bluuebunny/crossref_metadata_2025 huggingface dataset:
Interventions for Intrapartum Fetal Heart Rate Abnormalities
Authors: ELLER ALEXANDRA G.
Published: July 2020

Intrapartum fetal heart rate (FHR) decelerations may represent interrupted oxygen transfer to the fetus. In many cases, these interruptions are transient and do not result in progressive fetal acidemia with risk for asphyxia and neurological compromise. When significant FHR decelerations are present, reversible causes of reduced fetal oxygen delivery should be considered and corrective measures should be undertaken to optimize oxygenation. In this review, we describe potential intrapartum causes of reduced fetal oxygen delivery and the efficacy of common interventions for an abnormal FHR tracing.
LONGITUDINAL FOLLOW-UP OF TUBERCULAR SERPIGINOUS-LIKE CHOROIDITIS USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: Agarwal Aniruddha , Aggarwal Kanika , Mandadi Spoorti Krishna Reddy , Kumar Aman , Grewal Dilraj , Invernizzi Alessandro , Bansal Reema , Sharma Aman , Sharma Kusum , Gupta Vishali ,   for OCTA Study Group
Published: July 2020

Purpose:

To analyze and describe serial follow-up of choriocapillaris alterations in tubercular serpiginouslike choroiditis (SLC) using optical coherence tomography angiography (OCTA) and to compare it with multimodal imaging.

Methods:

In this prospective cohort study, patients with active tubercular SLC underwent OCTA using Optovue RTVue XR Avanti and other imaging techniques including enhanced-depth imaging OCT (EDI-OCT) (Heidelberg Spectralis; Heidelberg Engineering, Heidelberg, Germany), fundus autofluorescence, fluorescein angiography, and indocyanine green angiography. Serial imaging was performed for a total follow-up of 3 months. Choriocapillaris alterations at the site of lesions were analyzed on OCTA imaging, and their mean lesion areas were calculated.

Results:

Twenty-six eyes (26 patients; 20 males; mean age: 32.68 ± 10.56 years) were included. Fourteen eyes had active multifocal lesions (n = 39), whereas 12 eyes had active placoid lesions (n = 12). At baseline, OCTA showed hyporeflective flow deficit lesions corresponding to the hypofluorescent lesions on indocyanine green angiography in all eyes. In the multifocal type of SLC, the mean lesion area decreased in all eyes compared with baseline, and lesions with a lesion area less than 0.1 mm2 on OCTA showed near-complete resolution with minimal choriocapillaris atrophy. In comparison, all eyes with a placoid type of SLC showed no significant reduction in the lesion area and showed extensive choriocapillaris atrophy.

Conclusion:

Optical coherence tomography angiography has the unique ability to demonstrate pathological flow impairment at the level of choriocapillaris in active tubercular SLC. Serial OCTA analysis reveals that large tubercular SLC lesions result in choriocapillaris atrophy as the lesions heal, whereas smaller multifocal lesions show resolution of choriocapillaris hypoperfusion with minimal atrophy.
Lurasidone Efficacy in Mixed Depressive States
Authors: Vöhringer Paul A. , Sani Gabriele , Barroilhet Sergio A. , Mao Yongcai , Ghaemi S. Nassir
Published: July 2020

Introduction

A new mood rating scale for mixed states of depression along with manic-like excitatory symptoms, the Koukopoulos Mixed Depression Rating Scale (KMDRS), was assessed in a post hoc analysis of a randomized clinical trial of lurasidone versus placebo in major depressive disorder (MDD) with mixed features.

Methods

The KMDRS was compared with the Montgomery Asberg Depression Rating Scale (MADRS) and the Young Mania Rating Scale (YMRS). Item weighting was performed and compared with an original KMDRS validation data set. Weighting was used to provide imputed KMDRS scores in the lurasidone study, based on observed MADRS and YMRS scores.

Results

Standardized effect sizes were larger for MADRS (0.61) and YMRS (0.79) than for KMDRS (0.44, Cohen d).

Conclusions

This analysis did not find that the KMDRS produced a larger effect size than the MADRS in Diagnostic and Statistical Manual for Mental Disorder-5 (DSM-5) defined MDD with mixed features. The lower utility of KMDRS may be due to the imputed nature of this analysis, or also to the DSM-5 defined patient population, which may reflect mixed hypomania rather than mixed depression.
A Prospective Study for Prediction of Psychotic Relapse Using the Korean Early Signs Scale in Patients With Schizophrenia
Authors: Kwon Jun Soo , Lee Junhee , Kim Euitae , Kim Sung-Wan , Jung Hee Yeon , Lee Kyu Young , Ryu Vin , Lee Seung Jae , Chon Myong-Wuk , Choi GumJee , Koh MinJung , Kim SuYoun
Published: July 2020

Introduction

A psychotic relapse of schizophrenia is commonly preceded by nonpsychotic behavioral symptoms and signs, and detection of these early signs may enable prevention of relapse of schizophrenia. This study aimed to test the predictive validity of a Korean version of Early Signs Scale (K-ESS) for psychotic relapse for detecting the early signs.

Materials and Methods

In this multicenter noninterventional 52-week prospective study, outpatients diagnosed as having schizophrenia within 5 years were recruited. The K-ESS and Clinical Global Impression-Severity (CGI-S) scale were administered monthly until the end of the study or the relapse. The primary objective was to determine an optimal cutoff point of K-ESS score for prediction of psychotic relapse. The secondary objective was to assess the concurrent validity of the K-ESS using CGI-S scale.

