bluuebunny/crossref_metadata_2025_split huggingface dataset:
ELYPSE 2: A prospective randomized trial comparing filgrastim (G-CSF) in primary and secondary prophylaxis in patients (pts) at high risk for febrile neutropenia (FN)
Authors: Biron P. , Ray-Coquard I. , Le Cesne A. , Dussart S. , Goilliot C. , Bachelot T. , Thyss A. , Gilles E. , Chabaud S. , Blay J. 
Published: April 2020

8614 Background: FN is a frequent life-threatening consequence of cytotoxic chemotherapy (CT). G-CSF reduces the risk of FN, but primary (1ry) prophylaxis using G-CSF may be cost efficient only if FN incidence is ≥20%. The identification of pts at high risk for FN with simple criterias would be useful in clinical practice. Here we report a randomized phase II trial comparing G-CSF in 1ry vs 2ry prophylaxis in a high risk group of pts (based on our risk model JCO 1996;14:737, Br J Cancer 2003;88:181). Methods: Pts ≥18 years with solid tumors or NHL at high risk for FN after CT were incluable: these were pts with day 1 or day 5 lymphocytes (Ly) count ≤700/μL AND “high risk CT” (HRCT) In pts with d1 and d5 Ly ≤700/μL, the observed incidence of FN was 40% and 66% respectively G-CSF (300 to 480μg/d from d6–12) was randomized either as in 1ry prophylaxis (Arm 1), or as 2ry prophylaxis after FN (Arm 2). Primary endpoint was the rate of grade 4 FN. Hypothesis was a reduction of 40% of the risk of FN with 1ry prophylaxis. Results: Between 03/97 and 12/04, 137 pts were included in 7 centers. The median age was 53 years (range 18–80) with 54% males. Most frequent tumors were sarcomas (36%), breast carcinomas (18%), lymphomas (15%), head and neck carcinomas (10%), and lung carcinomas (6%). 23% patients had PS>1 at the first line of chemotherapy. No difference was observed in terms of duration of hospitalization or antibiotherapy. Median number of days of G-CSF administration was 14 days (0–24) vs 0 (0–17) days (p<0.0000). After the 1st course, grade 4 FN was 38% in Arm 2 (2ry prophylaxis) and 25% in Arm 1 (1ry prophylaxis), showing a 34% reduction of FN in arm 1 (p=0.14): 1ry prophylaxis was associated with a significant reduction of FN using logistic regression (p=0.04). Incidence of FN after the 2 course in pts receiving 2ry prophylaxis was 22%. Among the subgroup of pts with PS>2 and Ly ≤700/μL, (a group with a reported 20% risk for early death, Br J Cancer 2001;85:816), 2 of 8 patients (25%) died after the 1st course, vs 0/13 in the G-CSF group (p=0.05). This difference was not significant in the whole group. Conclusions: This study confirms that lymphopenic pts receiving HRCT are a high risk group of pts for FN for whom 1ry prophylaxis with G-CSF reduces the incidence of FN. [Table: see text]
Ondansetron oral spray (Zensana) versus ondansetron oral tablets in a randomized, bioavailability study in adult subjects
Authors: Yates W. , Berk G. I. , Wolter M. , Nino S. , Kollipara S. , Chavira R. , Kisicki J. 
Published: April 2020

