Feasibility of a Type 2 Diabetes Prevention Program at Nationwide Level in General Practice: A Pilot Study in Italy.

BACKGROUND: Lifestyle interventions halt the progression of prediabetes to frank type 2 diabetes (T2D). However, the feasibility of a diabetes prevention program promoting tailored interventions on a national scale and conducted by primary care physicians is unclear. METHODS: General practitioners located in ten different regions throughout Italy enrolled random subjects without known metabolic diseases to identify individuals with prediabetes and prescribe them an intervention based on physical activity. Using a simple stepwise approach, people referring to their primary care physician for any reason were screened for their diabetes risk with a web-based app of the Findrisc questionnaire. Those at risk for T2D, i.e., with a Findrisc score >9, were invited to come back after overnight fasting to measure fasting glycaemia (FG). Those with 100 ≤ FG < 126 mg/dL were considered as people with prediabetes and compiled the Physical Activity Readiness Questionnaire (PAR-Q) to then receive a personalised prescription of physical activity. RESULTS: Overall, 5928 people were enrolled and compiled the questionnaire. Of these, 2895 (48.8%) were at risk for T2D. Among these, FG was measured in 2168 subjects (participation rate 75%). The numbers of individuals with undetected prediabetes and T2D according to FG were 755 and 79 (34.8% and 3.6% of those assessing FG), respectively. Of the 755 subjects in the prediabetes range, 739 compiled the PAR-Q and started a personalised program of physical activity (participation rate 97%). Physicians involved in the study reported a mean of 6 min to perform the screening. CONCLUSIONS: Overall, these data suggest the feasibility of a national diabetes prevention program developed by general practitioners using a simple stepwise approach starting from a web app to intercept individuals with prediabetes.

Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention.

INTRODUCTION: Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. METHODS AND ANALYSIS: The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. ETHICS AND DISSEMINATION: This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's course and findings through regular meetings. TRIAL REGISTRATION NUMBER: NCT05339841.

TLR4 Expression in Ex-Lichenoid Lesions-Oral Squamous Cell Carcinomas and Its Surrounding Epithelium: The Role of Tumor Inflammatory Microenvironment.

Toll-like receptors (TLRs) regulate innate and adaptive immune responses. Moreover, TLRs can induce a pro-survival and pro-proliferation response in tumor cells. This study aims to investigate the expression of TLR4 in the epithelium surrounding oral squamous cell carcinomas (OSCC) in relation to its inflammatory microenvironment. This study included 150 human samples: 30 normal oral control (NOC), 38 non-lichenoid epithelium surrounding OSCC (NLE-OSCC), 28 lichenoid epithelium surrounding OSCC (LE-OSCC), 30 OSCC ex-non oral lichenoid lesion (OSCC Ex-NOLL), and 24 OSCC ex-oral lichenoid lesion (OSCC Ex-OLL). TLR4 expression was investigated by immunohistochemistry and the percentage of positive cells was quantified. In addition, a semiquantitative analysis of staining intensity was performed. Immunohistochemical analysis revealed that TLR4 is strongly upregulated in LE-OSCC as compared to normal control epithelium and NLE-OSCC. TLR4 expression was associated with the inflammatory environment, since the percentage of positive cells increases from NOC and NLE-OSCC to LE-OSCC, reaching the highest value in OSCC Ex-OLL. TLR4 was detected in the basal third of the epithelium in NLE-OSCC, while in LE-OSCC, TLR4 expression reached the intermediate layer. These results demonstrated that an inflammatory microenvironment can upregulate TLR4, which may boost tumor development.

Detection of familial hypercholesterolemia in patients from a general practice database.

