneumonia suspicious for COVID-19 was significantly higher during the COVID period (7.1%) compared with that found in the pre-COVID (5.35%) and control periods (5.15%) (p < 0.001). Instead, no significant difference among pre-COVID and control periods was present. The prevalence of interstitial pneumonia detected at PET/CT was directly associated with geographic virus diffusion, with the higher rate in Northern Italy. Among 284 interstitial pneumonia detected during COVID period, 169 (59%) were FDG-avid (average SUVmax of 4.1). CONCLUSIONS: A significant increase of interstitial pneumonia incidentally detected with [18F]FDG PET/CT has been demonstrated during the COVID-19 pandemic. A majority of interstitial pneumonia were FDG-avid. Our results underlined the importance of paying attention to incidental CT findings of pneumonia detected at PET/CT, and these reports might help to recognize early COVID-19 cases guiding the subsequent management.

Prognostic role of baseline 18F-FDG PET/CT metabolic parameters in elderly HL: a two-center experience in 123 patients.

Elderly Hodgkin lymphoma (HL) is an aggressive lymphoma subgroup with high 18F-FDG avidity at 18F-FDG-PET/CT but no shared criteria for PET/CT in treatment evaluation and prediction of outcome are available. The aim of our bicentric study was to investigate whether the metabolic baseline PET/CT parameters can predict treatment response and prognosis in elderly HL. We retrospectively included 123 patients who underwent baseline 18F-FDG-PET/CT and end of treatment PET/CT scans. The PET images were analyzed visually and semi-quantitatively by measuring the lesion to liver SUVmax ratio (L-L SUV R), lesion to blood-pool SUVmax ratio (L-BP SUV R), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Survival curves were plotted according to the Kaplan-Meier method. At a median follow-up of 40 months, the median PFS and OS were 29 and 37 months. L-BP SUV R, L-L SUV R, MTV, and TLG were significantly higher in patients with no complete response compared with complete response group at end of treatment. Moreover, these parameters were demonstrated to be independent prognostic factors for PFS together with tumor stage, while only L-L SUV R and L-BP SUV R for OS. End of treatment PET/CT results using Deauville criteria were significantly correlated with outcome survival. End of treatment PET/CT results (using Deauville criteria) and semiquantitative baseline PET/CT parameters were significantly correlated with response to treatment and long-term outcome.

Effectiveness and Safety of Remdesivir in Treating Hospitalised Patients with COVID-19: A Propensity Score Analysis of Real-Life Data from a Monocentric Observational Study in Times of Health Emergency.

BACKGROUND AND OBJECTIVES: Remdesivir is an antiviral agent, which was shown to be safe and effective in treating early COVID-19, but its favourable impact in hospitalised patients with non-critical disease is still under investigation. The present study aimed to assess the effectiveness and safety of remdesivir as a treatment for hospitalised patients with COVID-19 by a propensity score analysis of observational data. METHODS: In this monocentric retrospective cohort study, the effectiveness and safety of a 5-day course of remdesivir (200 mg intravenously at Day 1, then 100 mg from Days 2-5) in association with the standard of care were assessed in comparison with the standard of care only. The primary endpoint was the proportion of recovery on Day 14. RESULTS: Of 3662 eligible inpatients who tested positive for the severe acute respiratory syndrome coronavirus 2 genome by nasopharyngeal swab at admission, 861 (24%) non-critical patients were included in a propensity score analysis and 281 (33%) were exposed to remdesivir. In total, 242/281 (86.1%) and 435/580 (75.0%) patients recovered in exposed and non-exposed, respectively, with a relative improvement of 11.1% (95% CI + 5.8 to 16.5%; unadjusted odds ratio: 2.07, 95% CI 1.40-3.05, p = 0.0001; after adjustment by propensity score weighting, odds ratio: 1.92, 95% CI 1.30-2.83, p = 0.001). In treated patients, 1 (0.03%) anaphylactic reaction and 1 (0.03%) acute reaction during drug injection were reported, and 24 (8.5%) patients stopped the treatment due to adverse reactions. No significant differences were found with respect to the secondary efficacy endpoints (in-hospital all-cause death, need for intensive care treatments, clinical improvement score at Day 28) and safety endpoints (any and serious adverse reactions). CONCLUSION: A 5-day course of remdesivir in association with the standard of care effectively promoted recovery from COVID-19 among non-critical in-hospital patients and had an acceptable safety profile.

