Interrater Agreement of Height Assessment by Rigid Proctoscopy/Rectoscopy for Rectal Carcinoma.

BACKGROUND: Some guidelines for rectal carcinoma consider 12 cm, measured by rigid endoscopy, to be the cutoff tumor height for optional neoadjuvant chemoradiation therapy. Measuring differences of only a few centimeters may predetermine the choice of further therapy. However, rigid endoscopy may exhibit similar operator dependence to most other clinical examination methods. OBJECTIVES: Evaluation of concordance of rigid rectoscopic tumor height measurements performed by 4 experienced examiners, 2 measuring with patients in the lithotomy position and 2 in the left lateral position. Assessment of tumor palpability and distance of the anal verge to the anocutaneous line were also evaluated. DESIGN: This study used a prospective observational design. SETTING: This study was conducted at an academic teaching hospital that is a referral center for colorectal surgery. PATIENTS: There were 50 patients, of whom 35 were men (70%). The median age was 72.5 years (53-88 years). MAIN OUTCOME MEASURES: Interrater agreement of tumor height assessment and tumor height of less than or greater than the 12-cm height limit. RESULTS: With an intraclass correlation coefficient of 0.947 (95% CI, 0.918-0.967, p < 0.001), interrater reliability of tumor height assessment was statistically rated "excellent." Despite this, in 26% of patients, there was no agreement regarding the allocation of the tumor <12- or >12-cm height limit. Furthermore, there was also considerable disagreement concerning tumor palpability and the distance of the anal verge to the anocutaneous line. Patient positioning was not found to influence results. LIMITATIONS: Single-center study. CONCLUSIONS: Rigid rectal endoscopy may not be a sound pivotal basis for the consideration of optional chemoradiation therapy in rectal carcinoma. Application of a universally valid height limit ignores biological variability in body frame, gender, and acquired pelvic descent. Eligibility for neoadjuvant therapy should not rely on height measurements alone. Uniform MRI or CT imaging protocols, based on agreed upon terminology, including factors such as tumor height relative to the pelvic frame and peritoneal reflection, may be an important diagnostic addition to such a decision. See Video Abstract .Clinical trial registration: DRKS00012758 (German National Study Registry), ST-D 406 (German Cancer Society). ACUERDO ENTRE EVALUADORES EN LA EVALUACIN DE LA ALTURA MEDIANTE PROCTO/ RECTOSCOPIA RGIDA PARA EL CARCINOMA DE RECTO: ANTECEDENTES:Algunas guías para el carcinoma de recto consideran que 12 cm, medidos mediante endoscopia rígida, es la altura de corte del tumor para la quimiorradiación neoadyuvante opcional. Por lo tanto, una diferencia de medición de sólo unos pocos centímetros puede predeterminar la elección de una terapia adicional. Sin embargo, la endoscopia rígida puede presentar una dependencia del operador similar a la de la mayoría de los demás métodos de examen clínico.OBJETIVOS:Evaluación de la concordancia de las mediciones de la altura del tumor rectoscópico rígido realizadas por cuatro examinadores experimentados, dos en litotomía y dos en posición lateral izquierda. También se evaluó la evaluación de la palpabilidad del tumor y la distancia del borde anal a la línea anocutánea.DISEÑO:Estudio observacional prospectivo.LUGAR:Hospital universitario, centro de referencia para cirugía colorrectal.PACIENTES:50 pacientes, 35 varones (70%), mediana de edad 72,5 años (53-88 años).PRINCIPALES MEDIDAS DE RESULTADOS:Acuerdo entre evaluadores en la evaluación de la altura del tumor y la asignación del tumor por debajo o más allá del límite de altura de 12 cm.RESULTADOS:Con un coeficiente de correlación intraclase de 0,947 (IC del 95%: 0,918-0,967, p < 0,001), la confiabilidad entre evaluadores de la evaluación de la altura del tumor se calificó estadísticamente como "excelente". A pesar de esto, en el 26% de los pacientes no hubo acuerdo sobre la asignación del tumor por debajo o por encima del límite de 12 cm de altura. Además, también hubo un considerable desacuerdo con respecto a la palpabilidad del tumor y la distancia del borde anal a la línea anocutánea. No se encontró que la posición del paciente influyera en los resultados.LIMITACIONES:Estudio unicéntrico.CONCLUSIONES:La endoscopia rectal rígida puede no ser una base sólida y fundamental para considerar la quimiorradiación opcional en el carcinoma de recto. La aplicación de un límite de altura universalmente válido obviamente ignora la variabilidad biológica en la constitución corporal, el género y el descenso pélvico adquirido. La elegibilidad para la terapia neoadyuvante no debe depender únicamente de las mediciones de altura. Los protocolos uniformes de imágenes por resonancia magnética o tomografía computarizada, basados en una terminología acordada, incluidos factores como la altura del tumor en relación con la estructura pélvica y la reflexión peritoneal, pueden ser una adición diagnóstica importante para tal decisión. (Traducción-Yesenia Rojas-Khalil )Clinical trial registration: DRKS00012758 (German National Study Registry), ST-D 406 (German Cancer Society).