OBJECTIVES: Familial hypercholesterolemia (FH) is the most common monogenic lipid disorder associated with premature coronary heart disease. Early cholesterol-lowering therapy could effectively reduce cardiovascular disease morbidity and mortality in these patients. However, the majority of people with FH are undiagnosed, also due to low awareness and knowledge of FH in general practice, despite the high number of contacts GPs have with most of their patients which allows a systematic and effective approach to the detection of this condition. Here, we present a simple method to improve detection and to enhance awareness of FH in primary care using GP electronic health records. METHODS: We used electronic data from the Co.S. Consortium, involving more than 600 Italian affiliated GPs. Electronic data include demographic information, laboratory test results, recorded history of vascular disease and prescription of an HMG-CoA reductase inhibitor class medication. We performed a partial assessment of the Dutch Lipid Clinic Network (DLCN) score using those data that were recorded or available. We also sought to determine the prevalence of possible FH based on age-specific LDL-cholesterol thresholds employed by the diagnostic criteria of MEDPED and the non-age adjusted cut-off point (LDL-C ≥190 mg/dL). RESULTS: Data on LDL-C were available for 162,864 subjects. Mean LDL-C levels (SD) were 124.3 (33.6) mg/dL for non-treated subjects and 106.4 (38.5) mg/dL for statin-treated subjects. The cut-off of LDL-C ≥190 mg/dL yielded a prevalence of 2.9% among non-treated subjects and of 3.5% among statin-treated patients. Using the cut-off of ≥250 mg/dL, the prevalence was 0.1% among non-treated subjects and 0.3% among statin-treated patients. Using the cut-off ≥330 mg/dL (suggesting a probable diagnosis of FH according to the DLCN score) the prevalence was 0.01% and 0.02%. According to the stratification proposed by MEDPED criteria for the general population, the age-specific LDL-cholesterol thresholds identified 0.7% among non-treated subjects and 18.5% among statin-treated patients. CONCLUSION: The diagnosis of FH is possible in general medicine and should be an integral part of the GP's activity.

[Role of intensive medical training on Law 38 to improve pain management in primary care]. / La gestione del dolore nella medicina primaria: esiti di un progetto di fomazione sulla Legge 38/2010.

The Italian Law no. 38/2010 requires that the physician reports in the medical record the type and the intensity of pain, analgesic therapies and clinical results. We developed a training model for 256 primary care physicians (GPs). After a period of intensive training on the content of the law no. 38, diagnostic and pharmacological approach of pain, we carried out a clinical audit by a web based clinical record to assess doctor's compliance to Law no. 38 and the use of opioids. 2631 patients were assessed (age 71,5±13,7 years; median 74). The mean of chronic non oncologic pain intesity was 5.41±2.0 (static) and 6.10±2.32 (dynamic). After a systematic measurement of pain, a better control of patients was achieved (2.22±2.12 points lower for static, 2.37±2.34 lower for dynamic pain (p<0.001 vs basal time). An increased use of opioids have been detected. GPs have also used strong opioids in opioid-naïve patients, avoiding the first or the second step if intensity of pain detected was severe. In fact, a greater pain control was achieved with oxycodone compared to tramadol or codeine (all of them with normal release and combined with acetaminophen). Chronic non cancer pain remains one of the major clinical problems in the primary care setting, especially in the elderly. The standard measurement of parameters related to pain and the proper use of opioids depends on the scientific update and how this is delivered. GPs are crucial to implement the Law 38 and to increase the degree of complexity of the patient to be properly admitted to a SPOKE/HUB center.

Characteristics of people with chronic lung disease who rest during the six-minute walk test.

OBJECTIVES: To examine the incidence of resting during the 6-minute-walk test (6MWT) in patients with chronic lung disease (CLD) and to explore differences in functional exercise capacity and response to pulmonary rehabilitation (PR) between resters and nonresters. DESIGN: Retrospective chart review. SETTING: Inpatient PR program. PARTICIPANTS: Individuals (N=211) who performed the 6MWT at admission and discharge from PR. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Primary outcomes were total distance walked (6-minute walk distance [6MWD]) and rest frequency and duration. Secondary outcomes were walking speed, end-test dyspnea, and the Chronic Respiratory Questionnaire (CRQ). RESULTS: At admission, 45 people (21%) rested 1 to 4 times during the 6MWT (total duration, 105±80s) and 166 people walked continuously. At discharge, 9 people continued to rest (total duration, 28±55s). At admission, nonresters walked 315±93m, whereas resters walked 197±83m (P<.0001), and 6MWD increased in both groups after PR (P<.0001). Nonresters increased their walking speed at discharge, but resters did not (interaction P<.001). At admission, the mastery domain of the CRQ was 0.8 point lower in resters (3.7±1.2) compared with nonresters (4.5±1.7; P=.01). Resters' end-test dyspnea scores decreased from 5.7±0.3 to 4.3±0.2 from admission to discharge, whereas nonresters' end-test dyspnea scores did not significantly change from 4.5±0.2 to 4.2±0.2 at discharge (interaction P<.05). CONCLUSIONS: One in 5 individuals with CLD rest during the 6MWT. Decreasing rest duration or increasing walking speed reflects different strategies used to improve 6MWD after rehabilitation, both suggesting a positive effect of PR. This may be related to improvements in an individual's sense of control over dyspnea. Future work should investigate potential factors related to resting during the 6MWT.

