bluuebunny/crossref_metadata_2025_split huggingface dataset:
First case of Dolutegravir and Darunavir/r multi drug-resistant HIV-1 in Cameroon following exposure to Raltegravir: lessons and implications in the era of transition to Dolutegravir-based regimens
Authors: Fokam Joseph , Takou Desire , Semengue Ezechiel Ngoufack Jagni , Teto Georges , Beloumou Grace , Dambaya Beatrice , Santoro Maria-Mercedes , Mossiang Leonella , Billong Serge Clotaire , Cham Fatim , Sosso Samuel Martin , Temgoua Edith Saounde , Nanfack Aubin Joseph , Moudourou Sylvie , Kamgaing Nelly , Kamgaing Rachel , Ngako Pamen Joelle Nounouce , Etame Mireille Mpoudi Ngole , Bissek Anne-Cecile Z.-K. , Elat Jean-Bosco N. , Moussi Emmanuel Eben , Colizzi Vittorio , Perno Carlo-Federico , Ndjolo Alexis ,   On behalf of the VIROFORUM
Published: August 2020

Abstract
Background
Sub-Saharan African countries are transitioning to dolutegravir-based regimens, even for patients with extensive previous drug exposure, including first-generation integrase strand-transfer inhibitors (INSTI) such as raltegravir. Such exposure might have implications on cross-resistance to dolutegravir-based antiretroviral therapies (ART).

Case presentation
We report a 65 years old Cameroonian, previously exposed to raltegravir, and failing on third-line treatment with multi-drug resistance to darunavir/r and dolutegravir. Genotypic resistance testing (GRT) and viral tropism were performed during monitoring time points. The patient initiated ART in August 2007. At the time point of the first (29.04.2010), second (01.12.2017) and third (08.08.2019) GRT, prior ART exposure included 3TC, d4T, NVP and EFV; additionally TDF, DRV/r and RAL; and additionally ABC and DTG respectively. First GRT revealed mutations associated with resistance only to first-generation Non-nucleoside reverse transcriptase inhibitors (NNRTI). Second GRT revealed mutations associated with high-level resistance to all NRTIs, first generation NNRTIs, all ritonavir boosted protease inhibitors (PI/r), and all INSTI, while viral tropism (using geno2pheno) revealed a CCR5-tropic virus with a false positive rate (FPR) of 60.9% suggesting effectiveness of maraviroc (MRV). The third GRT showed high-level resistance to NRTI, NNRTI, all PI and all INSTI, with additional mutations (H221HY for NNRTI and S147G for INSTI), and a CCR5-tropic virus with a slightly reduced FPR (57.0%). Without any locally available active therapeutic option, the patient has been on a maintenance therapy with “DRV/r (600mg x 2/day)+TDF+3TC” and patient/family-centered adherence has been reinforced. Since the first viral load (VL) measurement in 2010, the patient has had 12 VL tests with the VL ranging from 4.97 Log to 6.44 Log copies/mL and the CD4 count never exceeded 200 cells/μL.

Conclusions
As African countries transition to dolutegravir-based regimens, prior raltegravir-exposure may prompt selection (and potential transmission) of dolutegravir-resistance, supporting case surveillance.
Delay in seeking treatment before emergent heart failure readmission and its association with clinical phenotype
Authors: Takei Makoto , Harada Kazumasa , Shiraishi Yasuyuki , Matsuda Junya , Iwasaki Yoichi , Yamamoto Yoshiya , Matsushita Kenichi , Miyazaki Tetsuro , Miyamoto Takamichi , Iida Kiyosi , Tanimoto Shuzo , Nagatomo Yuji , Hosoda Toru , Kohsaka Shun , Yamamoto Takeshi , Nagao Ken , Takayama Morimasa 
Published: August 2020

Abstract
Background
Many patients with emergent heart failure (HF) readmission have a delay between symptom onset and hospitalization. The present study aimed to characterize the interval between symptom onset and hospitalization in patients being readmitted for HF and to compare the clinical phenotypes of patients with delay before emergent readmission with those who presented to the hospital earlier.

