Search

Summary Background In DISCOVER, a multinational, randomised controlled trial, emtricitabine and tenofovir alafenamide compared with emtricitabine and tenofovir disoproxil fumarate showed non-inferior efficacy for HIV prevention and improved bone mineral density and renal safety biomarkers at week 48. We report outcomes analysed after all participants had completed 96 weeks of follow-up. Methods This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in Europe and North America. Adult cisgender men and transgender women who have sex with men, both with a high risk of acquiring HIV as determined by self-reported sexual behaviour or recent sexually transmitted infections, were randomly assigned (1:1) to receive either emtricitabine and tenofovir alafenamide (200/25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine and tenofovir disoproxil fumarate (200/300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). The primary efficacy outcome was incident HIV infection. Incidence of HIV-1 infection per 100 person-years was assessed when the last participant had completed 96 weeks of follow-up. This trial is registered with ClinicalTrials.gov , number NCT02842086 . Findings Between Sept 13, 2016, and June 30, 2017, 5387 participants were randomly assigned to receive emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693), contributing 10 081 person-years of follow-up. At 96 weeks of follow-up, there were eight HIV infections in participants who had received emtricitabine and tenofovir alafenamide (0·16 infections per 100 person-years [95% CI 0·07–0·31]) and 15 in participants who had received emtricitabine and tenofovir disoproxil fumarate (0·30 infections per 100 person-years [0·17–0·49]). Emtricitabine and tenofovir alafenamide maintained its non-inferiority to emtricitabine and tenofovir disoproxil fumarate for HIV prevention (IRR 0·54 [95% CI 0·23–1·26]). Approximately 78–82% of participants reported taking study medication more than 95% of the time across all study visits. Rates of sexually transmitted infections remained high and similar across groups (21 cases per 100 person-years for rectal gonorrhoea and 28 cases per 100 person-years for rectal chlamydia). Emtricitabine and tenofovir alafenamide continued to show superiority over emtricitabine and tenofovir disoproxil fumarate in all but one of the six prespecified bone mineral density and renal biomarkers. There was more weight gain among participants who had received emtricitabine and tenofovir alafenamide (median weight gain 1·7 kg vs 0·5 kg, p Interpretation Emtricitabine and tenofovir alafenamide is safe and effective for longer-term pre-exposure prophylaxis in cisgender men and transgender women who have sex with men. Funding Gilead Sciences.

Laser speckle contrast analysis (LASCA) is a non-contact technique able to quantify peripheral blood perfusion (PBP) over large skin areas. LASCA has been used to study hand PBP in several clinical conditions. These include systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) and LASCA showed that PBP was significantly lower in these conditions than in healthy subjects (HS). Moreover, it has been demonstrated that LASCA is a safe technique also able to monitor digital ulcer perfusion and their evolution in SSc patients, during systemic and local treatment. The use of LASCA, coupled with reactivity tests is commonplace in the field of microvascular function research. Post-occlusive hyperemia reactivity (POHR) and local thermal hyperemia, associated with laser techniques are reliable tests in the evaluation of perfusion in SSc patients. Other studies used laser speckled techniques, together with acetylcholine and sodium nitroprusside iontophoresis, as specific tests of endothelium function. In conclusion, LASCA is a safe, non-contact reliable instrument for the quantification of PBP at skin level and can also be associated with reactivity tests to monitor disease progression and response to treatment in different connective tissue diseases.

Background. Some studies with inconclusive results have reported a link between sarcoidosis and an increased risk of pulmonary embolism (PE). This study aimed at assessing a possible correlation between potential risk factors and PE in sarcoidosis patients. Methods. A total of 256 sarcoidosis patients (84 males and 172 females, mean age at diagnosis 49 ± 13) were enrolled after giving written informed consent. Clinical evaluations, laboratory and radiology tests were performed to evaluate the presence of pulmonary embolism. Results. Fifteen sarcoidosis patients with PE (4 males and 11 females, mean age at diagnosis 50 ± 11), diagnosed by lung scintigraphy and 241 sarcoidosis patients without PE (80 males and 161 females, mean age at diagnosis 47 ± 13), were observed. There was a statistically significant increase of the presence of antiphospholipid antibodies in the sarcoidosis group with pulmonary embolism. There was no statistically significant difference between the two groups as to smoking habit, obesity or hereditary thrombophilia frequency (p &gt, 0.05, respectively). Conclusions. This study demonstrates a significant correlation between the presence of antiphospholipid antibody positivity and the pulmonary embolism events in our sarcoidosis patients. Furthermore, we propose screening for these antibodies and monitoring, aimed at timely treatment.

