Definition Of Treatment Failure Research Articles

Management of failed flow diversion for intracranial aneurysm beyond the first 6 months of follow-up: an international Delphi consensus.

The placement of flow-diverting devices has become a common method of treating unruptured intracranial aneurysms of the internal carotid artery. The progressive improvement of aneurysm occlusion after treatment-with low complication and rupture rates-has led to a dilemma regarding the management of aneurysms in which occlusion has not occurred within 6-24 months. The authors aimed to identify clinical consensus regarding management of intracranial aneurysms displaying persistent filling 6-24 months after flow diversion and to ascertain questions that may drive future investigation. An international panel of 67 experts was invited to participate in a multistep Delphi consensus process on the treatment of intracranial aneurysms after failed flow diversion. Of the 67 experts invited, 23 (34%) participated. Qualitative analysis of an initial survey with open-ended questions resulted in 51 statements regarding management of aneurysms showing persistent filling after flow diversion. The statements were grouped into 8 categories, and in the second round, respondents rated the degree of their agreement with each statement on a 5-point Likert scale. Flow diverters with surface modifiers did not influence administration of dual-antiplatelet therapy according to 83%. Consensus was also reached regarding the definition of treatment failure at specific time points, including at 6 months if there is aneurysm growth or persistent rapid flow through the entirety of the aneurysm (96%), at 12 months if there is aneurysm growth or symptom onset (78%), and at 24 months if there is persistent filling regardless of size and filling characteristics (74%). Although experts agreed that the degree of intimal hyperplasia or in-device stenosis could not be ascertained by noninvasive imaging alone (83%), only 65% chose digital subtraction angiography as the preferred modality. At 6 and 12 months, retreatment is preferred if there is persistent filling with aneurysm growth (96%, 96%), device malposition (48%, 87%), or a history of subarachnoid hemorrhage (65%, 70%), respectively, and at 24 months if there is persistent filling without reduction in aneurysm size (74%). Experts favored treatment with an additional flow diverter (87%) over aneurysm clipping, applying the same principles for follow-up (83%) and treatment failure (91%) as for the first flow diverter. The authors present the consensus practices of experts in the management of intracranial aneurysms without occlusion 6-24 months after treatment with a flow-diverting device.

Cellulitis in the Emergency Department: A prospective cohort study with patient-centred follow-up.

There is substantial practice variation in the management of cellulitis with limited prospective studies describing the course of cellulitis after diagnosis. We aimed to describe the demographics, clinical features (erythema, warmth, swelling and pain), patient-reported disease trajectory and medium-term follow-up for ED patients with cellulitis. Prospective observational cohort study of adults diagnosed with cellulitis in two EDs in Southeast Queensland, Australia. Patients with (peri)orbital cellulitis and abscess were excluded. Data were obtained from a baseline questionnaire, electronic medical records and follow-up questionnaires at 3, 7 and 14 days. Clinician adjudication of day 14 cellulitis cure was compared to patient assessment. Descriptive analyses were conducted. Three-hundred patients (mean age 50 years, SD 19.9) with cellulitis were enrolled, predominantly affecting the lower limb (75%). Cellulitis features showed greatest improvement between enrolment and day 3. Clinical improvement continued gradually at days 7 and 14 with persistent skin erythema (41%) and swelling (37%) at day 14. Skin warmth was the feature most likely to be resolved at each time point. There was a discrepancy in clinician and patient assessment of cellulitis cure at day 14 (85.8% vs. 52.8% cured). A clinical response of cellulitis features can be expected at day 3 with ongoing slower improvement over time. Over one third of patients had erythema or swelling at day 14. Patients are less likely than clinicians to deem their cellulitis cured at day 14. Future research should include parallel patient and clinician evaluation of cellulitis to help develop clearer definitions of treatment failure and cure.

Consensus on the definition and criteria for failure of surgical treatment in bacterial arthritis of a native joint: An international Delphi study.

