Validation of a German version of the dementia screening questionnaire for individuals with intellectual disabilities (DSQIID-G) in Down's syndrome.

BACKGROUND: People with Down's syndrome (DS) are at high risk of developing Alzheimer dementia (DS-AD) due to a triplication of the amyloid precursor protein gene. While several tools to diagnose and screen for DS-AD, such as the dementia screening questionnaire for individuals with intellectual disabilities (DSQIID), are available in English, validated German versions of such instruments are scarce. METHODS: A German version of the DSQIID questionnaire (DSQIID-G) was completed by caregivers before attending our specialist outpatient department for DS-AD. All participants were assessed blind to DSQIID-G scoring using clinical and neuropsychological examinations, including the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). ICD-10 and amyloid/tau/neurodegeneration (A/T/N) criteria were applied to detect and categorise cognitive decline. RESULTS: Of 86 participants, 43 (50%) showed evidence of cognitive decline. A definite diagnosis of DS-AD was reached in 17 (19.8%) and mild cognitive impairment in seven (8.3%) participants. Secondary causes of cognitive decline were determined among 13 (15.1%) participants, and in six (7%) cases, the diagnosis remained unclassifiable due to co-morbidities. Compared with cognitively stable individuals, participants with cognitive decline (n = 43) displayed higher DSQIID-G total scores [median (range): 3 (0-21) vs. 19 (0-48), P < 0.001]. A total score of >7 provided a sensitivity of 0.94 against a specificity of 0.76, to discriminate DS-AD and participants without cognitive decline according to ROC analysis. The convergent validity against the CAMDEX-DS interview score was good (r = 0.74), and split-half reliability (r = 0.96), internal consistency (Cronbach's α r = 0.96), test-retest reliability (r = 0.88) (n = 25) and interrater reliability (r = 0.81) (n = 31) were excellent. CONCLUSIONS: The DSQIID-G showed excellent psychometric properties, including concurrent and internal validity and reliability. The cut-off value for screening was lower than in the original English validation study. For a screening instrument like DSQIID-G, a lower cut-off is preferable to increase case detection.

Substance use among HIV-infected adolescents in Uganda: rates and association with potential risks and outcome factors.

This article sets out to investigate alcohol and substance use (ASU) among adolescents living with HIV (ALWH) in the sub-Saharan African setting of Uganda. A cross-sectional analysis of the records of 479 adolescents (aged between 12and 17 years) attending the study, "Mental health among HIV infected CHildren and Adolescents in KAmpala and Masaka, Uganda (the CHAKA study)" was undertaken. ASU was assessed through both youth self-report and caregiver report using the Diagnostic and Statistical Manual of Mental Disorders-5 referenced instruments, the Youth Inventory-4R and the Child and Adolescent Symptom Inventory-5 (CASI-5). Rates and association with potential risk and outcome factors were investigated using logistic regression models. The rate of ASU was 29/484 (5.9%) with the most frequently reported ASU being alcohol 22/484 (4.3%) and marijuana 10/484 (2.1%). Functional impairment secondary to ASU was reported by 10/484 (2.1%) of the youth. ASU was significantly associated with urban residence, caregiver psychological distress and the psychiatric diagnosis of post-traumatic stress disorder. On associations with negative outcomes, ASU was significantly associated with only "ever had sex". Health care for ALWH in sub-Saharan Africa should include ASU prevention and management strategies.

[A German version of the Cambridge examination for mental disorders of older people with Down's syndrome and others with intellectual disabilities : A diagnostic procedure for detecting dementia in people with Down's syndrome]. / Eine deutsche Fassung der Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities : Ein Diagnoseverfahren zur Erfassung von Demenz bei Menschen mit einem Down-Syndrom.