A generalizable deep voxel-guided morphometry algorithm for the detection of subtle lesion dynamics in multiple sclerosis.

Introduction: Multiple sclerosis (MS) is a chronic neurological disorder characterized by the progressive loss of myelin and axonal structures in the central nervous system. Accurate detection and monitoring of MS-related changes in brain structures are crucial for disease management and treatment evaluation. We propose a deep learning algorithm for creating Voxel-Guided Morphometry (VGM) maps from longitudinal MRI brain volumes for analyzing MS disease activity. Our approach focuses on developing a generalizable model that can effectively be applied to unseen datasets. Methods: Longitudinal MS patient high-resolution 3D T1-weighted follow-up imaging from three different MRI systems were analyzed. We employed a 3D residual U-Net architecture with attention mechanisms. The U-Net serves as the backbone, enabling spatial feature extraction from MRI volumes. Attention mechanisms are integrated to enhance the model's ability to capture relevant information and highlight salient regions. Furthermore, we incorporate image normalization by histogram matching and resampling techniques to improve the networks' ability to generalize to unseen datasets from different MRI systems across imaging centers. This ensures robust performance across diverse data sources. Results: Numerous experiments were conducted using a dataset of 71 longitudinal MRI brain volumes of MS patients. Our approach demonstrated a significant improvement of 4.3% in mean absolute error (MAE) against the state-of-the-art (SOTA) method. Furthermore, the algorithm's generalizability was evaluated on two unseen datasets (n = 116) with an average improvement of 4.2% in MAE over the SOTA approach. Discussion: Results confirm that the proposed approach is fast and robust and has the potential for broader clinical applicability.

Laparoscopic resection rectopexy significantly affects preexisting urinary symptoms in female patients.

PURPOSE: It has previously been noted that following rectopexy, some patients report changes in urinary function. So far, not much is known about the extent of such changes. This study assesses the effects of laparoscopic rectopexy on urinary symptoms. METHODS: Prospective observational study with 100 consecutive female patients indicated for laparoscopic resection rectopexy. Stated urinary symptoms, pre- and postoperative "International Consultation on Incontinence Questionnaire" (ICIQ), supplemented by a "quality of life " (QoL) visual analogue scale, and residual urine measurements (RUM) were compared and correlated. RESULTS: Postoperative QoL was significantly improved, irrespective of preexisting urinary symptoms. Twenty-four (24%) patients noticed improved urinary function. This corresponded with 42% of 45 patients who had positive preoperative ICIQ scores indicating preexisting urinary symptoms. Conversely, 14 (14%) patients noticed a postoperative increase of urinary complaints. The stated symptom change was only in part reflected by changes of the ICIQ scoring. Comparing ICIQ, 19 (19%) patients scored "better" postoperatively against 8% scoring worse; 5 of the 8 patients experienced "de novo" symptoms. The improved postoperative ICIQ scoring was highly significant. RUM did not sufficiently correlate to symptoms/ICIQ for any meaningful conclusion. CONCLUSIONS: Laparoscopic resection rectopexy had predominantly beneficial and to a lesser extent detrimental effects on urinary symptoms. Effects were highly significant; they were mainly noted in patients with preexisting urinary complaints. So far, it is not possible to predict such effects on an individual basis. It appears likely that similar effects may be found for most of the alternative operative procedures for the treatment of rectal prolapse. Without more factual knowledge and awareness about the extent of potential "collateral" effects of pelvic floor repair procedures, expert guidance of patients appears limited.

Long-term dynamics of multiple sclerosis iron rim lesions.