The literature presents a wide range of success rates for a single surgical intervention of bacterial-septic-arthritis, and there is a lack of clear criteria for identifying treatment failure and making decisions about reintervention. This Delphi study aims to establish a consensus among an international panel of experts regarding the definition of treatment failure and the criteria for reintervention in case of bacterial arthritis. The conducting and reporting Delphi studies (CREDES) criteria were used. Data from a systematic review was provided as the basis for the study. A list of 100 potential experts were identified. The study was designed and conducted as follows: (I) identification and invitation of an expert panel, (II) informing the participating expert panel on the research question and subject, and (III) conducting two or three Delphi rounds to reach consensus on explicit research items. Potential criteria were rated on a five-point Likert scale. Sixty orthopaedic experts from nine countries participated in this Delphi study, with 55 completing all three rounds. The mean experience as an orthopaedic surgeon was 15 years (SD ± 9). Strong (96%) consensus was reached on the definition of treatment failure: the persistence of physical signs of arthritis (e.g., pain and swelling) and/or systemic inflammation (e.g., fever and no improvement in CRP) despite surgical and antibiotic treatment. Furthermore, consensus (>80%) was reached on six criteria influencing the decision for reintervention; pain (81%), sepsis (98%), fever (88%), serum CRP (93%), blood culture (82%), and synovial fluid culture (84%). The definition of treatment failure for bacterial arthritis after a single surgical intervention was established through a three-round Delphi study. Additionally, consensus was reached on six criteria that are helpful for determining the need for reintervention. This definition and these criteria may help in the development of clinical guidelines, and will empower physicians to make more precise and consistent decisions regarding reintervention for patients, ultimately aiming to reduce over- and undertreatment and improve patient outcomes. Level V.

Reoperation for prolapse recurrence after sacrospinous mesh hysteropexy: characteristics of women choosing retreatment.

Factors that contribute to reoperation and surgical approaches for the management of recurrent uterovaginal prolapse after vaginal mesh hysteropexy (mesh hysteropexy) are unknown. We aimed to describe surgical management of pelvic organ prolapse recurrence after vaginal mesh hysteropexy, and patient characteristics in those who chose reoperation. This is a descriptive analysis of women who experienced treatment failure within 5 years of mesh hysteropexy in a multi-site randomized trial. The composite definition of treatment failure included retreatment (pessary or reoperation), prolapse beyond the hymen, or bothersome prolapse symptoms. Characteristics of those pursuing and not pursuing repeat prolapse surgery, measures of prolapse, and symptom severity are described. Over 5-year follow up,31/91(34%) of the hysteropexy group met treatment failurecriteria. All seven women who pursued reoperation reported bothersome prolapse symptoms; six were anatomic failures. Most seeking reoperation were early treatment failures; six (86%) by the 12-month visit and all by the 18-month visit. Compared to those electing expectant management, those pursuing reoperation had more apical prolapse, POP-Q point C median (IQR) -5.5 (-6.0, -4.0) cm versus +1.0 (-1.0, 3.0) cm respectively. Hysterectomy was performed in 6/7 reoperations (three vaginal, three endoscopic), with apical suspension in 5/6 hysterectomies. One participant with posterior compartment prolapse underwent transvaginal enterocele plication, uterosacral ligament suspension with posterior colpoperineorrhaphy. At a mean surgical follow-up of 34.3 (15.8) months, all women remained without anatomic or symptomatic failure. When recurrent prolapse after mesh hysteropexy occurred, most women did not choose reoperation. Those who pursued surgery experienced more significant apical prolapse and were universally symptomatic. NCT01802281.

Percutaneous treatment options for acute pulmonary embolism: a clinical consensus statement by the ESC Working Group on Pulmonary Circulation and Right Ventricular Function and the European Association of Percutaneous Cardiovascular Interventions.

