Respiratory depression after administration of single-dose neuraxial morphine for post-cesarean delivery analgesia: a retrospective cohort study.

BACKGROUND: Neuraxial administration of long-acting opioid is the "gold standard" for the management of postoperative pain following cesarean delivery. Respiratory depression, however, remains a concerning complication. METHODS: This retrospective single-center study of 4963 patients evaluated the frequency of respiratory depression after neuraxial morphine administration in a post-cesarean delivery population. The spinal dose of morphine varied from 100 to 450 µg intrathecally, and from 3 to 5 mg epidurally. The primary outcome was the initiation of a Rapid Response Team (RRT) event for respiratory failure due to neuraxial opioid in the 24 h following morphine administration. Secondary outcomes studied included oxygen desaturation events (SpO2 <90%), initiation of oxygen therapy and naloxone administration. RESULTS: There were no respiratory RRT events within the study period (95% confidence interval [CI] 0 to 7 per 10 000). There were no desaturation events recorded and no patients received supplemental oxygen therapy or naloxone (95% CI 0 to 7 per 10 000). CONCLUSION: Clinically significant respiratory depression is rare among patients receiving neuraxial morphine for post-cesarean delivery analgesia.

Proactive vs. reactive psoriasis therapy: a long-term evaluation with dermoscopic and confocal microscopy assessment.

OBJECTIVE: The PSO-LONG trial demonstrated that proactive management of psoriasis based on the regular application of the fixed-dose combination calcipotriol and betamethasone dipropionate (Cal/BD) foam twice a week for 52 weeks prolonged the time to first relapse and reduced the number of relapses, compared with the reactive management. Nevertheless, data about proactive management in clinical practice are still poor. This observational study compares the Cal/BD foam proactive management of psoriasis with the reactive scheme in consecutive patients with localized mild-to-moderate psoriasis. The degree of the skin atrophy was also assessed with dermoscopic and confocal microscopy analyses. PATIENTS AND METHODS: This retrospective observational study was conducted at the Federico II University Dermatological Clinic of Naples in adult patients treated with the fixed-dose combination Cal/BD foam (Enstilar®, Leo Pharma, Ballerup, Denmark) according to either a proactive or a reactive scheme (on-demand treatment). The observation time was 52 weeks. RESULTS: 149 patients were involved. The effectiveness of the proactive therapy was sustained by the significant reduction of the mean number of relapses (p=0.004) and by the significant increase of the median time to relapse (p=0.014) compared to the reactive regimen. Compared to the baseline values, significant improvements in the Psoriasis Area and Severity Index (PASI) score, Investigator Global Assessment (IGA) score, and Skindex-16 index were reported. Dermoscopy and confocal microscopy analyses showed the absence of cutaneous atrophy during the proactive treatment and improved the lesion's appearance. CONCLUSIONS: The proactive regimen represents a valuable therapeutic novelty in treating mild-to-moderate psoriasis.

Anti-interleukin-23 for psoriasis in elderly patients: guselkumab, risankizumab and tildrakizumab in real-world practice.

BACKGROUND: Elderly patients (aged ≥ 65 years) represent an increasing proportion of patients with psoriasis and 15% of these have moderate to severe disease. Biologics are being used frequently in this group of patients even though safety and efficacy data are limited. In addition, owing to anti-interleukin (IL)-23 therapies being a relatively recent option, no data have been reported about their use in elderly patients with psoriasis. AIM: To evaluate and compare the safety and efficacy of guselkumab, risankizumab and tildrakizumab in real-world practice in elderly patients. METHODS: This was a single-centre retrospective study that enrolled patients aged ≥ 65 years with moderate to severe plaque psoriasis, treated with guselkumab, risankizumab or tildrakizumab. The length of the study for each group depended on the drug (44 weeks for risankisumab, 40 weeks for guselkumab and 28 weeks for tildrakizumab, owing to its more recent availability in Italy). RESULTS: In total, 34 patients were enrolled (n = 20 on guselkumab; n = 8 on risankizumab; n = 6 on tildrakizumab). At Week 4, 29.4% reached 90% improvement in Psoriasis Area and Severity Index (PASI90) and 8.8% reached 100% improvement in PASI (PASI100); at Week 28, PASI90 and PASI100 was reached by 58.8% and 29.4%, respectively. At the final follow-up (Week 40 or 44, depending on drug), data were available only for the risankizumab (Week 40) and guselkumab (Week 44) and groups, and showed that 71.4% of patients had reached PASI90 and 53.5% had reached PASI100. Four patients (11.7%) discontinued treatment. No significant differences were found between the three groups. The limitations of the study included its retrospective nature of the study, small sample size, and different numbers of patients and follow-up duration for the different groups (highest for guselkumab, lowest for tildrakizumab). CONCLUSION: The three anti-IL-23 therapies assessed are promising, safe and effective options in elderly patients, and there was no significant difference between them. However, more data are needed to confirm our results and to understand their role in the management of this group of patients.

Review of oral minoxidil as treatment of hair disorders: in search of the perfect dose.