Negative prognostic impact of electrolyte disorders in patients hospitalized for Covid-19 in a large multicenter study.

BACKGROUND: The prognostic impact of electrolyte disorders in hospitalized COVID-19 patients is unclear. METHODS: The study included all adult patients hospitalized for COVID-19 in four hospitals in Northern Italy between January 2020 and May 2021 with at least one serum potassium and sodium measurement performed within 3 days since admission. Primary outcome was in-hospital death; secondary outcome was Intensive Care Unit (ICU) admission. A cause-specific Cox proportional-hazards regression model was used for investigating the association between potassium and sodium (as either categorical or continuous variables) and mortality or admission to ICU. RESULTS: Analyses included 3,418 adult hospitalized COVID-19 patients. At multivariable analysis, both hyperkalemia (Hazard Ratio, [HR] 1.833, 95% Confidence Interval [CI] 1.371-2.450) and sK above the median (K 5.1 vs 4.1 mmol/L: HR 1.523, 95% CI 1.295-1.798), and hypernatremia (HR 2.313, 95%CI 1.772-3.018) and sNa above the median (Na 149 vs 139 mmol/L: HR 1.442, 95% CI 1.234-1.686), were associated with in-hospital death, whereas hypokalemia and hyponatremia were not. Hyponatremia was associated with increased hazard of ICU admission (HR 1.884, 95%CI 1.389-2.556). CONCLUSIONS: Electrolyte disorders detected at hospital admission may allow early identification of COVID-19 patients at increased risk of adverse outcomes.

Trends in all-cause mortality of hospitalized patients due to SARS-CoV-2 infection from a monocentric cohort in Milan (Lombardy, Italy).

Background: Robust data on case fatality rate (CFR) among inpatients with COVID-19 are still lacking, and the role of patient characteristics in in-hospital deaths remains under-investigated. This study quantified the overall CFR and described its trend in a cohort of hospitalized patients with SARS-CoV-2 in Italy. Admission to ICU, death, or discharge were the secondary outcomes. Methods: This retrospective study is based on administrative health data and electronic case records of inpatients consecutively admitted to Niguarda Hospital between 21 February and 8 November 2020. Results: An overall CFR of 18% was observed. CFR was significantly reduced during the second wave of contagion (1 June to 30 September, 16%) compared with the first wave (21 February to 31 May, 21% p = 0.015). Such reduction was mainly observed among male inpatients between 40 and 80 years with limited comorbidities. Admission to ICU was associated with a high risk of mortality in both waves. The incidence of severe disease and the need for ICU admission were lower in the second wave. Conclusion: CFR in SARS-CoV-2 inpatients was demonstrated to decrease over time. This reduction may partly reflect the changes in hospital strategy and clinical practice. The reasons for this improvement should be further investigated to plan an exit strategy in case of future outbreaks. Key messages: What is already known on this topic Before the advent of anti-COVID-19 vaccines, a multi-wave pattern of contagion was observed, and this trend conditioned the inpatient case fatality rate (CFR), which varied over time accordingly to the waves of contagion.Only preliminary results on the in-hospital mortality trend are available, along with a partial analysis of its determinants. Consequently, robust data on CFR among inpatients with SARS-CoV-2 infection are still lacking, and the role of patient characteristics in in-hospital deaths remains under-investigated. What this study adds This study shows that the in-hospital mortality in patients with SARS-CoV-2 infection decreases over time.Such reduction was mainly observed among male inpatients between 40 and 80 years with limited comorbidities. Admission to ICU was invariably associated with a high risk of mortality during the whole study period (21 February to 8 November 2020), but the incidence of severe disease and the need for ICU admission were lower in the second wave of contagions (1 October to 8 November 2020). This reduction may partly reflect the impact of changes in hospital strategy and clinical practice. The reasons for this improvement should be further investigated to inform the response to future outbreaks and to plan exit strategy by prioritizing high-risk populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-021-01675-y.

Incident Atrial Fibrillation and In-Hospital Mortality in SARS-CoV-2 Patients.