BACKGROUND: Although people with Down's syndrome (DS) are at a high risk of developing an Alzheimer type dementia (AD) due to a triplication of the amyloid precursor gene, there are practically no internationally available test procedures to detect cognitive deficits in this at risk population in the German language. OBJECTIVE: The aim was to provide a German translation and intercultural adaptation of the Cambridge examination for mental disorders of older people with Down's syndrome and others with intellectual disabilities (CAMDEX-DS), which is available in English and Spanish. This instrument for diagnostics and monitoring consists of a psychological test examination (CAMCOG-DS) and a caregiver interview. METHODS: The translation and adaptation of the CAMDEX-DS were achieved through a multistep translation process, whereby two independent forward and back translations were provided by professional translators and a consensus version was finalized and tested. The final version of the caregiver interview was applied to 11 subjects and the CAMCOG-DS was conducted with 28 patients. RESULTS: The German version of the CAMDEX-DS proved to be easily administered. The CAMCOG-DS could be fully administered to 21 out of 28 patients (75%). The CAMCOG-DS values were much lower for older patients aged ≥45 years than for younger patients (46/109 vs. 73.5/109; p = 0.033). DISCUSSION: The German version of the CAMDEX-DS provides an internationally recognized tool for the diagnostics and monitoring of cognitive decline in Down's syndrome. Furthermore, the German version can standardize medical care of these patients. In particular it provides a means of participation in international research trials for this at risk population.

The relationship between cognitive change and physical health and behavioural outcomes in a Ugandan cohort of adults living with HIV - a longitudinal study.

We investigated changes in cognitive function and physical health and behavioural outcomes (HIV disease progression, health-seeking behaviour, adherence to HIV medications and risky sexual behaviour) at baseline and 12 months later among 1126 Ugandan adults living with HIV. Overall, cognitive function improved from baseline to follow-up, except for gait speed, which was slower at follow-up compared to baseline. There were improvements in physical health and behavioural outcomes by follow-up, with greater improvements among individuals on ART compared to those not on ART. Change in gait speed over time significantly predicted risky sexual behaviours at follow-up. This is the first study to investigate the longitudinal relationships between cognitive function and health outcomes among Ugandan adults living with HIV and provide insights into the possible links between cognitive function and negative clinical and behavioural health outcomes in people living with HIV.

Near-threshold photodissociation of cool OH+ to O + H+ and O+ + H.

We have measured the spectrum of laser photodissociation of OH+ molecular ions to O + H+ and O+ + H fragments for photon energies of 38 100-40 900 cm-1. The OH+ ions were stored as a fast beam (5.50 MeV) in the storage ring TSR for several seconds to achieve rovibrational cooling into the lowest rotations N'' = 0-11 of the vibrational ground state X3Σ-(v'' = 0), close to room temperature (≈300 K). The many resonances in the spectra reveal the energies, widths, and O/O+ branching ratios of 44 predissociating quasibound levels (Feshbach resonances) that lie between the fine-structure states of the O fragment and belong to the last, near-threshold vibrational states v' = 9 and 10 of the A3Π electronic state. For the A3Π0,1 substates, isolated levels with v' = 11 are observed and attributed to double-well distortions of these curves due to nonadiabatic interactions. Another five isolated levels are assigned to the v' = 0 and 1 states of the shallow 15Σ- electronic state, borrowing oscillator strength from nearby A3Π levels. Together, the near-threshold levels deliver a new value D0 = 40 253.8(1.1) cm-1 for the dissociation energy of OH+. Through a two-step photodissociation process, 72 levels from the lower bound states A3Π(v' = 7-8) appear as well and are rotationally analyzed. The level energies are used to construct improved A3Π and 15Σ- Born-Oppenheimer potentials. The totality of the spectral data (energies, widths, intensities, and branching ratios) can provide tight constraints for the potentials and nonadiabatic interactions assumed in future coupled-channel calculations of OH+ photodissociation or of the related charge-exchange reaction O + H+ → O+ + H.

Blood product wastage reduction by utilising low-cost, low-impact multimodal physician-to-physician communication initiatives.

