Short-term effectiveness of dapagliflozin versus DPP-4 inhibitors in elderly patients with type 2 diabetes: a multicentre retrospective study.

AIM: To compare effectiveness of dapagliflozin versus DPP-4 inhibitors on individualized HbA1c targets and extra-glycaemic endpoints among elderly patients with type 2 diabetes (T2D). METHODS: This was a multicentre retrospective study on patients aged 70-80 years with HbA1c above individualized target and starting dapagliflozin or DPP-4 inhibitors in 2015-2017. The primary outcome was the proportion reaching individualized HbA1c targets. Confounding by indication was addressed by inverse probability of treatment weighting (IPTW), multivariable adjustment (MVA), or propensity score matching (PSM). RESULTS: Patients initiating dapagliflozin (n = 445) differed from those initiating DPP-4i (n = 977) and balance between groups was achieved with IPTW or PSM. The median follow-up was 7.5 months and baseline HbA1c was 8.3%. A smaller proportion of patients initiating dapagliflozin attained individualized HbA1c target as compared to those initiating DPP-4 inhibitors (RR 0.73, p < 0.0001). IPTW, MVA, and PSM yielded similar results. Between-group difference in the primary outcome was observed among patients with lower eGFR or longer disease duration. Dapagliflozin allowed greater reductions in body weight and blood pressure than DPP-4 inhibitors. CONCLUSIONS: Elderly patients with T2D initiating dapagliflozin had a lower probability of achieving individualized HbA1c targets than those initiating DPP-4 inhibitors but displayed better improvements in extra-glycaemic endpoints.

Real-world study on the effectiveness and safety of basal insulin IDegLira in type 2 diabetic patients previously treated with multi-injective insulin therapy.

OBJECTIVE: Achieving glycemic target is paramount to control diabetes mellitus (DM) and reduce micro-vascular and macro-vascular complications. Despite the mostly recent-developed drugs, most patients still show an above desired glycated hemoglobin (HbA1c) level due to DM complex pathophysiology, therapeutic and dietary compliance and clinical inertia in introducing or intensifying insulin therapy. To support the promising results of clinical trials on the effectiveness and safety of the degludec/liraglutide combination (IDegLira) in type 2 DM patients with C-peptide values >1 ng/ml who were previously treated with basal-bolus multiple daily-dose insulin injections. PATIENTS AND METHODS: This observational, prospective and non-randomized trial enrolled type 2 DM patients referred to our outpatient clinic between January 2019 and December 2019, who were shifted from multiple daily-dose insulin injection therapy to degludec/liraglutide combination as per the physician's decision. The main assessment was HbA1c variation at 6 months from baseline. Secondary assessments included variation in fasting glycemia, routine anthropometric assessments, blood chemistry, blood pressure and patients' quality of life (measured by the Diabetes Treatment Satisfaction Questionnaire [DTSQ]), from baseline to 6 months. RESULTS: HbA1c (8.4 vs. 7.4%; p<0.0001) and body weight (94.1 vs. 93 kg; p<0.0001) were significantly lower after 6 months for patients on the degludec/liraglutide combination. A similar trend was observed in fasting glycemia levels (159 vs. 125 mg/dl; p<0.0001). An improved glycemic control was achieved with degludec/liraglutide despite a reduction in total daily insulin units (42 U at 6 months vs. 22 U at baseline; p<0.0001). In addition, higher scores in the DTSQ were registered after 6 months on degludec/liraglutide (mean score: 27 vs. 20; p<0.0001). The combination therapy also proved more convenient than basal-bolus therapy in terms of costs, with an average per-patient cost difference of €-0.41±0.59/die (p<0.0001). CONCLUSIONS: These real-world findings show that degludec/liraglutide seems to be more effective than basal-bolus insulin in achieving glycemic control, allowing cost sustainability and improving patient satisfaction.

Coronary Microvascular Dysfunction Predicts Long-Term Outcome in Simultaneous Pancreas-Kidney Transplantation.