Results

Among the 162 included patients, 14 (8.6%) relapsed during the 52-week study period. The optimal cutoff score of K-ESS was 15 with a sensitivity of 71.43% and a specificity of 52.70%, indicating poor predictive accuracy of K-ESS. A lower cutoff K-ESS score of 3 and a higher cutoff score of 28 were found in the subgroups with milder (CGI-S = 1–2) and severer (CGI-S = 3–4) symptom severity, respectively, with fair to good predictive accuracy. The K-ESS showed acceptable concurrent validity with CGI-S and concordance rate between self-rated and informant-rated scores.

Discussion

The predictive accuracy of K-ESS was limited by evaluation interval of a month. At least fortnightly follow-up would be needed for detection of early signs to prevent a psychotic relapse in schizophrenia.
Predictors and Management of Failed Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection
Authors: Tariq Raseen , Saha Srishti , Solanky Dipesh , Pardi Darrell S. , Khanna Sahil
Published: July 2020

Background and Goals:

Clostridioides difficileinfection (CDI) recurs in 10% to 15% after fecal microbiota transplantation (FMT). We identify predictors, and describe management and outcome of patients with recurrent CDI after FMT in a predominantly outpatient cohort.

Methods:

A nested case-control study of patients undergoing FMT for recurrent CDI from August 2012 to January 2017 was performed. FMT failure was defined as recurrent diarrhea with positiveC. difficilestool test during follow-up (≥2 mo). Controls (patients without FMT failures) were matched to cases 1:1 for sex and timing of FMT±1 month.

Results:

Overall, 522 patients underwent FMT; 70 [13.4%; median age 53.8 years (range, 18 to 89 y), 54.3% females] recurred within a median 5.6 months (range, 0.2 to 34.9 mo). Number of prior CDI episodes, prior CDI treatment, and prior CDI-related hospitalizations were similar in cases and controls. Systemic antibiotics after FMT (54.3% vs. 21.4%,P<0.0001), inflammatory bowel disease (IBD) (34.3% vs. 15.7%,P=0.01), pseudomembranes at FMT (4.3% vs. 0%,P=0.03), and poor bowel preparation (68.5% vs. 31.4%,P=0.01) were associated with FMT failure. On multivariate analysis, IBD [odds ratio (OR) 4.34; 95% confidence interval (CI), 1.24-15.15], systemic antibiotics (OR 7.39; 95% CI, 3.02-18.07), and poor bowel preparation (OR 3.84; 95% CI, 1.59-9.28) predicted FMT failure with an area under the curve of 0.78. Among FMT failures, 37 (52.8%) were managed with antibiotics, 32 (45.7%) with repeat FMT after antibiotics and 1 with colectomy.

Conclusions:

Use of systemic antibiotics, IBD, and poor bowel preparation predict FMT failure. Patients with FMT failure can be managed with antibiotics and/or repeat FMT.
Obstructive sleep apnea in pulmonary fibrosis
Authors: Schiza Sophia E. , Bouloukaki Izolde , Bolaki Maria , Antoniou Katerina M.
Published: July 2020

Purpose of review

In previous years, there was limited research related to the role of sleep in interstitial lung diseases (ILDs). Physicians treating ILD patients tended to focus mainly on the daily disabling symptoms overlooking the possible significant role of coexisting sleep disorders, such as obstructive sleep apnea (OSA). However, recently, there has been a growing interest in OSA in ILDs, as well as OSA effect on sleep, life quality and outcome in these patients with emphasis on idiopathic pulmonary fibrosis (IPF).

Recent findings

OSA has been recognized as an important, high-prevalence comorbidity for the diagnosis and management of IPF. This publication provides a summary of the most relevant recent evidence with regard to OSA in various ILDs and especially IPF, including prevalence, clinical presentation, complications, screening and diagnosis. It also provides updated evidence on the role of OSA therapy in improving sleep, quality of life and disease outcome.

It is too early to characterize OSA and ILDs association as an ‘overlap’ syndrome. In depth research is needed, including studies with large numbers of ILDs and IPF patients. The main priority is to increase the awareness among physicians for early diagnosis of OSA in ILDs patients.
Current treatment of sarcoidosis
Authors: Sellarés Jacobo , Francesqui Joel , Llabres Marta , Hernandez-Gonzalez Fernanda , Baughman Robert P.
Published: July 2020

Purpose of review

Sarcoidosis is a granulomatous systemic disease of unknown cause where the lung is the most frequently affected organ. Therapeutic management of the disease is challenging as clinical presentation and prognosis are very heterogeneous. In the present review, we will summarize the main advances in sarcoidosis therapy.

Recent findings

Current sarcoidosis therapies are categorized in three lines: glucocorticoids (first line), immunosuppressants (second line), and biologics (third line). Recent glucocorticoid studies have reported that efficacy could be similar with high and low doses, but with an increase in side effects with higher doses. In immunosuppressants, recent publications in mycophenolate and repository corticotropin injection (RCI) have added more information in their use and efficacy. Finally, new evidence has been published in the use of antitumor necrosis factor (anti-TNFα) agents in refractory cardiac sarcoidosis and neurosarcoidosis.

Sarcoidosis therapy is constantly evolving, and new drugs have been added to the recommended treatments. However, extensive clinical trials are still necessary to optimize the current recommendations.
Nonsevere hemophilia A: often overlooked, but not forgotten
Authors: Lim Ming Y. , Buckner Tyler W.
Published: July 2020

Purpose of review

Nonsevere hemophilia A (NSHA) patients have received relatively little clinical and research attention as compared with their severe counterparts. There is increasing recognition that despite their milder bleeding phenotype, the management of NSHA can be a challenge, with most management decisions largely inferred from severe hemophilia A data. This review focuses on some of the more recent developments in the field of NSHA.