There is a growing clinical and scientific interest in catheter-directed therapy (CDT) of acute pulmonary embolism (PE). Currently, CDT should be considered for patients with high-risk PE, in whom thrombolysis is contraindicated or has failed. Also, CDT is a treatment option for initially stable patients in whom anticoagulant treatment fails, i.e., those who experience haemodynamic deterioration despite adequately dosed anticoagulation. However, the definition of treatment failure (primary reperfusion therapy or anticoagulation alone) remains an important area of uncertainty. Moreover, several techniques for CDT are available without evidence supporting one over the other, and variation in practice with regard to periprocedural anticoagulation is considerable. The aim of this position paper is to describe the currently available CDT approaches in PE patients and to standardise patient selection, the timing and technique of the procedure itself as well as anticoagulation regimens during CDT. We discuss several clinical scenarios of the clinical evaluation of the "efficacy" of thrombolysis and anticoagulation, including treatment failure with haemodynamic deterioration and treatment failure based on a lack of improvement. This clinical consensus statement serves as a practical guide for CDT, complementary to the formal guidelines.

P47 The conundrums of Macrophage activation syndrome (MAS) - when to consider a Haematopoietic Stem Cell Transplant (HSCT)

P47 The conundrums of Macrophage activation syndrome (MAS) - when to consider a Haematopoietic Stem Cell Transplant (HSCT)

Guideline for the treatment of chronic lymphocytic leukaemia

Guideline for the treatment of chronic lymphocytic leukaemia

Retear bigger than preoperative tear size would lead to treatment failure after rotator cuff repair

This study aimed to (1) define treatment failure using the referred patient acceptable symptomatic state (PASS) values for pain visual analog scale (PVAS), American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), and Single Assessment Numeric Evaluation (SANE) clinical scores and (2) identify the factors that lead to patient dissatisfaction after arthroscopic rotator cuff repair (ARCR). We analyzed the arthroscopic rotator cuff surgery registry data from January 2015 to December 2016. Patients were followed for ≥2 years and categorized as dissatisfied or satisfied based on our own definition of treatment failure at 2 years postoperatively. For defining treatment failure, the referred PASS values for the PVAS, ASES, and SANE scores were used. Patients who failed to attain the PASS value for the PVAS, ASES, or SANE score were categorized into the dissatisfied group. Pre- and postoperative imaging and basic demographic data were compared between groups. Univariable and multivariable logistic regression analyses were performed to identify the factors affecting patient satisfaction at 2 years after rotator cuff repair. Of 117 patients, 30 (25.6%) were defined as the dissatisfied group (mean follow-up period, 37.5 months). Seventeen patients (14.5%) had confirmed retear on follow-up magnetic resonance imaging. In the univariate analysis, sex significantly differed between the groups (female, satisfied vs. dissatisfied groups: 39 [44.8%] vs. 22 [73.3%]; P = .010). Retear alone did not affect patient satisfaction in the univariate analysis (P = .11). Progressed retear size featured a significantly higher risk of patient dissatisfaction (P = .024; odds ratio 6.430, 95% confidence interval 1.270-32.541) in the multivariable analysis using symptom duration, sex, preoperative ASES score, preoperative tear size, retear, and progressed retear size as variables. Moreover, female sex had an increased odds for dissatisfaction (odds ratio 4.646, 95% confidence interval 1.590-13.578; P = .005). Two years after ARCR, most patients (74.4%) reported satisfaction with their outcomes. However, satisfaction levels can be altered by female sex or progressed retear size compared with the preoperative state.

Treatment failure in persistent tic disorders: an expert clinicians' consensus-based definition.

