bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of fixed‐dose combination rilpivirine‐tenofovir‐emtricitabine (RPV/TDF/FTC) in treatment‐experienced patients infected with HIV‐1
Authors: Cevik M , Sonecha S , Nelson M 
Published: November 2012

Purpose of the studyRilpivirine (RPV) is a new non‐nucleoside reverse transcriptase inhibitor (NNRTI) which has shown non‐inferiority to efavirenz (EFV) in terms of efficacy and safety profiles. The vast majority of clinical data has been performed in the treatment naïve population and has not been studied in depth in treatment‐experienced patients. We sought to explore the safety and efficacy of RPV/TDF/FTC in treatment‐experienced patients attending our clinics.MethodsHIV‐infected individuals commenced on RPV/TDF/FTC from December 2011 to June 2012 were retrospectively identified from a patient database. Patient demographics were extracted. Biochemical, virological and immunological parameters were collated. At baseline, 1 month and 3 month time points the following laboratory results were compared using the Kruskal‐Wallis test: CD4 count, HIV viral load, amino transferase (ALT), cholesterol, triglyceride and HDL/cholesterol ratio.Summary of resultsSixty‐five patients (4 female) were identified. Median age was 38 years (range: 25–73). Fifty‐six patients were treatment experienced (2 re‐start); 39 on NNRTI‐based (33 on EFV), 10 on PI‐based and 4 on other regimens. 9 patients were naïve to treatment. The reasons for switch are illustrated in Fig. 1. Fifty‐four patients had HIV‐RNA‐1<40 copies/mL at the time of switch and all remained undetectable at 3 months. At baseline, the median CD4 count was 555 cells/mm3 (range: 209–1586) in the switch group, which increased significantly to 638 cells/mm3 (p<0.005) 3 months after switch. Switch to RPV/TDF/FTC had a favorable effect on lipid profile. At baseline the median cholesterol, triglyceride and HDL/cholesterol ratio levels were 4.8 mmol/L, 1.78 mmol/L and 4.37 respectively. At 1 month post‐switch this decreased to 4.5 mmol/L, 1.65 mmol/L and 4.24 and at 3 months post‐switch decreased to 4.1 mmol/L, 1.44 mmol/L and 4.04. Median HIV‐RNA‐1 in treatment‐naïve patients (n=9) at baseline was 50298 copies/mL, at 1 month four patients had HIV‐RNA‐1<40 copies/mL and at 3 months eight patients had HIV‐RNA‐1<40 copies/mL. RPV/TDF/FTC had no favourable effect on lipid profile in treatment‐naïve group and had no effect on ALT levels in either the switch or the treatment‐naïve group.ConclusionIn this cohort, RPV/TDF/FTC has been shown to have a safe virological efficacy and safety profile as a switch therapy for patients suppressed on their current standard of care and are experiencing adverse events.image
Lamivudine plus a boosted‐protease inhibitor as simplification strategy in HIV‐infected patients with toxicity to nucleoside analogues
Authors: Casado J , De la Calle C , Del Palacio M , Bañon S , Pérez Elías M , Moreno A , Moreno S 
Published: November 2012