OBJECTIVES: To assess a multimodal physician-to-physician communication initiative that is low in cost and impact to daily workflow to reduce blood product wastage. BACKGROUND: Blood product stewardship is an important issue in all hospital systems. Previous studies have proposed low-cost interventions to reduce blood product wastage, but few have evaluated improvements in communication between the blood bank and providers. We undertook a prospective quality improvement project focusing on improving communication to reduce blood product wastage. METHODS: We conducted a prospective quality improvement project over the first quarter of 2017, identifying patients with issued but unused blood products. Each service overseeing the care of patients identified on the unit status report was contacted through two possible methods: (i) phone or (ii) proprietary Health Insurance Portability and Accountability Act of 1996 compliant digital messaging application. Collected variables included reserved blood product type and participant time spent. Outcomes included the rate of blood product release and changes in wastage compared with historical data tracked by the blood bank. RESULTS: Eight hundred and forty products were reserved during the study period, of which 436 (52%) were released. Average participant times ranged from 2 ± 1 min to 15 ± 4 min with no significant differences in time spent between participants (P = 0·194). Compared with the average product wastage 10 months prior to project initiation, there were significant reductions in the average wastage for platelets (5·3 ± 2·5 units vs 2·5 ± 1·5 units, P = 0·05), RBCs (6·1 ± 3·7 units vs 0 ± 0 units, P = 0·01) and overall wastage (58·3 ± 14·9 units vs 40 ± 15·7 units, P = 0·05). CONCLUSION: Efforts focusing on improving provider-to-provider communication can reduce blood product wastage.

[Tauopathies : From molecule to therapy]. / Tauopathien : Vom Molekül zur Therapie.

BACKGROUND: The microtubule-associated tau protein is the defining denominator of a group of neurodegenerative diseases termed tauopathies. OBJECTIVE: Provide a timely state of the art review on recent scientific advances in the field of tauopathies. MATERIAL AND METHODS: Systematic review of the literature from the past 10 years. RESULTS: Tau proteins are increasingly being recognized as a highly variable protein, underlying and defining a spectrum of molecularly defined diseases, with a clinical spectrum ranging from dementia to hypokinetic movement disorders. Genetic variation at the tau locus can trigger disease or modify disease risk. Tau protein alterations can damage nerve cells and propagate pathologies through the brain. Thus, tau proteins may serve both as a serological and imaging biomarker. Tau proteins also provide a broad spectrum of rational therapeutic interventions to prevent disease progression. This knowledge has led to modern clinical trials. CONCLUSION: The field of tauopathies is in a state of dynamic and rapid progress, requiring close interdisciplinary collaboration.

Infant adiposity following a randomised controlled trial of a behavioural intervention in obese pregnancy.

OBJECTIVES: Randomised controlled trials are required to address causality in the reported associations between maternal influences and offspring adiposity. The aim of this study was to determine whether an antenatal lifestyle intervention, associated with improvements in maternal diet and reduced gestational weight gain (GWG) in obese pregnant women leads to a reduction in infant adiposity and sustained improvements in maternal lifestyle behaviours at 6 months postpartum. SUBJECTS AND METHODS: We conducted a planned postnatal follow-up of a randomised controlled trial (UK Pregnancies Better Eating and Activity Trial (UPBEAT)) of a complex behavioural intervention targeting maternal diet (glycaemic load (GL) and saturated fat intake) and physical activity in 1555 obese pregnant women. The main outcome measure was infant adiposity, assessed by subscapular and triceps skinfold thicknesses. Maternal diet and physical activity, indices of the familial lifestyle environment, were assessed by questionnaire. RESULTS: A total of 698 (45.9%) infants (342 intervention and 356 standard antenatal care) were followed up at a mean age of 5.92 months. There was no difference in triceps skinfold thickness z-scores between the intervention vs standard care arms (difference -0.14 s.d., 95% confidence interval -0.38 to 0.10, P=0.246), but subscapular skinfold thickness z-score was 0.26 s.d. (-0.49 to -0.02; P=0.03) lower in the intervention arm. Maternal dietary GL (-35.34; -48.0 to -22.67; P<0.001) and saturated fat intake (-1.93% energy; -2.64 to -1.22; P<0.001) were reduced in the intervention arm at 6 months postpartum. Causal mediation analysis suggested that lower infant subscapular skinfold thickness was partially mediated by changes in antenatal maternal diet and GWG rather than postnatal diet. CONCLUSIONS: This study provides evidence from follow-up of a randomised controlled trial that a maternal behavioural intervention in obese pregnant women has the potential to reduce infant adiposity and to produce a sustained improvement in maternal diet at 6 months postpartum.

