Evaluating patient perspectives of endovascular created arteriovenous fistulas for dialysis access (EndoAVF).

BACKGROUND: Patient reported experience measures are contemporary quality indicators that focus on evaluation of healthcare delivery processes. While surgical arteriovenous fistulas (otherAVF) are preferred for haemodialysis vascular access, fears about surgery and complications often result in refusal/delays. A new technique of endovascular arteriovenous fistula creation (EndoAVF) has been developed and as part of it's ongoing introduction into our unit, the patient perspective was felt critical to its evaluation. The Vascular Access Questionnaire (VAQ) provides a mechanism for identifying and scoring perceptions in this setting. METHOD: Patients who had previously undergone EndoAVF formation were approached to undertake the VAQ as part of a service evaluation of their experience. In addition to the components of the VAQ, data questions relating to the patient's perception of their access were gathered. Results were compared with a matched historical cohort of surgically created fistulas (otherAVF) patients. RESULTS: Patient satisfaction and self-reported ease of use with EndoAVF were high. Overall VAQ scores were similar between the EndoAVF and the surgically created cohort. Functionally, there was no significant difference in perception of their fistula by patients, irrespective of them being created surgically or radiologically. CONCLUSION: Although numbers in this report are small limiting exploration of preserved inherent heterogeneity, we provide a useful initial patient reported experience and perspectives on comparative functional use of radiologically and surgically created AVFs. As real world experience gathers, future larger cohorts with adequate sampling may allow exploration of patient reported experiences and outcome measures.

Effects of atherectomy on major adverse limb events for femoropopliteal interventions: Vascular Quality Initiative registry.

BACKGROUND: Atherectomy use in treatment of femoropopliteal disease has significantly increased despite scant evidence of benefit to long-term clinical outcomes. AIMS: We investigated the clinical benefits of atherectomy over standard treatment for femoropopliteal interventions. METHODS: Using data from the Society of Vascular Surgery's Vascular Quality Initiative (VQI) registry, we identified patients who underwent isolated femoropopliteal interventions for occlusive disease. We compared 13,423 patients treated with atherectomy with 47,371 receiving standard treatment; both groups were allowed definitive treatment with a drug-coated balloon or stenting. The primary endpoint was major adverse limb events (MALEs), which is a composite of target vessel re-occlusion, ipsilateral major amputation, and target vessel revascularization. RESULTS: Mean age was 69 ± 11 years, and patients were followed for a median of 30 months. Overall rates of complications were slightly higher in the atherectomy group than the standard treatment group (6.2% vs. 5.9%, p < 0.0001). In multivariable analysis, after adjusting for demographic and clinical covariates, atherectomy use was associated with a 13% reduction in risk of MALEs (adjusted odds ratio [aOR]: 0.87; 95% confidence interval [CI]: 0.77-0.98). Rates of major and minor amputations were significantly lower in the atherectomy group (3.2% vs. 4.6% and 3.3% vs. 4.3%, respectively, both p < 0.001), primarily driven by a significantly decreased risk of major amputations (aOR 0.69; 95% CI: 0.52-0.91). There were no differences in 30-day mortality, primary patency, and target vessel revascularization between the atherectomy and standard treatment groups. CONCLUSIONS: In adults undergoing femoropopliteal interventions, the use of atherectomy was associated with a reduction in MALEs compared with standard treatment.

Single incision laparoscopy versus conventional multiport laparoscopy for colorectal surgery: a systematic review and meta-analysis.

INTRODUCTION: There has been an increase in colorectal cancer resections worldwide and in the UK. Initially conducted as an open procedure, this was replaced with the conventional multiport technique. Laparoscopic colectomy became the standard surgical technique in 1991. With innovation in surgical technology, single incision laparoscopy (SIL) has attracted more attention as the possible next step in colorectal resection. The aim of this review was to compare outcomes between SIL and conventional laparoscopy (CL). METHODS: A literature search was carried out in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. The PubMed®, MEDLINE®, Embase®, Google Scholar™ and Cochrane Library databases were used to extract randomised controlled trials (RCTs) published between January 2000 and May 2021. Statistical analysis was performed with RevMan software. RESULTS: A total of 11 RCTs were extracted with 1,370 patients (686 SIL, 684 CL). There was no significant difference between SIL and CL for operative time (standardised mean difference [SMD]: 0.01, 95% confidence interval [CI]: -0.19 to 0.22, z=0.11, p=0.91), length of hospital stay (SMD: -0.10, 95% CI: 0.22 to 0.02, z=1.61, p=0.11) or overall complications (odds ratio [OR]: 0.99, 95% CI: 0.75 to 1.30, z=0.09, p=0.93). SIL had a shorter mean incision (SMD: -0.99, 95% CI: -1.35 to -0.62, z=5.25, p<0.00001). Patients undergoing SIL had a higher conversion rate to CL or an open approach (OR: 3.10, 95% CI: 0.95 to 10.14, z=1.87, p=0.06) but this just missed statistical significance. CONCLUSIONS: SIL can be considered a safe alternative to CL if performed by experienced surgeons.