Recent findings

Epidemiologic studies suggest that NSHA remain under-recognized and under-diagnosed globally. As the NSHA population ages, they are susceptible to age-related comorbidities. Large cohort studies of NSHA report that the most common primary cause of death is malignancy. NSHA patients have a lifetime risk of inhibitor development with increasing exposure to factor VIII concentrate. Even so, not all patients with inhibitors will require eradication treatment, irrespective of bleeding phenotype at time of inhibitor development.

As there are currently no evidence-based strategies for inhibitor eradication in NSHA patients, preventive strategies are critical to mitigate inhibitor risk in NSHA. There is a need for active surveillance of NSHA patients by hemophilia treatment centers to address hemophilia-related issues and other age-related comorbidities, in collaboration with primary care physicians and other subspecialists.
The interaction between the complement system and hemostatic factors
Authors: Oncul Selin , Afshar-Kharghan Vahid
Published: July 2020

Purpose of review

To discuss the crosstalk between the complement system and hemostatic factors (coagulation cascade, platelet, endothelium, and Von Willebrand Factor), and the consequences of this interaction under physiologic and pathologic conditions.

Recent findings

The complement and coagulation systems are comprised of serine proteases and are genetically related. In addition to the common ancestral genes, the complement system and hemostasis interact directly, through protein–protein interactions, and indirectly, on the surface of platelets and endothelial cells. The close interaction between the complement system and hemostatic factors is manifested both in physiologic and pathologic conditions, such as in the inflammatory response to thrombosis, thrombosis at the inflamed area, and thrombotic complications of complement disorders.

The interaction between the complement system and hemostasis is vital for homeostasis and the protective response of the host to tissue injury, but also results in the pathogenesis of several thrombotic and inflammatory disorders.
Clinical application of Fluciclovine PET, choline PET and gastrin-releasing polypeptide receptor (bombesin) targeting PET in prostate cancer
Authors: Ceci Francesco , Castellucci Paolo , Polverari Giulia , Iagaru Andrei
Published: July 2020

Purpose of review

The aim of this review is to explore the clinical application of different PET radiopharmaceuticals in prostate cancer (PCa), beyond inhibitors of the prostate-specific membrane antigen (PSMA).

Recent findings

Choline PET represented in the last decades the standard of reference for PET imaging in PCa and has been recently included in clinical trials evaluating the efficacy of metastasis-directed therapy in oligo-metastatic disease. Fluciclovine, as synthetic amino acid, has been proposed for investigating PCa. The results obtained by the first prospective studies led to FDA approval in 2016 in patients with biochemical recurrence. Recently, phase II/III trials explored its accuracy compared with PSMA PET and its impact on patient management. Imaging the gastrin-releasing polypeptide receptor (GRPR) recently drawn attention. Radio-labelled GRPR antagonists have the potential to be used as theranostic agents. Further evaluation is needed to understand the relation between GRPR expression and hormonal-resistant PCa, and for tumors characterized by heterogeneity of receptors expressed (e.g. PSMA-negative) on their cell surface.

Other new generation PET tracers may play an important role in PCa, namely in case of PSMA-negative phenotypes.
Prostate-specific membrane antigen PET/computed tomography for staging prostate cancer
Authors: Ravi Kumar Aravind S. , Lawrentschuk Nathan , Hofman Michael S.
Published: July 2020

Purpose of review

Molecular imaging with PET/CT targeting the prostate-specific membrane antigen (PSMA) receptor is increasingly utilized in men with prostate cancer (PCa), with clinical indications now expanding beyond biochemical recurrence. PSMA PET/CT often detects sub-centimetre size pathologic nodes and low-volume bone marrow disease that are occult on conventional imaging when the lesion does not cause sclerosis or osteoblastic reaction in surrounding bone. This review focuses on recent evidence for PSMA PET/CT in initial disease staging.

Recent findings

Several recent studies including a large randomized trial have evaluated the clinical impact of PSMA PET/CT in initial staging of PCa. PSMA PET/CT is more sensitive and accurate than the conventional imaging standard of CT and bone scan. Change in treatment plan or modality of therapy occurs frequently when PSMA PET/CT forms part of the diagnostic algorithm. Hybrid PET/MRI also has potential utility, particularly in evaluating pelvic disease, but evidence base remains very limited.

PSMA PET/CT has emerged as a new standard in primary staging of PCa. Reimbursement by national funding bodies and incorporation into international clinical guidelines is anticipated within the next few years.
Smoking and bladder cancer: review of the recent literature
Authors: Mori Keiichiro , Mostafaei Hadi , Abufaraj Mohammad , Yang Lin , Egawa Shin , Shariat Shahrokh F.
Published: July 2020

Purpose of review

This review summarizes the current knowledge regarding the relationship between smoking and bladder cancer (BCa), especially with respect to treatment outcomes for muscle and nonmuscle-invasive BCa (MIBC/NMIBC).

Recent findings

PubMed/Medline databases were searched for recent reports investigating the association of smoking with BCa. Smoking is associated with an increased risk of recurrence in patients with NMIBC and may impair Bacillus Calmette-Guerin treatment efficacy. Moreover, smoking is associated with poor responses to neoadjuvant chemotherapy, poor survival outcomes and high complication rates in patients undergoing radical cystectomy. Smoking cessation mitigates these negative effects, especially. However, the amount of patient counselling provided regarding this important matter and patient knowledge regarding smoking and BCa risk are inadequate. Currently, the impact of secondhand smoke on BCa risk remains uncertain.

Tobacco smoking is responsible for approximately half of BCa cases, and is associated with poor oncological outcomes for both NMIBC and MIBC. Despite smoking being a well known risk factor, counselling and knowledge in this area are insufficient. Appropriate smoking cessation interventions and patient information are required to improve patient health and optimize BCa survival.
Aristolochic acid and its effect on different cancers in uro-oncology
Authors: Rebhan Katharina , Ertl Iris E. , Shariat Shahrokh F. , Grollman Arthur P. , Rosenquist Thomas
Published: July 2020

Purpose of review

To acquaint urologists with aristolochic acid nephropathy, an iatrogenic disease that poses a distinct threat to global public health. In China alone, 100 million people may currently be at risk. We illustrate the power of molecular epidemiology in establishing the cause of this disease.