[Pathomechanisms and clinical aspects of frontotemporal lobar degeneration]. / Pathomechanismen und klinische Aspekte der frontotemporalen Lobärdegeneration.

BACKGROUND: Frontotemporal lobar degeneration (FTLD) includes a spectrum of heterogeneous clinical and neuropathological diseases. In a strict sense this includes the behavioral variant of frontotemporal dementia (bvFTD) and primary progressive aphasia (PPA) and both variants can be associated with amyotrophic lateral sclerosis (FTD-ALS). In a broader sense FTLD also includes progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). In recent years the strong genetic component of FTLD has become increasingly clear. OBJECTIVE: The association between clinical presentation, neuropathology, genetics and pathophysiological mechanisms of FTLD are presented. RESULTS: The diagnostic criteria and tools for the clinical differential diagnosis of FTLD are presented. At autopsy patients show neuronal and glial inclusions of Tau, TDP-43 or FUS. While Tau pathology is often associated with extrapyramidal symptoms, patients with TDP-43 and FUS inclusions often also show signs of ALS. Pathogenic mutations directly increase the aggregation propensity of these proteins or impair protein degradation through autophagy or the proteasome. Pathogenic mutations in most FTLD genes trigger cytoplasmic missorting and aggregation of the RNA-binding protein TDP-43 and thus lead to a nuclear loss of TDP-43 function. Microgliosis and mutations in GRN and TREM2 suggest an important role of neuroinflammation in FTLD. CONCLUSION: There is still no causal therapy for FTLD but preclinical studies focusing on pathogenic mutations in C9orf72, GRN and Tau may lead to clinical trials soon; therefore, establishing large well characterized patient cohorts is crucial for trial readiness.

[Amyloid positron-emission-tomography with [18 F]-florbetaben in the diagnostic workup of dementia patients]. / Amyloid-Positronenemissionstomographie mit [18 F]-Florbetaben in der Demenzdiagnostik.

BACKGROUND: To this day the definite diagnosis of Alzheimer's disease still relies on post-mortem histopathological detection of neurofibrillary tangles and beta-amyloid deposits. Amyloid positron emission tomography (PET) is a new diagnostic tool that enables the in vivo quantification of pathological beta-amyloid deposits. The aim of the current study was to evaluate to what extent 18F-florbetaben-PET (FBB-PET) influences the diagnosis of patients with dementia. MATERIAL AND METHODS: Imaging with FBB-PET was performed on 33 patients from our outpatient department for cognitive neurology. Beforehand all patients underwent a comprehensive clinical, neuropsychiatric and laboratory examination as well as imaging by means of magnetic resonance imaging (MRI) and fluorodeoxyglucose-PET. The working diagnoses before and after FBB-PET imaging were compared. RESULTS: 17 out of 33 patients were scored as FBB-PET positive. In four cases the initial diagnosis had to be changed to Alzheimer's disease (three cases) and cerebral amyloid angiopathy (one case) due to the positive FBB-PET scan. 16 patients showed a negative FBB-PET scan. In three patients the initial diagnosis of Alzheimer's disease could be ruled out due to the negative FBB-PET scan. Overall, in 7 out of 33 examined patients the initial diagnosis had to be changed because of the findings of the FBB-PET scan. In 24 patients the initial diagnosis was confirmed by the results of the FBB-PET scan. CONCLUSION: Amyloid-PET is currently no standard procedure in the diagnosis of dementia; however, it can be a helpful additional diagnostic tool when used according to the "Appropriate Use Criteria" and the S3 guidelines on dementia in cases of unclear clinical presentation, atypically early age of onset as well as in patients with persistent or progressive unexplained mild cognitive impairment. By facilitating early diagnosis amyloid-PET imaging allows patient selection for therapeutic drug trials.