(1) Background: Among the different cardiovascular (CV) manifestations of the coronavirus disease 2019 (COVID-19), arrhythmia and atrial fibrillation (AF) in particular have recently received special attention. The aims of our study were to estimate the incidence of AF in patients hospitalized for COVID-19, and to evaluate its role as a possible predictor of in-hospital all-cause mortality. (2) Methods: We enrolled 3435 people with SARS-CoV2 infection admitted to three hospitals in Northern Italy from February 2020 to May 2021. We collected data on their clinical history, laboratory tests, pharmacological treatment and intensive care unit (ICU) admission. Incident AF and all-cause in-hospital mortality were considered as outcomes. (3) Results: 145 (4.2%) patients developed AF during hospitalization, with a median time since admission of 3 days (I-III quartile: 0, 12). Patients with incident AF were admitted more frequently to the ICU (39.3 vs. 12.4%, p < 0.001), and more frequently died (37.2 vs. 16.9%, p < 0.001). In the Cox regression model, the significant determinants of incident AF were age (HR: 1.041; 95% CI: 1.022, 1.060 per year), a history of AF (HR: 2.720; 95% CI: 1.508, 4.907), lymphocyte count (HR: 0.584; 95% CI: 0.384, 0.888 per 103/µL), estimated glomerular filtration rate (eGFR, HR: 0.988; 95% CI: 0.980, 0.996 per mL/min) and ICU admission (HR: 5.311; 95% CI: 3.397, 8.302). Incident AF was a predictor of all-cause mortality (HR: 1.405; 95% CI: 1.027, 1.992) along with age (HR: 1.057; 95% CI: 1.047, 1.067), male gender (HR: 1.315; 95% CI: 1.064; 1.626), dementia (HR: 1.373; 95% CI: 1.045, 1.803), lower platelet (HR: 0.997; 95% CI: 0.996, 0.998 per 103/µL) and lymphocyte counts (HR: 0.843; 95% CI: 0.725, 0.982 per 103/µL), C-Reactive protein values (HR: 1.004; 95% CI: 1.003, 1.005 per mg/L), eGFR (HR: 0.990; 95% CI: 0.986, 0.994 per mL/min), and ICU admission (HR: 1.759; 95% CI: 1.292, 2.395). (4) Conclusions: Incident AF is a common complication in COVID-19 patients during hospitalization, and its occurrence strongly predicts in-hospital mortality.

Covid and Cardiovascular Diseases: Direct and Indirect Damages and Future Perspective.

SARS-CoV-2 infection determines a disease that predominantly affects lungs. However the cytokines storms, determined by the huge immune response to the infection, could affect also other organs and apparatus such as heart and vessels. Beyond the acute inflammation itself also hypercoagulative status has been linked to SARSCoV-2 infection and this surely relates to the increase seen in prevalence of pulmonary embolism and myocardial infarction. A number of cardiac abnormalities and pathologies have been observed, with special attention to cardiac arrhythmias and myocardial involvement. Furthermore, indirect damages determined by the reduction in acute and chronic cardiovascular care, results in a strong mortality and morbidity outcomes in cardiological patients. In this review we will summarise current knowledge on both direct and indirect cardiovascular damages determined by the SARS-CoV-2 pandemia.

Atrial Fibrillation and Clinical Outcomes in a Cohort of Hospitalized Patients with Sars-Cov-2 Infection and Chronic Kidney Disease.

The aim of the study was to investigate the role of chronic kidney disease (CKD) on in-hospital mortality and on incident atrial fibrillation (AF) in patients infected with SARS-CoV-2. The incidence of acute kidney injury (AKI) was also investigated. Multivariable regression models were used to assess the association between renal function groups (estimated Glomerular Filtration Rate, eGFR, >60 mL/min, 30-59 mL/min, <30 mL/min) and in-hospital all-cause mortality and incident AF and AKI. A cohort of 2816 patients admitted in one year for COVID-19 disease in two large hospitals was analyzed. The independent predictors of mortality were severe CKD [HR 1.732 (95%CI 1.264-2.373)], older age [HR 1.054 (95%CI 1.044-1.065)], cerebrovascular disease [HR 1.335 (95%CI (1.016-1.754)], lower platelet count [HR 0.997 (95%CI 0.996-0.999)], higher C-reactive protein [HR 1.047 (95%CI 1.035-1.058)], and higher plasma potassium value 1.374 (95%CI 1.139-1.658). When incident AKI was added to the final survival model, it was associated with higher mortality [HR 2.202 (1.728-2.807)]. Incident AF was more frequent in patients with CKD, but in the multivariable model only older age was significantly related with a higher incidence of AF [OR 1.036 (95%CI 1.022-1.050)]. Incident AF was strongly associated with the onset of AKI [HR 2.619 (95%CI 1.711-4.009)]. In this large population of COVID-19 patients, the presence of severe CKD was an independent predictor of in-hospital mortality. In addition, patients who underwent AKI during hospitalization had a doubled risk of death. Incident AF became more frequent as eGFR decreased and it was significantly associated with the onset of AKI.