Methods
Data for a total of 2073 consecutive patients was collected from the Tokyo CCU Network database; the patients were divided into delayed (those who sought medical help > 2 days after symptom onset; n = 271) and early groups (remaining patients; n = 1802), and their clinical characteristics and mode of presentation were compared.

Results
Age, sex, and laboratory findings including brain natriuretic peptide and serum creatinine levels were not significantly different between the two groups. Patients in the delayed group had greater chronic fluid retention and symptoms not associated with respiratory failure, whereas those in the early group were more likely to have acute respiratory distress, faster heart and respiration rates, and higher systolic blood pressure.

Conclusions
More than one in ten patients with HF readmission delay seeking treatment > 2 days after symptom onset. Patients who delayed seeking treatment showed the phenotype of chronic fluid retention, whereas those who presented to the hospital earlier had the phenotype of acute respiratory failure.
Micronutrient status of Palestinian school children following salt and flour fortification: a cross-sectional study
Authors: Massad Salwa , Gebre-Medhin Mehari , Dary Omar , Abdalla Marwah , Holleran Steve , Karmally Wahida , Bordelois Paula , Khammash Umaiyeh , Deckelbaum Richard J. 
Published: August 2020

Abstract
Background
In 1996 and in 2006, Palestine initiated salt iodization and multiple micronutrient fortification of wheat flour, respectively as a strategy to prevent deficiencies of these nutrients. In 2009, we assessed the impact of these interventions on the health and nutritional status of schoolchildren residing in the West Bank.

Methods
We surveyed a sample of 22 schools run by the UN Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) and the Palestinian Government. We randomly selected students from the first (mean age 6.7 years [SD 0.5]), sixth (11.8 years [0.6]), and ninth grades (14.8 years [0.6]). Data were obtained from 1484 (99%) of 1500 students planned for enrollment.

Results
Our results suggest that iodine intake appears adequate and there was essentially no iodine deficiency. As to the status of other micronutrients, the main nutritional micronutrient risks for schoolchildren in the West Bank continue to be low serum levels of iron, zinc, and vitamin B-12; folate levels were seemingly high. The overall prevalence of anemia was 9.6%, but there were pockets of anemia in certain districts. Almost 42% of the anemia in our sample was explained by iron deficiency. There were significant differences in iron deficiency between girls and boys, 29.5% vs. 15.7%, respectively (p = 0.0001). There were no cases of lead toxicity in the studied sample.

Conclusions
Wheat flour and salt fortification has had a major influence on improving the micronutrient status of Palestinian children, for some but not all micronutrients. The recommended key blood and biochemical parameters to be incorporated in the surveillance system are iron, zinc, and vitamin B12.
UMBRELLA protocol: systematic reviews of multivariable biomarker prognostic models developed to predict clinical outcomes in patients with heart failure
Authors: Vazquez-Montes Maria D. L. A. , Debray Thomas P. A. , Taylor Kathryn S. , Speich Benjamin , Jones Nicholas , Collins Gary S. , Hobbs F. D. R. Richard , Magriplis Emmanuella , Maruri-Aguilar Hugo , Moons Karel G. M. , Parissis John , Perera Rafael , Roberts Nia , Taylor Clare J. , Kadoglou Nikolaos P. E. , Trivella Marialena ,   on behalf of the proBHF group
Published: August 2020

