Long-term cost-effectiveness analysis of sacral neuromodulation in the treatment of severe faecal incontinence.

AIM: The aim of this study was to evaluate the long-term cost-effectiveness of sacral neuromodulation in the treatment of severe faecal incontinence as compared with symptomatic management. METHODS: In the public health field, a micro-costing evaluation method was conducted from the perspectives of the health system and the society. The incremental cost-effectiveness ratio was used as a decision index, and we considered various scenarios to evaluate the impact of the cost of symptomatic management and percutaneous nerve evaluation success rate in its calculation. Clinical data were retrieved from a consecutive cohort of 93 patients with severe faecal incontinence undergoing sacral neuromodulation after a failure of conservative (pharmacological and biofeedback) and/or surgical (sphincteroplasty) first-line treatments were considered. RESULTS: The long-term incremental cost-effectiveness ratio comparing sacral neuromodulation versus symptomatic management was 14347€/QALY and 28523€/QALY from the societal and health service provider's perspectives, respectively. If the definitive pulse generator implant success rate was 100%, incremental cost-effectiveness would correspond to 6831€/QALY and 16761€/QALY, respectively. CONCLUSIONS: Sacral neuromodulation may be considered a cost-effective technique in the long-term treatment of severe faecal incontinence from the societal and health care sector perspectives. Improving patient selection and determining the predictive outcome factors for successful sacral neuromodulation in the treatment of faecal incontinence would improve cost-effectiveness.

Fistulectomy and endorectal advancement flap repair for cryptoglandular anal fistula: recurrence and functional outcome over 10 years of follow-up.

PURPOSE: To examine long-term recurrence and anal continence of patients with anal fistula treated by fistulectomy and endorectal advancement flap repair. METHOD: Retrospective analysis of a prospective cohort of 115 patients (77.4% males, mean age 48.9 years) requiring 130 procedures, with a minimum follow-up of 10 years. Recurrence included reappearance of fistula after wound healing or presence of an abscess or chronic suppuration in the operated area at follow-up. Fecal incontinence was evaluated by the Cleveland Clinic Florida (CCF-FI) fecal incontinence scoring system. RESULTS: The mean and SD duration of the follow-up period was 155.5 (21.7) months. Recurrence developed in 31 (23.8%) cases, 28 (90.3%) of which within the first year, with a mean time to recurrence of 4.9 (2.9) months. The success rate was 76.2%. Anal continence was normal in 80% of patients before surgery, 63.8% at 1-year follow-up, and 71.5% at the end of follow-up (p < 0.001). Overall, continence worsened in 16.9% of cases. The mean (95% CI) CCF-FI score was 0.78 (0.35-1.21) preoperatively, 1.04 (0.64-1.43) at 1 year after surgery, 0.90 (0.52-1.29) at 5 years, and 1.16 (0.66-1.67) at the end of the study (p < 0.05). Neither recurrence nor continence was significantly associated with previous anal or fistula surgical procedures or complexity of the fistula. CONCLUSION: In this study, fistulectomy and endorectal advancement flap repair was associated with a long-term high rate of success. Most recurrences occurred within the first year and continence showed a mild deterioration over time. CLINICAL TRIAL REGISTRATION: Not applicable.

Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients With Bone Metastases: A Randomized Clinical Trial.