BACKGROUND: Several studies have pointed out that seemingly chronic multiple sclerosis (MS) lesions may also be in inflammatory states. In pathological studies, up to 40% of chronic MS lesions are characterized as "chronic active" or "smoldering" lesions that are characterized by a rim of iron-laden proinflammatory macrophages/microglial cells at the lesion edge with low-grade continuous myelin breakdown. In vivo, these lesions can be visualized as "iron rim lesions" (IRLs) on susceptibility-weighted imaging (SWI). The aim of this study was to investigate the long-term dynamics of IRLs in vivo for a more detailed evolution of dynamic lesion volume changes occurring over time. METHODS: We retrospectively identified patients with MS who were followed for at least 36 months (up to 72 months) and underwent at least an annual MRI on the same 3 Tsystem. Using Voxel-Guided Morphometry (VGM) we investigated regional volume changes within lesions and correlated these findings with SWI for the presence of a characteristic hypointense lesion rim. To estimate tissue damage, apparent diffusion coefficient (ADC) values for every lesion at baseline and follow-up MRIs were determined. RESULTS: Forty-three patients were included in the study. Overall, we identified 302 supratentorial non-confluent MS lesions (52 persistent IRLs, nine transient IRLs, 228 non-IRLs and 13 acute contrast-enhancing lesions). During follow-up, persistent IRLs significantly enlarged, whereas non-IRLs showed a tendency to shrink. At baseline MRI, ADC values were significantly higher in persistent IRLs (1.23 × 10-3 mm/s2) compared to non-IRLs (1.01 × 10-3 mm/s2; p < 0.001), but not compared to transient IRLs (1.06 × 10-3 mm/s2; p = 0.15) and contrast-enhancing lesions (1.15 × 10-3 mm/s2; p = 1.0). During follow-up, ADC values significantly increased more often in persistent IRLs compared to all other lesion types (p < 0.0001). CONCLUSIONS: Our long-term data demonstrate that persistent IRLs enlarge during disease duration, whereas non-IRLs show a tendency to shrink. Furthermore, IRLs are associated with sustained tissue damage, supporting the notion that IRLs could represent a new imaging biomarker in MS.

Characterization of chronic active multiple sclerosis lesions with sodium (23 Na) magnetic resonance imaging-preliminary observations.

BACKGROUND AND PURPOSE: There has been an increasing interest in chronic active multiple sclerosis (MS) lesions as a new magnetic resonance imaging (MRI) marker of disease progression. Chronic active lesions are characterized by progressive tissue matrix damage, axonal loss and chronic inflammation. Sodium (23 Na) MRI provides a biochemical marker of cell integrity and tissue viability in a quantitative manner. The aim of this study was to investigate with 23 Na MRI tissue abnormalities in chronic active lesions as indicators of tissue destruction. METHODS: To identify chronic active lesions, two 3D magnetization-prepared rapid acquisition gradient-echo datasets obtained 12 months apart were processed using the voxel-guided morphometry algorithm. Cross-sectional 23 Na MRI was performed during the 12-month follow-up period. Total sodium concentration was calculated in chronic active lesions compared to shrinking, chronic stable and acute contrast-enhancing lesions. RESULTS: Overall, 70 MS lesions (21 chronic active, 10 shrinking, 29 chronic stable lesions, 10 acute contrast-enhancing lesions) in 12 patients were included. Total sodium concentration in chronic active lesions (49.57 ± 8.47 mM) was significantly higher than in shrinking (42.16 ± 3.9 mM; p = 0.03) and chronic stable lesions (39.92 ± 4.82 mM; p < 0.001). Chronic active lesions showed similar sodium values compared to acute contrast-enhancing lesions (48.06 ± 6.65 mM; p = 0.97). No differences between shrinking and chronic stable lesions were observed (p = 0.89). CONCLUSION: High sodium values in chronic active MS lesions may be an indicator of ongoing inflammation and tissue damage.

Quantitative MRI texture analysis in chronic active multiple sclerosis lesions.