Early Thoracic Endovascular Aortic Repair of Uncomplicated Type B Thoracic Aortic Dissection: An Aorta Team Approach.

BACKGROUND: Although uncomplicated Type B aortic dissection (uTBAD) is traditionally treated with optimal medical therapy (OMT) as per guidelines, recent studies, performed primarily in interventional radiology or surgical operating rooms, suggest superiority of thoracic endovascular aortic repair (TEVAR) over OMT due to recent advancements in endovascular technologies. We report a large, single-center, case control study of TEVAR versus OMT in this population, undertaken solely in a cardiac catheterization laboratory (CCL) with a cardiologist and surgeon. We aimed to determine if TEVAR for uTBAD results in better outcomes compared with OMT. METHODS: This was a retrospective chart review of all patients with uTBAD during the last 13 years, with 46 cases (TEVAR group) and 56 controls (OMT group). RESULTS: In the TEVAR group, the procedure duration of 2.5 hours resulted in 100% procedural success for stent placement, with 63% undergoing protective left subclavian artery bypass, 0% mortality or stroke, and a lower readmission rate (1 vs. 2%; p = 0.04 in early TEVAR cases), but a longer length of stay (12.9 vs. 8.5 days: p = 0.006). The risk of all-cause long-term mortality was markedly reduced in the TEVAR group (RR = 0.38; p = 0.01), irrespective of early (<14 days) versus late intervention. On follow-up computed tomography imaging, the false lumen stabilized or decreased in 85% of cases, irrespective of intervention timing. CONCLUSION: TEVAR performed solely in the CCL is safe and effective, with lower all-cause mortality than OMT. These data, in collaboration with previous data on TEVAR in different settings, call for consideration of an update of practice guidelines.

The role of serotonin neurotransmission in rapid antidepressant actions.

RATIONALE: Ketamine has rapid antidepressant effects that represent a significant advance in treating depression, but its poor safety and tolerability limit its clinical utility. Accreting evidence suggests that serotonergic neurotransmission participates in the rapid antidepressant effects of ketamine and hallucinogens. Thus, understanding how serotonin contributes to these effects may allow identification of novel rapid antidepressant mechanisms with improved tolerability. OBJECTIVE: The goal of this paper is to understand how serotonergic mechanisms participate in rapid antidepressant mechanisms. METHODS: We review the relevance of serotonergic neurotransmission for rapid antidepressant effects and evaluate the role of 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 receptors in synaptic plasticity, BDNF signaling, and GSK-3ß activity. Subsequently, we develop hypotheses on the relationship of these receptor systems to rapid antidepressant effects. RESULTS: We found that 5-HT1A and 5-HT1B receptors may participate in ketamine's rapid antidepressant mechanisms, while agonists at 5-HT2A and 5-HT4 receptors may independently behave as rapid antidepressants. 5-HT1A, 5-HT2A, and 5-HT4 receptors increase synaptic plasticity in the cortex or hippocampus but do not consistently increase BDNF signaling. We found that 5-HT1A and 5-HT1B receptors may participate in rapid antidepressant mechanisms as a consequence of increased BDNF signaling, rather than a cause. 5-HT2A and 5-HT4 receptor agonists may increase BDNF signaling, but these relationships are tenuous and need more study. Finally, we found that ketamine and several serotonergic receptor systems may mechanistically converge on reduced GSK-3ß activity. CONCLUSIONS: We find it plausible that serotonergic neurotransmission participates in rapid antidepressant mechanisms by increasing synaptic plasticity, perhaps through GSK-3ß inhibition.

GP access to FIT increases the proportion of colorectal cancers detected on urgent pathways in symptomatic patients in Nottingham.