A standardized definition of treatment failure in the management of tics is currently lacking. Such definition would prevent persistent use of unnecessary interventions and help clinicians to determine when to offer less established treatments (e.g., deep brain stimulation surgery). To achieve an expert consensus-based definition of failure of medical treatments for tics, we used a multi-step, multi-round, web-based Delphi approach involving international specialist clinicians with specific expertise in tic disorders. These experts were identified through professional networks or consortia related to chronic tic disorders. We created a survey and reviewed the questions with stakeholders prior to two rounds of Delphi surveys, followed by a final review and discussion among research team members. Both survey rounds were completed using a sample of 36 expert stakeholders from 14 countries, including neurologists, psychiatrists, and clinical psychologists. The Delphi process led to consensus on 10 statements which formed the final definition of treatment failure. The definition was structured and operationalized according to two separate sections, one for behavioral and one for pharmacological treatments. Core components of the definition and its operationalization included lack of efficacy, adherence, and tolerability, as well as a definition of failure of behavioral therapies as a whole, and of pharmacological therapies as a whole. The group concluded that the components of this specific definition reflect the range and complexity of characteristics to consider in establishing tic-related treatment failure. Future research should assess the feasibility of this operational definition and whether it will change clinical decision-making and improve management outcomes.

Treatment failure in pediatric acute otitis media: How do you define?

IntroductionReaching the point of treatment failure in the management of pediatric acute otitis media (AOM) is decision-changing, and is often associated with switching to a broader coverage antibiotic with/without middle ear surgical drainage. Yet, still there is no consensus on the definition of what is treatment failure, which may lead to confusion for clinical decision-making purposes. We sought to review the heterogeneity of treatment failure definitions in AOM. MethodsWe searched for relevant English language manuscripts using the following key-words: ['otitis media' (OM) or (AOM)] AND ['treatment failure' or 'failure' or 'response failure' or 'response'] AND 'human' in various electronic databases from 1/1/2005 through 10/31/2020. ResultsIn the 60 retrieved papers, treatment failure was considered only when antibiotics had been prescribed beforehand, but not when watchful waiting had been adopted. We categorized the manuscripts into 5 major treatment failure definition subgroups, which occasionally overlapped: unimprovement or worsening of symptoms or signs of failure in otoscopy (n = 36), specialist(s) referral or hospital admission (n = 12), changing or adding antibiotic treatment (n = 22), failure to eradicate causative bacteria (n = 7) and failure as perceived by parents (n = 4). ConclusionsWe suggest a broader definition of AOM treatment failure including physical examination findings and degree of initial treatment response, which will enable an unbiased, uniform comparison of treatments for pediatric AOM.

Statistical considerations in clinical trial design with event-free survival as the primary efficacy endpoint.

In late-phase confirmatory clinical trials in the oncology field, time-to-event (TTE) endpoints are commonly used as primary endpoints for establishing the efficacy of investigational therapies. Among these TTE endpoints, overall survival (OS) is always considered as the gold standard. However, OS data can take years to mature, and its use for measurement of efficacy can be confounded by the use of post-treatment rescue therapies or supportive care. Therefore, to accelerate the development process and better characterize the treatment effect of new investigational therapies, other TTE endpoints such as progression-free survival and event-free survival (EFS) are applied as primary efficacy endpoints in some confirmatory trials, either as a surrogate for OS or as a direct measure of clinical benefits. For evaluating novel treatments for acute myeloid leukemia, EFS has been gradually recognized as a direct measure of clinical benefits. However, the application of an EFS endpoint is still controversial mainly due to the debate surrounding definition of treatment failure (TF) events. In this article, we investigate the EFS endpoint with the most conservative definition for the timing of TF, which is Day 1 since randomization. Specifically, the corresponding non-proportional hazard pattern of the EFS endpoint is investigated with both analytical and numerical approaches.

The management of suspected or confirmed laryngopharyngeal reflux patients with recalcitrant symptoms: A contemporary review.