Heart Rate in Patients with SARS-CoV-2 Infection: Prevalence of High Values at Discharge and Relationship with Disease Severity.

The most common arrhythmia associated with COronaVIrus-related Disease (COVID) infection is sinus tachycardia. It is not known if high Heart Rate (HR) in COVID is simply a marker of higher systemic response to sepsis or if its persistence could be related to a long-term autonomic dysfunction. The aim of our work is to assess the prevalence of elevated HR at discharge in patients hospitalized for COVID-19 and to evaluate the variables associated with it. We enrolled 697 cases of SARS-CoV2 infection admitted in our hospital after February 21 and discharged within 23 July 2020. We collected data on clinical history, vital signs, laboratory tests and pharmacological treatment. Severe disease was defined as the need for Intensive Care Unit (ICU) admission and/or mechanical ventilation. Median age was 59 years (first-third quartile 49, 74), and male was the prevalent gender (60.1%). 84.6% of the subjects showed a SARS-CoV-2 related pneumonia, and 13.2% resulted in a severe disease. Mean HR at admission was 90 ± 18 bpm with a mean decrease of 10 bpm to discharge. Only 5.5% of subjects presented HR > 100 bpm at discharge. Significant predictors of discharge HR at multiple linear model were admission HR (mean increase = ß = 0.17 per bpm, 95% CI 0.11; 0.22, p < 0.001), haemoglobin (ß = -0.64 per g/dL, 95% CI -1.19; -0.09, p = 0.023) and severe disease (ß = 8.42, 95% CI 5.39; 11.45, p < 0.001). High HR at discharge in COVID-19 patients is not such a frequent consequence, but when it occurs it seems strongly related to a severe course of the disease.

Clinical and prognostic role of interim 18F-FDG PET/CT in elderly Hodgkin lymphoma: a dual-center experience.

Hodgkin lymphoma (HL) has a bimodal age distribution curve, with a second peak in people aged more than 60 years. Interim PET/CT (iPET/CT) is highly predictive for PFS and OS in young HL, but it has not been sufficiently studied in the elderly. In this retrospective dual-center study, 82 patients with HL and aged 65 or more who performed iPET/CT were included. At iPET/CT, 60 patients had a complete metabolic response, 18 partial responses, and 4 progressions of disease. Baseline PET/CT metabolic features were not significantly correlated with the metabolic response at interim. In patients with interim complete metabolic response, PFS and OS were significantly longer than in patients without complete response(p < 0.001 and p = 0.004). Patients with negative iPET had 2-year PFS and OS rates of 57 and 88% compared with 24 and 58% in patients with positive iPET (p < 0.001). iPET/CT results demonstrated to be independent prognostic factors for PFS and OS.

Effects of Environmental Factors on Severity and Mortality of COVID-19.

Background: Most respiratory viruses show pronounced seasonality, but for SARS-CoV-2, this still needs to be documented. Methods: We examined the disease progression of COVID-19 in 6,914 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application. Findings: Meta-analysis of the mortality risk in seven European hospitals estimated odds ratios per 1-day increase in the admission date to be 0.981 (0.973-0.988, p < 0.001) and per increase in ambient temperature of 1°C to be 0.854 (0.773-0.944, p = 0.007). Statistically significant decreases of comparable magnitude in median hospital stay, probability of transfer to the intensive care unit, and need for mechanical ventilation were also observed in most, but not all hospitals. The analysis of individually reported symptoms of 37,187 individuals in the UK also showed the decrease in symptom duration and disease severity with time. Interpretation: Severity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation.

The Role of FDG-PET in Patients with Epilepsy Related to Periventricular Nodular Heterotopias: Diagnostic Features and Long-Term Outcome.

