Investigating coping and stigma in people living with HIV through narrative medicine in the Italian multicentre non-interventional study DIAMANTE.

Antiretroviral therapy (ART) significantly reduced Human Immunodeficiency Virus (HIV) morbidity and mortality; nevertheless, stigma still characterises the living with this condition. This study explored patients' coping experience by integrating narrative medicine (NM) in a non-interventional clinical trial. From June 2018 to September 2020 the study involved 18 centres across Italy; enrolled patients were both D/C/F/TAF naïve and previously ART-treated. Narratives were collected at enrolment (V1) and last visit (V4) and then independently analysed by three NM specialist researchers through content analysis. One-hundred and fourteen patients completed both V1 and V4 narratives. Supportive relationships with clinicians and undetectable viral load facilitated coping. Conversely, lack of disclosure of HIV-positive status, HIV metaphors, and unwillingness to narrate the life before the diagnosis indicated internalised stigma. This is the first non-interventional study to include narratives as patient reported outcomes (PROs). Improving HIV awareness and reducing the sense of guilt experienced by patients helps to overcome stigma and foster coping.

Post-operative analgesia following TPLO surgery: A comparison between cimicoxib and tramadol.

OBJECTIVE: To compare the analgesic effects of oral administration of cimicoxib and tramadol over a 30 day period following Tibial Plateau Leveling Osteotomy and partial menisectomy in dogs. DESIGN: Randomized, double blinded, prospective clinical trial. ANIMALS: 42 adult client-owned dogs with unilateral cranial cruciate ligament disease and partial meniscal tears. METHODS: Dogs were allocated into 2 treatment groups (cimicoxib or tramadol). Weight bearing while standing, thigh circumference, flexion and extension range of motions, wound classification, adverse effects, Visual Analogue Scale (VAS), Glasgow Composite Measure Pain Scale (CMPS-SF) and Helsinki Chronic Pain Index (HCPI) questionnaire and limb function by means of pressure platform gait analysis were recorded before surgery and at several time points after surgery for 30 days. Outcome measures were compared at each time point among groups. RESULTS: A significant improvement in two objective measures of gait of the cimicoxib group: the vertical impulse on day 1 and day 20 and the peak vertical force on day 20 were significantly improved when compared to the tramadol group. However, no difference was seen for the VI or PVF of dogs on the other days compared. In addiction there was no difference in the weight bearing while standing, thigh circumference, wound classification, adverse effects, VAS, CMPS-SF and HCPI. We did not observe a difference in the number of adverse effects measured in this study with the exception of hock edaema. CONCLUSIONS AND CLINICAL RELEVANCE: A significant difference was not found in long-term postoperative analgesia provided by cimicoxib or tramadol in dogs undergoing TPLO when subjective parameters (with the exception of knee joint range of motion) were evaluated, but use of the force plate analysis revealed a significant difference between groups at T20 for both PVF and VI. The use of cimicoxib improved the limb function and ROM and reduced the occurrence of hock edema, in the first 20 days after surgery, without any additional side effects, compared to tramadol. Thus, the use of cimicoxib should be preferred to tramadol alone in clinical cases similar to the ones included in this study.

Cardiovascular adverse events during treatment with darunavir-based regimens in an Italian observational study.

Background: The protease inhibitor (PI) darunavir (DRV) has proven to be highly effective and well tolerated for HIV treatment. The DAD (Data collection on Adverse Effects of Anti-HIV Drugs) cohort showed an increased 5-year cumulative cardiovascular (CV) risk in patients given various PIs, including DRV, whereas two other recent studies found no association between DRV and CV diseases. Methods: We performed a post-hoc analysis of CV adverse events (CVAEs) in an Italian cohort, the TMC114-HIV4042 observational study, where 875 patients treated with ritonavir-boosted DRV-based regimens were followed for a total of 1,566 patient-years. Results: We observed 23 CVAEs of any type, including 17 [12 (95%CI, 7-19) per 1,000 patient-years] primary; 14 [10 (95%CI, 5-17) per 1,000 patient-years] were primary Framingham-type general CVAEs, close to what expected according to the Framingham algorithm based on traditional risk factors. Age and systolic blood pressure (SBP) at the time of study enrolment were the only relevant (p<0.01) independent predictors of CVAEs in all models; patients with any CVAE were on average 10 years older and had an SBP 14 mmHg higher than patients without CVAEs. When controlling for age and SBP, the association with other traditional factors, including serum lipids, and with HIV-specific factors was not statistically significant (p>0.05). Models that also adjusted for previous ARV exposure showed no statistically significant association between any-type CVAEs and either DRV doses, 1,200 or 800 mg/daily (as also suggested by propensity score stratification), or previous DRV exposure duration. Conclusion : We found no evidence of a relationship between DRV use and increased CV risk.