Topical minoxidil has been used for many years as treatment for different hair disorders. Even though it is an effective therapy, many patients show poor compliance due to the cosmesis, cost and side-effects. During the last few years, low-dose oral minoxidil has proven to be an alternative for patients with alopecia. We performed a literature search including all the articles that used oral minoxidil as a primary treatment in various hair diseases in order to evaluate the efficacy and safety of low-dose oral minoxidil as an alternative to topical minoxidil. Androgenetic alopecia was the most common studied condition, but others included telogen effluvium, tractional alopecia, postchemotherapy-induced alopecia, monilethrix, loose anagen hair syndrome, alopecia areata and scarring alopecias (frontal fibrosing alopecia and lichen planopilaris). Larger randomized comparative studies including standardized objective measurements should be done in order to clarify the best treatment protocol, including dosage and treatment duration. Oral minoxidil has proven to be a successful and well-tolerated alternative for patients with hair loss, including those with poor adherence to other therapies. Different dosing regimens have been utilized in scarring and non-scarring alopecia, varying from 0.25 to 5 mg daily. Higher doses have not been studied in men or women. Available literature suggests women require lower doses, from 0.25 to 2.5 mg daily, while men require higher doses for maximal efficacy, from 1.25 to 5 mg a day.

Is kinesiophobia a predictor of early functional performance after total hip replacement? A prospective prognostic cohort study.

BACKGROUND: Considerable attention has been paid to the role of kinesiophobia with respect to knee prosthesis but it has not yet been studied as a prognostic factor of short-term functional performance following total hip replacement. The main purpose of the present study is to examine the possible predictors of early functional performance of patients undergoing total primary hip arthroplasty, including demographics as age, sex and body mass index, preoperative functional ability, type of anaesthesia, level of haemoglobin, pain and level of kinesiophobia before surgery. Secondly, we want to describe the main characteristics of the population with the highest levels of kinesiophobia. METHODS: A prospective, prognostic cohort study was carried out. Patients undergoing primary hip replacement were recruited consecutively. The main outcome is the early functional performance achieved by patients after surgery and measured using the Iowa Level of Assistance (ILOA) scale on the fifth postoperative day. Preoperative kinesiophobia was measured by the Tampa Scale and the preoperative functional ability by the Western Ontario and McMaster Osteoarthritis Index (WOMAC). The multivariate analysis was performed by the General Linear Model. The analysis of the population with high levels of kinesiophobia was conducted by identifying a cut-off of 40 compared to the Tampa Scale. RESULTS: Statistical analysis was performed on 269 patients. The average ILOA score recorded was 19.5 (DS 8.3). The levels of kinesiophobia, showed an average score of 35.1 (7.8) and it was not associated with early functional performance. The independent predictive factors include age, sex and body mass index. Kinesiophobia high levels were recorded in 30% of the population and this population had a higher level of pre-operative WOMAC score. CONCLUSIONS: Early functional performance after hip replacement surgery was not correlated with the level of kinesiophobia. Three significant factors that describe a population most at risk of not achieving optimal functional performance are increased age, being female and increase in body mass index. In the preoperative phase, high levels of kinesiophobia were associated with more impaired preoperative functional ability. TRIAL REGISTRATION: Current Controlled Trials NCT02786121 , May 2016. Retrospectively registered.

Serum biomarkers for sepsis in children with febrile neutropenia and cancer.

The National Institute for Health and Care Excellence (NICE) defines febrile neutropenia or "neutropenic sepsis" as a patient with an absolute neutrophil count (ANC) less than 0.5 x 109/L and temperature >38°C or signs and symptoms of sepsis.

Impact of malnutrition on survival and infections among pediatric patients with cancer: a retrospective study.

OBJECTIVE: Recognizing and managing malnutrition among hospitalized children affected by cancer is a rising need. Awareness and consideration of malnutrition among clinicians are still largely insufficient. This can principally be explained by the lack of consciousness and the shortage of easy and objective tools to identify malnutrition status. The aim of this study is to explore the impact of malnutrition on survival and infections among a population of pediatric patients with cancer. PATIENTS AND METHODS: All children aged between 3 and 18 years, newly diagnosed with a malignancy between August 2013 and April 2018, were included in our study. We assessed nutritional risk at diagnosis (with STRONGkids), then we evaluated anthropometric measurements (BMI Z-scores and weight loss), data about survival and number of hospitalization for febrile neutropenia (FN) in the first year after diagnosis. Cut-off values for malnourishment were chosen as BMI Z-score ≤-2.0. RESULTS: One hundred twenty-six pediatric cancer patients were included in the study. At diagnosis 36 pediatric cancer patients (28.6%) were at high risk of malnutrition (STRONGkids 4 or 5), whereas 6 (4.7%) others were malnourished (BMI Z-score≤-2.0). The risk of mortality and the rate of infections (≥3 hospitalizations for FN episodes) were significantly increased by malnutrition and rapid weight loss in the initial phase of treatment (3-6 months after diagnosis). Multivariate analysis confirmed the independent effect of weight loss≥ 5% at 3 months on both survival and infections, and the independent impact of a high risk of malnutrition at diagnosis on infections. CONCLUSIONS: A personalized evaluation of nutritional risk at diagnosis and a close monitoring of nutritional status during the initial phase of treatment are crucial for ensuring a timely and personalized nutritional intervention, which may potentially improve tolerance to chemotherapy and survival, and prevent prolonged hospitalization for infections in childhood cancer patients.