Purpose of the studyDual therapy with lamivudine plus a PI boosted with ritonavir (PI/r) could be an alternative to standard triple therapy or PI/r monotherapy as a simplification strategy in patients with toxicity to nucleoside analogues (NA).MethodsRetrospective cohort study of 44 HIV‐infected patients on suppressive HAART, with no chronic HBV, who simplified to this dual therapy since 2008. Virological and immunological outcome, lipids and renal changes were evaluated.Summary of resultsMean age was 50 years (38‐70), 66% were male, and the median time of HIV infection was 18.6 years. The median nadir CD4+ count was 150 cells/ml (2–407). At inclusion, patients were receiving therapy with lamivudine plus atazanavir/r in 5 cases, lopinavir/r in 12, and darunavir/r in 27, and they had an HIV RNA level<50 copies/ml for a median time of 794 days (129–2344, 90% >6 months). The NA discontinued was tenofovir (27), didanosine (12), AZT (3), and d4T (2). The reasons for changing were toxicity in 76% of cases, especially renal impairment. They had received a mean of 8 regimens before (2–20), and 55% were in CDC‐stage C. In 11 cases, history of resistance was available (to NA in 7 cases, including the 210W mutation in four). The mutations 184V was not observed, but four patients (9%) had a previous failure to therapy including 3tC. Mutations in the protease gene were observed in 8 patients (2 to 7 mutations, the most frequent 77I and 93L), without resistance to the current PI/r. During 62.8 patient‐years of follow‐up (median, 802 days), only 2 patients failed (4.5%), due to incomplete adherence, at 27 and 141 days. Of note, these two patients had no previous failed with 3tC or PI. Overall, CD4+ count increased for 55 cells/ml. No new adverse events were observed, but total cholesterol (from 180 to 246 mg/dl, p=0.007) and triglycerides (from 166 to 195, p=0.01) increased during the first 24 weeks with improvement at 48 weeks. On the other hand, estimated glomerular filtration rate improved during follow up (from 74.2 ml/min to 83.08 ml/min after 48 weeks, p=0.1).ConclusionsDual therapy with lamivudine plus a boosted PI is safe and effective as simplification strategy in patients with toxicity to NA. This combination could be an alternative to mono or triple therapy in hard to treat patients, although an initial increase in lipid parameters could be observed.
Effectiveness and safety of a single‐tablet regimen of emtricitabine/efavirenz/tenofovir in HIV‐1‐infected patients in infectious diseases department
Authors: Xerinda S , Neves N , Santos S , Piñeiro C , Poínhos R , Soares J , Serrão R , Sarmento A 
Published: November 2012

ObjectiveEvaluate the effectiveness and safety of simplification of tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV) in selected treatment‐experienced HIV‐1‐infected patients who have been virologically suppressed for>3 months on their current regimen.MethodsWe selected patients who started the simplified regimen between December 1st 2008 and March 31st 2012. Exclusion criteria: prior therapeutic failure, presence of resistance mutations to any component of TDF/FTC/EFV and patients previously observed in other centers. Efficacy and safety assessments were performed at baseline, 4 weeks after switch and then every 12–24 weeks. Statistical analysis was performed with SPSS version 20.0.Results384 patients were evaluated; 302 (79%) male; mean age 47 (SD=10) years; median CD4 cells count was 504 cells/mm3 (367–710). Baseline median glomerular filtration rate (eGFR; Cockcroft‐Gault equation) was 100 mL/min (86–116) and median ALT was 33 U/L (21–47). Median total cholesterol (TC) was 205 mg/dL (176‐236), high‐density lipoproteins (HDL) 45 mg/dL (38–54); low‐density lipoproteins (LDL) 130 mg/dL (108–151); triglycerides (TG) 125 mg/dL (84–176). Prior NNRTI‐based regimen in 327 (85%) patients (TDF/FTC and EFV in 76%); protease inhibitor in 52 (14%) and integrase inhibitor in 5 (1%). Discontinuation of treatment occurred in 49 patients (13%) after a mean time of 1.1 years (SD=1.1) of follow‐up: nervous system symptoms (n=11), decreased eGFR (n=5), virological failure (n=5), pregnancy (n=5), gastrointestinal symptoms (n=3), rash (n=1), other reasons (n=2); 12 patients dropped out the treatment and 5 died. Occurrence of blips (transient increase in VL ≤200 copies/mL) was documented in 98 (26%) patients; in 70, VL decreased to <20 copies/mL after the blips and in 28 VL is not yet available. 317 patients (83%) achieved≥48 weeks of follow‐up after simplification. Compared with baseline, significantly higher levels of CD4 cells count, HDL and eGFR were found and lower levels of TC, LDL and TG.