OBJECTIVE: Service evaluation of GP access to Faecal Immunochemical Test (FIT) for colorectal cancer (CRC) detection in Nottinghamshire and use of FIT for "rule out", "rule in" and "first test selection". DESIGN: Retrospective audit of FIT results, CRC outcomes and resource utilisation before and after introduction of FIT in Primary Care in November 2017. Data from the new pathway up to December 2018 was compared with previous experience. RESULTS: Between November 2017 and December 2018, 6747 GP FIT test requests yielded 5733 FIT results, of which 4082 (71.2%) were <4.0 µg Hb/g faeces, 579 (10.1%) were 4.0-9.9 µg Hb/g faeces, 836 (14.6%) were 10.0-149.9 µg Hb/g faeces, and 236 (4.1%) were ≥150.0 µg Hb/g faeces. The proportion of "rule out" results <4.0 µg Hb/g faeces was significantly higher than in the Getting FIT cohort (71.2% vs 60.4%, Chi squared 42.8, p < 0.0001) and the proportion of "rule in" results ≥150.0 µg Hb/g faeces was significantly lower (4.1% vs 8.1%, Chi squared 27.3,P < 0.0001). There was a 33% rise in urgent referrals across Nottingham overall during the evaluation period. 2 CRC diagnoses were made in 4082 patients who had FIT<4.0 µg Hb/g faeces. 58.4% of new CRC diagnoses associated with a positive FIT were early stage cancers (Stage I and II). The proportion of all CRC diagnoses that follow an urgent referral s rose after introduction of FIT. CONCLUSIONS: FIT allows GP's to select a more appropriate cohort for urgent investigation without a large number of missed diagnoses. FIT appears to promise a "stage migration" effect which may ultimately improve CRC outcomes.

The vascular access questionnaire: a single centre UK experience.

BACKGROUND: Haemodialysis is capable of prolonging life in patients with end stage renal disease, however this therapy comes with significant negative impact on quality of life. For patients requiring haemodialysis, the need for an adequately functioning vascular access (VA) is an everyday concern. The Vascular Access Questionnaire (VAQ) provides a mechanism for identifying and scoring factors in haemodialysis that impact on patients' quality of life and perception of their therapy. METHODS: Between April 2017-18 the VAQ was administered to prevalent haemodialysis patients at 10 units in the West Midlands via structured interviews. RESULTS: 749 of 920 potentially eligible patients completed the survey. The mean VAQ score was seen to improve significantly with age (7.7 in < 55 vs. 3.8 in 75+) and the duration of access (8.9 if less than 1 month old vs. 5.0 at a year). Better average scores were demonstrated for Arteriovenous fistulas (AVF) than other modalities (AVF 5.1 vs. AVG (arteriovenous grafts) 7.2 vs. CVC (central venous catheter) 6.6). There was no significant difference in scores between fistulas on non-dominant or dominant arms, with both having a mean of 5.2 (p = 0.341). CONCLUSIONS: Overall, better satisfaction scores were seen in AVF. The presence of an AVF on the non-dominant arm was not a concern for the majority of patients and did not affect the VAQ score. A number of factors were identified that can influence VAQ satisfaction score.

The directional and non-directional associations of periodontitis with chronic kidney disease: A systematic review and meta-analysis of observational studies.

This systematic review aimed to assess the current evidence on the directional and non-directional associations of periodontitis with chronic kidney disease (CKD). Electronic search for observational studies on the association of periodontitis with CKD was performed in MEDLINE, EMBASE, PubMed, Open GREY and Cochrane library up to June 5, 2017. Two reviewers conducted study selection, data collection and assessment of methodological quality using the original and modified Newcastle-Ottawa Scale. Cohort, case-control and cross-sectional studies were included, which clearly defined periodontitis and CKD or reported acceptable clinical parameters of these 2 diseases in adults. Meta-analysis was employed to estimate the pooled odds ratio on the non-directional association and the incidence rate ratio (IRR) for the directional association. Among 2530 potential eligible articles, 47 were finally included. Most of them investigated a non-directional association of periodontitis with CKD, including 7 case-control studies and 38 cross-sectional studies; 24 studies had statistical analysis on the non-directional association and 75% of them reported significant results, which were supported further by the meta-analysis (random: odds ratio = 2.12, P < .001; χ2  = 25.74, I2  = 88.3%). None of the studies focused on the directional association of CKD (as the exposure) with periodontitis (as the outcome), whereas 2 retrospective cohort studies explored a directional association of periodontitis (as the exposure) with CKD (as the outcome) (random: IRR=2.10, P > .05; fixed: IRR=1.76, P < .05; χ2  = 4.65, I2  = 78.3%). Overall, the high heterogeneity of studies limits the significance of these results. There is substantial evidence on the non-directional association of periodontitis with CKD, while there are limited studies on the directional association. Well-designed prospective studies with longer follow-ups in representative communities are needed to clarify the directional association and enhance the quality of the evidence on this topic.