Renal health after long-term exposure to tenofovir disoproxil fumarate (TDF) in HIV/HBV positive adults in Ghana.

OBJECTIVES: The study assessed markers of renal health in HIV/HBV co-infected patients receiving TDF-containing antiretroviral therapy in Ghana. METHODS: Urinary protein-to-creatinine ratio (uPCR) and albumin-to-protein ratio (uAPR) were measured cross-sectionally after a median of four years of TDF. At this time, alongside extensive laboratory testing, patients underwent evaluation of liver stiffness and blood pressure. The estimated glomerular filtration rate (eGFR) was measured longitudinally before and during TDF therapy. RESULTS: Among 101 participants (66% women, median age 44 years, median CD4 count 572 cells/mm3) 21% and 17% had detectable HIV-1 RNA and HBV DNA, respectively. Overall 35% showed hypertension, 6% diabetes, 7% liver stiffness indicative of cirrhosis, and 18% urinary excretion of Schistosoma antigen. Tubular proteinuria occurred in 16% of patients and was independently predicted by female gender and hypertension. The eGFR declined by median 1.8 ml/min/year during TDF exposure (IQR -4.4, -0.0); more pronounced declines (≥ 5 ml/min/year) occurred in 22% of patients and were associated with receiving ritonavir-boosted lopinavir rather than efavirenz. HBV DNA, HBeAg, transaminases, and liver stiffness were not predictive of renal function abnormalities. CONCLUSIONS: The findings mandate improved diagnosis and management of hypertension and suggest targeted laboratory monitoring of patients receiving TDF alongside a booster in sub-Saharan Africa.

Clinical tools to assess nutritional risk and malnutrition in hospitalized children and adolescents.

Malnutrition in children and adolescents may be underestimated during hospital stay. In western countries, children were often hospitalized for acute or chronic diseases that are not necessarily related to malnutrition. However, acute or chronic injuries may hamper nutritional status, prolonging recovery after admission and consequently length of hospital stay. Several methods and techniques are known to investigate malnutrition in children, even if their use is not widespread in clinical practice. Many of these are simple and easy to perform and could be useful to a better management of every kind of illness. In this review, we will focus on clinical tools necessary to reveal a nutritional risk at admission and to assess nutritional status in hospitalized children and adolescents.

Pharmacometric Modeling of Liver Metastases' Diameter, Volume, and Density and Their Relation to Clinical Outcome in Imatinib-Treated Patients With Gastrointestinal Stromal Tumors.

Three-dimensional and density-based tumor metrics have been suggested to better discriminate tumor response to treatment than unidimensional metrics, particularly for tumors exhibiting nonuniform size changes. In the developed pharmacometric modeling framework based on data from 77 imatinib-treated gastrointestinal patients, the time-courses of liver metastases' maximum transaxial diameters, software-calculated actual volumes (Vactual ) and calculated ellipsoidal volumes were characterized by logistic growth models, in which imatinib induced a linear dose-dependent size reduction. An indirect response model best described the reduction in density. Substantial interindividual variability in the drug effect of all response assessments and additional interlesion variability in the drug effect on density were identified. The predictive ability of longitudinal tumor unidimensional and three-dimensional size and density on overall survival (OS) and progression-free survival (PFS) were compared using parametric time-to-event models. Death hazard increased with increasing Vactual . This framework may guide early clinical interventions based on three-dimensional tumor responses to enhance benefits for patients with gastrointestinal stromal tumors (GIST).

Imaging of acute and chronic thromboembolic disease: state of the art.

Acute pulmonary embolism (PE) is a life-threatening condition that requires prompt diagnosis and treatment. Recent advances in imaging allow acute and rapid recognition even by the non-specialist radiologist. Most acute emboli resolve on anticoagulation without sequelae; however, some emboli fail to fully resolve becoming endothelialised with the development of chronic thromboembolic disease (CTED). Increased pulmonary vascular resistance arising from CTED may lead to chronic thromboembolic pulmonary hypertension (CTEPH) a debilitating disease affecting up to 5% of survivors of acute PE. Diagnostic evaluation is more complex in CTEPH/CTED than acute PE with subtle imaging features often being overlooked or misinterpreted. Differentiation of acute from chronic PE and from other forms of pulmonary hypertension has profound therapeutic implications. Diverse imaging techniques are available to diagnose and monitor PEs both in the acute and chronic setting. Broadly they include techniques that provide data on lung parenchymal perfusion (ventilation-perfusion [VQ] scintigraphy), angiographic techniques (computed tomography [CT], magnetic resonance imaging [MRI], and invasive angiography) or a combination of both (MR angiography and time-resolved angiography or dual-energy CT angiography). This review aims to describe state of the art imaging highlighting the strength and weaknesses of individual techniques in the diagnosis of acute and chronic PE.