CD4
AST
ALT
TC
HDL
LDL
TG
eGFR

Baseline

Median
501
27
32
203
46
130
123
100

Percentiles 25
358
22
22
174
39
108
84
85

Percentiles 75
712
36
45
236
54
151
179
113

Follow‐up

Median
541
28
32
196
49
123
115
111

Percentiles 25
397
22
22
174
41
101
80
96

Percentiles 75
734
36
46
223
57
141
155
133

p‐value
<0.001
0.395
0.513
<0.001
<0.001
<0.001
<0.001
<0.001

ConclusionSimplification to TDF/FTC/EFV was shown to be an efficient and safe option in virologically suppressed patients and without a previous virological failure.
Intensification with maraviroc in HIV‐infected individuals (with or without liver cirrhosis) with a discordant CD4 response to cART
Authors: Blanco J , Guardo A , González‐Cordón A , Pérez I , Mallolas J , Martinez E , Arberas H , Laguno M , Martinez‐Rebollart M , Lonca M , Gatell J , Plana M 
Published: November 2012

BackgroundPatients with a discordant response to cART, defined as persistent CD4 + T‐cell counts <200 cells/mm3 and lack CD4 increase despite virologic suppression on HAART, have an increased risk of morbidity and mortality. Several studies have suggested a potential benefit of intensification with maraviroc (MVC) on CD4+T‐cell recovery.MethodsA 24‐week prospective, open‐label, randomized, controlled study. Subjects on cART, plasma HIV RNA <37 copies/mL for at least 12 months, and CD4 < 200 cells/L, with CD4‐gain in the previous 12 months <50 cells/µL, were randomized to add MVC (A) or continuing same cART (B). Randomisation was stratified by the presence of liver cirrhosis (CH) (n = 10) and non‐CH (n = 28). We measured by flow cytometry changes in the following parameters of CD4 + and CD8 + T‐cell subsets: activation (CD38, HLA‐DR), senescence (CD28, CD57, CD45RA and RO), coreceptors (CCR5 and CXCR4) and apoptosis (Annexin‐V).ResultsThirty‐eight subjects were included at the final analysis. Median values were: age 51 years (IQR, 44–57), time with VL < 37 copies/mL before entry 43 months (IQR 24–62 months), baseline CD4 + T‐cell count 144 cells/µL (IQR 106–181). Four subjects were lost of follow‐up (3 in A, 1 in B). One subject from group B experienced confirmed virologic failure at week 24. Adverse events were similar in both arms. Median increase in CD4 + T‐cell count from baseline to weeks 2,4 and 24 in both groups were +15.5 vs ‐1 (p = 0.025); +16.5 vs ‐2.5 (p = 0.158); +46.5 vs + 6.50 (p = 0.190). Similar trend towards a higher CD4 increase were seen in both CH and non‐CH individuals. At W24, 8 subjects from arm A vs 1 subject from arm B achieved a CD4 + T‐cell count above 200 cells/µL (p < 0.05). Markers of immune activation (CD38 and HLA‐DR) decreased during MVC intensification, especially in CD8+ T cells (p < 0.01) whereas apoptosis did not. Additionally CCR5 expression tended to increase (p = 0.051) in CD8 T cells from arm A subjects. No significant differences were found in the immunological assay between cirrhotic and non cirrhotic individuals.ConclusionsMVC intensification was safe and was associated with a significant a trend towards increasing CD4 + T‐cell counts both in cirrhotic as well as non‐cirrhotic patients with discordant response. The addition of MVC was associated with a decrease in markers of immune activation in both groups.
An improved finite frequency approach to robust filter design for LTI systems with polytopic uncertainties
Authors: Lee Dong Hwan 
Published: November 2012

