bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-1 Drug Resistance Among Ugandan Adults Attending an Urban Out-Patient Clinic
Authors: von Braun Amrei , Sekaggya-Wiltshire Christine , Bachmann Nadine , Ssemwanga Deogratius , Scherrer Alexandra U. , Nanyonjo Maria , Kapaata Anne , Kaleebu Pontiano , Günthard Huldrych F. , Castelnuovo Barbara , Fehr Jan , Kambugu Andrew 
Published: May 2018

Background:
Little is known about prevalence of drug resistance among HIV-infected Ugandans, a setting with over 15 years of public sector access to antiretroviral therapy (ART) and where virological monitoring was only recently introduced.

Setting:
This study was conducted in the adults' out-patient clinic of the Infectious Diseases Institute, Kampala, Uganda.

Methods:
HIV genotyping was performed in ART-naive patients and in treatment-experienced patients on ART for ≥6 months with virological failure (≥1000 copies/mL).

Results:
A total of 152 ART-naive and 2430 ART-experienced patients were included. Transmitted drug resistance was detected in 9 (5.9%) patients. After a median time on ART of 4.7 years [interquartile range: 2.5–8.7], 190 patients (7.8%) had virological failure with a median viral load of 4.4 log10 copies per milliliter (interquartile range: 3.9–4.9). In addition, 146 patients had a viral load between 51 and 999 copies per milliliter. Most patients with virological failure (142, 74.7%) were on first-line ART. For 163 (85.8%) ART-experienced patients, genotype results were available. Relevant drug-resistance mutations were observed in 135 (82.8%), of which 103 (63.2%) had resistance to 2 drug classes, and 11 (6.7%) had resistance to all drug classes available in Uganda.

Conclusion:
The prevalence of transmitted drug resistance was lower than recently reported by the WHO. With 92% of all patients virologically suppressed on ART, the prevalence of virological failure was low when a cutoff of 1000 copies per milliliter is applied, and is in line with the third of the 90-90-90 UNAIDS targets. However, most failing patients had developed multiclass drug resistance.
Raltegravir 1200 mg Once Daily vs 400 mg Twice Daily, With Emtricitabine and Tenofovir Disoproxil Fumarate, for Previously Untreated HIV-1 Infection: Week 96 Results From ONCEMRK, a Randomized, Double-Blind, Noninferiority Trial
Authors: Cahn Pedro , Sax Paul E. , Squires Kathleen , Molina Jean-Michel , Ratanasuwan Winai , Rassool Mohammed , Bloch Mark , Xu Xia , Zhou Yan , Homony Brenda , Hepler Deborah , Teppler Hedy , Hanna George J. , Nguyen Bach-Yen , Greaves Wayne ,   for the ONCEMRK Study Group
Published: May 2018

Background:
Raltegravir 1200mg (2×600mg tablets) once daily (QD) demonstrated noninferior efficacy and similar safety to raltegravir 400mg twice daily (BID) at week 48 of the ONCEMRK trial. Here, we report the week 96 results from this study.

Methods:
ONCEMRK is a phase 3, multicenter, double-blind, noninferiority trial comparing raltegravir 1200mg QD with raltegravir 400mg BID in treatment-naive HIV-1–infected adults. Participants were assigned (2:1) to raltegravir 2×600mg QD or 400mg BID, both with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) for 96 weeks. Randomization was stratified by screening HIV-1 RNA and hepatitis B/C status. Efficacy was assessed as the proportion of participants with HIV-1 RNA <40 copies per milliliter (Food and Drug Administration Snapshot approach); the noninferiority margin was 10 percentage points.

Results:
Of the 797 participants who received study therapy (84.6% were men, 59.3% were white, and mean age was 35.9 years), 694 completed 96 weeks of treatment (87.6% QD; 84.4% BID), with few discontinuations because of lack of efficacy (1.1% for both groups) or adverse events (1.3% QD; 2.3% BID). At week 96, 81.5% (433/531) of QD recipients and 80.1% (213/266) of BID recipients achieved HIV-1 RNA <40 copies per milliliter (difference 1.4%, 95% confidence interval: −4.4 to 7.3). CD4+ T-cell counts increased >260 cells/mm3 from baseline in both groups. Resistance to raltegravir was infrequent, occurring in 0.8% of each treatment group through week 96. Adverse event rates were similar for the 2 regimens.