Systemic sclerosis (SSc) is an autoimmune disease, characterized by the presence of generalized vasculopathy and tissue fibrosis. Collagen vascular disorder in SSc is due to fibroblast and endothelial cell dysfunctions. This leads to collagen overproduction, vascular impairment and immune system abnormalities and, in the last stage, multi-organ damage. Thus, to avoid organ damage, which has a poor prognosis, all patients should be carefully evaluated and followed. This is particularly important in the initial disease phase, so as to facilitate early identification of any organ involvement and to allow for appropriate therapy. Pulmonary disease in SSc mainly involves interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). High-resolution computed tomography (HRCT) and pulmonary function tests (PFT) have been proposed to monitor parenchymal damage. Although transthoracic echocardiography is the most commonly used screening tool for PAH in SSc patients, definitive diagnosis necessitates confirmation by right heart catheterization (RHC). Moreover, some studies have demonstrated that nailfold videocapillaroscopy (NVC) provides an accurate evaluation of the microvascular damage in SSc and is able to predict internal organ involvement, such as lung impairment. This review provides an overview of the correlation between lung damage and microvascular involvement in SSc patients.

Background. Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD). This prospective observational study aimed at the evaluation of any correlation between genetic variants associated with IPF susceptibility and high-resolution computed tomography (HRCT) patterns. It also aimed at evidencing any differences in the HRTC pattern between the familial and sporadic form at diagnosis and after two years. Methods. A total of 65 IPF patients (mean age at diagnosis 65 ± 10) were enrolled after having given written informed consent. HRCT and genetic evaluations were performed. Results. A total of 19 familial (mean age 62 ± 15) and 46 sporadic (mean age 70 ± 9) IPF patients were enrolled. A statistically significant difference was evidenced in the HRTC pattern at diagnosis between the two groups. Sporadic IPF patients had a predominantly usual interstitial pneumonia (UIP) pattern compared with those patients with familial IPF (60.0% vs. 21.1%, respectively). Moreover, familial IPF patients had more alternative diagnoses than those with sporadic IPF (31.6% vs. 2.2%, respectively). Furthermore, there was a slight increase in the typical UIP pattern in the familial IPF group at two years from diagnosis. Conclusions. Genetic factors play a pivotal role in the risk of developing IPF. However, further studies are required to clarify how these genetic factors may guide clinical treatment decisions.

The diagnosis and classification of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is essential to improve the prognosis of systemic sclerosis (SSc) patients. The risk-stratification of disease severity and follow-up requires a multidisciplinary approach, integrating high-resolution computed tomography (HRTC) of the lung, pulmonary function tests (PFT), along with clinical and symptomatic evaluations. The use of HRCT in detecting SSc-ILD is not so much based on a definitive validation, but rather reflects the widespread clinician recognition of dissatisfaction with other modalities. However, due to the heterogeneity of SSc-ILD and the potential absence of symptoms in early or mild disease, it is prudent to consider as many parameters as possible in the assessment and monitoring of newly diagnosed patients. An early diagnosis meets the primary goal, i.e., the prevention of disease progression. The current first line treatment regimens are mainly centered on immunosuppressive therapy. This review assesses the role HRCT plays in optimizing care and improving clinical outcomes in SSc-ILD patients.

Background Patient-reported outcomes (PROs) can provide important information about treatment tolerability in HIV-1-infected patients. Objective The aim of this study was to evaluate PROs following switching from a boosted protease inhibitor-based regimen to the single-tablet regimen (STR) of rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) in the 48-week open-label Switching Boosted PI to Rilpivirine in Combination with Truvada as a Single-Tablet Regimen (SPIRIT) trial. Methods In the open-label SPIRIT trial, patients were randomized to receive an STR of RPV/FTC/TDF (n = 317) for 48 weeks or stay on their baseline regimen of a ritonavir-boosted protease inhibitor and two nucleoside/nucleotide analog reverse transcriptase inhibitors (PI + RTV + 2NRTIs, n = 159) for 24 weeks before switching to RPV/FTC/TDF for another 24 weeks. PRO assessments included the HIV Treatment Satisfaction Questionnaire (TSQ) and the HIV Symptom Index Questionnaire (SIQ). Results At week 24, the mean HIV TSQ improvement from baseline was significantly greater in the RPV/FTC/TDF group than the PI + RTV + 2NRTIs group (p