Maintaining Patency of Vascular Access for Haemodialysis.

All types of vascular access, a necessity for haemodialysis, are prone to thrombosis and if untreated this results in failure. Thrombosis results from the combination of impaired blood flow, endothelial and vessel wall injury and a propensity towards pro-coagulative states, either intrinsic or aggravated by dialysis or dehydration. The treatment of access thrombosis relies on removal of the clot (thrombectomy) and treatment of the underlying problem. In most cases this is stenosis secondary to neointimal hyperplasia which can occur early (failure to mature) or later. Pharmacological approaches have largely been shown to be ineffective at prevention of thrombosis. The mainstay of preventing access failure may be in surveillance and detecting stenosis prior to occlusion although the optimal protocol to achieve this remains undefined. Management of thrombosed access is via either surgical and radiological approaches. Multiple techniques and devices are available for thrombectomy and the choice is usually based on local expertise and availability rather than evidence as few trials have been performed to allow robust comparisons. This paper outlines the basis of access thrombosis and discusses the currently available techniques for treatment.

A legal perspective on athlete screening and disqualification.

Physicians participate in the screening, routine medical supervision, and disqualification of student-athletes. In doing so, they should understand that eligibility/disqualification decisions inevitably have associated liability issues. It is the responsibility of physicians to take the lead role in the student-athlete medical assessment process to allow for optimum safety in sports programmes. The first duty of the physician is to protect the health and well-being of the student-athlete. However, because there is potential liability associated with the screening/disqualification process, physicians are wise to develop sound and reasonable strategies that are in strict compliance with the standard of care. This article focusses on cardiac screening and disqualification for participation in sports.

Mechanism of Enhanced HIV Restriction by Virion Coencapsidated Cytidine Deaminases APOBEC3F and APOBEC3G.

The APOBEC3 (A3) enzymes, A3G and A3F, are coordinately expressed in CD4+ T cells and can become coencapsidated into HIV-1 virions, primarily in the absence of the viral infectivity factor (Vif). A3F and A3G are deoxycytidine deaminases that inhibit HIV-1 replication by inducing guanine-to-adenine hypermutation through deamination of cytosine to form uracil in minus-strand DNA. The effect of the simultaneous presence of both A3G and A3F on HIV-1 restriction ability is not clear. Here, we used a single-cycle infectivity assay and biochemical analyses to determine if coencapsidated A3G and A3F differ in their restriction capacity from A3G or A3F alone. Proviral DNA sequencing demonstrated that compared to each A3 enzyme alone, A3G and A3F, when combined, had a coordinate effect on hypermutation. Using size exclusion chromatography, rotational anisotropy, and in vitro deamination assays, we demonstrate that A3F promotes A3G deamination activity by forming an A3F/G hetero-oligomer in the absence of RNA which is more efficient at deaminating cytosines. Further, A3F caused the accumulation of shorter reverse transcripts due to decreasing reverse transcriptase efficiency, which would leave single-stranded minus-strand DNA exposed for longer periods of time, enabling more deamination events to occur. Although A3G and A3F are known to function alongside each other, these data provide evidence for an A3F/G hetero-oligomeric A3 with unique properties compared to each individual counterpart. IMPORTANCE: The APOBEC3 enzymes APOBEC3F and APOBEC3G act as a barrier to HIV-1 replication in the absence of the HIV-1 Vif protein. After APOBEC3 enzymes are encapsidated into virions, they deaminate cytosines in minus-strand DNA, which forms promutagenic uracils that induce transition mutations or proviral DNA degradation. Even in the presence of Vif, footprints of APOBEC3-catalyzed deaminations are found, demonstrating that APOBEC3s still have discernible activity against HIV-1 in infected individuals. We undertook a study to better understand the activity of coexpressed APOBEC3F and APOBEC3G. The data demonstrate that an APOBEC3F/APOBEC3G hetero-oligomer can form that has unique properties compared to each APOBEC3 alone. This hetero-oligomer has increased efficiency of virus hypermutation, raising the idea that we still may not fully realize the antiviral mechanisms of endogenous APOBEC3 enzymes. Hetero-oligomerization may be a mechanism to increase their antiviral activity in the presence of Vif.