OBJECTIVE: Recently, there has been an increasing interest in "chronic enlarging" or "chronic active" multiple sclerosis (MS) lesions that are associated with clinical disability. However, investigation of dynamic lesion volume changes requires longitudinal MRI data from two or more time points. The aim of this study was to investigate the application of texture analysis (TA) on baseline T1-weighted 3D magnetization-prepared rapid acquisition gradient-echo (MPRAGE) images to differentiate chronic active from chronic stable MS lesions. MATERIAL AND METHODS: To identify chronic active lesions as compared to non-enhancing stable lesions, two MPRAGE datasets acquired on a 3 T MRI at baseline and after 12 months follow-up were applied to the Voxel-Guided Morphometry (VGM) algorithm. TA was performed on the baseline MPRAGE images, 36 texture features were extracted for each lesion. RESULTS: Overall, 374 chronic MS lesions (155 chronic active and 219 chronic stable lesions) from 60 MS patients were included in the final analysis. Multiple texture features including "DISCRETIZED_HISTO_Energy", "GLCM_Energy", "GLCM_Contrast" and "GLCM_Dissimilarity" were significantly higher in chronic active as compared to chronic stable lesions. Partial least squares regression yielded an area under the curve of 0.7 to differentiate both lesion types. CONCLUSION: Our results suggest that multiple texture features extracted from MPRAGE images indicate higher intralesional heterogeneity, however they demonstrate only a fair accuracy to differentiate chronic active from chronic stable MS lesions.

Venous Diameter Changes in Chronic Active Multiple Sclerosis Lesions.

BACKGROUND AND PURPOSE: To investigate the temporal evolution of venous diameter in chronic active and nonenhancing shrinking multiple sclerosis (MS) lesions in a longitudinal magnetic resonance imaging (MRI) study including susceptibility-weighted images (SWI). METHODS: We compared the venous diameter in chronic active and nonenhancing shrinking lesions to the venous diameter in nonenhancing stable lesions on two 3 T MRI data sets obtained 12 months apart. Chronic active and nonenhancing shrinking lesions were identified by Voxel-Guided Morphometry. Coregistered, overlaid fluid-attenuated inversion recovery/SWI were analyzed for the presence of a central vein. Quantitative calculation of the venous diameter for each time point was performed on the reconstructed veins. RESULTS: Sixty-two relapsing-remitting MS patients (50 women; mean age: 36 ± 11 years; mean disease duration: 4 ± 7 years) were included in the study. Overall, we identified 222 chronic MS lesions (48 chronic active, 48 shrinking, 126 stable) with a corresponding intralesional central vein. On baseline MRI, the mean venous diameter did not statistically differ between all subgroups, whereas on follow-up MRI, the mean intralesional venous diameter was smaller in chronic active (0.92 ± 0.15 mm) and shrinking lesions (0.90 ± 0.19 mm) compared to stable lesions (1.10 ± 0.18 mm; P < .001). CONCLUSION: Our findings demonstrate venous narrowing in chronic active and nonenhancing shrinking MS lesions. The smaller diameter of intralesional veins during follow up in these lesions may reflect structural, degenerative, and metabolic changes due to chronic inflammation, (perivascular) fibrosis, collagenous thickening, and increased levels of oxygenated hemoglobin.

A survey of patient and physician acceptance of skin toxicities from anti-epidermal growth factor receptor therapies.

BACKGROUND: Inhibition of the epidermal growth factor receptor (EGFR) extends patient survival in multiple tumor types. Skin toxicities are the most common adverse event (AE) elicited by EGFR inhibitors. Here, we provide deeper insights into patients' and physicians' acceptance of the risk/benefit trade-offs of skin toxicities during cancer therapy, including comparison of their perceptions and experiences with dermatologic AEs. METHODS: A multinational survey of 195 patients and 120 physicians was conducted to gauge attitudes regarding skin toxicities as an AE during cancer therapy. RESULTS: Skin toxicities were identified by patients and physicians as the AE that is most discouraging to patients when undergoing cancer therapies. Skin toxicities were cited as causing pain, impairing quality of life, and proving difficult to manage. Despite these negative influences, the majority of patients (71%) indicated they were willing to accept skin toxicities as an AE of an effective therapy. Indeed, the majority of patients and physicians preferred a more effective therapy that induces more severe skin toxicities than a less efficacious therapy that induces less severe skin toxicities; interestingly, patients were willing to accept a higher likelihood of severe skin toxicities than physicians. CONCLUSION: In this examination of patients' perspectives, we found that patients were willing to accept skin toxicities if they were the anticipated byproduct of a more effective therapeutic regimen. Important differences were observed between patients' and physicians' attitudes regarding risk/benefit trade-offs during cancer therapy, suggesting that patient's considerations and shared decision-making are key to cancer care.