8622 Background: Zensana ondansetron oral spray (ZSN) is the first oral spray 5-HT3 antagonist to deliver ondansetron, the most commonly prescribed anti-emetic for chemotherapy induced nausea and vomiting (CINV) through the oral cavity. ZSN achieves therapeutic drug levels by delivering small droplets of concentrated drug solution over the oral mucosa, which has a rich blood supply and has been shown to be an alternative drug delivery route. ZSN may offer certain advantages to patients experiencing CINV who have difficulty swallowing and holding down pills. Methods: This was a randomized, crossover, pharmacokinetic (PK) study where ZSN, administered as 4mg, 8mg, 12mg, and 8mg with a 30-sec hold before swallowing was evaluated in healthy subjects against an 8mg ondasetron (Zofran [ZFR]) tablet (reference). Treatments were separated by 48 hrs. PK samples were measured during the 24 hrs after dosing and were assayed using LC/MS/MS techniques. PK parameters were analyzed using a cross-over ANOVA model. Two treatments were concluded bioequivalent if the 90% CI of the geometric mean ratios for ln-transformed Cmax, AUC0-t, and AUC0-inf fell between the FDA guideline of 80% to 125%. Results: Thirty-two subjects (17 women, 15 men) received each of the 5 treatments, except for one man who did not receive the 12mg dose. The geometric mean ratios and the 90% CI for Cmax, AUC0-t, and AUC0-inf respectively, for each pair of treatments were as follows: ZSN 4mg vs 8mg tablet (TAB): 41%(39–43%); 45%(43–47%), and 47%(45–49%); ZSN 8mg vs 8mg TAB: 87%(83–91%), 98%(94–102%), and 99%(94–103%); ZSN 12mg vs 8mg TAB: 145%(138–152%), 157%(150–164%), and 157%(150–164%); and ZSN 8mg with a 30 sec hold vs 8mg TAB: 86%(82–90%), 99%(94–103%), and 99%(95–104%). There were no serious or unexpected adverse events (AE) and the safety profile was similar across all treatments. The most commonly reported AEs were constipation (11/32[34%]), headache (10/32[31%]), and dizziness (5/32[16%]) which were mild to moderate in severity. Conclusions: ZSN 8mg falls within the FDA criteria for bioequivalence, and is bioequivalent to an 8mg ZFR tablet. ZSN 4, 8, or 12mg has a similar safety profile as a ZFR 8 mg tablet. [Table: see text]
Incidence of venous thromboembolic (VTE) in chronic lymphocytic leukemia (CLL) patients (pts) treated with immunomodulating agents (IMiDs)
Authors: Depaolo D. , Miller K. , Musial L. , Marshall P. , Coignet J. , Padmanabhan S. , Chanan-Khan A. A. 
Published: April 2020

8625 Introduction: We recently reported the clinical activity of IMiDs (both thalidomide (T) and lenalidomide (L)) in pts with CLL. VTE is a commonly reported complication of these agents requiring prophylaxis. Most available information is in pts treated for multiple myeloma (MM), a disease with a high baseline incidence of VTE. To determine whether the incidence of IMiDs associated VTE is similar in CLL pts we reviewed all CLL pts treated with IMiDs at our institute. Method: All CLL pts treated at our institute with T or L either alone or in combination with other antileukemic agents such as rituximab (R) or fludarabine (F)) were evaluable for this analysis. All pts were treated on IRB approved clinical trials and signed informed consent. Prophylaxis for VTE was recorded. Dose range for T was 100–300mg/day, while that of L was 5–25mg/day. Results: To date a total of 55 pts (35 on L and 20 on T) are treated with IMiDs at our center. All pts treated with L received single agent L while those treated with T received concurrent F (FT). All T treated pts also received low-dose warfarin (1 or 2 mg for body weight ≤ or > than 70 kg respectively) for VTE prophylaxis. No prophylaxis was given to L treated pts. VTE was noted in 2 (6%) pts on L and 2 (10%) on FT. Thus the cumulative incidence of IMiDs associated VTE in CLL pts at our center was 7% (4/55). Conclusion: VTE is a known side effect of IMiDs. Its incidence in CLL treated pts is unknown. Our experience with both T and L in CLL pts suggest that VTE remains a concern in this pt population as well though the incidence may be lower. Three other studies investigated T either alone (n=28)1, with F (n=18)2 or with dexamethasone/cyclophosphamide (n=3)3. Only 1 episode of VTE was reported in these studies.3 Our current analysis failed to reveal any apparent risk factors for VTE in CLL pts treated with IMiDs. Several pts on the L clinical trial continue to be on therapy. Updated results with prolonged L treatment will be presented at the meeting. 1. Kay N et al: ASH 2003 2. Furman RR et al: ASCO 2005 3. Trompeter S et al: IWCLL 2005 [Table: see text]
Cognitive dysfunction, brain-derived neurotrophic factor and IL-6 levels in cancer patients with depression
Authors: Jehn C. F. , Becker B. , Pfeiffer S. , Krebs M. , Possinger K. , Flath B. , Dieing A. 
Published: April 2020