BACKGROUND AND PURPOSE: Periventricular nodular heterotopias (PNHs) are frequently associated with drug-resistant epilepsy (DRE). Although magnetic resonance imaging (MRI) can define the morphological features of PNHs, still there is a need to assess their metabolic activity in order to provide useful information on epileptogenicity and long-term outcome. To that end, we investigated the ability of 18 F-FDG PET to identify seizure onset zone in order to assess the metabolic activity of the ectopic neurons and to provide prognostic information on the postsurgical outcome. METHODS: Sixteen patients (6 men and 10 women; ranging between 24 and 53 years of age) with PNHs-related DRE were evaluated. All patients underwent clinical evaluation, Stereo-electroencephalogram (SEEG), brain MRI, and 18 F-FDG brain PET/CT. PET images were superimposed on the patient-specific 3-dimensional-brain MRI. The metabolic activity of each nodule and of their cortex was visually and semiquantitatively assessed. The outcome after intervention was assessed in all patients using Engel classification. RESULTS: Thirty-one heterotopic sites were identified. Twenty-one of 23 nodules with detectable electric activity on SEEG were identified by PET (91.3%), while 5 of 8 of nodules without electric activity showed no metabolism on PET (62.5%). Overall, the concordance between SEEG and FDG-PET was 26/31 (83.9%). Furthermore, cortical metabolic alterations were depicted, correlating with epileptogenic areas. A favorable postsurgical outcome was reported in 13 patients (81.3%). The presence of a hypometabolic nodule significantly correlated with a worse outcome after surgical therapy (P = .036). CONCLUSIONS: In PNHs-related epilepsy, FDG-PET more accurately identifies epileptogenic foci, which aids surgical planning and in postoperative seizure control.

Predictive and prognostic value of left ventricular mechanical dyssynchrony assessed by myocardial perfusion single photon emission computed tomography in asymptomatic patients under hemodialysis.

BACKGROUND: Patients under hemodialysis (HD) have an increased risk of major adverse cardiac events (MACEs). In these patients, myocardial perfusion scintigraphy (MPS) provides useful prognostic information. Left ventricular mechanical dyssynchrony (LVD) has been proven to predict all-cause death in patients under HD. It remains unclear, whether the same prognostic value pertains also to the prediction of MACEs. PATIENTS AND METHODS: Ninety patients under HD (duration range: 2-216 months) with neither history nor symptoms of coronary artery disease at the time of MPS were retrospectively evaluated. All underwent clinical evaluation and MPS with dipyridamole stress test. MPS was reprocessed to derive left ventricular ejection fraction (EF), perfusion scores [summed stress score (SSS) and summed difference score (SDS)] and LVD (phase histogram bandwidth and phase SD).ResultsMACEs were reported in 10 (11.1%) patients as assessed at more than 2 years of follow-up (median 29 months). At univariate analysis, a correlation was demonstrated between MACEs and LVD (P<0.001), BMI (P=0.04), ECG changes during stress (P=0.03), dyspnea (P=0.02), SSS (P=0.04) and SDS (P=0.02). At stepwise multivariate analysis, only LVD (P<0.001), SSS (P=0.01) and SDS (P=0.001) were independent predictors of MACEs. No thresholds of SSS or SDS showed predictive value (P=0.79 for SSS ≥4, P=0.10 for SSS >8 and P=0.66 for SDS ≥2). At survival analysis, patients with LVD had a significantly shorter MACE-free survival (P<0.001). This predictive value held true even in patients with an unremarkable pattern of perfusion. CONCLUSION: In asymptomatic patients without known coronary artery disease under HD, LVD is highly predictive of the onset of MACEs at more than 2 years of follow-up and provides incremental value over perfusion scores alone. A phase analysis on gated MPS should be routinely performed in these patients to yield useful prognostic information.

PET/CT in nononcological lung diseases: current applications and future perspectives.

Positron emission tomography (PET) combined with computed tomography (CT) is an established diagnostic modality that has become an essential imaging tool in oncological practice. However, thanks to its noninvasive nature and its capability to provide physiological information, the main applications of this technique have significantly expanded.(18)F-labelled fluorodeoxyglucose (FDG) is the most commonly used radiopharmaceutical for PET scanning and demonstrates metabolic activity in various tissues. Since activated inflammatory cells, like malignant cells, predominantly metabolise glucose as a source of energy and increase expression of glucose transporters when activated, FDG-PET/CT can be successfully used to detect and monitor a variety of lung diseases, such as infections and several inflammatory conditions.The added value of FDG-PET/CT as a molecular imaging technique relies on its capability to identify disease in very early stages, long before the appearance of structural changes detectable by conventional imaging. Furthermore, by detecting the active phase of infectious or inflammatory processes, disease progression and treatment efficacy can be monitored.This review will focus on the clinical use of FDG-PET/CT in nonmalignant pulmonary diseases.