To summarise current knowledge about the prevalence, aetiology and management of recalcitrant laryngopharyngeal reflux (LPR) patients-those who do not respond to anti-reflux medical treatment. A literature search was conducted following the PRISMA guidelines to identify studies that reported success of anti-reflux medical treatment with emphasis on studies that attempted to be rigorous in defining a population of LPR patients and which subsequently explored the characteristics of non-responder patients (ie aetiology of resistance; differential diagnoses; management and treatment). Three investigators screened publications for eligibility from PubMED, Cochrane Library and Scopus and excluded studies based on predetermined criteria. Design, diagnostic method, exclusion criteria, treatment characteristics, follow-up and quality of outcome assessment were evaluated. Of the 139 articles screened, 45 met the inclusion criteria. The definition of non-responder patients varied substantially from one study to another and often did not include laryngopharyngeal signs. The reported success rate of conventional therapeutic trials ranged from 17% to 87% and depended on diagnostic criteria, treatment scheme, definition of treatment failure and treatment outcomes that varied substantially between studies. The management of non-responders differed between studies with a few differential diagnoses reported. No study considered the profile of reflux (acidic, weakly acid, non-acid or mixed) or addressed personalised treatment with the addition of alginate or magaldrate, low acid diet, or other interventions that have emerging evidence of efficacy. To date, there is no standardised management of LPR patients who do not respond to traditional treatment approached. A diagnostic and therapeutic algorithm is proposed to improve the management of these patients. Future studies will be necessary to confirm the efficacy of this algorithm through large cohort studies of non-responder LPR patients. 2a.

Management of Non–Muscle-Invasive Bladder Cancer

Non–muscle-invasive bladder cancer (NMIBC) makes up 75% of the fifth most common cancer in North America. With a high rate of recurrence and progression, which leads to significant treatment burden for patients and high costs to healthcare systems, NMIBC poses several critical clinical challenges. Enhanced cystoscopic techniques are improving detection and optimal resection of these tumors. The administration of intravesical therapies, including especially cytotoxic chemotherapy and bacillus Calmette-Guérin (BCG) therapy, continues to evolve, and several promising agents are under development. Refined definitions of treatment failure are promoting clinical trial activity in this domain. The optimal timing of radical cystectomy for BCG therapy–unresponsive patients continues to be a key unresolved question, but advances in the molecular characterization of NMIBC are likely to enhance individualized, risk-adapted therapy in the near future. This review contains 3 Figures, 10 Tables and 91 references Key words: bladder cancer; cystoscopy; narrow band imaging; fluorescence cystoscopy; transurethral resection of bladder tumor (TURBT); intravesical chemotherapy; bacillus Calmette-Guérin (BCG) therapy; urine markers.