Importance: Zoledronic acid, a third-generation aminobisphosphonate, reduces the incidence of skeletal-related events and pain in patients with bone metastases. The optimal dosing interval for zoledronic acid is uncertain. Objective: To determine whether zoledronic acid administered every 12 weeks is noninferior to zoledronic acid administered every 4 weeks. Design, Setting, Participants: Randomized, open-label clinical trial conducted at 269 academic and community sites in the United States. Patients (n = 1822) with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma who had at least 1 site of bone involvement were enrolled between May 2009 and April 2012; follow-up concluded in April 2014. Interventions: Patients were randomized to receive zoledronic acid administered intravenously every 4 weeks (n = 911) vs every 12 weeks (n = 911) for 2 years. Main Outcomes and Measures: The primary end point was the proportion of patients having at least 1 skeletal-related event (defined as clinical fracture, spinal cord compression, radiation to bone, or surgery involving bone) within 2 years after randomization and a between-group absolute difference of 7% as the noninferiority margin. Secondary end points included the proportion of patients with at least 1 skeletal-related event by disease type, pain as assessed by the Brief Pain Inventory (range, 0-10; higher scores indicate worse pain), Eastern Cooperative Oncology Group performance status (range, 0-4; higher scores indicate worse disability), incidence of osteonecrosis of the jaw, kidney dysfunction, skeletal morbidity rate (mean number of skeletal-related events per year), and, in a subset of 553 patients, suppression of bone turnover (assessed by C-terminal telopeptide levels). Results: Among 1822 patients who were randomized (median age, 65 years; 980 [53.8%] women; 855 with breast cancer, 689 with prostate cancer, and 278 with multiple myeloma), 795 completed the study at 2 years. A total of 260 patients (29.5%) in the zoledronic acid every 4-week dosing group and 253 patients (28.6%) in the every 12-week dosing group experienced at least 1 skeletal-related event within 2 years of randomization (risk difference of -0.3% [1-sided 95% CI, -4% to ∞]; P < .001 for noninferiority). The proportions of skeletal-related events did not differ significantly between the every 4-week dosing group vs the every 12-week dosing group for patients with breast cancer, prostate cancer, or multiple myeloma. Pain scores, performance status scores, incidence of jaw osteonecrosis, and kidney dysfunction did not differ significantly between the treatment groups. Skeletal morbidity rates were numerically identical in both groups, but bone turnover was greater (C-terminal telopeptide levels were higher) among patients who received zoledronic acid every 12 weeks. Conclusions and Relevance: Among patients with bone metastases due to breast cancer, prostate cancer, or multiple myeloma, the use of zoledronic acid every 12 weeks compared with the standard dosing interval of every 4 weeks did not result in an increased risk of skeletal events over 2 years. This longer interval may be an acceptable treatment option. Trial Registration: clinicaltrials.gov Identifier: NCT00869206.

Vismodegib or cixutumumab in combination with standard chemotherapy for patients with extensive-stage small cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E1508).

BACKGROUND: Preclinical targeting of the hedgehog pathway by vismodegib and of insulin-like growth factor 1 receptor by cixutumumab enhances the efficacy of chemotherapy and also demonstrates activity against the tumor cell fraction responsible for disease recurrence in small cell lung cancer. METHODS: Patients with newly diagnosed extensive-stage small cell lung cancer (SCLC-ED) were randomized to receive four 21-day cycles of cisplatin and etoposide alone (cisplatin at 75 mg/m(2) on day 1 and etoposide at 100 mg/m(2) on days 1-3; arm A) or in combination with either vismodegib (150 mg/d by mouth; arm B) or cixutumumab (6 mg/kg/wk intravenously on day 1; arm C). The primary endpoint was progression-free survival (PFS). Circulating tumor cells (CTCs) were isolated/enumerated with the Veridex CellSearch platform at the baseline. RESULTS: One hundred fifty-two eligible patients were treated. Patient demographics and disease characteristics were well balanced between the 3 arms except for the higher rate with a performance status of 0 in arm B (P = .03). The median PFS times in arms A, B, and C were 4.4, 4.4, and 4.6 months, respectively; the median overall survival (OS) times were 8.8, 9.8, and 10.1 months, respectively; and the response rates were 48%, 56%, and 50%, respectively. None of the comparisons of these outcomes were statistically significant. The median OS was 10.5 months for those with low CTC counts (≤100/7.5 mL) at baseline and 7.2 months for those with high CTC counts (hazard ratio, 1.74; P = .006). CONCLUSIONS: There was no significant improvement in PFS or OS with the addition of either vismodegib or cixutumumab to chemotherapy in patients with SCLC-ED. A low baseline CTC count was associated with a favorable prognosis. Cancer 2016;122:2371-2378. © 2016 American Cancer Society.