Recent findings

Molecular epidemiologic approaches and novel mechanistic information established a causative linkage between exposure to aristolochic acid and urothelial carcinomas of the bladder and upper urinary tract. Noninvasive tests are available that detect urothelial cancers through the genetic analysis of urinary DNA. Combined with cytology, some of these tests can detect 95% of patients at risk of developing bladder and/or upper urothelial tract cancer. Robust biomarkers, including DNA-adduct and mutational signature analysis, unequivocally identify aristolochic acid-induced tumours. The high mutational load associated with aristolochic acid-induced tumours renders them candidates for immune-checkpoint therapy.

Guided by recent developments that facilitate early detection of urothelial cancers, the morbidity and mortality associated with aristolochic acid-induced bladder and upper tract urothelial carcinomas may be substantially reduced. The molecular epidemiology tools that define aristolochic acid-induced tumours may be applicable to other studies assessing potential environmental carcinogens.
Antimicrobial categories in describing multidrug resistance, extensive drug resistance and pan-drug resistance in Pseudomonas aeruginosa and Acinetobacter baumannii: a systematic review
Authors: Douzandeh-Mobarrez Banafsheh , Alizade Hesam , Kafil Hossein S. , Karmostaji Afsaneh
Published: July 2020

Introduction and objectives:

Employment of different terms in expressing resistance in Pseudomonas aeruginosa and Acinetobacter baumannii is a controversial issue. The aim of this systematic review is to assess antimicrobial categories for the terms multidrug resistance (MDR), extensive-drug resistance (XDR) and pan-drug resistance (PDR) for P. aeruginosa and A. baumannii.

Materials and methods:

We searched the database in the medical literature for relevant studies from 2006 up to 2016. Out of the 164 studies analyzed, 106 articles focused on definitions of MDR, XDR and PDR in A. baumannii, 53 articles focused on P. aeruginosa while five articles discussed both bacteria.

Results:

The most prevalent MDR, XDR and PDR A. baumannii was defined as acquired resistance to amikacin (42; 64.6%), ceftazidime (42; 64.6%) and imipenem (40; 61.5%) in MDR definition and (11; 34.4%) in XDR definition. The term MDR P. aeruginosa more often refers to resistance state to the drugs such as imipenem, ciprofloxacin (26; 76.5%) and amikacin (22; 64.7%). The most common antibiotic resistance in XDR P. aeruginosa was related to ceftazidime, piperacillin-tazobactam, ciprofloxasin (11; 73.3%) and meropenem (10; 66.7%). The term PDR P. aeruginosa was used in two studies for antibiotics such as amikacin, gentamicin and tobramycin, ceftazidime, cefepime, imipenem, meropenem and ciprofloxacin (100%).

Conclusion:

The current study lists the antibiotics which may be useful in clearly describing the extent of antibiotic resistance of P. aeruginosaand A. baumannii for each term.
Morphologic and Immunohistochemical Characteristics of Fluorescent In Situ Hybridization Confirmed TFE3-Gene Fusion Associated Renal Cell Carcinoma
Authors: Akgul Mahmut , Saeed Omer , Levy David , Mann Steven A. , Cheng Liang , Grignon David J. , Eble John N. , Idrees Muhammad T.
Published: July 2020

TFE3-fusion associated renal cell carcinoma (TFE3-RCC) accounts for up to 5% adults and 40% of childhood RCC. Their comprehensive immunohistochemical (IHC) profile in correlation to fluorescence in situ hybridization (FISH) testing and their role in the diagnostic approach are not well documented because of lacking published data. FISH confirmed TFE3-RCC between years 2010 and 2020 were identified from institutional electronic database and retrospectively reviewed. Eighty-five TFE3-RCC were identified. Seventy-six of 85 (89.4%) TFE3-RCC cases had positive TFE3 expression, with diffuse and strong/moderate TFE3 expression in 45 (54.2%). Three (3.5%) TFE3-RCC had negative TFE3 expression whereas 6 (7%) cases had equivocal TFE3 expression. On the other hand, positive TFE3-IHC expression was observed in 17/29 (58.6%) TFE3-FISH negative RCC cases, although only 8 (27.5%) had diffuse and moderate/strong TFE3 expression. Diffuse and strong TFE3-IHC expression was statistically significant in predicting TFE3-FISH positivity (P<0.0001) regardless of morphologic features. After univariate and multivariate analyses, TFE3-IHC was the only parameter with significant predictive value for detecting positive TFE3-FISH (P<0.0001). On univariate analysis, sex, classic morphology, age, negative AE1/AE3 or cytokeratin 7 were not predictive of TFE3-FISH positivity. Diffuse and strong nuclear TFE3-IHC expression is significantly associated with TFE3-FISH positivity and can be used as a surrogate marker to confirm translocation associated cases. TFE3-rearranged RCCs show variable histomorphologic features and TFE3-FISH should be performed in cases presenting at a younger age or, regardless of the age, tumors with unusual morphology. Despite previous reports, negative pancytokeratin and positive cathepsin K expression may not be reliable markers for TFE3-RCC.
Pain Reduction Emergency Protocol
Authors: Guiner Alessandra , Street Megan H. , Oke Oluwaesun , Young Virginia B. , Hennes Halim
Published: July 2020

Objectives

Pain control remains suboptimal in pediatric emergency departments (EDs). Only 60% of pediatric patients requiring pain medications receive them in the ED, with an average time of administration being 90 minutes after arrival. Although pain protocols (PP) have been proposed and evaluated in children with long-bone fractures, data on PP utility for general pediatric patients with acute pain are limited. Our objective is to introduce a nursing-initiated PP with medication algorithms for use in triage, measure the improvement in management of severe pain on arrival to the ED and determine the effect on parental satisfaction.