Efficacy and safety of boosted darunavir-based antiretroviral therapy in HIV-1-positive patients: results from a meta-analysis of clinical trials.

Darunavir/ritonavir (DRV/r) is a second-generation protease inhibitor used in treatment-naïve and -experienced HIV-positive adult patients. To evaluate efficacy and safety in these patient settings, we performed a meta-analysis of randomized controlled trials. We considered eight studies involving 4240 antiretroviral treatment (ART)-naïve patients and 14 studies involving 2684 ART-experienced patients. Regarding efficacy in the ART-naive patients, the virological response rate was not significantly different between DRV/r and the comparator. For the ART-experienced failing patients, the virological response rate was significantly higher with DRV/r than with the comparator (RR 1.45, 95% CI: 1.01-2.08); conversely, no significant differences were found between the treatment-experienced and virologically controlled DRV/r and comparator groups. Regarding safety, the discontinuation rates due to adverse events (AEs) and DRV/r-related serious adverse events (SAEs) did not significantly differ from the rates in the comparator group (RR 0.84, 95% CI: 0.59-1.19 and RR 0.78, 95% CI: 0.57-1.05, respectively). Our meta-analysis indicated that DRV/r-based regimens were effective and tolerable for both types of patients, which was consistent with published data.

Demagnetization harmonic effects on the magnetization of granular systems on a macroscopic scale: the superconducting case.

A model has been developed to determine the effective ac magnetic response of magnetic systems, taking into account the demagnetization effects arising from the sample geometry which determine the out-of-phase components of the applied fundamental frequency and higher harmonic components. Indeed, demagnetization fields and their intermodulation can significantly affect the ac magnetic response. This approach provides a system of self-consistent linear equations relating the magnetic response to the external magnetic field by means of nonlinear magnetic susceptibility. The model is extended to the magnetic response of granular systems in terms of the contributions of the individual grains and of the whole sample in the presence of demagnetization effects of the whole sample and of the grains on a macroscopic scale. In particular, our model is applied to a granular superconducting system. The comparison between the performed numerical simulations and the experimental data shows that the demagnetization fields of the single grains and of the whole sample, and their intermodulation, are relevant if magnetic measurements are used to extract detailed information about the analyzed material.

Shielding of relativistic protons.

Protons are the most abundant element in the galactic cosmic radiation, and the energy spectrum peaks around 1 GeV. Shielding of relativistic protons is therefore a key problem in the radiation protection strategy of crewmembers involved in long-term missions in deep space. Hydrogen ions were accelerated up to 1 GeV at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, New York. The proton beam was also shielded with thick (about 20 g/cm2) blocks of lucite (PMMA) or aluminium (Al). We found that the dose rate was increased 40-60% by the shielding and decreased as a function of the distance along the axis. Simulations using the General-Purpose Particle and Heavy-Ion Transport code System (PHITS) show that the dose increase is mostly caused by secondary protons emitted by the target. The modified radiation field after the shield has been characterized for its biological effectiveness by measuring chromosomal aberrations in human peripheral blood lymphocytes exposed just behind the shield block, or to the direct beam, in the dose range 0.5-3 Gy. Notwithstanding the increased dose per incident proton, the fraction of aberrant cells at the same dose in the sample position was not significantly modified by the shield. The PHITS code simulations show that, albeit secondary protons are slower than incident nuclei, the LET spectrum is still contained in the low-LET range (<10 keV/microm), which explains the approximately unitary value measured for the relative biological effectiveness.