Quality standards for predialysis education: results from a consensus conference.

This position statement was compiled following an expert meeting in March 2013, Zurich, Switzerland. Attendees were invited from a spread of European renal units with established and respected renal replacement therapy option education programmes. Discussions centred around optimal ways of creating an education team, setting realistic and meaningful objectives for patient education, and assessing the quality of education delivered.

[Current status of the prevention and treatment of stoma complications. A narrative review]. / Estado actual de la prevención y tratamiento de las complicaciones de los estomas. Revisión de conjunto.

The aim of our study was to perform a review of the literature to assess the results of prevention and treatment of stoma complications. Medline, EMBASE medical database and the Cochrane Library were searched up to December 2012. Stomal complications are prevalent and associated with a worse quality of life and increased health-economic burdens. The most common complications are attributed to stoma construction. Attention to the finer technical points performed by experienced surgeons reduces morbidity. The use of mesh reduces the risk of parastomal hernia and recurrence rates in hernia repair. Preoperative stoma site marking and postoperative care by a stomatherapist are crucial for the patients' successful adaption, improving quality of life, promoting their independence and reducing the rates of complications.

Long-term outcomes of sacral neuromodulation for low anterior resection syndrome after rectal cancer surgery.

PURPOSE: This study assessed the long-term outcomes and quality of life in patients who underwent sacral neuromodulation (SNM) due to low anterior resection syndrome (LARS). METHODS: This single-center retrospective study, conducted from 2005 to 2021, included 30 patients (21 men; median age, 70 years) who had undergone total mesorectal excision with stoma closure and had no recurrence at inclusion. All patients were diagnosed with LARS refractory to conservative treatment. We evaluated clinical and quality-of-life outcomes after SNM through a stool diary, Wexner score, LARS score, the Fecal Incontinence Quality of Life (FIQL) questionnaire, and EuroQol-5D (EQ-5D) questionnaire. RESULTS: Peripheral nerve stimulation was successful in all but one patient. Of the 29 patients who underwent percutaneous nerve evaluation, 17 (58.62%) responded well to SNM and received permanent implants. The median follow-up period was 48 months (range, 18-153 months). The number of days per week with fecal incontinence episodes decreased from a median of 7 (range, 2-7) to 0.38 (range, 0-1). The median number of bowel movements recorded in patient diaries fell from 5 (range, 4-12) to 2 (range, 1-6). The median Wexner score decreased from 18 (range, 13-20) to 6 (range, 0-16), while the LARS score declined from 38.5 (range, 37-42) to 19 (range, 4-28). The FIQL and EQ-5D questionnaires demonstrated enhanced quality of life. CONCLUSION: SNM may benefit patients diagnosed with LARS following rectal cancer surgery when conservative options have failed, and the treatment outcomes may possess long-term sustainability.

Baiona's Consensus Statement for Fecal Incontinence. Spanish Association of Coloproctology.

Faecal incontinence (FI) is a major health problem, both for individuals and for health systems. It is obvious that, for all these reasons, there is widespread concern for healing it or, at least, reducing as far as possible its numerous undesirable effects, in addition to the high costs it entails. There are different criteria for the diagnostic tests to be carried out and the same applies to the most appropriate treatment, among the numerous options that have proliferated in recent years, not always based on rigorous scientific evidence. For this reason, the Spanish Association of Coloproctology (AECP) proposed to draw up a consensus to serve as a guide for all health professionals interested in the problem, aware, however, that the therapeutic decision must be taken on an individual basis: patient characteristics/experience of the care team. For its development it was adopted the Nominal Group Technique methodology. The Levels of Evidence and Grades of Recommendation were established according to the criteria of the Oxford Centre for Evidence-Based Medicine. In addition, expert recommendations were added briefly to each of the items analysed.

Clinical Characteristics and Management of Patients with Secondary Hyperparathyroidism Undergoing Hemodialysis: A Feasibility Analysis of Electronic Health Records Using Natural Language Processing.