Heterometallic modular metal-organic 3D frameworks assembled via new tris-ß-diketonate metalloligands: nanoporous materials for anion exchange and scaffolding of selected anionic guests.

The modular engineering of heterometallic nanoporous metal-organic frameworks (MOFs) based on novel tris-chelate metalloligands, prepared using the functionalised ß-diketone 1,3-bis(4'-cyanophenyl)-1,3-propanedione (HL), is described. The complexes [M(III)L(3)] (M=Fe(3+), Co(3+)) and [M(II)L(3)](NEt(4)) (M=Mn(2+), Co(2+), Zn(2+), Cd(2+)) have been synthesised and characterised, all of which exhibit a distorted octahedral chiral structure. The presence of six exo-oriented cyano donor groups on each complex makes it a suitable building block for networking through interactions with external metal ions. We have prepared two families of MOFs by reacting the metalloligands [M(III)L(3)] and [M(II)L(3)](-) with many silver salts AgX (X=NO(3)(-), BF(4)(-), PF(6)(-), AsF(6)(-), SbF(6)(-), CF(3)SO(3)(-), tosylate), specifically the [M(III)L(3)Ag(3)]X(3)·Solv and [M(II)L(3)Ag(3)]X(2)·Solv network species. Very interestingly, all of these network species exhibit the same type of 3D structure and crystallise in the same trigonal space group with similar cell parameters, in spite of the different metal ions, ionic charges and X(-) counteranions of the silver salts. We have also succeeded in synthesising trimetallic species such as [Zn(x)Fe(y)L(3)Ag(3)](ClO(4))((2x+3y))·Solv and [Zn(x)Cd(y)L(3)Ag(3)](ClO(4))(2)·Solv (with x+y=1). All of the frameworks can be described as sixfold interpenetrated pcu nets, considering the Ag(+) ions as simple digonal spacers. Each individual net is homochiral, containing only Δ or Λ nodes; the whole array contains three nets of type Δ and three nets of type Λ. Otherwise, taking into account the presence of weak Ag-C σ bonds involving the central carbon atoms of the ß-diketonate ligands of adjacent nets, the six interpenetrating pcu networks are joined into a unique non-interpenetrated six-connected frame with the rare acs topology. The networks contain large parallel channels of approximate hexagonal-shaped sections that represent 37-48% of the cell volume and include the anions and many guest solvent molecules. The guest solvent molecules can be reversibly removed by thermal activation with retention of the framework structure, which proved to be stable up to about 270°C, as confirmed by TGA and powder XRD monitoring. The anions could be easily exchanged in single-crystal to single-crystal processes, thereby allowing the insertion of selected anions into the framework channels.

[Gender differences of at risk patients with overt heart failure in the real world of general practice. Data from the GIPSI (Gestione Integrata Progetto Scompenso in Italia) registry]. / Differenze tra la popolazione maschile e femminile a rischio ed affetta da insufficienza cardiaca nel mondo reale della medicina generale. I dati del registro GIPSI (Gestione Integrata Progetto Scompenso in Italia).

BACKGROUND: Controlled clinical trials have defined the characteristics of specialized world populations, different from the real world population. On this basis, the GIPSI registry was created, aiming to collect data from heart failure populations managed by general practitioners, focusing on gender differences. METHODS: The registry was based on family history, clinical and laboratory data collection from general practitioners. Patients were considered as being at risk for heart failure if data applied to stage A/B, or presenting overt heart failure if data applied to stage C/D of the American College of Cardiology/American Heart Association classification. RESULTS: From June 2006 to October 2007, 757 consecutive patients (475 male, 62.7%) were enrolled from 260 general practitioner's practices; 227 patients (143 male, 63.0%) had overt heart failure. In the female population at risk, higher systolic and diastolic blood pressure values were observed, whereas males showed more frequently ischemic heart disease, hypercholesterolemia and hypertriglyceridemia, and were more often prescribed with statins and antiplatelet drugs. There were more heart failure females with diabetes and of advanced age. Moreover, females showed a higher pulse pressure and a significantly lower estimated glomerular filtration rate (by simplified MDRD equation) than males. CONCLUSIONS: The data collected in a real world population show that heart failure has significantly different gender characteristics, especially for risk factors, age, blood pressure and renal function. This kind of investigation should be extended to larger patient populations for a better understanding of the disease.