Methods

Prospective prestudy and poststudy conducted from June to October 2017. Patients aged 3 to 17 years presenting to a large tertiary pediatric ED with acute pain were eligible. Preprotocol demographics, clinical data, and pain interventions were obtained over a 6-week period. A convenience sample of parents completed a satisfaction survey rating their experience with ED pain management during this time. In the 4-week intervention phase, the PP was introduced to our ED nurses. Postintervention data were collected in the same fashion as the preintervention phase. Analysis was done using independent sample t test and χ2 models.

Results

There were 1590 patients evaluated: preprotocol (n = 816), postprotocol (n = 774). Approximately 10% more patients with severe pain received pain medication in the post-PP sample compared with pre-PP (85.6% and 75.9% respectively). Parental satisfaction was higher in patients who received analgesic medications within 90 minutes of arrival to the ED (P = 0.007).

Conclusions

The introduction of a PP in the ED setting improved the treatment of pain. There was a significant increase in patients with severe pain receiving analgesic medications. Additionally, parents were more satisfied if their children received pain medication in a more timely fashion. Pediatric EDs should consider introducing PPs to improve appropriate and timely administration of pain medication in triage.
The Problem of Cancer Drugs Costs
Authors: Newcomer Lee N.
Published: July 2020

Chemotherapy and supportive drugs constitute 70% of a cancer patient’s medical costs during active therapy. Payers use several approaches to keep those costs affordable including paying lower margins for “buy and bill” oncologists, prior authorization, pathways, or performance-based compensation. Payers also utilize financial tools such as deductibles, copayments, or coinsurance to shift more of the cost of health care coverage to employees or the insured. The strengths and weaknesses of those approaches are reviewed in this article. Policy changes that address drug protection from competition or negotiation, monopoly status of health care systems, and Food and Drug Administration approval of new medications will affect how effective any payer strategy will be in the future.
Serum soluble urokinase plasminogen activator receptor in adolescents: interaction of chronic pain and obesity
Authors: Raff Hershel , Phillips Jonathan M. , Simpson Pippa M. , Weisman Steven J. , Hainsworth Keri R.
Published: July 2020

Introduction:

Obesity in adolescents is increasing in frequency and is associated with short-term and long-term negative consequences that include the exacerbation of co-occurring chronic pain.

Objective:

To determine whether the interaction between chronic pain and obesity would be reflected in changes in serum soluble urokinase plasminogen activator receptor (suPAR) concentrations, a novel marker of systemic inflammation associated with obesity, insulin resistance, and cardiovascular disease.

Methods:

We measured serum suPAR levels in 146 adolescent males and females with no pain or obesity (healthy controls; n = 40), chronic pain with healthy weight (n = 37), obesity alone (n = 41), and the combination of chronic pain and obesity (n = 28).

Results:

Serum suPAR (median [interquartile range]) was not increased by chronic pain alone (2.2 [1.8–2.4] ng/mL) or obesity alone (2.2 [2.0–2.4] ng/mL) but was increased significantly with the combination of chronic pain and obesity (2.4 [2.1–2.7] ng/mL; P < 0.019). This finding confirms the proposition that pain and obesity are inflammatory states that display a classic augmenting interaction.

Conclusion:

We propose that measurement of serum suPAR can be added to the armamentarium of serum biomarkers useful in the evaluation of mechanisms of inflammation in adolescent obesity and chronic pain.
Adverse perinatal outcomes associated with antiretroviral therapy regimens: systematic review and network meta-analysis
Authors: Tshivuila-Matala Chrystelle O.O. , Honeyman Susan , Nesbitt Charlotte , Kirtley Shona , Kennedy Stephen H. , Hemelaar Joris
Published: July 2020

Objective:

Assess adverse perinatal outcomes associated with antenatal antiretroviral therapy (ART) regimens.

Design:

Systematic review and network meta-analysis of randomized controlled trials (RCTS).

Methods:

We conducted a systematic literature review by searching PubMed, CINAHL, Global Health, EMBASE, and the Cochrane Central Register of Controlled Trials and four clinical trial databases from 1 January 1980 to 28 April 2018. We included RCTs of antenatal ART regimens in HIV-positive pregnant women, which assessed preterm birth (PTB), spontaneous preterm birth (sPTB), very preterm birth (VPTB), low birthweight (LBW), very low birthweight (VLBW), small-for-gestational-age (SGA), neonatal death (NND), and mother-to-child-transmission. We used random-effects network meta-analysis models to calculate relative risks for treatment comparisons and the hierarchy of treatments.

Results:

Of 83 260 citations identified, 10 manuscripts were included, assessing 6285 women. Compared with zidovudine (ZDV) monotherapy, we found a higher risk of LBW after exposure to zidovudine/lamivudine/efavirenz (ZDV/3TC/EFV; relative risk 1.61; 95% CI 1.03–2.51), tenofovir disoproxil fumarate/emtricitabine/ritonavir-boosted lopinavir (TDF/FTC/LPV/r; 1.64; 1.18–2.29), or zidovudine/lamivudine/ritonavir-boosted lopinavir (ZDV/3TC/LPV/r; 1.87; 1.58–2.20). TDF/FTC/LPV/r carried an increased risk of VLBW, compared with ZDV monotherapy (5.40; 1.08–27.08). ZDV/3TC/LPV/r posed a higher risk of PTB than ZDV monotherapy (1.43; 1.08–1.91) and a higher risk of sPTB than zidovudine/lamivudine/abacavir (ZDV/3TC/ABC) (1.81; 1.21–2.71). LPV/r-containing regimens also carried the highest risks of VPTB, SGA and NND, although the limited data showed no significant differences.