8632 Background: Increased proinflammatory cytokines (IL-6) and decreased brain-derived neurotrophic factor (BDNF) levels have been implicated in the pathophysiology of depression. Depression has been shown to be associated with cognitive dysfunction. The objective of this study was to assess the correlations between cognitive dysfunction, IL-6 and BDNF in cancer patients (pts) with depression. Methods: Depression was assessed in 55 patients with metastatic cancer by the Hospital Anxiety and Depression Scale (HADS) and diagnosis was established according to DSM-IV criteria. Cognitive function was assessed by the Auditory Verbal Learning Test (AVLT). Plasma concentrations of Interleukin-6 and BDNF were measured at 8 AM the same day. In the statistical analysis the Mann-Whitney test and the Pearson correlation were applied. Results: Pts characteristics (n=55): median age 60 y (25–85); 76.9% Females, 23.1% males. 52% of pts had depression. There were no significant differences in mean age or Karnofsky-index between pts with and without depression. Depression was associated with a significant higher median IL-6 level (14.8 vs. 3.7 pg/ml; p<0,001). For Cognitive function only the longterm memory was significantly reduced in depression (p=0.01). However, there was no difference in BDNF levels between both groups (p=0.164). There were correlations between HADS-D score and IL6 (r=4.11; p=0.002), IL-6 and BDNF (r= −0.42; p=0.001), BDNF and longterm memory (r=0.48; p=0.02). No correlations were found for level of depression (HADS-D score) and BDNF levels (r= −0.20; P=0.14). Conclusions: Depression and increased plasma IL-6 concentrations are strongly associated in pts with cancer. There seems to be no association between BDNF and depression in cancer pts. However there is a positive correlation between the cognitive function, at least for longterm memory, with BDNF. No significant financial relationships to disclose.
Relationship of C-peptide levels to duration of Type 1 diabetes – A study from Sindh, Pakistan
Authors: Fawwad Asher , Waris Nazish , Askari Saima , Ogle Graham , Ahmedani Muhammad Yakoob , Basit Abdul 
Published: April 2020

Objective: To determine the relationship of C-peptide levels with duration of type 1 diabetes mellitus.
Methods: This prospective study was conducted at Baqai Institute of Diabetology and Endocrinology (BIDE), Baqai Medical University (BMU), Karachi-Pakistan from December 2013 to December 2015. A total of 184 subjects were recruited during the study period, 100 in Group-A and 84 in Group-B. Subjects clinically diagnosed with type 1 diabetes Mellitus (T1DM) were categorized into two groups based on duration of diabetes: Group-A (with ≤1-year duration of diabetes) and Group-B (with >1-year duration of diabetes). Ninety-nine of the 100 enrolled subjects in Group-A were diagnosed as having T1DM, with one subject who presented at 11.9 years of age and diagnosed with T2DM excluded from this study. Blood samples were drawn for biochemical parameters. Data for baseline characteristics and clinical parameters (HbA1c and C-peptide) were obtained from hospital management system of BIDE.
Results: Fifty-seven (57.6%) subjects in Group-A, and 39 (46.4%) in Group-B were males. Mean±SD duration of diabetes (years) was 0.64±0.6 (range 0-1) in Group-A, and 7.65±5.5 (range 1-23) in Group-B. Family history of T1DM and T2DM was 1(1%) and 27(27.3%) in Group-A, and 8(9.52%) and 21(25%) in Group-B, respectively. Twenty-one (21.2%) subjects presented in diabetic ketoacidosis (DKA) in Group-A and 18(21.4%), in Group-B. Mean±SD for HbA1c was non-significantly higher in Group-A 11.12±2.31 compared to Group-B 10.42±1.45. Mean±SD for C-peptide was 1.91±1.53 ng/mL (0.60±0.481 nmol/L) in Group-A, and 1.82±1.01 (0.57±0.32 nmol/L) in Group-B (p=0.984).
Conclusion: The study found that subjects with longer duration of T1DM had non-significantly decreased C-peptide levels compared to a group in which C-peptide was measured at or soon after diagnosis. Furthermore, C-peptide levels in many subjects with longer duration were higher than expected in classic T1DM.
doi: https://doi.org/10.12669/pjms.36.4.1531
How to cite this:Fawwad A, Waris N, Askari S, Ogle G, Ahmedani MY, Basit A. Relationship of C-peptide levels to duration of Type 1 diabetes – A study from Sindh, Pakistan. Pak J Med Sci. 2020;36(4):765-769. doi: https://doi.org/10.12669/pjms.36.4.1531
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Mechanical properties of an experimental resin based composite containing silver nanoparticles and bioactive glass
Authors: Hanif Amjad , Ghani Fazal 
Published: April 2020