This paper draws on data obtained in the first year of a longitudinal study designed to monitor the effect of the general practitioner contract and the 1990 NHS and Community Care Act. The study focuses on the care received by people over the age of 75 living in areas covered by four first wave community trusts. One objective of the first year of this study was to examine the impact of the general practitioner (GP) contract particularly with regard to drug consumption and nursing input. Random samples of older people were obtained from family health services authorities in the four trust areas. Health visitors were recruited in each locality and were trained to conduct the interviews. A total of 775 people were interviewed and assessed for functional, physical, mental, emotional and social status. Each person was asked whether they had been given a health check, who had been involved and where this was carried out. They were also asked to show those medicines they had taken in the 24 h before they were interviewed. Multivariate analysis showed that after controlling for physical symptoms, functional ability, pathology, admission to hospital in the previous 12 months, socio-economic class, self-health ratings and consultations with their doctor, those who had been given a health check had consumed fewer drugs. The implications of these findings for the drugs budget are calculated. The results of the study suggest that savings on the drugs budget may offset to a large extent the additional costs of employing practice nurses to undertake health checks but further research is indicated.

Exposure to trauma has always been part of human existence (Marsella, Friedman & Spain, 1996). Extreme stress has been depicted by authors throughout the ages. In Homer’s Odyssey (4 000 years ago) and Shakespeare’s Henry VI (1591), for example, portray post-traumatic stress reactions to war (Wade, 2009). In 1993 the American Psychiatric Association (APA) defined trauma in the Third Diagnostic and Statistical Manual (DSM III) as a catastrophic stressor that would evoke significant symptoms of stress in most people. Trauma was thought to be “a rare and overwhelming event, generally outside the range of usual human experiences” (APA, 2000:467). Events that fitted this definition of trauma included rape, assault, incarceration, military combat, accidents and domestic violence. After many debates about the concept of trauma, the definition was changed in the DSM IV to focus not on the event(cause) itself, but on the person’s response(effect) to the event or the symptoms the person showed after the event (APA, 2000; Wade, 2009). The APA acknowledged that people give different meanings to events and therefore not all seemingly traumatic events are experienced as traumatic by all people. The DSM IV constructed criteria or symptoms for the condition “post-traumatic stress disorder” (PTSD) to describe the condition in the following way: “The person experienced, witnessed or was confronted with an event or events that involved actual or threatened death or serious injury, or a threat to the physical integrity of self and others” (APA, 2000:467). This definition excludes other events that are not life threatening. The person’s symptoms, according the DSM IV, could include intense fear, helplessness or horror (APA, 2000:467). This would imply that events such as the destruction of one’s home, or a threat to life, would qualify as being traumatic, but divorce or illness would not qualify if physical threats were not present (Norris, 1992).

Two hundred and fifteen colostomy patients were interviewed at 10 weeks after surgery from a stratified random sample of 12 health districts in which stoma-care nurses were employed and eight other districts: 85 survivors who did not have restorative surgery were reinterviewed 1 year later. The Present State Examination (PSE) was used to assess the prevalence of affective disorder on both occasions. Analysis of covariance of the 10-week PSE scores revealed that age was unrelated to psychological adjustment after controlling for the extent and severity of patients' symptoms and that patients in districts which employed stoma-care nurses had significantly lower PSE scores. Single and widowed males appeared to enjoy better emotional health than married men and than women. Analysis of covariance of PSE scores obtained 1 year later also revealed that age was unrelated to psychological adjustment after controlling for the patients' physical state. No difference was found between patients who had access to a National Health Service stoma-care nurse and patients in other districts, many of whom had seen a representative from one of the appliance companies. The finding that single and widowed males appeared to fare better than married men was repeated. Ten per cent of patients who felt completely well were anxious or depressed. Psychiatric referral may be inappropriate for the majority of depressed patients who may instead benefit from medical treatment or from nursing intervention to deal with physical symptoms such as pain or urinary incontinence.

The effectiveness and safety of prescribed medication theoretically depends on the patient correctly following the prescriber's instructions. However, patient compliance is often difficult to achieve. This paper discusses reasons for this in relation to elderly people, and attempts to remedy the situation are reviewed.