Conclusions:
In HIV-1–infected treatment-naive adults receiving FTC/TDF, raltegravir 1200mg QD demonstrated noninferior efficacy to raltegravir 400mg BID that was durable to week 96, with a safety profile similar to raltegravir 400mg BID.
Patterns and Correlates of Participant Retention in a Multi-City Pre-Exposure Prophylaxis Demonstration Project
Authors: Doblecki-Lewis Susanne , Liu Albert Y. , Feaster Daniel J. , Cohen Stephanie E. , Elion Richard , Bacon Oliver , Coleman Megan , Cardenas Gabriel , Kolber Michael A. 
Published: May 2018

Background:
Safe and effective use of pre-exposure prophylaxis (PrEP) depends on retention in care after initial engagement.

Setting:
The United States PrEP Demonstration Project offered daily oral tenofovir/emtricitabine to participants in San Francisco, Miami, and Washington, D.C. for 48 weeks from 2012 to 2014.

Methods:
The Demo Project participants' patterns of retention were assigned to 1 of 3 categories: early loss to follow-up (ELTF) within the first 12 weeks of the study, retention throughout the study, or intermittent retention in which missed or delayed visits resulted in gaps in medication availability. For each group, baseline characteristics were tabulated. A two-step multivariable analysis was performed.

Results:
Overall, 366/554 (66.1%) of enrolled participants were retained for all study visits, 127/554 (22.9%) had intermittent retention, and 61/554 (11.0%) ELTF. In multivariable analysis, Miami compared with San Francisco site was associated with ELTF rather than full retention [aOR 2.84; confidence interval (CI): 1.24 to 6.47] and also with intermittent rather than full retention (aOR 2.70; CI: 1.43 to 5.11). Younger age was associated with ELTF (aOR 1.80 for each 10-year decrement in age; CI: 1.26 to 2.57) and intermittent retention (aOR 1.47; CI: 1.17 to 1.84) compared with full retention. Factors associated with ELTF (but not intermittent retention) compared with full retention were black compared with white (aOR 3.32; CI: 1.09 to 10.16), reporting sex work (aOR 4.67; CI: 1.49 to 14.58), lack of regular employment (aOR 2.53; CI: 1.27 to 5.05), and lack of previous PrEP awareness (aOR 2.01; CI: 1.01 to 3.96).

Conclusions:
Tailored interventions addressing causes and risk factors for loss from PrEP care may improve retention and consistency of PrEP use.
A Successful Model of Expedited Antiretroviral Therapy for Clinically Stable Patients Living With HIV in Haiti
Authors: Guiteau Moise Colette , Rivera Vanessa R. , Hennessey Kelly A. , Bellot Clovy , Nicholas Chris , Fang Anna P. , Verdier Rose Irène , Severe Patrice , Sainvil Alix , Charles Benedict , Dorval Derothy , St. Amour Juseline , Pape Jean W. , Koenig Serena P. 
Published: May 2018

Background:
Recommendations for universal antiretroviral therapy have greatly increased the number of HIV-infected patients who qualify for treatment, particularly with early clinical disease. Less intensive models of care are needed for clinically stable patients.

Setting:
A rapid pathway (RP) model of expedited outpatient care for clinically stable patients was implemented at the Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections (GHESKIO) Center, Port-au-Prince, Haiti. Expedited visits included nurse-led assessments and point-of-service antiretroviral therapy dispensing.

Methods:
We conducted a retrospective analysis including patients who initiated RP care between June 1, 2014, and September 30, 2015, comparing outcomes of patients with timely visit attendance (never >3 days late) with patients with ≥1 nontimely visit within 6 months before RP enrollment. We calculated retention in care and adherence at 12 months, and assessed predictors of both outcomes.

Results:
Of the 2361 patients who initiated RP care during the study period, 1429 (61%) had timely visit attendance and 932 (39%) had ≥1 nontimely visit before RP enrollment. Among RP-enrolled patients, 94% were retained at 12 months and 75% had ≥90% adherence, with higher proportions in those with timely pre-RP visits (95% vs. 92%; 87% vs. 55%). In multivariable analysis, pre-RP visit timeliness was associated with both retention (adjusted odds ratio: 1.67; 95% confidence interval: 1.08 to 2.59) and adherence (adjusted odds ratio: 4.53; 95% confidence interval: 3.58 to 5.72).