A systematic review comparing single-incision versus multi-incision laparoscopic surgery for inguinal hernia repair with mesh.

OBJECTIVE: The objective of this article is to evaluate whether the surgical outcomes differ between single incision laparoscopic surgery (SILS) versus multi-incision laparoscopic surgery (MILS) for the repair of inguinal hernia. METHODS: A systematic review of the literature on published studies reporting the surgical outcomes following SILS versus MILS for inguinal hernia repair was undertaken using the principles of meta-analysis. RESULTS: Fifteen comparative studies on 1651 patients evaluating the surgical outcomes in patients undergoing SILS versus MILS for inguinal hernia repair were systematically analysed. The post-operative recovery time was significantly quicker [odds ratio, -0.35 (CI, -0.57 - 0.14), p = 0.001] following SILS compared to MILS procedure. However, the statistical equivalence was seen in outcomes of length of hospital stay, operative time both for unilateral and bilateral hernias, post-operative pain score, one-week pain score, hernia recurrence [odds ratio, 1.24 (CI, 0.47-3.23), p = 0.66], conversion [odds ratio, 1.07 (CI, 0.37-3.12), p = 0.90], and post-operative complications [odds ratio, 0.95 (CI, 0.66-1.36, p = 0.78] between two approaches. The sub-group analysis of four included randomized, controlled trials showed similarities between outcomes following SILS and MILS except slightly higher postoperative pain score in MILS group. CONCLUSIONS: Both SILS and MILS approaches of inguinal hernia repair are feasible, safe and can be offered to patients depending upon the availability of expertise and resources.

Cardiogenic shock from atypical Takotsubo cardiomyopathy attributed to acute disseminated encephalomyelitis lesion involving the medulla.

We present here a case of atypical Takotsubo cardiomyopathy arising as a result of a lesion in the medulla oblongata. The patient was diagnosed with acute disseminated encephalomyelitis, and had improvement with intravenous steroids.

Fingerprint changes in CSF composition associated with different aetiologies in human neonatal hydrocephalus: glial proteins associated with cell damage and loss.

BACKGROUND: In hydrocephalus an imbalance between production and absorption of cerebrospinal fluid (CSF) results in fluid accumulation, compression and stretching of the brain parenchyma. In addition, changes in CSF composition have a profound influence on the development and function of the brain and together, these can result in severe life-long neurological deficits. Brain damage or degenerative conditions can result in release of proteins expressed predominantly in neurons, astroglia, or oligodendroglia into the brain interstitial fluid, CSF and blood. Determination of such products in the CSF might be of value in diagnosing cause, aetiology and/or assessing the severity of the neurological damage in patients with hydrocephalus. We therefore analysed CSF from human neonates with hydrocephalus for these proteins to provide an insight into the pathophysiology associated with different aetiologies. METHODS: CSF was collected during routine lumbar puncture or ventricular tap. Samples were categorized according to age of onset of hydrocephalus and presumed cause (fetal-onset, late-onset, post-haemorrhagic or spina bifida with hydrocephalus). Glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), vimentin and 2' , 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) were analysed through Western blotting of hydrocephalic CSF samples (n = 17) and compared with data from CSF of normal infants without neurological deficits (n = 8). RESULTS: GFAP was significantly raised only in CSF from post-haemorrhagic hydrocephalus while MBP was significantly raised in post-haemorrhagic and in spina bifida with hydrocephalus infants. Vimentin protein was only detected in some CSF samples from infants with late-onset hydrocephalus but not from other conditions. Surprisingly, CNPase was found in all neonatal CSF samples, including normal and hydrocephalic groups, although it was reduced in infants with late onset hydrocephalus compared with normal and other hydrocephalic groups. CONCLUSIONS: Apart from CNPase, which is an enzyme, the markers investigated are intracellular intermediate filaments and would be present in CSF only if the cells are compromised and the proteins released. Raised GFAP observed in post-haemorrhagic hydrocephalus must reflect damage to astrocytes and ependyma. Raised MBP in post-haemorrhagic and spina bifida with hydrocephalus indicates damage to oligodendrocytes and myelin. Vimentin protein detected in some of the late-onset hydrocephalic samples indicates damage to glial and other progenitors and suggests this condition affects periventricular regions. The presence of CNPase in all CSF samples was unexpected and indicates a possible novel role for this enzyme in brain development/myelination. Less CNPase in some cases of late-onset hydrocephalus could therefore indicate changes in myelination in these infants. This study demonstrates differential glial damage and loss in the developing human neonatal hydrocephalic brain associated with different aetiologies.