AbstractBackgroundHeart failure (HF) is a chronic and common condition with a rising prevalence, especially in the elderly. Morbidity and mortality rates in people with HF are similar to those with common forms of cancer. Clinical guidelines highlight the need for more detailed prognostic information to optimise treatment and care planning for people with HF. Besides proven prognostic biomarkers and numerous newly developed prognostic models for HF clinical outcomes, no risk stratification models have been adequately established. Through a number of linked systematic reviews, we aim to assess the quality of the existing models with biomarkers in HF and summarise the evidence they present.MethodsWe will search MEDLINE, EMBASE, Web of Science Core Collection, and the prognostic studies database maintained by the Cochrane Prognosis Methods Group combining sensitive published search filters, with no language restriction, from 1990 onwards. Independent pairs of reviewers will screen and extract data. Eligible studies will be those developing, validating, or updating any prognostic model with biomarkers for clinical outcomes in adults with any type of HF. Data will be extracted using a piloted form that combines published good practice guidelines for critical appraisal, data extraction, and risk of bias assessment of prediction modelling studies. Missing information on predictive performance measures will be sought by contacting authors or estimated from available information when possible. If sufficient high quality and homogeneous data are available, we will meta-analyse the predictive performance of identified models. Sources of between-study heterogeneity will be explored through meta-regression using pre-defined study-level covariates. Results will be reported narratively if study quality is deemed to be low or if the between-study heterogeneity is high. Sensitivity analyses for risk of bias impact will be performed.DiscussionThis project aims to appraise and summarise the methodological conduct and predictive performance of existing clinically homogeneous HF prognostic models in separate systematic reviews.Registration: PROSPERO registration number CRD42019086990
Preliminary clinical assessment of dynamic carbon-11 methionine positron-emission tomography/computed tomography for the diagnosis of the pathologies in patients with musculoskeletal lesions: a prospective study
Authors: Shinya Takayoshi , Otomi Yoichi , Nishisho Toshihiko , Beuthien-Baumann Bettina , Kubo Michiko , Otsuka Hideki , Bando Yoshimi , Yanagawa Hiroaki , Sairyo Koichi , Harada Masafumi 
Published: August 2020

Abstract
Background
This study prospectively assessed the diagnostic capacity of dynamic carbon-11 methionine (C-11 MET) positron-emission tomography (PET)/computed tomography for the diagnosis of pathologies in patients with primary unknown musculoskeletal lesions (MSLs). In total, 13 patients with MSLs underwent dynamic scans (5–10 [phase 1], 10–15 [phase 2], 15–20 [phase 3], 20–25 [phase 4], 25–30 [phase 5], and 30–35 [phase 6] min post-injection of C-11 MET). We statistically compared the maximum standardised uptake values (SUVmax) and corresponding retention index for dynamic scans (RI-SUV) for five benign MSLs (BMSLs), five primary malignant musculoskeletal tumours (PMMSTs), four metastatic musculoskeletal tumours (MMSTs), and three malignant lymphoma (ML) cases and explored their diagnostic capacities using receiver operating characteristic (ROC) curve analyses.

Results
SUVmax gradually decreased or remained similar with minimal fluctuations in all BMSL cases and four of five PMMST cases. In contrast, SUVmax increased over time in one case of PMMST and in all cases of MMST and ML. Significant differences were observed in SUVmax for all time phases and RI-SUV between BMSLs and MMSLs, in SUVmax for all time phases between PMMSTs and BMSLs, in SUVmax for all time phases and RI-SUV between non-PMMST-malignant tumours and BMSL, and in RI-SUV between non-PMMST-malignant tumours and PMMST. In ROC analyses, the areas under the curve yielded the highest values at 1.00 for differentiating most intergroup comparisons.

Conclusions
Dynamic C-11 MET PET scans have the potential to be good predictors of discriminating MSLs in patients with primary unknown MSLs in clinical practice.
Childbearing and mortality among women with personality disorders: nationwide registered-based cohort study
Authors: Kouppis Efthymios , Björkenstam Charlotte , Gerdin Bengt , Ekselius Lisa , Björkenstam Emma 
Published: August 2020

Background
People with a personality disorder have a higher mortality and reduced life expectancy than the general population. Childbearing is thought to have a protective effect on morbidity and mortality. Yet, there are no studies on whether childbearing is related to a lower mortality among women with personality disorder.

Aims
This study examined associations between childbearing and mortality among women with personality disorder. Our hypothesis was that parity would be associated with lower mortality.