Introduction: This study aimed to assess the feasibility of applying natural language processing (NLP) to analyze real-world data (RWD) and resolve clinical problems in patients with secondary hyperparathyroidism and chronic kidney disease undergoing hemodialysis (SHPT/CKD-HD). The primary objective was to evaluate how well the guideline-recommended analytical goals are achieved in a Spanish cohort of SHPT/CKD-HD patients based on RWD. Methods: Unstructured data in the electronic health records (EHRs) from 8 hospitals were retrospectively analyzed using the EHRead® technology, based on NLP and machine learning. Variables extracted from EHRs included demographics, CKD-related clinical characteristics, comorbidities and complications, mineral and bone disorder parameter levels, and treatments at baseline, 6-month, and 12-month follow-up. Results: A total of 623 prevalent SHPT/CKD-HD patients were identified; of those, 282 fulfilled the inclusion criteria. They were predominantly elderly males with cardiovascular comorbidities, and the first cause of CKD was diabetic nephropathy. Diagnosis of SHPT was associated with an improvement in median values for PTH, calcium, and phosphate. However, the percentage of patients with normal PTH ranges remained stable during the study period (52.8-60.4%), while the percentage of patients with within-target range serum calcium or phosphate values showed an increasing trend (43.2-60% and 38.8-50%). At baseline, 74.1% of patients were using SHPT-related medication, including at least one vitamin D or analog (63.1%), phosphate binders (46.8%), and/or calcimimetics (9.6%). Conclusions: This study represents the first attempt to use clinical NLP to analyze SHPT/CKD-HD patients based on unstructured clinical data. This methodology is useful to address clinical problems based on RWD and identified a high rate of out-of-range mineral-bone analytical values in patients with HPT/CKD-HD and an increasing trend of out-of-range values for serum calcium and phosphate.

Etiopathogenesis of chronic kidney disease-associated pruritus: putting the pieces of the puzzle together.

Defined as the unpleasant sensation that causes the desire to scratch, pruritus is the most common skin symptom associated with uremia and appears in almost half of patients with advanced chronic kidney disease (CKD). Beyond its direct impact on quality of life, CKD-associated pruritus (CKD-aP) is an independent predictor of mortality that also has a synergistic effect with other quality of life-related symptoms, such as insomnia, depression, and anxiety. Although different mechanisms have been proposed to explain the origin of Pa-ERC, its etiopathogenesis is still not fully understood. Since new therapeutic targets have been identified and several clinical trials have recently shown promising results, our current understanding of the interrelationships has expanded significantly and the pathophysiological mechanisms underlying CKD-aP are now considered to be multifactorial. The potential triggers of pruritus in patients with CKD are discussed in this review, including hypotheses about skin xerosis, accumulation of uremic toxins, dysregulation of the immune system and systemic inflammation, uremic neuropathy, and imbalances in the endogenous opioid system. Other non-uremic causes of pruritus are also discussed, with the aim of guiding the physicians to apply an adequate aetiopathogenic approach to CKD-aP in their day-to-day clinical practice.

Perception of Spanish nephrologists on an old unsolved problem: Pruritus associated with chronic kidney disease (CKD-aP).