Dermatologic events from EGFR inhibitors: the issue of the missing patient voice.

PURPOSE: As epidermal growth factor receptor (EGFR) inhibitors are associated with a variety of dermatologic adverse events (dAEs), the purpose of this study was to develop an overview of current knowledge of dAEs associated with EGFR inhibitors and to identify knowledge gaps regarding incidence, treatment, impact on quality of life (QOL), and patient acceptance. METHOD: A structured literature search was conducted using MEDLINE/PubMed (January 1983 to January 2014). In total, 71 publications published from 2004 to 2014 were identified for consideration in the final evidence review. RESULTS: The majority of published articles concentrate on the incidence of skin reactions, duration, treatment, and prevention strategies. Different grading systems based on the symptoms of skin rash or on health-related QOL (HRQOL) are used. An additional topic is the possible correlation between acneiform rash and efficacy of EGFR inhibitors. Knowledge gaps identified in the literature were how dAEs impact QOL compared with other AEs from a patient's perspective, patients' acceptance of dAEs (willingness to tolerate), and the impact of physician-patient communication on treatment decisions. CONCLUSIONS: Research is needed on the impact of dAEs on patients' acceptance of cancer treatments. Systematic studies are missing that compare the impact of dAEs with other toxicities on therapy decisions from both physician's and patient's view, and that investigate the balance between efficacy and avoidance of acneiform rash in treatment decisions. Such studies could provide deeper insights into the acceptance of the risk of untoward dermatologic events by both physicians and patients when treating advanced cancers.

Rectal prolapse traumatizes rectal neuromuscular microstructure explaining persistent rectal dysfunction.

PURPOSE: Internal rectal prolapse is common and correlates with age. It causes a plug-like physical obstruction and is a major cause of defecation disorder. The progressive distortion of the prolapsing rectum likely causes secondary defects in the rectal wall, which may exacerbate rectal dysfunction. We undertook a prospective observational study to detect and quantify the neurologic and histopathologic changes in the rectal wall. METHODS: We examined dorsal and ventral rectal wall specimens from consecutive patients with internal rectal prolapse undergoing stapled transanal rectal resection (STARR). We subjected specimens to histopathologic and neuropathologic assessment, including immunohistochemistry. We also recorded patients' clinical and demographic characteristics and sought correlations between these and the pathologic findings. RESULTS: We examined 100 specimens. The severity of rectal prolapse and the extent of descent of the perineum correlated significantly with age. Concomitant hemorrhoidal prolapse was noted in all male patients and in 79 % of female patients. Muscular and neuronal defects were detected in 94 and 90 % of the specimens, respectively. Only four specimens (4 %) were free of significant structural defects. CONCLUSION: Rectal prolapse traumatizes the rectum causing neuromuscular defects. The tissue trauma is due to shearing forces and ischemia caused by the intussusception. This initiates a self-reinforcing vicious circle of physical and functional obstruction, further impairing rectal evacuation and causing constipation and incontinence. The correlation between extent of prolapse and age suggests that internal rectal prolapse can be considered a degenerative disorder. Neural and motor defects in the wall of the rectum caused by rectal prolapse are likely irreversible.

Individual Assessment of Brain Tissue Changes in MS and the Effect of Focal Lesions on Short-Term Focal Atrophy Development in MS: A Voxel-Guided Morphometry Study.

We performed voxel-guided morphometry (VGM) investigating the mechanisms of brain atrophy in multiple sclerosis (MS) related to focal lesions. VGM maps detect regional brain changes when comparing 2 time points on high resolution T1-weighted (T1w) magnetic resonace imaging (MRI). Two T1w MR datasets from 92 relapsing-remitting MS patients obtained 12 months apart were analysed with VGM. New lesions and volume changes of focal MS lesions as well as in the surrounding tissue were identified by visual inspection on colour coded VGM maps. Lesions were dichotomized in active and inactive lesions. Active lesions, defined by either new lesions (NL) (volume increase > 5% in VGM), chronic enlarging lesions (CEL) (pre-existent T1w lesions with volume increase > 5%), or chronic shrinking lesions (CSL) (pre-existent T1w lesions with volume reduction > 5%) in VGM, were accompanied by tissue shrinkage in surrounding and/or functionally related regions. Volume loss within the corpus callosum was highly correlated with the number of lesions in its close proximity. Volume loss in the lateral geniculate nucleus was correlated with lesions along the optic radiation. VGM analysis provides strong evidence that all active lesion types (NL, CEL, and CSL) contribute to brain volume reduction in the vicinity of lesions and/or in anatomically and functionally related areas of the brain.