BACKGROUND: Patients with diabetes are at increased cardiovascular risk. Simultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice in patients with type 1 diabetes mellitus and diabetic nephropathy. We assessed coronary flow reserve (CFR) by transthoracic echocardiography as a marker of major adverse cardiac events (MACE) in SPKT patients. METHODS: We studied 48 consecutive SPKT patients (28 male, age at SPKT 54 ± 8 years). Time from transplantation was 8.5 ± 3 years. Follow-up was 4.6 ± 1.8 years. Coronary flow velocity in the left anterior descending coronary artery was detected by Doppler echocardiography at rest and during adenosine infusion. CFR was the ratio of hyperemic diastolic flow velocity (DFV) to resting DFV. A CFR ≤ 2 was considered abnormal and a sign of coronary microvascular dysfunction. MACE were cardiac death, myocardial infarction, and heart failure. RESULTS: CFR was 2.55 ± 0.8. CFR was ≤2 in 13 (27%) patients. CFR was lower in SPKT patients with MACE (2.1 ± 0.7 vs 2.7 ± 0.8, P = .03) and patients with MACE had a higher incidence of CFR ≤ 2 (P = .03). Time from transplantation was shorter in patients with MACE (P < .0001). Patients with CFR ≤ 2 had a lower MACE-free survival (P = .03). CFR ≤ 2 predicted the risk of MACE (P = .007) independently from coronary artery disease and metabolic control. However, this predicted role is lost when adjusted for the time from transplantation, which plays a protective role (P = .001). CONCLUSIONS: In SPKT, CFR ≤ 2 may be a reliable marker for MACE, independent of coronary artery disease diagnosis. However, this role seems to be reduced over time. This finding suggests a gradual reduction of cardiovascular risk in SPKT patients.

Effects of dose escalating liraglutide from 1.2 to 1.8 mg in clinical practice: a case-control study.

PURPOSE: Randomized trials show that liraglutide 1.8 mg is more effective than 1.2 mg in reducing HbA1c, but dose escalation is neither routinely considered nor recommended by some guidelines. We report real world data on the effects of dose-escalating liraglutide from 1.2 to 1.8 mg. METHODS: In a pseudo-prospective, case-control study, patients who underwent liraglutide dose escalation to 1.8 mg for not having met individualized targets while on the 1.2 mg dose (n = 52) were compared to matched patients who remained on 1.2 mg (n = 52) for having shown good response, as defined by the patient's own diabetologist. HbA1c was recorded at ≤6-month intervals until the end of observation. RESULTS: The two groups were matched for all clinical characteristics, including baseline HbA1c (8.5 %). During a 12-month follow-up, patients who remained on liraglutide 1.2 mg showed a maximal HbA1c reduction of 1.29 ± 0.15 %. Patients who escalated to 1.8 mg showed a lower HbA1c reduction during therapy with 1.2 mg than controls (0.58 ± 0.16 %; p = 0.0017). Escalation to 1.8 mg resulted in a further HbA1c reduction of 0.62 ± 0.17 %. During a total 18-month follow-up, patients who escalated to 1.8 mg showed a total maximal HbA1c reduction of 0.84 ± 0.22 %. At the end of the observation, HbA1c was 7.54 ± 0.17 % in patients who remained on 1.2 mg and 7.92 ± 0.21 in patients who escalated to 1.8 mg (p = 0.13). Escalation to 1.8 mg also helped further body weight reduction. CONCLUSIONS: Escalating liraglutide dose to 1.8 mg in patients who responded less than expected to 1.2 mg helps in reducing HbA1c and reaching therapeutic targets.

Development of metabolic syndrome and electrocardiographic features of left ventricular hypertrophy in middle-aged working subjects.

BACKGROUND AND AIMS: Metabolic syndrome (MS) leads to excess cardiovascular disease, including heart failure. Left ventricular hypertrophy (LVH) is common in MS patients, but it is unknown whether onsets of MS and LVH coincide. Herein, we tested the association between development of MS and of electrocardiographic LVH in a cohort of middle-aged individuals. METHODS: We included 303 working subjects (mean age 43.0 ± 6.2; 41% males), followed- up for 4.3 ± 0.8 yr. ATP-III MS components were determined. Electrocardiographic LVH features were assessed by Sokolow and Cornell voltage indexes and Romhilt-Estes (RE) score. RESULTS: At baseline, Cornell index was significantly higher in subjects with (no.=55; 18.2%) than in those without MS (12.8 ± 6.4 vs 10.9 ± 5.4 mm; p=0.023), while Sokolow index and RE score were not different. At followup, individuals who developed (no.=51) compared to those who did not develop MS showed a significant increase in Cornell voltage index (1.0 ± 0.6 vs -0.55 ± 0.3 mm; p=0.035) and RE score (0.17 ± 0.17 vs -0.08 ± 0.04; p=0.028). The change in Cornell index over time was directly correlated with the change in the number of MS components (r=0.133; p=0.02) and in homeostasis model assessment of insulin resistance (r=0.117; p=0.046). The association between MS onset and the increase in Cornell index/RE score was independent from confounders. CONCLUSIONS: In a young population of working subjects, the development of MS is associated with worsening features of LVH. Early LVH electrocardiographic screening in young subjects who develop MS should be considered and performed using Cornell voltage index.

[Is viscoelastic the corneal tissue?]. / Il tessuto corneale è viscoelastico?