Conclusion:

Of the ART regimens assessed in RCTs in pregnancy, LPV/r-containing regimens were associated with the highest risks of adverse perinatal outcomes.
Internalized HIV stigma predicts subsequent viremia in US HIV patients through depressive symptoms and antiretroviral therapy adherence
Authors: Christopoulos Katerina A. , Neilands Torsten B. , Dilworth Samantha , Lisha Nadra , Sauceda John , Mugavero Michael J. , Crane Heidi M. , Fredericksen Rob J. , Mathews William C. , Moore Richard D. , Mayer Kenneth H. , Napravnik Sonia , Johnson Mallory O.
Published: July 2020

Objective:

We sought to examine the prospective association between internalized HIV stigma and unsuppressed viral load and to investigate whether this relationship was sequentially mediated by depressive symptoms and antiretroviral therapy (ART) adherence.

Design:

Longitudinal study in a multisite observational clinical cohort.

Methods:

The Center for AIDS Research Network of Integrated Clinical Systems patient-reported outcomes survey measures internalized HIV stigma yearly using a four-item assessment (response scale 1 = strongly disagree to 5 = strongly agree). We obtained patient-reported outcome, lab, and appointment data from six center for AIDS research network of integrated clinical systems sites. We used multivariable logistic regression to examine the association between mean stigma and subsequent viremia. We then used Bayesian sequential mediation to fit a longitudinal sequential path model spanning four time points to test if depressive symptoms at T1 and ART adherence at T2 mediated the effect of stigma at T0 on viral load at T3, adjusting for baseline covariates.

Results:

Between February 2016 and November 2018, 6859 patients underwent stigma assessment and were 81% cis-men, 38% Black, 16% Latinx, 32% heterosexual-identified, and 49% at least 50 years of age. Mean stigma level was 2.00 (SD 1.08). Stigma was significantly associated with subsequent viremia (adjusted odds ratio = 1.16, 95% confidence interval: 1.05–1.28, P = 0.004), as were younger age and Black race. The chained indirect effect from stigma to unsuppressed viral load through depressive symptoms and then adherence was significant (standardized β = 0.002; SD = 0.001).

Conclusion:

Internalized HIV stigma positively predicts subsequent viremia through depressive symptoms and ART adherence. Addressing the link between stigma and depressive symptoms could help improve viral suppression.
Dual antiretroviral therapies are effective and safe regimens in the central nervous system of neurologically symptomatic people living with HIV
Authors: Trunfio Mattia , Rugge Walter , Mighetto Lorenzo , Vai Daniela , Atzori Cristiana , Nigra Marco , Domini Simone , Borgogno Enrica , Guastamacchia Giulia , Bonora Stefano , Di Perri Giovanni , Calcagno Andrea
Published: July 2020

Objective:

Aim of this study was to compare cerebrospinal fluid (CSF) virological control, biomarkers and neurocognition of neurologically symptomatic patients on dual antiretroviral therapies (dual therapy) vs. 2 nucleoside reverse transcriptase inhibitors-based three-drug regimens (triple therapy).

Design:

Retrospective monocentric cross-sectional study.

Methods:

We analysed data from people living with HIV undergoing lumbar puncture for clinical/research reasons with plasma HIV-RNA less than 200 copies/ml and neurological/neurocognitive symptoms without significant contributing comorbidities. We measured CSF HIV-RNA, inflammation, blood–brain barrier integrity, neuronal damage and astrocytosis biomarkers (five biomarkers by ELISA and five indices by immunoturbidimetry) and recorded the neurocognitive performance (14 tests). CSF escape was defined as any case of CSF HIV-RNA 0.5 Log10 higher than viraemia or any case of detectable CSF HIV-RNA coupled with undetectable viraemia.

Results:

A total of 78 patients on triple therapy and 19 on dual therapy were included. Overall, 75.3% male, median age 51 years (46–58), current CD4+ count 545 cells/μl (349–735), time on current regimens 18 months (8–29), but length of plasma suppression 32 months (14–94). The two groups did not differ in terms of HIV-associated neurological diagnoses, demographic and viro-immunological features. Undetectable CSF HIV-RNA (73.7% in dual therapy vs. 78.2% in triple therapy, p.67) and CSF escape (21.1% in dual therapy vs. 19.2% in triple therapy, p.86) did not differ. No difference was observed in depression, anxiety, neurocognition (in 63 participants) nor in any tested biomarker.

Conclusion:

In people living with HIV with neurological/neurocognitive symptoms, peripherally effective dual therapy can show CSF virosuppression, inflammation, neuronal and astrocyte integrity and neurocognition comparable to triple therapy.
High nonnucleoside reverse transcriptase inhibitor resistance levels in HIV-1-infected Zambian mother–infant pairs
Authors: Bennett Sydney J. , Chunda-Liyoka Catherine , Poppe Lisa K. , Meinders Katie , Chileshe Chisanga , West John T. , Wood Charles
Published: July 2020

Objective(s):

To elucidate relationships in antiretroviral resistance between HIV-1-infected mother–infant pairs by defining the resistance profiles in the mothers and infants and quantifying drug resistance prevalence in the pairs post-Option B+ implementation.

Design:

Collection of dried blood spots from mother–infant pairs during routine HIV-1 screens in Lusaka, Zambia from 2015 to 2018.