SUMMARYIn this paper, the finite frequency robust filtering problem (‐FFRFP), design of a robust filter minimizing the norm from the disturbance input to the estimation error evaluated over a prescribed finite frequency domain, is considered for continuous‐time and discrete‐time linear time‐invariant (LTI) systems with polytopic parameter uncertainties. By means of the generalized Kalman–Yakubovich–Popov (KYP) lemma in combination with a result known as Finsler's lemma, the ‐FFRFP is cast as a linear matrix inequality (LMI) optimization. Examples are given to demonstrate that the proposed condition can achieve improvement over the previous ones in the literature. Copyright © 2012 John Wiley & Sons, Ltd.
Effects of Confinement on Microstructure and Charge Transport in High Performance Semicrystalline Polymer Semiconductors
Authors: Himmelberger Scott , Dacuña Javier , Rivnay Jonathan , Jimison Leslie H. , McCarthy‐Ward Thomas , Heeney Martin , McCulloch Iain , Toney Michael F. , Salleo Alberto 
Published: November 2012

AbstractThe film thickness of one of the most crystalline and highest performing polymer semiconductors, poly(2,5‐bis(3‐tetradecylthiophen‐2‐yl)thieno[3,2‐b]thiophene) (PBTTT), is varied in order to determine the effects of interfaces and confinement on the microstructure and performance in organic field effect transistors (OFETs). Crystalline texture and overall film crystallinity are found to depend strongly on film thickness and thermal processing. The angular distribution of crystallites narrows upon both a decrease in film thickness and thermal annealing. These changes in the film microstructure are paired with thin‐film transistor characterization and shown to be directly correlated with variations in charge carrier mobility. Charge transport is shown to be governed by film crystallinity in films below 20 nm and by crystalline orientation for thicker films. An optimal thickness is found for PBTTT at which the mobility is maximized in unannealed films and where mobility reaches a plateau at its highest value for annealed films.
Tröpfchen‐Mikrofluidik für die Einzelzellanalyse
Authors: Joensson Haakan N. , Andersson Svahn Helene 
Published: November 2012

AbstractDie tröpfchenbasierte Mikrofluidik dient der Isolierung und Manipulation von einzelnen Zellen und Reagentien innerhalb von monodispersen, pikolitergroßen Flüssigkapseln bei einem Umsatz von tausenden Tröpfchen pro Sekunde. Diese Qualitäten machen die Tröpfchen‐Mikrofluidik geeignet für viele Anforderungen der Einzelzellanalyse. Durch die Monodispersität lässt sich die Konzentration in den Tröpfchen quantitativ einstellen. Die Tröpfchen bieten der Zelle und ihrer unmittelbaren Umgebung ein isoliertes Kompartiment, und bei einem Durchsatz von tausenden Tröpfchen pro Sekunde ist es möglich, zehntausende bis millionen verkapselte Zellen zu prozessieren. Heterogene Zellpopulationen lassen sich somit exakt beschreiben oder seltene Zellarten identifizieren. Das kleine Volumen der Tröpfchen macht auch sehr große Screenings ökonomisch machbar. Dieser Aufsatz gibt einen Überblick über den aktuellen Stand der Einzelzellanalyse durch die Tröpfchen‐Mikrofluidik und nennt Beispiele, bei denen sie biologische Vorgänge besser verstehen hilft.
Droplet Microfluidics—A Tool for Single‐Cell Analysis
Authors: Joensson Haakan N. , Andersson Svahn Helene 
Published: November 2012

AbstractDroplet microfluidics allows the isolation of single cells and reagents in monodisperse picoliter liquid capsules and manipulations at a throughput of thousands of droplets per second. These qualities allow many of the challenges in single‐cell analysis to be overcome. Monodispersity enables quantitative control of solute concentrations, while encapsulation in droplets provides an isolated compartment for the single cell and its immediate environment. The high throughput allows the processing and analysis of the tens of thousands to millions of cells that must be analyzed to accurately describe a heterogeneous cell population so as to find rare cell types or access sufficient biological space to find hits in a directed evolution experiment. The low volumes of the droplets make very large screens economically viable. This Review gives an overview of the current state of single‐cell analysis involving droplet microfluidics and offers examples where droplet microfluidics can further biological understanding.
Flow‐injection chemiluminescence determination of diazepam by oxidation with N‐bromosuccinimide
Authors: Han Suqin , Jia Shize , Guo Liang 
Published: November 2012