Objective: To compare the elastic modulus, flexural strength, and hardness of an experimental resin based composite (RBC) with and without containing silver nanoparticles (AgNPs) and bioactive glass (BAG) with a commercially available RBC.
Methods: This study was conducted, during the period August 2016-May 2018, at the Department of Dental Materials, Peshawar Dental College, Peshawar (Pakistan) and Department of Chemistry, University of Montreal, Canada. Test specimens made in the commercial RBC acted as Group-1 (G1). An experimental RBC containing 70 wt % filler content was synthesized. It was first used as such to prepare test specimens to act as the experimental control group (G2). This RBC was then modified by adding various amounts of BAG (5%, 10% and 15%) and a fixed amount of 0.009% AgNPs to use the so modified RBCs for preparing the test specimens to belong to three groups (G3, G4 & G5). The AgNPs had been synthesized in situ by reduction of salt during photo-polymerization. Flexural strength (FS), elastic modulus (EM) and Vickers hardness were determined using universal testing machine and hardness tester respectively. Data were analyzed using one-way ANOVA and Tukey post-hoc test.
Results: Except for G3 restorations showing significantly lower mean FS value, the FS for those in the other groups were not significantly different (p>0.05). Elastic modulus of the experimental RBC restorations was though higher than those of the others but the difference was statistically insignificant (p>0.05). Reduced Vickers hardness values were documented for the restorations in the G4 and G5 compared to those in the G3 but again the difference was insignificant (p>0.05). Flexural strength and hardness values of the test specimens in the experimental RBCs were significantly lower than those made in the commercial hybrid RBC (p<0.05).
Conclusion: BAG and AgNPs addition to the experimental RBC in the mentioned concentration adversely affected the tested mechanical properties.
doi: https://doi.org/10.12669/pjms.36.4.1913
How to cite this:Hanif A, Ghani F. Mechanical properties of an experimental resin based composite containing silver nanoparticles and bioactive glass. Pak J Med Sci. 2020;36(4):776-781. doi: https://doi.org/10.12669/pjms.36.4.1913
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Leishmaniasis in Saudi Arabia: Current situation and future perspectives
Authors: Abass Elfadil , Al-Hashem Zainab , Yamani Lamya Zohair 
Published: April 2020

Background and Objective: Leishmaniasis is endemic in Saudi Arabia with cases reported in many regions. This review refers to publications on leishmaniasis in Saudi Arabia and discusses issues related to parasite species, clinical manifestation and diagnosis.
Methods: This research was done at Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia by systematic literature search on PubMed and Google Scholar databases from 1989 to 2018. Selection criteria included original articles reporting on visceral leishmaniasis (VL) or cutaneous leishmaniasis (CL) in Saudi Arabia.
Results: The search identified 16 eligible articles, six for VL and 10 for CL. VL was reported in areas known to be non-endemic. Leishmania donovani was the main cause for human VL while Leishmania infantum seemed to cause the disease in animals. Dogs were considered the main reservoir hosts and black rats (Rattus rattus) were potential hosts. VL mainly affected infants and young children. It is important to note that VL diagnosis was based on either invasive parasite detection procedures or serologically using indirect hemagglutination test. CL represented the most frequent clinical form with the main endemic foci reported in the South-West and Eastern regions. CL appeared to have no demographic or socioeconomic restriction; it affected both rural and urban citizens, with the majority occurring among farmers. Travelling was recognized as an important risk factor. Leishmania tropica and Leishmania major were recognized as the main causes for CL.
Conclusion: This report summarizes the potential risks for VL and CL in Saudi Arabia in areas known to be non-endemic. There are substantial gaps in knowledge and practices in regard to leishmaniasis in Saudi Arabia, highlighting the need for more research and medical surveillance targeting the disease in humans and animals.
doi: https://doi.org/10.12669/pjms.36.4.2121
How to cite this:Abass E, Al-Hashem Z, Yamani LZ. Leishmaniasis in Saudi Arabia: Current situation and future perspectives. Pak J Med Sci. 2020;36(4):836-842. doi: https://doi.org/10.12669/pjms.36.4.2121
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Widespread use of the “ascidian” mitochondrial genetic code in tunicates
Authors: Pichon Julien , Luscombe Nicholas M. , Plessy Charles 
Published: April 2020

Background:Ascidians, a tunicate class, use a mitochondrial genetic code that is distinct from vertebrates and other invertebrates. Though it has been used to translate the coding sequences from other tunicate species on a case-by-case basis, it is has not been investigated whether this can be done systematically. This is an important because a) some tunicate mitochondrial sequences are currently translated with the invertebrate code by repositories such as NCBI GenBank, and b) uncertainties about the genetic code to use can complicate or introduce errors in phylogenetic studies based on translated mitochondrial protein sequences.Methods:We collected publicly available nucleotide sequences for non-ascidian tunicates including appendicularians such as Oikopleura dioica, translated them using the ascidian mitochondrial code, and built multiple sequence alignments covering all tunicate classes.Results:All tunicates studied here appear to translate AGR codons to glycine instead of serine (invertebrates) or as a stop codon (vertebrates), as initially described in ascidians. Among Oikopleuridae, we suggest further possible changes in the use of the ATA (Ile → Met) and TGA (Trp → Arg) codons.Conclusions:We recommend using the ascidian mitochondrial code in automatic translation pipelines of mitochondrial sequences for all tunicates. Further investigation is required for additional species-specific differences.
Gender-based violence: Experiences from two tertiary care settings in Sri Lanka
Authors: Pathiraja Dasuni Yahanika , Pathiraja Ramya  Priyanwada , Senanayake Lakshmen , Edirisinghe Rukshani Mayawanthi , Mapitigama Nethanjalie 
Published: April 2020