INTRODUCTION: Pruritus associated with chronic kidney disease is defined as the sensation of itching, in people with chronic kidney disease, in a one area or all over the body that causes the need to scratch, after having ruled out other dermatological or systemic causes. It is an old and known problem whose prevalence has been able to decrease with the improvement of dialytic techniques but which still persists and is underdiagnosed. OBJECTIVES: The objective of this study was to analyse the current perception of nephrologists about this problem that influences the quality of life of people with chronic kidney disease through a survey. RESULTS: 135 nephrologists, most of them engaged in haemodialysis, participated. 86% considered that pruritus associated with chronic kidney disease is still a problem today that affects the quality of life. Most nephrologists believe that the main pathophysiological cause is uremic toxins (60%) and only 16% believe that it is due to the dysregulation of the opioid system/endorphins-dynorphins. Only 16% comment that the prevalence of pruritus in their centre is greater than 20%. 40% believe that the diagnosis is made because it is manifested by the patient and only 27% because it is asked by the doctor. Moreover, it is not usual to use scales to measure it or the codification in the medical records. The main treatment used is antihistamines (96%), followed by moisturizers/anaesthetics (93%) and modification of the dialysis regimen (70%). CONCLUSIONS: Pruritus associated with chronic kidney disease is still a current problem, it is underdiagnosed, not codified and with a lack of indicated, effective and safe treatments. Nephrologists do not know its real prevalence and the different pathophysiological mechanisms involved in its development. Many therapeutic options are used with very variable results, ignoring their efficacy and applicability at the present time. The new emerging kappa-opioid-receptor agonist agents offer us an opportunity to reevaluate this age-old problem and improve the quality of life for our patients with chronic kidney disease.

Chronic Kidney Disease-Associated Pruritus and Quality of Life: Learning from Our Patients.

Chronic kidney disease-associated pruritus is itching directly related to kidney disease that cannot be explained by any other condition. Despite technological advances in the different aspects of dialysis sessions and the best treatment for chronic kidney disease patients, it is still a common problem in our patients. The many complex physiological mechanisms involved, the different hypotheses made over the years on the aetiology of the condition, and the great clinical variability may partially explain the limited knowledge about this problem and the difficulties in treating it. The presence of all these factors leads to the persistence of unpleasant symptoms, which must affect the disease burden and quality of life of kidney patients. Through the presentation of an illustrative clinical case, the aim of this review article is to highlight the need for adequate diagnosis and an improved approach to all aspects of chronic kidney disease-associated pruritus, in view of the heavy burden of the disease and the huge impact on the patient's quality of life.

Evidence on outsourcing dialysis services: a scoping review.

INTRODUCTION: Chronic kidney disease represents an important health problem, due to its high incidence and prevalence, as well as its significant morbidity and mortality and socioeconomic cost. AIMS: compare the effectiveness and economic consequences of outsourcing versus hospital dialysis. METHOD: A scoping review, for which different databases were consulted, using controlled and free terms. Those articles that compared concerted versus in hospital dialysis in terms of effectiveness were included. Likewise, those publications that compared, in the Spanish field, the cost between both modes of service provision and the public price rates of the different Autonomous Communities were included. RESULTS: 11 articles were included in this review: 8 on comparison of effectiveness, all of them in the USA, and 3 on costs. A higher rate of hospitalization was observed in subsidized centers, but no differences in mortality were observed. Additionally, greater competition among providers was associated with lower hospitalization rates. The cost studies reviewed show that hospital hemodialysis is more expensive than in subsidized centers, due to the structural costs. The data of the public rates of the different Autonomous Communities show a wide heterogeneity in the payment of the concerts. CONCLUSIONS: the coexistence in Spain of public and subsidized centers, the variability in the provision and costs of dialysis techniques, and the low of evidence on the effectiveness of outsourcing treatment show all the need to continue promoting strategies that result in improvement in the care for Chronic Kidney Disease.

Economic burden of long-term treatment of severe fecal incontinence.

INTRODUCTION: Find out the long-term economic cost associated with the treatment of severe fecal incontinence by SNS versus symptomatic conservative treatment and definitive colostomy. METHODS: Detailed descriptive study of the costs of the healthcare process (interventions, consultations, devices, complementary tests, hospitalization, etc.) of 3 treatment alternatives for fecal incontinence using analytical accounting tools of the Health Service based on clinical activity data. The frequency of use of health resources or the quantity of products dispensed in pharmacies (medication, diapers, ostomy material, etc.) was estimated in each case. Costs derived from adverse situations were included. Patients with severe fecal incontinence, defined by a score greater than 9 on the Wexner severity scale, in whom first-line treatments had failed, were included. Data from a consecutive cohort of 93 patients who underwent an SNS between 2002 and 2016 were used; patients who underwent definitive colostomy (n=2); parastomal hernia (n=3); and colostomy stenosis (n=1). RESULTS: The mean cumulative cost in 10 years per patient in each alternative was: € 10,972.9 symptomatic treatment (62% diapers); € 17,351.57 SNS (95.83% interventions; 81.6% devices); € 25,858.54 definitive colostomy (70.4% ostomy material and accessories). CONCLUSIONS: Management of severe fecal incontinence implies a great burden in economic terms. The colostomy is the alternative that generates the most direct cost, followed by SNS and symptomatic treatment.