Lipid profile, lipid-lowering medications, and intracerebral hemorrhage after tPA in get with the guidelines-stroke.

BACKGROUND AND PURPOSE: Symptomatic intracerebral hemorrhage (sICH) after tissue plasminogen activator for acute ischemic stroke is associated with poor outcome. There are conflicting data on sICH risk related to lipid levels and use of lipid-lowering medications. We evaluated whether there are associations between lipid levels, lipid-lowering medications, and sICH in Get With the Guidelines-Stroke. METHODS: We identified acute ischemic stroke patients in the Get With the Guidelines-Stroke data set who were treated with IV tissue plasminogen activator between April 2003 and September 2009 and had complete data on lipid profiles and complications. Potential predictors of sICH were tested in univariate and multivariate analysis. RESULTS: The analysis included 22 216 IV tissue plasminogen activator-treated acute ischemic stroke patients. Overall, 1104 (4.97%) experienced sICH (National Institute of Neurological Disorders and Stroke definition). In univariate analysis, patients with sICH were more often taking antihypertensive, lipid-lowering, and diabetes mellitus medications. There was no relationship between low density lipoprotein or total cholesterol and sICH in univariate analysis. However, the risk of sICH increased with higher high density lipoprotein, 6.1% in Q4 versus 4.7% in Q1, P=0.0013; and lower triglyceride levels, 5.9% in Q1 versus 4.2% in Q4, P<0.0001. In multivariable models, although the high density lipoprotein and triglyceride levels were modestly associated with sICH, low density lipoprotein and total cholesterol were not. Lipid-lowering medications were not independently associated with sICH. CONCLUSIONS: We found that low density lipoprotein and total cholesterol levels are not associated with risk of sICH after tissue plasminogen activator, although higher high density lipoprotein and lower triglyceride levels were modest risk factors. Lipid-lowering medications are not associated with risk of sICH.

The ABCs of left ventricular assist device echocardiography: a systematic approach.

Echocardiography is an important imaging modality used to determine the indication of left ventricular assist device (LVAD) implantation for patients with advanced heart failure (HF) and for serial follow-up to make management decisions in patient care post-implant. Continuous axial-flow LVAD therapy provides effective haemodynamic support for the failing left ventricle, improving both the clinical functional status and quality of life. Echocardiographers must develop a systematic approach to echocardiographic assessment of LVAD implantation and post-LVAD implant cardiac morphology and physiology. This approach must include the evaluation of left and right heart chamber morphology and physiology and the anatomy and physiology of the inflow and outflow cannulas and the rotor pump, and the determination of the degree of tricuspid regurgitation and the presence of interatrial shunts and aortic regurgitation. Collaboration among the echocardiography and HF/transplant teams is essential to obtain this comprehensive evaluation. We outline a systematic approach to evaluating patients with HF who have failed conventional therapy and require LVAD therapy as a bridge to cardiac transplantation or destination therapy.

Comparison of three T-Wave Delineation Algorithms based on Wavelet Filterbank, Correlation and PCA.

There is a large interest in analysing the QT-interval, as a prolonged QT-interval can cause the development of ventricular tachyarrhythmias such as Torsade de Pointes. One major part of QT-analysis is T-end detection. Three automatic T-end delineation methods based on wavelet filterbanks (WAM), correlation (CORM) and Principal Component Analysis PCA (PCAM) have been developed and applied to Physionet QT database.All algorithms tested on Physionet QT database showed good results, while PCAM produced better results than WAM and CORM achieved best results. Standard deviation in sampling points (f(s)=250Hz) have been 33.3 (WAM), 8.0 (PTDM) and 7.8 (CORM). It could be shown that WAM is prone to interference while CORM is the most stable method even under bad conditions. Furthermore it was possible to detect significant QT-prolongation caused by Moxifloxacin in Thorough QT Study # 2 using CORM. QT-prolongation is significantly correlated to blood plasma concentration of Moxifloxacin.