Methods:

DNA was extracted from the dried blood spots, the HIV-1 pol region was amplified, and the purified proviral DNA was sequenced using Sanger sequencing. Drug resistance mutations (DRM) were identified in sequenced DNA using the Stanford HIVdb (https://hivdb.stanford.edu/).

Results:

DRM were detected in 45% (44/97) of samples, and these samples were found to harbor resistance to at least two antiretrovirals. The prevalence of nonnucleoside reverse transcriptase inhibitor resistance was significantly higher than that of other antiretroviral classes. DRM were detected disproportionately in infants (67%; 33/49) compared with mothers (23%; 11/48), but the magnitude of resistance did not differ when resistance was detected. The disparity in drug resistance profiles was reinforced in pairwise comparison of resistance profiles in mother–infant pairs.

Conclusion:

While Option B+ is effective in reducing mother-to-child transmission, in cases where this regimen fails, high-level nonnucleoside reverse transcriptase inhibitor resistance is frequently detected in infants. This underscores the importance of pretreatment drug resistance screening in both mothers and infants and emphasizes the necessary change to protease inhibitor-based and integrase inhibitor-based regimens for treatment of HIV-1-infected infants and mothers.
Syndemic burden and systemic inflammation, HIV health status, and blood pressure among women with unsuppressed HIV viral loads among women living with HIV
Authors: Jones Deborah L. , Rodriguez Violeta J. , Alcaide Maria Luisa , Carrico Adam , Fischl Margaret A. , Chichetto Natalie E. , Rodriguez Carlos J. , Welsch Michael A. , Farah-Abraham Rachael , Adimora Adaora A. , D'Souza Gypsyamber , Cohen Mardge H. , Shitole Sanyog , Merenstein Daniel , Lazar Jason
Published: July 2020

Introduction:

Smoking, low education, obesity, and depressive symptoms are all associated with HIV health status, increased blood pressure, and inflammation, and constitute a syndemic burden that may contribute to poor health outcomes. The current study examined syndemic burden and health outcomes among women living with HIV.

Methods:

Women were participants enrolled in the Women's Interagency HIV Study. Outcomes included blood pressure, HIV health status (HIV-1 RNA viral load and CD4+T-cell counts), and IL-6. Syndemic burden was defined as a count variable of low education, obesity, cigarette use, and depressive symptoms.

Results:

Women (N = 131) were an average of 60.54 years of age (SD = 8.86), and 49% were non-Hispanic Black. In multivariable analyses, syndemic burden was not significantly associated with SBP (P = 0.342) or DBP (P = 0.763), IL-6 (P = 0.168), or CD4+cell count (P = 0.846). However, syndemic burden was associated with increased viral load (age adjusted β = 0.35,P < 0.001). Comparing women with high versus low syndemic burden, also controlling for women's age, women with high syndemic burden had higher DBP and HIV viral load.

Discussion:

Syndemic burden appeared to play an important role in HIV health status and could potentially increase the risk of HIV transmission. High syndemic burden, defined as at least two syndemic conditions, had the greatest effects of HIV viral load and DBP. Targeted interventions to address syndemic burden may help improve health outcomes in women living with HIV as well as reduce the risk of hypertension and HIV transmission.
Comparative performance of the laboratory assays used by a Diagnostic Laboratory Hub for opportunistic infections in people living with HIV
Authors: Medina Narda , Alastruey-Izquierdo Ana , Mercado Danicela , Bonilla Oscar , Pérez Juan C. , Aguirre Luis , Samayoa Blanca , Arathoon Eduardo , Denning David W. , Rodriguez-Tudela Juan Luis
Published: July 2020

Objectives:

We evaluated the comparative performance of different assays used in a Diagnostic Laboratory Hub that linked 13 HIV healthcare facilities for the diagnosis of tuberculosis (TB), histoplasmosis, and cryptococcosis, and describing its functions in Guatemala compared with other National Reference Laboratories.

Methods:

The following diagnostic techniques were analyzed in 24 months (2017–2018) in a cohort of patients with HIV: smear microscopy, mycobacterial and fungal cultures, isolator blood culture, PCR assays, and antigen detection tests.

Results:

A total of 4245 patients were included, 716 (16.2%) had an opportunistic infection: 249 (34.7%) TB, 40 (5.6%) nontuberculous mycobacteria, 227 (31.7%) histoplasmosis, 138 (19.3%) cryptococcosis, and 62 (8.6%) had multiple opportunistic infections. Two hundred sixty-three [92.6%; 95% confidence interval (CI), 89–95.1] of TB cases were diagnosed by PCR. Urine antigen assay detected 94% (95% CI, 89–96) of the disseminated histoplasmosis cases. A lateral flow assay to detect cryptococcal antigen diagnosed 97% (95% CI, 93.3–98.7%) of the cryptococcal cases. In 85 patients (51.5%) with a cerobrospinal fluid sample, cryptococcal meningitis was diagnosed in 55 (64.7%), of which 18 (32.7%) were only detected by cryptococcal antigen.

Conclusion:

Validated commercial antigen tests, as used in this program, should be the new gold standard for histoplasmosis and cryptococcosis diagnosis. In their absence, 35% of disseminated histoplasmosis and 32.7% of cryptococcal meningitis cases would have been missed. Patients with multiple opportunistic infections were frequently diagnosed and strategies should be designed to screen patients irrespective of their clinical presentation. In low resource settings, Diagnostic Laboratory Hubs can deliver quality diagnostics services in record time at affordable prices.
Echocardiographic Findings Among Virally Suppressed HIV-Infected Aging Asians Compared with HIV-Negative Individuals
Authors: Chattranukulchai Pairoj , Thimaporn Weerayut , Siwamogsatham Sarawut , Satitthunmmanid Sudarat , Sitticharoenchai Patita , Apornpong Tanakorn , Sangarlangkarn Aroonsiri , Kerr Stephen J. , Ruxrungtham Kiat , Boonyaratavej Smonporn , Avihingsanon Anchalee ,   on behalf of HIV-NAT 006/207 study team
Published: July 2020

Objectives:

Prevalence of cardiovascular disease increases with age. Little is known about the prevalence and risk factors for echocardiographic abnormalities among older people living with HIV (PLHIV) from Asia.