Recurrence and incidence of fistula after urgent drainage of an anal abscess. Long-term results.

INTRODUCTION: Anal abscess is the most frequent urgent proctological problem. The recurrence rate and reported incidence of fistula after drainage and debridement of an anal abscess is widely variable. The objective of this study is to analyse the long-term recurrence rate and the incidence of fistula after drainage and urgent debridement of an anal abscess. METHODS: Retrospective observational study of a prospective cohort with anal abscess of cryptoglandular origin. All patients (n = 303) were evaluated two months and one year after the intervention. At the 5th year, all the medical records were reviewed and a telephone call or appointment was made for an assessment if necessary. Specific antecedents of anal pathology, abscess characteristics, time and type of recurrence, presence of symptoms in the first revision and presence of clinical and/or ultrasound fistula were recorded. RESULTS: Mean follow-up 119.7 months. Recurrence rate 48.2% (82.2% in the first year). Two hundred twenty-two ultrasounds performed. Incidence of ultrasound fistula: 70% symptomatic vs. 2.4% asymptomatic (p < 0.001). Global incidence of fistula 40.3%. The history of anal pathology and the presence of symptoms in the postoperative review significantly increase the possibility of recurrence (p < 0.001). The fistula is statistically more frequent if the abscess recurs (p < 0.001). CONCLUSION: After drainage and debridement of an anal abscess, half of the patients relapse and 40% develop fistula especially in the first year, so longer follow-ups are not necessary. Endoanal ultrasound for the evaluation of the presence of fistula is highly questionable in the absence of signs or symptoms.

Effectiveness of treatments in Neuromyelitis optica to modify the course of disease in adult patients. Systematic review of literature.

BACKGROUND: Neuromyelitis Optica spectrum disorder (NMOSD) is an inflammatory disease, which manifests mostly as recurrent episodes of optic neuritis or myelitis that cause important disability. Early diagnosis and prompt initiation of immunosuppressive therapy are crucial in reducing relapses, disability, and mortality. Even though, there are few prospective randomized controlled trials, several drugs have proved to be both effective and safe. Azathioprine and Rituximab represent the standard of care and are used as first-line treatment agents worldwide. However, recent studies have unveiled new therapies, such as monoclonal antibodies. To make treatment recommendations and management guidelines, it is imperative to define an appropriate standard of care. METHODS: A systematic literature review was performed in MEDLINE, EMBASE, and LILACS databases using the following terms: "(NMO OR Devic OR Neuromyelitis Optica) AND (Azathioprine OR Prednisone OR Rituximab OR Tocilizumab OR Bortezomib OR Inebilizumab OR Eculizumab OR Satralizumab)" including both, randomized clinical trials and observational studies published between January 2006 and January 2021. The inclusion criteria comprised patients aged 18 or older, NMOSD diagnosis following the Wingerchuck criteria, two or more therapies been compared, and the evaluation of both efficacy and safety outcomes. All studies comparing treatment only with placebo were excluded. Quality was assessed according with the design of the study, and results were synthesized through comparative tables for each outcome evaluated, differentiating the results of randomized and non-randomized studies. RESULTS: Thirteen studies with 1447 patients were included. Twelve studies evaluated the expanded disability status scale (EDSS) before and after treatment; in five of seven evaluating rituximab, it outperformed its comparators in improving the disability degree. Eleven studies assessed the annual relapse rate (ARR). Again, in six of seven evaluating rituximab, it was superior to other therapies. Time to relapse (TTR) was reported in five studies. The three studies that included Rituximab revealed a longer time to relapse in this arm of treatment. Finding were consistent in randomized and non-randomized studies. The new molecules Satralizumab, Eculizumab and Tocilizumab were evaluated in one study each, proving to be highly effective and safe. The safety profile analysis showed a higher number of adverse events for Azathioprine. DISCUSSION: This systematic review demonstrates a superiority tendency of Rituximab upon the other treatments strengthening the available evidence about NMOSD management. Superiority in EDSS outcomes, annual relapse rate, time to first relapse and relapses during treatment time was evidenced in the Rituximab group compared to other medications, with lower rates of adverse events. New molecules Tocilizumab, Eculizumab and Satralizumab also showed superiority in the evaluated results, especially in the relapses during treatment time outcome, although with subtle differences in EDSS and ARR outcomes. CONCLUSION: Our results suggest that monoclonal antibodies are highly effective and safe for the treatment of NMOSD; Rituximab showed better performance on multiple outcomes and has more evidence available. New molecules: Eculizumab, Tocilizumab, Satralizumab are good options for treatment. Drugs like Azathioprine and Mycophenolate are effective, but with a worse risk-benefit ratio, therefore, they are useful alternatives in places that do not have access to monoclonal antibodies.