[A Pair of Siblings with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis and a Novel Thr462Lysfs Mutation in the TBK1 Gene]. / Ein Geschwisterpaar mit frontotemporaler Lobärdegeneration und amyotropher Lateralsklerose und einer neuen Mutation im TBK1-Gen (Thr462Lysfs).

We report on a pair of siblings with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) and a novel Thr462Lysfs mutation in the TANK-binding kinase 1 (TBK1) gene identified through the European Early-Onset Dementia Consortium. The patients presented at the age of 77 and 75 years and displayed dementia and bulbar symptoms as well as progressive paresis. After a progressive course, both of them died only a few months after diagnosis. Most recently, TBK1 mutations were identified in patients with FTD and ALS. A loss of expression of the mutant allele, leading to 50 % reduced TBK1 protein levels, seems to be causative. The occurrence of TBK1 mutations in FTD and ALS underlines the fact that FTD and ALS are part of the same disease spectrum. For future therapeutic trials, characterization of TBK1 mutation carriers in presymptomatic cohorts, such as the genetic frontotemporal dementia initiative (GENFI), is of great importance.

[Hereditary diffuse leukencephalopathy with spheroids: a microgliopathy due to CSF1 receptor impairment]. / Hereditäre diffuse Leukenzephalopathie mit Sphäroiden : Eine Mikrogliopathie durch Fehlfunktion des CSF1-Rezeptors.

Hereditary diffuse leukencephalopathy with spheroids (HDLS) is a rare progressive form of leukodystrophy with variable clinical presentation and little known pathophysiology. Characteristic pathological features at brain biopsy or postmortem can support the diagnosis. The genetic basis of HDLS was elusive until 2011 when mutations in the colony-stimulating factor 1 receptor (CSF1R) gene were identified as the cause. Mutations in the CSF1R gene had previously been associated with tumor development, including hematological malignancies. We report three patients with HDLS who carried missense mutations in the CSF1R gene, two of them novel (p.L582P and p.V383L). Particularly in younger patients with rapid cognitive decline and/or leukencephalopathy of unknown origin, HDLS appears to be more common than previously thought. Various compounds acting on the CSF1 receptor are available from the treatment of hemato-oncological malignancies, so novel therapeutic approaches could be developed for this devastating condition.

Efficacy of Mepliex® Ag Versus Xeroform® As A Split-Thickness Skin Graft Donor Site Dressing: Bad Habits Die Hard.

Autografting with split-thickness skin grafts (STSG) remains an essential procedure in burn and reconstructive surgery. The process of harvesting STSG, however, leaves behind a donor site, an exposed area of partial-thickness dermis left to heal by secondary intention. There has yet to be a consensus amongst surgeons regarding optimal management of the donor site. The ideal donor site dressing is one that allows for expeditious healing while minimizing pain and infection. Despite numerous studies demonstrating the superiority of moist wound healing, many surgeons continue to treat STSG donor sites dry, with petroleum-based gauze. In this study, two burn centers performed a retrospective review of burn patients whose STSG donor sites were treated with either Xeroform® or Mepilex® Ag dressings. Infections were documented and in a subgroup analysis of patients, postoperative pain scores were noted and total opiate usage during hospitalization was calculated. Analysis revealed an overall infection rate of 1.2% in the Mepilex® Ag group and 11.4% in the Xeroform® group (p<0.0001). Patients with Xeroform® donor site dressings had increased odds of donor site infection (OR=10.8, p=0.002). In subgroup analysis, there were no significant differences in maximum pain scores between Mepilex® Ag and Xeroform® groups, nor were there differences in opiate usage. STSG donor sites dressed with silver foam dressings have a lower rate of donor site infection relative to those dressed with petroleum-based gauze. Moist donor site dressings such as foam dressings (including Mepilex® Ag) should be the standard of care in STSG donor site wound care.