ABSTRACTA rapid and sensitive flow‐injection chemiluminescence (FI–CL) method is described for the determination of diazepam based on its reaction with N‐bromosuccinimide (NBS) in alkaline medium in the presence of dichlorofluorescein (DCF) as an effective energy‐transfer agent. Under optimum conditions, the proposed method allowed the measurement of diazepam over the range of 2.0 × 10−6 to 2.0 × 10−4 mol/L with a detection limit of 5.0 × 10−7 mol/L. The relative standard deviation for 11 parallel measurements of 2.0 × 10−5 mol/L diazepam was 2.1%. The method was applied satisfactorily for the determination of diazepam in pharmaceutical preparations, and the results agree well with those obtained by spectrophotometry. The use of the proposed system for the determination of diazepam in urine and plasma samples was also tested. The possible mechanism of the chemiluminescence reaction is discussed briefly. Copyright © 2012 John Wiley & Sons, Ltd.
Randomized clinical trial of trigger point infiltration with lidocaine to diagnose anterior cutaneous nerve entrapment syndrome
Authors: Boelens O B A , Scheltinga M R , Houterman S , Roumen R M 
Published: November 2012

Abstract

Background
Anterior cutaneous nerve entrapment syndrome (ACNES) is hardly considered in the differential diagnosis of chronic abdominal pain. Some even doubt the existence of such a syndrome and attribute reported successful treatment results to a placebo effect. The objective was to clarify the role of local anaesthetic injection in diagnosing ACNES. The hypothesis was that pain attenuation following lidocaine injection would be greater than that after saline injection.

Methods
Patients aged over 18 years with suspected ACNES were randomized to receive an injection of 10 ml 1 per cent lidocaine or saline into the point of maximal abdominal wall pain just beneath the anterior fascia of the rectus abdominis muscle. Pain was recorded using a visual analogue scale (VAS; 1–100 mm) and a verbal rating scale (VRS; 0, no pain; 4, severe pain) during physical examination just before and 15–20 min after injection. A reduction of at least 50 per cent on the VAS and/or 2 points on the VRS was considered a successful response.

Results
Between August 2008 and December 2010, 48 patients were randomized equally (7 men and 41 women, median age 47 years). Four patients in the saline group reported a successful response compared with 13 in the lidocaine group (P = 0·007).

Conclusion
Entrapped branches of intercostal nerves may contribute to the clinical picture in some patients with chronic abdominal pain. Pain reduction following local infiltration in these patients was based on an anaesthetic mechanism and not on a placebo or a mechanical (volume) effect. Registration number: NTR2016 (Nederlands Trial Register; http://www.trialregister.nl).
Recurrence pattern in patients with a pathologically complete response after neoadjuvant chemoradiotherapy and surgery for oesophageal cancer
Authors: van Hagen P , Wijnhoven B P L , Nafteux P , Moons J , Haustermans K , De Hertogh G , van Lanschot J J B , Lerut T 
Published: November 2012

Abstract

Background
Little is known about recurrence patterns in patients with a pathologically complete response (pCR) or an incomplete response after neoadjuvant chemoradiotherapy (CRT) followed by resection for oesophageal cancer. This study was performed to determine the pattern of recurrence in patients with a pCR after neoadjuvant CRT followed by surgery.

Methods
All patients who received neoadjuvant CRT followed by oesophagectomy between 1993 and 2009 were identified from a database, and categorized according to pathological tumour response. Recurrences were classified as locoregional or distant.

Results
One hundred and eighty-eight patients were included. Median potential follow-up was 71·6 months. A pCR was achieved in 62 (33·0 per cent) of 188 patients. Recurrence developed in 24 (39 per cent) of 62 patients with a pCR and 70 (55·6 per cent) of 126 without a pCR (P = 0·044). Locoregional recurrence with or without synchronous distant metastases occurred in eight patients (13 per cent) in the pCR group and 31 (24·6 per cent) in the non-pCR group (P = 0·095). Locoregional recurrences without synchronous distant metastases occurred four (6 per cent) and ten (7·9 per cent) patients respectively (P = 0·945). The overall 5-year survival rate was significantly higher in the pCR group than in the non-pCR group (52 versus 33·9 per cent respectively; P = 0·019).