Economic burden of long-term treatment of severe fecal incontinence. / Impacto económico del tratamiento a largo plazo de la incontinencia fecal grave.

INTRODUCTION: Find out the long-term economic cost associated with the treatment of severe fecal incontinence by SNS versus symptomatic conservative treatment and definitive colostomy. METHODS: Detailed descriptive study of the costs of the healthcare process (interventions, consultations, devices, complementary tests, hospitalization, etc.) of 3 treatment alternatives for fecal incontinence using analytical accounting tools of the Health Service based on clinical activity data. The frequency of use of health resources or the quantity of products dispensed in pharmacies (medication, diapers, ostomy material, etc.) was estimated in each case. Costs derived from adverse situations were included. Patients with severe fecal incontinence, defined by a score greater than 9 on the Wexner severity scale, in whom first-line treatments had failed, were included. Data from a consecutive cohort of 93 patients who underwent an SNS between 2002 and 2016 were used; patients who underwent definitive colostomy (n=2); parastomal hernia (n=3), and colostomy stenosis (n=1). RESULTS: The mean cumulative cost in 10 years per patient in each alternative was: € 10,972.9 symptomatic treatment (62% diapers); € 17,351.57 SNS (95.83% interventions; 81.6% devices); € 25,858.54 definitive colostomy (70.4% ostomy material and accessories). CONCLUSIONS: Management of severe fecal incontinence implies a great burden in economic terms. The colostomy is the alternative that generates the most direct cost, followed by SNS and symptomatic treatment.

Management of Kidney Failure in Patients with Diabetes Mellitus: What Are the Best Options?

Diabetic kidney disease (DKD) is the most frequent cause of kidney failure (KF). There are large variations in the incidence rates of kidney replacement therapy (KRT). Late referral to nephrology services has been associated with an increased risk of adverse outcomes. In many countries, when patients reach severely reduced glomerular filtration rate (GFR), they are managed by multidisciplinary teams led by nephrologists. In these clinics, efforts will continue to halt chronic kidney disease (CKD) progression and to prevent cardiovascular mortality and morbidity. In patients with diabetes and severely reduced GFR and KF, treating hyperglycemia is a challenge, since some drugs are contraindicated and most of them require dose adjustments. Even more, a decision-making process will help in deciding whether the patient would prefer comprehensive conservative care or KRT. On many occasions, this decision will be conditioned by diabetes mellitus itself. Effective education should cover the necessary information for the patient and family to answer these questions: 1. Should I go for KRT or not? 2. If the answer is KRT, dialysis and/or transplantation? 3. Dialysis at home or in center? 4. If dialysis at home, peritoneal dialysis or home hemodialysis? 5. If transplantation is desired, discuss the options of whether the donation would be from a living or deceased donor. This review addresses the determinant factors with an impact on DKD, aiming to shed light on the specific needs that arise in the management and recommendations on how to achieve a comprehensive approach to the diabetic patient with chronic kidney disease.