La greffes de peau mince (GPM) demeure une procédure essentielle dans la chirurgie de brûlure et de reconstruction. La zone donneuse de greffe (ZDG) représente une perte de substance cutanée superficielle, cicatrisant spontanément. Il n'y a pas de consensus concernant la prise en charge optimale de la ZDG. Le pansement idéal de la ZDG doit promouvoir la cicatrisation et réduire la douleur ainsi que le risque infectieux. Malgré les nombreuses publications montrant l'intérêt d'un environnement humide pour la cicatrisation, de nombreux chirurgiens réalisent des pansements secs vaselinés. Cette étude rétrospective effectuée dans 2 CTB compare les pansements de ZDG réalisés au Xéroform® ou au Mepilex Ag®. Les infections ont été documentées et, dans un sous-groupe, les scores de douleur et la consommation d'opiacés au long de l'hospitalisation ont été notés. Les taux d'infection sont de 1,2% dans le groupe Mepilex Ag® et 11,4% avec Xéroform® (p<0,0001). Le risque d'infection de la ZDG est augmenté (OR 10,8 ; p = 0,002) en cas d'utilisation de Xéroform®. Il n'y avait pas de différence de douleur et de consommation d'opiacés entre les 2 groupes. Les ZDG recouvertes d'un pansement hydrocellulaire imprégné d'argent s'infectent moins que celles traitées avec une gaze imprégnée de vaseline. L'utilisation sur les ZDG d'un pansement humide comme une mousse hydrocellulaire (par exemple Mepilex Ag®) devrait devenir la norme.

Axonal damage and astrocytosis are biological correlates of grey matter network integrity loss: a cohort study in autosomal dominant Alzheimer disease.

Brain development and maturation leads to grey matter networks that can be measured using magnetic resonance imaging. Network integrity is an indicator of information processing capacity which declines in neurodegenerative disorders such as Alzheimer disease (AD). The biological mechanisms causing this loss of network integrity remain unknown. Cerebrospinal fluid (CSF) protein biomarkers are available for studying diverse pathological mechanisms in humans and can provide insight into decline. We investigated the relationships between 10 CSF proteins and network integrity in mutation carriers (N=219) and noncarriers (N=136) of the Dominantly Inherited Alzheimer Network Observational study. Abnormalities in Aß, Tau, synaptic (SNAP-25, neurogranin) and neuronal calcium-sensor protein (VILIP-1) preceded grey matter network disruptions by several years, while inflammation related (YKL-40) and axonal injury (NfL) abnormalities co-occurred and correlated with network integrity. This suggests that axonal loss and inflammation play a role in structural grey matter network changes. Key points: Abnormal levels of fluid markers for neuronal damage and inflammatory processes in CSF are associated with grey matter network disruptions.The strongest association was with NfL, suggesting that axonal loss may contribute to disrupted network organization as observed in AD.Tracking biomarker trajectories over the disease course, changes in CSF biomarkers generally precede changes in brain networks by several years.

The impact of first year adherence to antiretroviral therapy on long-term clinical and immunological outcomes in the DART trial in Uganda and Zimbabwe.

OBJECTIVES: To describe associations between different summaries of adherence in the first year on antiretroviral therapy (ART) and the subsequent risk of mortality, to identify patients at high risk because of early adherence behaviour. METHODS: We previously described an approach where adherence behaviour at successive clinic visits during the first year on ART was seen as a Markov chain (MC), and the individually estimated transition probabilities between 'good', 'poor' and 'non-response' adherence states were used to classify HIV-infected adults in the DART trial into subgroups with similar behaviour. The impact of this classification and classifications based on traditional 'averaged' measures [mean drug possession ratio (DPR) and self-reported adherence] were compared in terms of their impact on longer-term mortality over the 2-5 years on ART using Cox proportional hazards models. RESULTS: Of 2960 participants in follow-up after 1 year on ART, 29% had never missed pills in the last month and 11% had 100% DPR throughout the first year. The poorest adherers by self-reported measures were more likely to have only none/primary education (P < 0.01). Being in the poorest adherence subgroup by MC and DPR was independently associated with increased mortality [HR = 1.57 (95% CI 1.02, 2.42); 1.82 (1.32, 2.51) respectively]. CONCLUSIONS: Classification based on dynamic adherence behaviour is associated with mortality independently of DPR. The classifications could be useful in understanding adherence, targeting focused interventions and improving longer-term adherence to therapy.

Surgical evaluation of a novel tethered robotic capsule endoscope using micro-patterned treads.