Laparoscopic surgery of benign entero-vesical or entero-vaginal fistulae.

PURPOSE: Entero-vesical or entero-vaginal fistulae (EVF) are an uncommon septic complication mainly of diverticular disease. The fistulae are usually situated within extensive and dense inflammatory masses occluding the entrance of the pelvis. There are still some controversies regarding laparoscopic feasibility and treatment modalities of this disorder. METHODS: A retrospective chart review of all patients with EVF operated at our department since 2008. Patients were identified by use of the computerized hospital information system. RESULTS: In nineteen patients (ten males), median age 68 years, 13 patients had entero-vesical fistulae, and 6 patients had entero-vaginal fistulae. The fistulae were caused by complicated diverticular disease in 16 patients (84 %), Crohn's disease (two patients), and ulcerative colitis (one patient). All cases were attempted laparoscopically. Operative treatment involved separation of the inflammatory mass and resection of the affected colorectal segment. There were three conversions (16 %), all three requiring bladder repair considered too extensive for laparoscopic means. In two further patients small bladder defects were sutured laparoscopically, the remaining patients required no bladder repair. The inferior mesentric artery (IMA) was preserved in all cases. Median operative time was 180 min. Two patients received a protective ileostomy: one converted patient and one cachectic patient with Crohn's disease under immune-modulating therapy. Both ileostomies were closed. Altogether, there were five complications in five patients (26 %), four of them were minor (Clavien grade I and II). The cachectic patient with Crohn's disease suffered a major (grade IIIb) complication (stoma prolapse, treated by early closure of the ileostomy). There was no anastomotic leakage and no mortality. Median hospital stay was 12 days. CONCLUSIONS: The laparoscopic approach is a safe option for the treatment of EVF of benign inflammatory origin. In most cases it offers all the advantages pertaining to minimally invasive surgery. For a definite and causal approach, the disorder belongs primarily within the therapeutic domain of the visceral surgeon. Following the separation of the inflammatory colon, most of the bladder lesions caused by EVF will heal without further surgical measures.

A simple tool to evaluate common disorders: validation of a "proctological symptom scale".

PURPOSE: Proctological symptomatology is of little complexity and therefore appears particularly suitable for comparative evaluation by visual scales. We devised a "proctological symptom scale" (PSS) with separate scales for four cardinal proctological symptoms: pain, itching/irritation, discharge/moisture, and bleeding. The objective of this study was to evaluate the PSS among proctological patients and non-proctological controls. METHODS: This was a single center non-interventional observational study on 229 proctological patients and 133 controls. The main outcome measures investigated were age- and sex-stratified comparison of the non-proctological cohort and the controls, effect of therapeutic intervention on scale values in a subset of patients with haemorrhoidal disease, and sensitivity of the PSS to detect therapeutic failure in this subset of patients. RESULTS: The PSS was found to significantly differentiate between proctological patients and controls. Gender and age had no significant influence on PSS values in the proctological cohort. The intervention (one session of rubber band ligation in patients with haemorrhoidal disease) was reflected by a significantly improved overall PSS. In 16 cases within this group, the PSS got worse. A case-by-case follow-up of these patients showed that 14 of the 16 patients ended up with surgery (or with the advice to have surgery). CONCLUSIONS: The PSS reliably differentiates proctological patients from non-proctological controls. Following intervention, the PSS reliably differentiated therapeutic success from failure. We find the PSS to be a simple and useful tool in our clinical routine since it provides an easily obtainable and reproducible basis for the visit-by-visit assessment of proctological patients. The PSS may also be suitable for studies to measure and compare symptomatic improvement and success of different therapies in proctology.

The PACT trial: PAtient Centered Telerehabilitation: effectiveness of software-supported and traditional mirror therapy in patients with phantom limb pain following lower limb amputation: protocol of a multicentre randomised controlled trial.