Conclusions:
RP care was associated with high levels of retention and adherence for clinically stable patients. Timeliness of pre-RP visits was predictive of outcomes after RP initiation.
Cognitive Burden of Common Non-antiretroviral Medications in HIV-Infected Women
Authors: Rubin Leah H. , Radtke Kendra K. , Eum Seenae , Tamraz Bani , Kumanan Krithika N. , Springer Gayle , Maki Pauline M. , Anastos Kathryn , Merenstein Daniel , Karim Roksana , Weber Kathleen M. , Gustafson Deborah , Greenblatt Ruth M. , Bishop Jeffrey R. 
Published: May 2018

Objective:
The aging HIV population has increased comorbidity burden and consequently non-antiretroviral medication utilization. Many non-antiretroviral medications have known neurocognitive-adverse effects (“NC-AE medications”). We assessed the cognitive effects of NC-AE medications in HIV+ and HIV− women.

Methods:
One thousand five hundred fifty-eight participants (1037 HIV+; mean age 46) from the Women's Interagency HIV Study completed a neuropsychological test battery between 2009 and 2011. The total number of NC-AE medications and subgroups (eg, anticholinergics) were calculated based on self-report. Generalized linear models for non-normal data were used to examine the cognitive burden of medications and factors that exacerbate these effects.

Results:
HIV+ women reported taking more NC-AE medications vs. HIV− women (P < 0.05). NC-AE medication use altogether was not associated with cognitive performance. However, among NC-AE medication subgroups, anticholinergic-acting medications, but not opioids or anxiolytics/anticonvulsants, were negatively associated with performance. HIV status moderated the association between these NC-AE medication subgroups and performance (P's < 0.05). HIV-serostatus differences (HIV− < HIV+) in global, learning, fluency, and motor function were greatest among women taking >1 anticholinergic medications. HIV-serostatus differences in performance on learning and psychomotor speed were also greatest among women taking 1 or more anxiolytics/anticonvulsants and 1 or more opioids, respectively.

Conclusions:
HIV+ women have increased cognitive vulnerabilities to anticholinergic, anxiolytic/anticonvulsant, and opioid medications. Potential synergy between these medications and HIV may explain some HIV-related cognitive impairments. It may be important clinically to consider these specific types of medications as a contributor to impaired cognitive performance in HIV+ women and assess the cost/benefit of treatment dosage for underlying conditions.
Barbed Hyoglossomandibulopexia: A Preclinical Study on Human Anatomic Models
Authors: Mantovani Mario , Rinaldi Vittorio , Torretta Sara , Trojsi Roberto , Carioli Daniela , Pignataro Lorenzo 
Published: May 2018

Abstract
The retrobasilingual space is the one of the most frequent sites of obstruction in patients with severe obstructive sleep apnea hypopnea syndrome, and several multilevel surgical procedures have been developed. The authors tested by means a preclinical study the feasibility of a new experimental surgical procedure called barbed hyoglossomandibulopexia (B.Hy.G.M.P.) which aims at advancing the tongue base with the hyoid bone (hyo-glossopexia) by multiple plicatures at the oral floor muscles.
B.Hy.G.M.P. was performed during cadaveric dissection on 12 human models. Retrobasilingual space enlargement was assessed by means of nasopharyngeal fiberendoscopy.
A 25% to 50% enlargement in the retrobasilingual space was documented by means of nasopharyngeal fiberendoscopy in all the patients.
The authors’ preclinical study documents the feasibility of the B.Hy.G.M.P. procedure on human models, and suggests the possible usefulness of this approach in obstructive sleep apnea hypopnea syndrome patients with retrobasilingual collapse. Dedicated clinical studies on living subjects are needed to assess the effectiveness and safety of this technique.
An Innovative and Easy Dome Holding Technique for Transdomal Suture in Rhinoplasty
Authors: Seneldir Sureyya , Durna Yusuf Muhammed 
Published: May 2018