Method
This register-based cohort study included 27 412 women treated for personality disorder in in-patient or specialised out-patient care between 1990 and 2015. We used nationwide population-based registers to obtain information on sociodemographics, child delivery, healthcare use and mortality. Mortality risk estimates were calculated as hazard ratios (HRs) with 95% CIs using Cox regression. Adjustments were made for year of birth, educational level, age at diagnosis, comorbidity and severity of personality disorder.

Results
Nulliparous women had a nearly twofold increased mortality risk (adjusted HR = 1.78, 95% CI 1.50–2.12) compared with parous women and over twofold mortality risk (adjusted HR = 2.29, 95% CI 1.72–3.04) compared with those giving birth after their first personality disorder diagnosis. Those giving birth before their first personality disorder diagnosis had a 1.5-fold higher risk of mortality than those giving birth after their first personality disorder diagnosis (adjusted HR = 1.48, 95% CI 1.06–2.07). There was a threefold risk of suicide in nulliparous women compared with those giving birth after their first personality disorder diagnosis (adjusted HR = 2.90, 95% CI 1.97–4.26).

Conclusions
Childbearing history should be an integral part of the clinical evaluation of women with personality disorder.
Patient-Centered Outcomes in ARIEL3, a Phase III, Randomized, Placebo-Controlled Trial of Rucaparib Maintenance Treatment in Patients With Recurrent Ovarian Carcinoma
Authors: Oza Amit M. , Lorusso Domenica , Aghajanian Carol , Oaknin Ana , Dean Andrew , Colombo Nicoletta , Weberpals Johanne I. , Clamp Andrew R. , Scambia Giovanni , Leary Alexandra , Holloway Robert W. , Gancedo Margarita Amenedo , Fong Peter C. , Goh Jeffrey C. , O’Malley David M. , Armstrong Deborah K. , Banerjee Susana , García-Donas Jesus , Swisher Elizabeth M. , Cella David , Meunier Juliette , Goble Sandra , Cameron Terri , Maloney Lara , Mörk Ann-Christin , Bedel Josh , Ledermann Jonathan A. , Coleman Robert L. 
Published: August 2020

PURPOSE To investigate quality-adjusted progression-free survival (QA-PFS) and quality-adjusted time without symptoms or toxicity (Q-TWiST) in a post hoc exploratory analysis of the phase III ARIEL3 study of rucaparib maintenance treatment versus placebo. PATIENTS AND METHODS Patients with platinum-sensitive, recurrent ovarian carcinoma were randomly assigned to rucaparib (600 mg twice per day) or placebo. QA-PFS was calculated as progression-free survival function × the 3-level version of the EQ-5D questionnaire (EQ-5D-3L) index score function. Q-TWiST analyses were performed defining TOX as the mean duration in which a patient experienced grade ≥ 3 treatment-emergent adverse events (TEAEs) or the mean duration in which a patient experienced grade ≥ 2 TEAEs of nausea, vomiting, fatigue, and asthenia. Q-TWiST was calculated as μTOX × TOX + TWiST, with μTOX calculated using EQ-5D-3L data. RESULTS The visit cutoff was Apr 15, 2017. Mean QA-PFS was significantly longer with rucaparib versus placebo in the intent-to-treat (ITT) population (375 randomly assigned to rucaparib v 189 randomly assigned to placebo; difference, 6.28 months [95% CI, 4.85 to 7.47 months]); BRCA-mutant cohort (130 rucaparib v 66 placebo; 9.37 months [95% CI, 6.65 to 11.85 months]); homologous recombination deficient (HRD) cohort (236 rucaparib v 118 placebo; 7.93 months [95% CI, 5.93 to 9.53 months]); and BRCA wild-type/loss of heterozygosity (LOH) low patient subgroup (107 rucaparib v 54 placebo; 2.71 months [95% CI, 0.31 to 4.44 months]). With TOX defined using grade ≥ 3 TEAEs, the difference in mean Q-TWiST (rucaparib v placebo) was 6.88 months (95% CI, 5.71 to 8.23 months), 9.73 months (95% CI, 7.10 to 11.94 months), 8.11 months (95% CI, 6.36 to 9.49 months), and 3.35 months (95% CI, 1.66 to 5.40 months) in the ITT population, BRCA-mutant cohort, HRD cohort, and BRCA wild-type/LOH low patient subgroup, respectively. Q-TWiST with TOX defined using select grade ≥ 2 TEAEs also consistently favored rucaparib. CONCLUSION The significant differences in QA-PFS and Q-TWiST confirm the benefit of rucaparib versus placebo in all predefined cohorts.
A phase I study of zoledronic acid (ZA) and low-dose cyclophosphamide (CTX) in children with recurrent/refractory neuroblastoma (NB): A New Approaches to Neuroblastoma Therapy (NANT) study
Authors: Russell H. , DeClerck Y. , Ara T. , Groshen S. , Villablanca J. G. , Marachelian A. , Park J. , Katzenstein H. , Matthay K. , Blaney S. 
Published: August 2020