Background: This study aimed to obtain an overview of survivors of gender-based violence GBV who seek care, different types and consequences of (GBV), their modes of referral, factors associated with GBV, characteristics of the perpetrators, health-seeking behavior of the care-seekers and the service provided by GBV Care Centers in two tertiary care settings Methods: A retrospective cross-sectional study was conducted from January 2017 to December 2019 at two GBV care centers in a Women’s Hospital and a General Hospital in Colombo, Sri Lanka. Sociodemographic details of care-seekers, referral methods, types of violence experienced and their consequences, factors associated with GBV, characteristics of the perpetrator, health seeking behavior of those seeking care, and the services provided, were obtained from the hospital records. Results: Records from all care seekers (n=495 women, no men) were obtained, and 488 were suitable for analysis. More women presented with GBV to the Women’s Hospital compared to the General Hospital (395 vs 93, p<0.001), and there were significant differences in modes of referral between the two hospitals. A large majority had suffered emotional and economic violence, although physical or sexual violence were the reasons for referral to the centers. Suicidal tendencies had been reported by 20%. In 94.2% of cases the husband, lover or partner was the perpetrator. Physical violence was more likely in married women, those who did not report a stable relationship, and in those who were employed. Of the 488 women, 37% were pregnant at the time of violence. Most of the women had confided with another female about the violence. Less than 5% came for follow-up. Conclusions: GBV care services should be offered in all hospitals, especially those providing maternity and gynaecological care. Emotional and economic violence are common but often overlooked. There is a need to increase public awareness about GBV.
A pneumococcal controlled human infection model in Malawi: Transfer of an established pneumococcal carriage model from Liverpool, UK to Blantyre, Malawi – A feasibility study
Authors: Morton Ben , Burr Sarah , Jambo Kondwani , Rylance Jamie , Henrion Marc Y.R. , Banda Ndaziona Peter , Nsomba Edna , Kapumba Blessings , Manda-Taylor Lucinda , Masesa Clemens , Ferrreira Daniela , Gordon Stephen B. ,   MARVELS Consortium
Published: April 2020

Streptococcus pneumoniae is the leading cause of morbidity and mortality due to community acquired pneumonia, bacterial meningitis and bacteraemia worldwide. Pneumococcal conjugate vaccines protect against invasive disease, but are expensive to manufacture, limited in serotype coverage, associated with serotype replacement and demonstrate reduced effectiveness against mucosal colonisation. As asymptomatic colonisation of the human nasopharynx is a prerequisite for pneumococcal disease, this is proposed as a marker for novel vaccine efficacy. Our team established a safe and reproducible pneumococcal controlled human infection model at Liverpool School of Tropical Medicine (LSTM). This has been used to test vaccine induced protection against nasopharyngeal carriage for ten years in over 1000 participants. We will transfer established standardised operating procedures from LSTM to Malawi and test in up to 36 healthy participants. Primary endpoint: detection of the inoculated pneumococci by classical culture from nasal wash recovered from the participants after pneumococcal challenge. Secondary endpoints: confirmation of robust clinical and laboratory methods for sample capture and processing. Tertiary endpoints: participant acceptability of study and methods. We will test three doses of pneumococcal inoculation (20,000, 80,000 and 160,000 colony forming units [CFUs] per naris) using a parsimonious study design intended to reduce unnecessary exposure to participants. We hypothesise that 80,000 CFUs will induce nasal colonisation in approximately half of participants per established LSTM practice. The aims of the feasibility study are: 1) Establish Streptococcus pneumoniae experimental human pneumococcal carriage in Malawi; 2) Confirm optimal nasopharyngeal pneumococcal challenge dose; 3) Confirm safety and measure potential symptoms; 4) Confirm sampling protocols and laboratory assays; 5) Assess feasibility and acceptability of consent and study procedures. Confirmation of pneumococcal controlled human infection model feasibility in Malawi will enable us to target pneumococcal vaccine candidates for an at-risk population who stand the most to gain from new and improved vaccine strategies.