BACKGROUND: The state-of-the-art technology for gastrointestinal (GI) tract exploration is a capsule endoscope (CE). Capsule endoscopes are pill-sized devices that provide visual feedback of the GI tract as they move passively through the patient. These passive devices could benefit from a mobility system enabling maneuverability and controllability. Potential benefits of a tethered robotic capsule endoscope (tRCE) include faster travel speeds, reaction force generation for biopsy, and decreased capsule retention. METHODS: In this work, a tethered CE is developed with an active locomotion system for mobility within a collapsed lumen. Micro-patterned polydimethylsiloxane (PDMS) treads are implemented onto a custom capsule housing as a mobility method. The tRCE housing contains a direct current (DC) motor and gear train to drive the treads, a video camera for visual feedback, and two light sources (infrared and visible) for illumination. RESULTS: The device was placed within the insufflated abdomen of a live anesthetized pig to evaluate mobility performance on a planar tissue surface, as well as within the cecum to evaluate mobility performance in a collapsed lumen. The tRCE was capable of forward and reverse mobility for both planar and collapsed lumen tissue environments. Also, using an onboard visual system, the tRCE was capable of demonstrating visual feedback within an insufflated, anesthetized porcine abdomen. CONCLUSION: Proof-of-concept in vivo tRCE mobility using micro-patterned PDMS treads was shown. This suggests that a similar method could be implemented in future smaller, faster, and untethered RCEs.

Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial.

BACKGROUND: HIV antiretroviral therapy (ART) is often managed without routine laboratory monitoring in Africa; however, the effect of this approach is unknown. This trial investigated whether routine toxicity and efficacy monitoring of HIV-infected patients receiving ART had an important long-term effect on clinical outcomes in Africa. METHODS: In this open, non-inferiority trial in three centres in Uganda and one in Zimbabwe, 3321 symptomatic, ART-naive, HIV-infected adults with CD4 counts less than 200 cells per microL starting ART were randomly assigned to laboratory and clinical monitoring (LCM; n=1659) or clinically driven monitoring (CDM; n=1662) by a computer-generated list. Haematology, biochemistry, and CD4-cell counts were done every 12 weeks. In the LCM group, results were available to clinicians; in the CDM group, results (apart from CD4-cell count) could be requested if clinically indicated and grade 4 toxicities were available. Participants switched to second-line ART after new or recurrent WHO stage 4 events in both groups, or CD4 count less than 100 cells per microL (LCM only). Co-primary endpoints were new WHO stage 4 HIV events or death, and serious adverse events. Non-inferiority was defined as the upper 95% confidence limit for the hazard ratio (HR) for new WHO stage 4 events or death being no greater than 1.18. Analyses were by intention to treat. This study is registered, number ISRCTN13968779. FINDINGS: Two participants assigned to CDM and three to LCM were excluded from analyses. 5-year survival was 87% (95% CI 85-88) in the CDM group and 90% (88-91) in the LCM group, and 122 (7%) and 112 (7%) participants, respectively, were lost to follow-up over median 4.9 years' follow-up. 459 (28%) participants receiving CDM versus 356 (21%) LCM had a new WHO stage 4 event or died (6.94 [95% CI 6.33-7.60] vs 5.24 [4.72-5.81] per 100 person-years; absolute difference 1.70 per 100 person-years [0.87-2.54]; HR 1.31 [1.14-1.51]; p=0.0001). Differences in disease progression occurred from the third year on ART, whereas higher rates of switch to second-line treatment occurred in LCM from the second year. 283 (17%) participants receiving CDM versus 260 (16%) LCM had a new serious adverse event (HR 1.12 [0.94-1.32]; p=0.19), with anaemia the most common (76 vs 61 cases). INTERPRETATION: ART can be delivered safely without routine laboratory monitoring for toxic effects, but differences in disease progression suggest a role for monitoring of CD4-cell count from the second year of ART to guide the switch to second-line treatment. FUNDING: UK Medical Research Council, the UK Department for International Development, the Rockefeller Foundation, GlaxoSmithKline, Gilead Sciences, Boehringer-Ingelheim, and Abbott Laboratories.