PURPOSE: To compare the known viscoelastic properties of soft tissues with singular published observations on the behaviour of corneal tissue. MATERIALS AND METHODS: The behaviour of the maxwellian element, typical viscoelastic biomechanical model, is compared with that of various previously studied soft tissues of animals. The same comparison can be made between stress-strain curves of riboflavin and UVA treated and untreated strips of human and porcine corneal tissue, stretched at constant velocity, from the literature. RESULTS: The asymptotic stress-strain curves of the various soft tissues previously examined could be faithfully simulated by the Maxwell viscoelastic element. The exponential stress-strain curves of samples of corneal tissue were clearly different. CONCLUSIONS: The observed divergence demonstrates incompatibility between the alleged behaviour of corneal tissue and the viscoelastic properties attributed to it. Thus there are two possibilities: either corneal tissue is viscoelastic and the experiment showing exponential behaviour suffers from some technical problem, or the data is correct and corneal tissue is not viscoelastic. In either case further research is necessary for correct interpretation of the mechanism of cross-linking and for consequent therapeutic choices.

Keratoconus, cross-link-induction, comparison between fitting exponential function and a fitting equation obtained by a mathematical model.

With reference to experimental data in the literature, we present a model consisting of two elastic elements, conceived to simulate resistance to stretching, at constant velocity of elongation, of corneal tissue affected by keratoconus, treated with riboflavin and ultraviolet irradiation to induce cross-linking. The function describing model behaviour adapted to stress and strain values. It was found that the Young's moduli of the two elastic elements increased in cross-linked tissues and that cross-linking treatment therefore increased corneal rigidity. It is recognized that this observation is substantially in line with the conclusion reported in the literature, obtained using an exponential fitting function. It is observed, however, that the latter function implies a condition of non-zero stresses without strain, and does not provide interpretative insights for lack of any biomechanical basis. Above all, the function fits a singular trend, inexplicably claimed to be viscoelastic, with surprising perfection. In any case, using the reported data, the study demonstrates that a fitting equation obtained by a modelling approach not only shows the evident efficacy of the treatment, but also provides orientations for studying modifications induced in cross-linked fibres.

[The new magnetic therapy TAMMEF in the treatment of simple shoulder pain]. / Il nuovo sistema di magnetoterapia TAMMEF nel trattamento della spalla dolorosa semplice.

AIMS: Numerous studies have demonstrated the utility of extremely low frequencies (ELF) electromagnetic fields in the treatment of pain. Moreover, the effects of these fields seems to depend on their respective codes (frequency, intensity, waveform). In our study we want to assess the effects of the TAMMEF (Therapeutic Application of a Musically Modulated Electromagnetic Field) system, whose field is piloted by a musical signal and its parameters (frequency, intensity, waveform) are modified in time, randomly varying within the respective ranges, so that all possible codes can occur during a single application. PATIENTS AND METHODS: Sixty subjects, affected by shoulder periarthritis were enrolled in the study and randomly divided into three groups of 20 patients each: A exposed to TAMMEF, B exposed to ELF, C exposed to a simulated field. All subjects underwent a cycle of 15 daily sessions of 30 minutes each and a clinical examination upon enrollment, after 7 days of therapy, at the end of the cycle and at a follow-up 30 days later. RESULTS: All the patients of groups A and B completed the therapy without the appearance of side effects: they presented a significant improvement of the subjective pain and the functional limitation, which remained stable at the follow-up examination. In group C, there was no improvement of the pain symptoms or articular functionality. CONCLUSIONS: This study suggests that the TAMMEF system is efficacious in the control of pain symptoms and in the reduction of functional limitation in patients with shoulder periarthritis. Moreover, the effects of the TAMMEF system cover those produced by the ELF field.

Efficacy and safety of a musically modulated electromagnetic field (TAMMEF) in patients affected by knee osteoarthritis.

OBJECTIVE: Numerous studies have demonstrated the utility of extremely low frequencies (ELF) electromagnetic fields in clinical practice. Moreover, the effects of these fields seems to depend on their respective codes (frequency, intensity, waveform). In our study we want to value the effects of the TAMMEF (Therapeutic Application of a Musically Modulated Electromagnetic Field) system, which field is piloted by a musical signal. METHODS: Ninety subjects, affected by primary osteoarthritis of the knee, were enrolled in the study and randomly divided into three groups of 30 patients each: A exposed to TAMMEF, B exposed to ELF, C exposed to a simulated field. All subjects underwent a cycle of 15 daily sessions of 30 minutes each and a clinical examination upon enrolment, after 7 days of therapy, at the end of the cycle and at a follow-up 30 days later: RESULTS: All the patients of groups A and B completed the therapy without the appearance of side effects: they presented a significant improvement of the subjective pain and the functional limitation, which remained stable at the follow-up examination. In group C, there was no improvement of the pain symptoms or articular functionality. CONCLUSIONS: This study suggests that the TAMMEF system is efficacious in the control of pain symptoms and in the reduction of functional limitation in patients with knee osteoarthritis. Moreover, the effects of the TAMMEF system cover those produced by the ELF field.