Abstract
Suture tip plasty is one the most used methods in nasal tip surgery. Transdomal suture (TDS) used for this purpose is utilized for providing the dome symmetry, thinning the nasal tip, and enhancing the nasal tip projection and rotation. However, there are not sufficient visual data on what the dome position should be during TDS. In this study, it was aimed to be directive in tip plasty and to define the convenient dome holding technique during TDS. Patients, 510 male and 621 female at the age of 18 to 50 years, who underwent the open technique septorhinoplasty between the years of 2003 to 2015 were included in the authors’ study. The length of the patient follow-up varies between 1 and 10 years. Patients, on which the lateral crural strut graft was used and which underwent dome division/vertical dome division in tip surgery, and patients who were diagnosed with the alar cartilage asymmetry and underwent dome excision for any pathological reason to demonstrate the effectiveness of the TDS holding technique. During the TDS, the dome area was administered with 5/0 polydioxanone by being held at an angle close to the cranial in the posterior and the caudal in the anterior with a dentated forceps. In this study according the authors’ pre and postoperative conclusions, the authors consider that this is a sufficient visual data on what the dome position should be during TDS by presenting video.
Imitating Incidents
Authors: Macrae Carl 
Published: May 2018

Summary Statement
One of the most fundamental principles of patient safety is to investigate and learn from the past in order to improve the future. However, healthcare organizations can find it challenging to develop the robust organizational processes and work practices that are needed to rigorously investigate and learn from safety incidents. Key challenges include difficulties developing specialist knowledge and expertise, understanding complex incidents, coordinating collaborative action, and positively changing practice. These are the types of challenges that simulation is commonly used to address. As such, this article proposes that there are considerable opportunities to integrate simulation more deeply and systematically into routine efforts to investigate and learn from safety incidents. This article explores how this might be performed by defining five key areas where simulation could be productively integrated throughout the investigation and learning process, drawing on examples of current practice and analogous applications in healthcare and other industries.
Range and Consistency of Outcomes Reported in Randomized Trials Conducted in Kidney Transplant Recipients: A Systematic Review
Authors: Sautenet Bénédicte , Tong Allison , Chapman Jeremy R. , Warrens Anthony N. , Rosenbloom David , Wong Germaine , Gill John , Budde Klemens , Rostaing Lionel , Marson Lorna , Josephson Michelle A , Reese Peter P. , Pruett Timothy L. , Evangelidis Nicole , Craig Jonathan C. 
Published: May 2018

Background
The potential for clinical trials to impact patient care may be limited if the outcomes reported vary by trial and lack direct relevance to patients. Despite the many trials conducted in kidney transplantation, premature death due to cardiovascular disease, infection, and malignancy remains high. We aimed to assess the range and consistency of outcomes reported in trials in kidney transplantation.

Methods
We searched for randomized trials conducted in kidney transplantation. We extracted the outcome measures, classified them into outcome domains, and into categories (clinical, surrogate or patient-reported outcome [PRO]). We assessed the measures used for the top 4 domains.

Results
Overall, 397 trials reported 12 047 outcomes measures and time points (median, 19 per trial; interquartile range, 9-42) across 106 different domains, of which 55 (52%) were surrogate, 35 (33%) clinical, and 16 (15%) PRO. The 4 most frequently reported were graft function (322 [81%] trials, 118 outcome measures), acute rejection (234 [59%], 93 measures), graft loss (215 [54%], 48 measures), and mortality (204 [51%], 51 measures). The remaining 102 domains were reported in less than 50% of trials.

Conclusions
Mortality- and graft-related outcome domains were frequently reported and assessed with a multiplicity of measures. Most outcome domains were surrogate outcomes, and the reporting of relevant life-threatening complications and PRO were uncommon. Establishing core outcomes based on the shared priorities of patients/caregivers and health professionals in kidney transplantation may improve the relevance and consistency of outcome reporting in trials to better inform clinical decision making.
Optimizing Temperature and Oxygen Supports Long-term Culture of Human Islets
Authors: Komatsu Hirotake , Rawson Jeffrey , Medrano Leonard , Cook Colin A. , Barriga Alyssa , Gonzalez Nelson , Salgado Mayra , Omori Keiko , Kandeel Fouad , Tai Yu-Chong , Mullen Yoko 
Published: May 2018

Background
Islet transplantation is a promising treatment for type-1 diabetes; however, donor shortage is a concern. Even when a pancreas is available, low islet yield limits the success of transplantation. Islet culture enables pooling of multiple low-yield isolations into an effective islet mass, but isolated islets rapidly deteriorate under conventional culture conditions. Oxygen (O2) depletion in the islet core, which leads to central necrosis and volume loss, is one of the major reasons for this deterioration.