10022 Background: ZA, a bisphosphonate, delays progression of bone metastases in adult malignancies. Bone metastases occur in 60% of children with advanced NB. A xenograft mouse model demonstrated ZA with low dose chemotherapy delayed progression of NB bone lesions prompting a phase I trial of ZA. Methods: Three dose levels of intravenous ZA (2, 3, or 4 mg/m2) administered every 28 days were evaluated with continuous daily oral CTX (25 mg/m2/day) in patients with recurrent/refractory NB and bone metastases. The primary objective was to determine a recommended dose of ZA for future trials. PKs with the first dose of ZA and serial serum IL-6 levels (stimulator of osteoclast activity) were evaluated. Results: 21 patients (14 male), median age 7.9 years (0.8–26.6 years), were enrolled at ZA dose levels 2 mg/m2 (n=4), 3 mg/m2 (n=3), and 4 mg/m2 (n=13). Seventy-five cycles were administered with median of 1 cycle per patient (range 1–18). Two DLT (Gr 3 hypophosphatemia) occurred at 4 mg/m2 ZA. Other Gr 3 or 4 toxicities included hypocalcemia (n = 2), elevated transaminases (n = 2), neutropenia (n = 2), anemia (n = 1), lymphopenia (n = 1), and hypokalemia (n = 1). A fracture related to osteosclerosis occurred after 18 cycles. There were no renal or dental complications. There was 1 complete response, 9 stable disease median 4.5 cycles (range 3–18), and 10 progressions (central review pending). At 4 mg/m2, mean serum IL-6 levels decreased from 3.9 pg/mL (95% CI: 2.8–5.2 pg/mL) (n = 11) to 2.9 pg/mL (95% CI: 1.8–4.4 pg/mL) after cycle 1 (n = 8). ZA PK were similar to adults. Conclusions: ZA with low dose CTX is well tolerated with evidence of clinical benefit in children with recurrent/refractory NB. The recommended ZA dose for future study is 4 mg/m2 every 28 days. No significant financial relationships to disclose.
Adolescent psychopathology and adult health behaviors in long-term survivors of childhood cancer: Findings from the Childhood Cancer Survivors Study
Authors: Krull K. R. , Huang S. , Hudson M. M. , Gurney J. G. , Srivastava D. K. , Klosky J. , Ness K. K. , Leisenring W. , Termuhlen A. , Robison L. L. 
Published: August 2020