Comparison between the analgesic and therapeutic effects of a musically modulated electromagnetic field (TAMMEF) and those of a 100 Hz electromagnetic field: blind experiment on patients suffering from cervical spondylosis or shoulder periarthritis.

The analgesic-therapeutic efficacy and tolerability of a low-frequency electromagnetic field (ELF), modulated at a frequency of 100 Hz with a sinusoidal waveform and mean induction of a few gauss, has been demonstrated by the authors in numerous previous studies of various hyperalgic pathologies, particularly of the locomotor apparatus. In the present study, the authors tested a new type of all-inclusive field, denoted TAMMEF, whose parameters (frequency, intensity, waveform) are modified in time, randomly varying within the respective ranges, so that all the possible codes can occur during a single application. For the comparison, 150 subjects (118 women and 32 men, between 37 and 66 years of age) were enrolled. They were affected by cervical spondylosis (101 cases) or shoulder periarthritis (49 cases). Unbeknownst to them, they were randomly divided into three groups of 50 subjects. One group was exposed to the new TAMMEF, another group to the usual ELF, and the third group to simulated treatment. The results show that the effects of the new TAMMEF therapy are equivalent to those obtained with the ELF.

[Evaluation of early biomarkers of cartilage degeneration in the diagnosis and clinico-therapeutic monitoring of primary osteoarthrosis]. / Valutazione degli indici bioumorali precoci di degenerazione cartilaginea nella diagnostica e nel monitoraggio clinico-terapeutico dell'osteoartrosi primitiva.

It is known that in the course of osteoarthritis (OA), articular cartilage develops biochemical and structural changes. In the last years, serum and urinary markers of both the synthesis and destruction of cartilage have been dosed, above all in order to carry out an early diagnosis of OA. Among them, the urinary excretion of pyridinoline seems to correlate with the entity of the degradation of cartilage. The aim of the present study is to evaluate the above mentioned markers in OA patients compared to control subjects. Moreover, the possible influence on cartilage of two different non steroidal antiinflammatory drugs (NSAIDs), in particular Nabumetone and Piroxicam, has been verified. The study shows that the urinary excretion of pyridinoline is able to express the severity of OA. At last, the study shows that the tested drugs do not interfere with the metabolism of cartilage.

A new model to assess tcpO2 changes during heat-dependent vasodilation: preliminary observations.

The transcutaneous pO2 (tcpO2) changes induced by the increase of temperature to 45 degrees C after electrode stabilization at 37 degrees C were continuously recorded. The mathematical analysis of the curve led us to identify three different parameters: the half-slope "b" time, the angular "mT" coefficient and the angular "mb" parameter, which are not simply the expression of the maximum vasodilation capacity but mainly of the dynamic response of the microcirculatory system to skin heating. These parameters derived from the computerized mathematical analysis of the curve can be also obtained by a graphical approach with a very good approximation. The angular "mb" coefficient was shown to possess the highest statistical power in discriminating the POAD patients from normal controls. The clinical relevance and the possible pathophysiological meaning of these preliminary observations have to be confirmed.

Miniature environments and subjective estimates of time.

A recent review of a century of studies describes the different conditions in which subjective estimates of time deviate, sometimes considerably, from clock time. With reference to experimental data published a few years ago, showing that prolonged observation of a scene in miniature induces the observer to ascribe durations contracted by the scale factor to events imaginable therein, it is demonstrated that a simple comparison with the time of the experimenter does not always reveal all the effects obtainable from the data. Avoiding questions of interpretation belonging to the field of psychology, the author applies the physical law of time contraction to a miniaturized scene to provide a time reference dependent on the scale factor, to be exact, proportional to its square root.

[Pulsed magnetic fields. Observations in 353 patients suffering from chronic pain]. / Campi magnetici pulsati. Osservazioni su 353 pazienti sofferenti per dolore cronico.

Three hundred-fifty-three patients with chronic pain have been treated with pulsed electromagnetic fields. In this work the Authors show the result obtained in the unsteady follow-up (2-60 months). The eventual progressive reduction of benefits is valued by Spearman's test. We noted the better results in the group of patients with post-herpetic pain (deafferentation) and in patients simultaneously suffering from neck and low back pain.