Methods
To promote long-term culture of human islets in PIM-R medium (used for islet research), we adjusted temperature (12°C, 22°C, and 37°C) and O2 concentration (21% and 50%). We simulated the O2 distribution in islets based on islet O2 consumption rate and dissolved O2 in the medium. We determined the optimal conditions for O2 distribution and volume maintenance in a 2-week culture and assessed viability and insulin secretion compared to noncultured islets. In vivo islet engraftment was assessed by transplantation into diabetic nonobese diabetic-severe combined immunodeficiency mouse kidneys. We validated our results using CMRL 1066 medium (used for clinical islet transplantation).

Results
Simulation revealed that 12°C of 50% O2 PIM-R culture supplied O2 effectively into the islet core. This condition maintained islet volume at greater than 90% for 2 weeks. There were no significant differences in viability and function in vitro or diabetic reversal rate in vivo between 2-week cultured and noncultured islets. Similar results were obtained using CMRL 1066.

Conclusions
By optimizing temperature and O2 concentration, we cultured human islets for 2 weeks with minimal loss of volume and function.
Impact of CMV PCR Blips in Recipients of Solid Organ and Hematopoietic Stem Cell Transplantation
Authors: Lodding Isabelle P. , Mocroft Amanda , da Cunha Bang Caspar , Gustafsson Finn , Iversen Martin , Kirkby Nikolai , Perch Michael , Rasmussen Allan , Sengeløv Henrik , Sørensen Søren S. , Lundgren Jens D. 
Published: May 2018

Background
Viral blips reflecting polymerase chain reaction (PCR) artefacts or transient low-level replication are well described in the human immunodeficiency virus setting. However, the epidemiology of such blips in transplant recipients screened for cytomegalovirus (CMV) with PCR remains uncertain and was investigated in a cohort of solid organ and hematopoietic stem cell recipients.

Methods
Eligible recipients had known donor/recipient CMV IgG serostatus, and 3 CMV PCRs ≥. The CMV PCR triplicates (3 consecutive CMV PCRs) were defined; the first CMV PCR was always negative, and the time between the second and third samples was 7 days ≤. A positive second but negative third sample represented a blip. Odds ratio (OR) for factors associated with a triplicate being a blip was estimated by binomial regression adjusted for repeated measurements. Whether blips affected the hazard ratio (HR) for subsequent CMV infection was determined with a Cox model.

Results
851 recipients generated 3883 CMV PCR triplicates. The OR of a triplicate representing a blip decreased with increasing viral load of the second sample (vs 273 IU/mL; >273-910 IU/mL: odds ratio [OR], 0.2; 95% confidence interval [CI], 0.1-0.5; >910 IU/mL: OR, 0.08; 95% CI, 0.02-0.2; P ≤ 0.0002) and increased with intermediary-/low-risk serostatus (vs high risk) (OR, 2.8; 95% CI, 1.2-5.5; P = 0.01). Cumulative exposure to DNAemia in the CMV blips greater than 910 IU/mL indicated increased HR of subsequent CMV infection (HR, 4.6; 95% CI, 1.2-17.2; P = 0.02).

Conclusions
Cytomegalovirus blips are frequent; particularly when the viral load of the first positive PCR is < 910 IU/mL, and serostatus risk is intermediary/low. Accumulating blips suggest intermittent low-level replication. If blips are suspected, confirmation of ongoing replication before initiation of treatment is prudent.
The expanding spectrum of paroxysmal movement disorders: update from clinical features to therapeutics
Authors: McGovern Eavan M. , Roze Emmanuel , Counihan Timothy J. 
Published: May 2018

Purpose of review
This review will discuss the expanding clinical spectrum of paroxysmal movement disorders and therapeutic options in light of emerging genotypic heterogeneity in these conditions.

Recent findings
Paroxysmal movement disorders comprise a heterogeneous group of rare neurological conditions characterized by intermittent episodes of abnormal movement associated with various triggers. As the clinical and genotypic spectrum of these disorders evolves, so also has the range of therapeutic options. Triheptanoin has recently been shown to be a very promising alternative to the ketogenic diet in paroxysmal exercise-induced dyskinesia. Four-aminopyridine is now considered first-line symptomatic therapy for episodic ataxia type-2, with pre-clinical findings indicating cerebellar neuroprotection.

Summary
In light of the newly emerging therapies, careful clinical phenotyping is needed to ensure diagnostic precision and timely initiation of appropriate therapies.