Fibrinogen-coated albumin microcapsules reduce bleeding in severely thrombocytopenic rabbits.

Severe thrombocytopenia frequently occurs in patients receiving chemotherapy and in patients with autoimmune disorders. Thrombocytopenia is associated with bleeding, which may be serious and life threatening. Current treatment strategies for thrombocytopenia may require transfusion of allogeneic platelets, which is associated with serious drawbacks. These include the occurrence of anti-platelet antibodies, which may result in refractoriness to further platelet transfusions, and the potential risk of transfer of blood-borne diseases. Therefore, we have recently developed a platelet substitute product (Synthocytes), which is composed of human albumin microcapsules with fibrinogen immobilized on their surface. Here we show that the intravenous administration of these microcapsules not only corrects the prolonged bleeding time in rabbits rendered thrombocytopenic either by anti-platelet antibodies or by chemotherapy, but also reduces bleeding from surgical wounds inflicted in the abdominal skin and musculature. No potential systemic prothrombotic effect of the microcapsules was observed in a model of rabbit venous thrombosis. As for the mechanism of action, experiments with normal and thrombocytopenic human blood in an endothelial cell matrix-coated perfusion chamber demonstrated an interaction between the fibrinogen-coated albumin microcapsules and native platelets. It was shown that the fibrinogen-coated albumin microcapsules could facilitate platelet adhesion to endothelial cell matrix and correct the impaired formation of platelet aggregates in relatively platelet-poor blood. This study indicates that fibrinogen-coated albumin microcapsules can act to improve primary hemostasis under thrombocytopenic conditions and may eventually be a promising agent for prophylaxis and treatment of bleeding in patients with severe thrombocytopenia.

Lower oxygen saturation targets in preterm infants are not associated with increased rates of pulmonary hypertension.

BACKGROUND: The optimal oxygen saturation target in preterm infants is not known. In this study, we aimed to assess the effect of lower oxygen saturation targets on the rate of bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and pulmonary hypertension (PH) in preterm infants. METHODS: Retrospective cohort study comparing BPD, ROP, and PH incidence among two cohorts of infants born at≤32 weeks gestation with different oxygen saturation targets at≥34 weeks post-menstrual age (PMA): cohort 1, 94-98% (n = 126); cohort 2, 92-97% (n = 121). Groups compared by Chi-square test, t-test, and multivariable logistic regression. RESULTS: When comparing cohort 1 (average gestational age 29.8 weeks, average birth weight 1271g) with cohort 2 (average gestational age 29.6 weeks, average birth weight 1299g), there was no difference in rate of BPD (24% vs. 19%, p = 0.38), ROP (4% vs. 3%, p = 0.49), or PH (2% vs. 4%, p = 0.44). CONCLUSION: An oxygen saturation target of 92-97% at≥34 weeks PMA was not associated with a higher rate of PH or lower rate of BPD or ROP when compared with a higher target of 94-98%.

Use of nail and oral pigmentation to determine ART eligibility among HIV-infected Ugandan adults.

OBJECTIVES: To evaluate the use of grey/distal banded nails as an indicator of advanced immunosuppression, and thus eligibility for ART, in resource poor settings. METHODS: We tested whether grey/distal banded nails and/or oral pigmentation could be used to identify patients with low CD4 cell counts at two cut-offs: <200 and <350 cells/microl in ART naive adults. RESULTS: Four hundred and three nail and oral cavities were photographed and assessed. Grey/distal banded nails and/or oral pigmentation were significantly associated with a CD4 cell count <200 cells/microl (P < 0.001), with a sensitivity of 66%, a specificity of 50% and a negative predictive value of 77%. However, there was no association when a CD4 cell count cut-off of <350 cells/microl was used. Inter-observer agreement (k 0.46) was fair/moderate. CONCLUSIONS: While grey/distal banded nails and/or oral pigmentation are associated with low CD4 counts, the sensitivity and kappa score are too low for this method to be recommended as a tool to guide ART initiation; large number of individuals eligible for ART would be missed.