INTRODUCTION: Non-pharmacological interventions such as mirror therapy are gaining increased recognition in the treatment of phantom limb pain; however, the evidence in people with phantom limb pain is still weak. In addition, compliance to self-delivered exercises is generally low. The aim of this randomised controlled study is to investigate the effectiveness of mirror therapy supported by telerehabilitation on the intensity, duration and frequency of phantom limb pain and limitations in daily activities compared to traditional mirror therapy and care as usual in people following lower limb amputation. METHOD: A three-arm multi-centre randomised controlled trial will be performed. Participants will be randomly assigned to care as usual, traditional mirror therapy or mirror therapy supported by telerehabilitation. During the first 4 weeks, at least 10 individual sessions will take place in every group. After the first 4 weeks, participants will be encouraged to perform self-delivered exercises over a period of 6 weeks. Outcomes will be assessed at 4 and 10 weeks after baseline and at 6 months follow-up. The primary outcome measure is the average intensity of phantom limb pain during the last week. Secondary outcome measures include the different dimensions of phantom limb pain, pain-related limitations in daily activities, global perceived effect, pain-specific self-efficacy, and quality of life. DISCUSSION: Several questions concerning the study design that emerged during the preparation of this trial will be discussed. This will include how these questions were addressed and arguments for the choices that were made.

Comparative efficacy of long-acting bronchodilators for COPD: a network meta-analysis.

BACKGROUND: Clinicians are faced with an increasingly difficult choice regarding the optimal bronchodilator for patients with chronic obstructive pulmonary disease (COPD) given the number of new treatments. The objective of this study is to evaluate the comparative efficacy of indacaterol 75/150/300 µg once daily (OD), glycopyrronium bromide 50 µg OD, tiotropium bromide 18 µg/5 µg OD, salmeterol 50 µg twice daily (BID), formoterol 12 µg BID, and placebo for moderate to severe COPD. METHODS: Forty randomized controlled trials were combined in a Bayesian network meta-analysis. Outcomes of interest were trough and post-dose forced expiratory volume in 1 second (FEV1), St. George's Respiratory Questionnaire (SGRQ) score and responders (≥4 points), and Transition Dyspnea Index (TDI) score and responders (≥1 point) at 6 months. RESULTS: Indacaterol was associated with a higher trough FEV1 than other active treatments (difference for indacaterol 150 µg and 300 µg versus placebo: 152 mL (95% credible interval (CrI): 126, 179); 160 mL (95% CrI: 133, 187)) and the greatest improvement in SGRQ score (difference for indacaterol 150 µg and 300 µg versus placebo: -3.9 (95% CrI -5.2, -2.6); -3.6 (95% CrI -4.8, -2.3)). Glycopyrronium and tiotropium 18 µg resulted in the next best estimates for both outcomes with minor differences (difference for glycopyrronium versus tiotropium for trough FEV1 and SGRQ: 18 mL (95% CrI: -16, 51); -0.55 (95% CrI: -2.04, 0.92). CONCLUSION: In terms of trough FEV1 and SGRQ score indacaterol, glycopyrronium, and tiotropium are expected to be the most effective bronchodilators.

Hepatitis C virus in Asia: utility values based on the Short Form-36 questionnaire.

Utility data are important in Asia, where the need for health economic evaluations is growing. A literature review was conducted across international and local bibliographical databases in four languages to evaluate the utilities for chronic hepatitis C (CHC) patients in Asia. The results showed a lack of research on the humanistic burden of CHC in Asia. Using mapping, the estimated utilities for CHC patients in Asia ranged between 0.68 and 0.86. The utilities of CHC patients were lower than that of healthy controls, with the differences ranging between 0.032 and 0.261 units. On-treatment utility values declined by 0.07-0.13 units for subjects without sustained virological response and by 0.03-0.06 units for sustained virological response subjects. The results provide empirical data on utility values among CHC patients in Asia that can be used in future cost-effectiveness analysis or health technology assessment.

Efficacy of indacaterol 75 µg versus fixed-dose combinations of formoterol-budesonide or salmeterol-fluticasone for COPD: a network meta-analysis.