Conclusion
Of patients with a pCR, 13 per cent still developed a locoregional recurrence. Although pCR is more favourable for survival, it is not synonymous with cure or complete locoregional disease control.
Long-term results of a randomized clinical trial comparing Roux-en-Y gastric bypass with vertical banded gastroplasty
Authors: Werling M , Fändriks L , Björklund P , Maleckas A , Brandberg J , Lönroth H , le Roux C W , Olbers T 
Published: November 2012

Abstract

Background
The long-term results of Roux-en-Y gastric bypass (gastric bypass) and vertical banded gastroplasty (VBG) from randomized studies have not been described in detail.

Methods
Patients were randomized to gastric bypass or VBG. Body mass index (BMI), body composition, eating habits and gastrointestinal hormones were reviewed after 6 years. The frequency of reoperation was assessed up to 10 years after surgery.

Results
Sixty-six (80 per cent) of the 82 subjects randomized were assessed for weight and BMI 6 years after surgery, 30 (81 per cent) in the gastric bypass group and 36 (80 per cent) in the VBG group. Intention-to-treat analysis demonstrated greater weight loss after gastric bypass compared with VBG, 6 years after surgery: BMI reduced from 41·8 (95 per cent confidence interval 41·3 to 42·3) to 30·3 (28·6 to 32·0) kg/m2 for gastric bypass and from 42·3 (42·8 to 44·8) to 32·9 (31·3 to 34·5) kg/m2 for VBG (P = 0·036). Gastric bypass caused a larger loss of fat mass (P = 0·026) and better preservation of lean tissue (P = 0·009). Patients having a gastric bypass had greater postprandial responses to the satiety hormones glucagon-like peptide 1 and peptide YY (P = 0·003 and P = 0·004 respectively). Ghrelin levels did not differ between the groups. Patients with a gastric bypass maintained a lower intake of fat compared with those having VBG (P = 0·013). Some 89 per cent of patients who initially had VBG had undergone, or were scheduled for, conversion to gastric bypass at latest follow-up.

Conclusion
Gastric bypass was superior to VBG regarding weight loss, body composition, dietary composition and postprandial satiety hormone responses.
Systematic review of phaeochromocytoma in pregnancy
Authors: Biggar M A , Lennard T W J 
Published: November 2012

Abstract

Background
Phaeochromocytoma in pregnancy is a rare and potentially dangerous situation for mother and fetus. This review aimed to assess current mortality rates and how medical and surgical management affect these.

Methods
Articles in English published between 2000 and 2011 were obtained from a MEDLINE search. Eligible publications presented women diagnosed with phaeochromocytoma in the antenatal or immediate postnatal period, and reported management and outcomes.

Results
A total of 135 reports were identified. After applying inclusion criteria, 77 pregnancies involving 78 fetuses were analysed. Fetal and maternal mortality rates were 17 per cent (13 of 78) and 8 per cent (6 of 77) respectively. Better outcomes were achieved when the diagnosis of phaeochromocytoma was made in the antenatal period than when it was made during labour or immediately postpartum (survival of both mother and fetus(es) in 48 of 56 versus 12 of 21 respectively; P = 0·012). When the diagnosis was made before 23 weeks' gestation, there was no difference in outcomes when phaeochromocytoma surgery was carried out in the second trimester, compared with when it was postponed to the third trimester or after delivery (fetal death 2 of 18 versus 2 of 8 respectively; P = 0·563).

Conclusion
This review, although limited by the rarity of the condition and level of available evidence, demonstrated that survival rates are improved if the diagnosis of phaeochromocytoma can be established antenatally. With diagnosis before 23 weeks' gestation, no definite advantage of proceeding with tumour removal during the second trimester could be demonstrated.