10027 Background: Psychological problems have been identified as important risk factors for poor health behavior in a variety of noncancer populations. We report the association between adolescent psychopathology and future health behaviors in adult survivors of childhood cancer. Methods: Study participants included 1,656 survivors of childhood cancer (50.8% female); 12 - 17 years old and ≥ 5 years post diagnosis at baseline assessment and 18 - 27 years of age at study follow-up. Parents provided medication information and ratings of psychopathology for adolescents at baseline, including symptoms of depression/anxiety, social withdrawal, inattention, and oppositional and antisocial behavior. Survivor self-report of health behavior was collected 6 - 10 years post baseline. Odds ratios (OR) were calculated comparing those with psychopathology to those without on outcomes of obesity, physical activity, smoking, and sunscreen use. Estimates were adjusted for cancer diagnosis, cancer therapy, sex, age, and history of special education. Results: Adult obesity was associated with adolescent social withdrawal (OR 1.5, 95% CI 1.1–2.1) and adolescent use of stimulant medications (OR 1.9, 95% CI 1.1–3.2). Physical inactivity among adults was also associated with adolescent social withdrawal (OR 1.7, 95% CI 1.1–2.5) and to antidepressant use during adolescence (OR 3.2, 95% CI 1.2–8.2). These impacts on obesity and inactivity were above and beyond the risk associated with high body mass index at baseline. Stimulant medication use was associated with decreased likelihood of poor sunscreen use as an adult (OR 0.4, 95% CI 0.2–0.8). Adult smoking was associated with adolescent antisocial behavior (OR 2.6, 95% CI 1.6–4.2). Conclusions: These results suggest that psychological problems in adolescence predict future health behavior in adult survivors of childhood cancer. Furthermore, psychopharmacologic therapy for such problems may increase risk for certain conditions, and decrease risk for others. Increased psychological screening and medication monitoring is warranted to reduce overall risk of poor outcomes. No significant financial relationships to disclose.
Quantitative assessment of HER2 status and correlation with efficacy for patients (pts) with metastatic breast cancer (MBC) in a phase II study of trastuzumab-DM1 (T-DM1)
Authors: Krop I. E. , Burris H. A. , Rugo H. , O'Shaughnessy J. , Vogel C. L. , Amler L. , Strauss A. , Wong E. K. , Klencke B. , Pippen J. 
Published: August 2020

1003 Background: The antibody-drug conjugate T-DM1 combines the biological activity of trastuzumab with targeted delivery of an anti-microtubule agent (DM1) to HER-2-expressing cancer cells. This analysis examines correlation of response to T-DM1 with HER-2 status, as assessed by fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), mRNA quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA) (HER-2 extracellular domain [ECD]), for pts enrolled in TDM4258g, a phase II study of T-DM1 in pts with MBC. Methods: TDM4258g is an open-label, single-arm study of T-DM1 administered at 3.6 mg/kg IV q3w. Pts had progressed on HER-2-directed therapy and received chemotherapy in the metastatic setting and were HER-2 + based on local testing. Archival tissue (paraffin block or >7 unstained tumor slides) was collected for retrospective central laboratory testing. HER-2 DNA amplification was determined by FISH, and protein levels by IHC. qRT-PCR for HER-2 was performed on extracted RNA; baseline HER-2 ECD ELISA was performed on pt sera. HER-2 data for each pt were compared with pt's best response. Results: As of August 29, 2008, 112 pts had enrolled; 107 were efficacy-evaluable pts with median 4.4 mos follow-up. There were 42/107 (39.3%) partial responses (PR) (investigator assessment). Of 86 pts centrally tested, 64 (74.4%) were confirmed HER-2+ (FISH+ and/or IHC 3+), with 32/64 (50%) PR. Of 76 pts tested by both FISH and IHC, 15/76 (19.7%) were confirmed HER-2- (FISH- and IHC 2+/1/0), with 2/15 (13.3%) PR. In HER-2+ pts, response rates did not correlate with high versus low FISH+ counts, nor with HER-2 ECD levels. Among 39 HER-2+ (FISH+ and/or IHC3+) efficacy-evaluable pts with qRT-PCR data, there were 13/19 (68.4%) PR for pts with qRT-PCR above median levels, and 7/20 (35.0%) PR for pts with qRT-PCR below median. Conclusions: HER-2+ pts (by central retesting) had better responses to T-DM1 than HER-2- pts, although a small number of PR were observed in HER-2- pts. Assessment of HER-2 expression by qRT-PCR may identify pts more likely to respond to T-DM1 therapy. Updated data, including additional diagnostic markers, will be presented at the meeting. [Table: see text]