Design:

A cross-sectional study was conducted among PLHIV aged >50 years (N = 298) on antiretroviral treatment (ART) and HIV-negative controls (N = 100) frequency matched by sex and age in Thailand.

Methods:

All participants underwent standard 2-dimensional transthoracic echocardiography performed by trained cardiologists who were blinded to the participant's care and HIV status. Logistic regression was used to examine the association between cardiac abnormalities and risk factors.

Results:

The median age was 54.7 years (60.8% men) with 37.2% having hypertension and 16.6% having diabetes mellitus. PLHIV was on ART for a median of 16.2 years with current CD4 cell counts of 616 cells per cubic millimeter. Echocardiogram abnormalities did not differ among PLHIV (55%) and the controls (60%). The major abnormalities in PLHIV were following: left ventricular (LV) hypertrophy: 37% men and 42.2% women, LV systolic dysfunction (0.7%), diastolic dysfunction (24.2%), and pulmonary hypertension (3.9%). From the multivariate analyses in PLHIV, being aged >60 years was independently associated with diastolic dysfunction, whereas female sex and left atrial volume index of >34 mL/m2were associated with pulmonary hypertension (P< 0.05). None of the ART was significantly associated with any major echocardiographic abnormalities.

Conclusions:

In this long-term, well-suppressed, older, Asian PLHIV cohort, the prevalence of asymptomatic LV systolic dysfunction and pulmonary hypertension were relatively low, whereas the diastolic dysfunction and LV hypertrophy were common. Echocardiographic findings did not differ between PLHIV and HIV-uninfected controls.
Evaluation of 3 Cognitive Load Measures During Repeated Simulation Exercises for Novice Anesthesiology Residents
Authors: Toy Serkan , Miller Christina R. , Daly Guris Rodrigo J. , Duarte Shirley S. , Koessel Sophia , Schiavi Adam
Published: July 2020

Introduction

Maintaining an appropriate level of cognitive load during simulations is crucial to optimize learning. We evaluated 3 subjective measures of cognitive load in a simulated operating room (OR) context across multiple scenarios of varying complexity.

Methods

This observational study of 25 first-year anesthesiology residents took place during a 5-day simulation “Boot Camp.” Each day, participants completed 2 different high-fidelity scenarios in a fully equipped simulated OR. After each simulation, participants completed 3 cognitive load measures: the Paas scale, NASA Task Load Index (TLX), and Cognitive Load Component (CLC) questionnaire. Two-way repeated-measures and mixed-design analyses of variance, with the cognitive load measures and scenarios as independent factors, were used to determine the effect of using different measures to report cognitive load.

Results

Cognitive load scores reported by all measures correlated significantly with one another (P < 0.01): TLX and Paas (r = 0.65); Paas and CLC (r = 0.63); and TLX and CLC (r = 0.61). The CLC subscale scores (intrinsic, extraneous, germane) also correlated significantly with composite TLX and Paas scores (P < 0.01). Scenarios and measures displayed significant interaction: F(10, 210) = 3.01, P = 0.001. Participants reported highest overall cognitive load using the Paas scale.

Conclusions

All cognitive load measures were sensitive to scenario variability and showed similar fluctuation patterns across the 10 scenarios. The findings suggest that cognitive load measures can help create benchmarks based on learner perceptions of cognitive burden for different simulation scenarios.
Affective traits, states, and breathlessness
Authors: von Leupoldt Andreas , Denutte Ysys
Published: July 2020

Purpose of review

Breathlessness is a prevalent and aversive symptom in various conditions and closely related to affect. Here, we review recent literature from the previous 18 months examining the interactions between affective traits and states with breathlessness.

Recent findings

Available studies used various qualitative, quantitative, and experimental research designs in diverse samples of patients with breathlessness and in healthy individuals. Most studies clearly demonstrated that nonspecific forms of negative affective personality traits such as anxiety and depression, disease or symptom-specific forms such as fear-of-dyspnea and fear-of-physical activity as well as short-lasting negative affective states such as experimentally induced fear were associated with greater breathlessness. Moreover, breathlessness was shown to evoke negative affect, whereas positive affect reduced breathlessness. Different treatment approaches demonstrated concurrent beneficial effects on both negative affect and breathlessness and several potential mechanisms underlying these interactions were suggested.

Negative affect is common in diverse patient groups suffering from breathlessness and is related to increased burden because of breathlessness. Future research is required to improve our understanding of the mechanisms underlying these associations together with increased clinical efforts for improved detection and treatment of negative affect in breathless patients.
Communication Challenges for People With Parkinson Disease
Authors: Altaher Abeer Muneer , Chu Shin Ying , Sathiyasenan Sai Tarishini , Harun Haryani binti , Mustaffa Kamal Rahayu
Published: July 2020

This study aimed to explore the changes in communicative functions as well as how these changes were perceived among individuals with Parkinson disease using the World Health Organization's International Classification of Functioning, Disability and Health framework. Semistructured interviews (n = 14) were conducted, transcribed verbatim, and analyzed using thematic analysis method. Five main themes and 14 subthemes were emerged from the interviews: “communication breakdown,” “physical functioning,” “social interaction,” “emotional reaction,” and “coping with Parkinson disease.” Applying International Classification of Functioning, Disability and Health framework gives a holistic description for patients' challenges and assists speech-language pathologists to improve their services.