BACKGROUND: The purpose of this study was to update our network meta-analysis in order to compare the efficacy of indacaterol 75 µg with that of a fixed-dose combination of formoterol and budesonide (FOR/BUD) and a fixed-dose combination salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on evidence identified previously in addition to two new randomized clinical trials. METHODS: Fifteen randomized, placebo-controlled clinical trials including COPD patients were evaluated: indacaterol 75 µg once daily (n = 2 studies), indacaterol 150 µg once daily (n = 5), indacaterol 300 µg once daily (n = 4), FOR/BUD 9/160 µg twice daily (n = 2), FOR/BUD 9/320 µg twice daily (n = 2), SAL/FP 50/500 µg twice daily (n = 4), and SAL/FP 50/250 µg twice daily (n = 1). All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained. Treatment-by-covariate interactions were included where possible to improve the similarity of the trials. Outcomes of interest were trough forced expiratory volume in 1 second (FEV(1)) and transitional dyspnea index at 12 weeks. RESULTS: Based on the results without adjustment for covariates, indacaterol 75 µg resulted in a greater improvement in FEV(1) at 12 weeks compared with FOR/BUD 9/160 µg (difference in change from baseline 0.09 L [95% credible interval 0.04-0.13]) and FOR/BUD 9/320 µg (0.07 L [0.03-0.11]) and was comparable with SAL/FP 50/250 µg (0.00 L [-0.07-0.07]) and SAL/FP 50/500 µg (0.01 L [-0.04-0.05]). For transitional dyspnea index, data was available only for indacaterol 75 µg versus SAL/FP 50/500 µg (-0.49 points [-1.87-0.89]). CONCLUSION: Based on results of a network meta-analysis with and without covariates, indacaterol 75 µg is expected to be at least as efficacious as FOR/BUD (9/320 µg and 9/160 µg) and comparable with SAL/FP (50/250 µg and 50/500 µg) in terms of lung function. In terms of breathlessness (transitional dyspnea index) at 12 weeks, the results are inconclusive given the limited data.

The Cost-Effectiveness and Budget Impact of Introducing Indacaterol into the Colombian Health System.

OBJECTIVES: The main objectives were to estimate the cost-effectiveness and budget impact of indacaterol (a once-daily, long-acting-beta2-agonist) compared with 1) salmeterol/fluticasone, 2) formoterol/budesonide, and 3) tiotropium for the treatment of chronic obstructive pulmonary disease in Colombia. METHODS: A Markov model was utilized to simulate the progressive course of chronic obstructive pulmonary disease, distinguished by forced expiratory volume in 1 second predicted according to the four Global Initiative for Chronic Obstructive Lung Disease severity stages by using prebronchodilation values. Efficacy was based on the initial improvement in forced expiratory volume in 1 second, taken from either a network meta-analysis (salmeterol/fluticasone and formoterol/budesonide) or a randomized controlled trial (tiotropium). Colombian direct costs and life tables were incorporated in the adaptation, and analysis was performed from a health care payer perspective, discounting future costs (presented as US dollars) and benefits at 5%. A budget impact model was built to estimate the cost impact of indacaterol in Colombia over 3 and 5 years. RESULTS: Indacaterol was found to be dominant (i.e., less costly and more effective) against both salmeterol/fluticasone and formoterol/budesonide per life year and quality-adjusted life-year gained after a 5-year time horizon. The average cost saving against salmeterol/fluticasone and formoterol/budesonide was US $411 and US $909 per patient, respectively. All probabilistic sensitivity analysis simulations indicated indacaterol to be less costly than salmeterol/fluticasone and formoterol/budesonide. Indacaterol was more effective and more costly than tiotropium, corresponding to an incremental cost-utility ratio of US $2584 per quality-adjusted life-year. CONCLUSIONS: The results indicate that by replacing salmeterol/fluticasone or formoterol/budesonide with indacaterol, there are possible cost savings for the Colombian health care system. This was demonstrated by both cost-effectiveness and budget impact models.

Physiological monitoring and control in hemodialysis: state of the art and outlook.

Medical devices for monitoring and feedback control of physiological parameters of the dialysis patient were introduced in the early 1990s. They have a wide range of applications, aiming at increasing the safety and ensuring the efficiency of the treatment, and at an improved restoration of physiological conditions, leading to an overall reduction in morbidity and mortality. Such devices include sensors for the measurement of temperature, optical parameters and sound speed in blood, and electrical characteristics of the human body, and other parameters. Essential for the development of these devices is a detailed understanding of the pathophysiological background of a therapeutical problem. There is still a large potential to introduce new devices for further therapy improvement and automation. Also, the size of the hemodialysis market appears attractive; however, a new product has to meet several specific requirements in order to also become commercially successful. This review describes the therapeutic and technical principles of several available devices, reports on concepts for possible future devices, and presents a short overview on the market environment.