Pembrolizumab Plus Ipilimumab Following Anti-PD-1/L1 Failure in Melanoma.

PURPOSE: Combination of antiprogrammed cell death protein-1 (PD-1) plus anti-cytotoxic T-cell lymphocyte-4 (anti-CTLA-4) immunotherapy shows greater response rates (RRs) than anti-PD-1 antibody alone in melanoma, but RR after initial anti-PD-1 and programmed death ligand-1 (PD-L1) antibody progression awaits robust investigation. Anti-CTLA-4 antibody alone after anti-PD-1/L1 antibody progression has a historical RR of 13%. We report the results of the first prospective clinical trial evaluating ipilimumab 1 mg/kg plus pembrolizumab following progression on anti-PD-1 immunotherapy. METHODS: Patients with advanced melanoma who had progressed on anti-PD-1/L1 antibody as immediate prior therapy (including non-anti-CTLA-4 antibody combinations) were eligible. Patients received pembrolizumab 200 mg plus ipilimumab 1 mg/kg once every 3 weeks for four doses, followed by pembrolizumab monotherapy. The primary end point was RR by irRECIST. After 35 patients, the trial met the primary end point and was expanded to enroll a total of 70 patients to better estimate the RR. RESULTS: Prior treatments included 60 on anti-PD-1 antibody alone and 10 on anti-PD-1/L1 antibody-based combinations. Thirteen patients had progressed in the adjuvant setting. The median length of prior treatment with anti-PD-1/L1 antibody was 4.8 months. Response assessments included five complete and 15 partial responses, making the irRECIST RR 29% among the entire trial population. The median progression-free survival was 5.0 months, and the median overall survival was 24.7 months. The median duration of response was 16.6 months. There was no difference in median time on prior anti-PD1/L1 or time to PD1 + CTLA4 initiation between responders and nonresponders. Grade 3-4 drug-related adverse events occurred in 27% of patients. Responses occurred in PD-L1-negative, non-T-cell-inflamed, and intermediate tumor phenotypes. CONCLUSION: To our knowledge, this is the first prospective study in melanoma of pembrolizumab plus low-dose ipilimumab after anti-PD-1/L1 immunotherapy failure, demonstrating significant antitumor activity and tolerability.

Growth, nonspecific immune characteristics, and survival upon challenge with Vibrio harveyi in Pacific white shrimp (Litopenaeus vannamei) raised on diets containing algal meal.

A 70-day growth trial was conducted with postlarvae 12 (PL12) Pacific white shrimp (Litopenaeus vannamei) to study the suitability of soybean meal and oil originating from a single-celled microorganism (thraustochytrid) as fishmeal and fish oil substitutes in practical diets for L. vannamei. The growth, survival rate and immune characteristics were evaluated. Seven experimental diets were designed with soybean meal used as the primary protein source; each formulation contained 33% crude protein and 8% lipid. Fish oil was completely substituted with 3% soybean oil and meals originating from single-celled heterotrophs rich in docosahexaenoic acid (DHA) and arachidonic acid (ARA) were added at different concentrations. A commercial shrimp feed was used as the control diet. The final weights and survival rates of the shrimp were not significantly different among all treatments. However, shrimp raised on diets supplemented with marine algal meals rich in DHA and ARA showed significant improvement in immune parameters, such as total hemocyte count, phenoloxidase activity, superoxide dismutase activity, and bactericidal activity. Additionally, the survival rate after challenge with Vibrio harveyi was increased. These findings demonstrated that substitution of thraustochytrid-derived meals as an alternative to fish-based ingredients in shrimp diets provided similar growth rates while increasing the immune parameters and providing vibriosis resistance.