Patients with known or suspected lung cancer: evaluation of clinical management changes due to 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) study.

AIM: To determine prospectively from the referring physician's point of view the impact of F-fluorodeoxyglucose positron emission tomography (F-FDG PET) results on the management decisions in patients with known or suspected lung cancer. METHODS: Seventy-five consecutive patients (58 men, 17 women; age range, 33-82 years; mean age, 64 years) with a diagnosis of a pulmonary lesion, obtained by means of morphological imaging studies and/or cytological sampling, were included in the study. The patient population consisted of three groups: (A) patients (n=18) with a solitary lung nodule; (B) patients (n=37) with untreated lung cancer; and (C) patients (n=20) with treated lung cancer. All were referred for whole-body F-FDG PET within 15 days (mean, 11 days) of lung lesion detection. To determine whether and how PET findings could modify the treatment strategy, a questionnaire was sent to the referring physician before and after the PET results. With regard to the treatment strategy, four major options were recognized: (1) further diagnostic investigations; (2) medical therapy; (3) surgical treatment; (4) wait-and-see. For data analysis, intermodality changes, defined as changes between treatment strategies related to PET findings, were considered. RESULTS: Before the PET study, the planned management for the overall patient population was as follows: further diagnostic investigations in 44 cases (58%), medical therapy in 17 (23%), surgical treatment in nine (12%) and wait-and-see in five (7%). After the PET study, further diagnostic tools were indicated in 27 cases (36%), medical therapy in 17 (23%), surgical treatment in 28 (37%) and wait-and-see in three (4%). Relative to the initially planned strategy, changes in patient management after PET imaging occurred in 34 (45%) cases. Overall, the most relevant variation after PET concerned the surgical treatment strategy. The highest percentage (67%) of changes in management after PET was found in patients with a solitary pulmonary nodule; the percentages of changes of the three patient groups were significantly different (chi-squared test; P=0.021). CONCLUSIONS: In patients with known or suspected lung cancer, F-FDG PET results determined significant variations in major clinical management decisions.

Drug compliance, co-payment and health outcomes: evidence from a panel of Italian patients.

This paper studies the relationship between medical compliance and health outcomes - hospitalization and mortality rates - using a large panel of patients residing in a local health authority in Italy. These data allow us to follow individual patients through all their accesses to public health care services until they either die or leave the local health authority. We adopt a disease specific approach, concentrating on hypertensive patients treated with ACE-inhibitors. Our results show that medical compliance has a clear effect on both hospitalization and mortality rates: health outcomes clearly improve when patients become more compliant to drug therapy. At the same time, we are able to infer valuable information on the role that drug co-payment can have on compliance, and as a consequence on health outcomes, by exploiting the presence of two natural experiments during the period of analysis. Our results show that drug co-payment has a strong effect on compliance, and that this effect is immediate.

11C-Radiosynthesis and preliminary human evaluation of the disposition of the ACE inhibitor [11C]zofenoprilat.

(4S)-1-[(S)-3-Mercapto-2-methylpropanoyl]-4-phenylthio-L-proline (Zofenoprilat, 2), the active metabolite of the potent ACE inhibitor Zofenopril Calcium (1), was labelled with carbon-11 (t1/2=20.4 min) to evaluate its pharmacokinetics behaviour in human body using Positron Emission Tomography (PET). [11C]2 labelling procedures were based on the use of immobilized Grignard reagent and the acylation of (S)-4-phenylthio-L-proline methyl ester (5) with 11C-labelled methacryloyl chloride, followed by a Michael addition with thiobenzoic acid. The radiochemical yield was 5-10% (EOB, decay corrected) and specific radioactivity ranged from 0.5 to 1.5 Ci/micromol (18.5-55.5 GBq/micromol). Preliminary in vivo human evaluation of [11C]2 showed that the drug accumulates in organs which express high levels of ACE, like lungs and kidneys, and in organs involved in drug metabolism such as the liver and gall bladder. Results of the distribution of [11C]2 showed a measurable concentration of the drug in the target tissues such as the kidney and to a minor extent, the heart, where it can afford organ protection.