Foot Osteomyelitis in Patients Without Diabetes—Editorial Comment

Relatively few articles have been written on the subject of foot osteomyelitis in patients without diabetes. Even a PubMed search using the terms “osteomyelitis, foot” yields a majority of articles on diabetic foot osteomyelitis. But is there a difference between the two? In this article, Mitbander et al1 conclude that foot osteomyelitis is not clinically distinct in patients with diabetes versus those without, and the approach to management need not differ. We commend the authors for their important and interesting article. It is the first study to our knowledge that seeks to directly compare the two. There are pitfalls for any investigator trying to study osteomyelitis, whether in patients with or without diabetes. The answers to the most basic questions such as definition of the condition, appropriate diagnosis, length and course of treatment, surgical versus medical therapies, and even the definition of a “cure” remain elusive. Various clinical practice guidelines have attempted to answer some of these questions, but most recommendations are based on relatively low levels of evidence and tend to comprise mostly consensus opinion. For the case definitions used to include patients into this study, the authors reference the International Working Group on the Diabetic Foot 2008 consensus statement. That this work was specifically looking at diabetic foot osteomyelitis is, in and of itself, demonstrative of the central premise of this work. Are criteria used to define osteomyelitis in the diabetic foot different from those in patients without diabetes? Should clear diagnostic criteria (was osteomyelitis diagnosed via positive bone culture, histopathology, changes on plain x-ray or magnetic resonance imaging, elevated erythrocyte sedimentation rate?) be required to define a case? The authors state that the frequency of peripheral arterial disease (PAD) was similar in both groups, yet the nondiabetes cohort was more frequently found to be smokers. The authors reference the relatively recent Society for Vascular Surgery “WIFI” consensus document to define PAD. These guidelines utilize not only ankle-brachial index but also ankle systolic pressure, toe pressures, and transcutaneous oximetry to stratify patients into 1 of 4 risk grades. Were any, or all, of these techniques used to diagnose PAD in this population? Is it possible that the cigarette smoking in the nondiabetic group led to microvascular disease of the toes that may not have been appreciated if only ankle-brachial index or ankle pressures were utilized? How is a cure defined other than “no further surgery being necessary”? This singular point is one of the reasons there are so few outcome studies on the treatment of osteomyelitis. No one can agree upon an end point! Is there a better definition of treatment failure, which the authors define as “unanticipated resection of additional bone from the initial area of infection or an above-ankle amputation because of ongoing infection”? It's not at all uncommon for patients with osteomyelitis, either with or without diabetes, to have to undergo serial bone debridements. This does not mean that the treatment is a “failure” but rather is part of the standard treatment. Likewise, it would be important to mention the length of treatment for each group. Do patients without diabetes require a longer or shorter course of therapy? The question of “how long to treat” is an important one and is usually based on radiographic studies, biomarkers, and clinical signs. Finally, given that the patient population was skewed toward older males because the study took place on the vascular service at a Veterans Administration Hospital (all but 2 patients were male, and only 20 subjects did not have diabetes), are these results generalizable across a broader population? It would be interesting to see if there were similar outcomes in future studies that included a more diverse demographics and a larger patient base. It was heartening to see the authors use oral antibiotics as their primary treatment regimen. Over the years, intravenous antibiotics have remained for many the perceived criterion standard for treating osteomyelitis. Many clinicians still doggedly cling to the notion that intravenous is superior to oral despite mounting evidence to the contrary. It is nice to see this timeworn dogma give way to an evidence-based approach. We look forward to more studies of this type and applaud the authors for taking the first step in answering the question: Are diabetic and nondiabetic foot osteomyelitis clinically distinct entities?

Inflammatory bowel disease and Clostridium difficile infection: contrasting views of international clinical professionals.

In patients with inflammatory bowel disease (IBD), Clostridium difficile infection (CDI) is a risk factor for both morbidity and mortality. Currently, appropriate management is unclear. Guidance on best practice in the diagnosis and treatment of CDI in IBD patients is therefore needed. A multidisciplinary group of clinicians involved in the treatment of patients with IBD and CDI developed 27 consensus statements. Respondents were asked to rate their agreement with each statement using a 4-point Likert scale. A modified Delphi methodology was used to review responses of 442 physicians from different specialties (including infectious disease specialists [n = 104], microbiologists [n = 95], and gastroenterologists [n = 73]). A threshold of 75 % agreement was predefined as consensus. Consensus was achieved for 17 of the 27 statements. Unprompted recognition of risk factors for CDI was low. Intensification of immunosuppressive therapy in the absence of clinical improvement was controversial. Clear definitions of treatment failure of antibiotic therapy in CDI and recurrence of CDI in IBD are needed. Respondents require further clarity regarding the place of fecal microbiota transplantation in CDI patients with IBD. Differences were observed between the perceptions of microbiologists and gastroenterologists, as well as between countries. Different perceptions both between specialties and geographical locations complicate the development of an internationally accepted algorithm for the diagnosis and treatment of CDI in patients with IBD. This study highlights the need for future studies in this area.

Redefining treatment failure for pediatric acute leukemia in the era of minimal residual disease testing

ABSTRACTTechnologies for the detection of minimal residual disease (MRD) in leukemia and our understanding of the prognostic implications of MRD at different phases of treatment have significantly improved over the past decade. As a result, definitions of treatment failure based on bone marrow morphology by light microscopy are becoming increasingly inadequate for clinical care and trial design. In addition, novel therapies that may have increased efficacy and decreased toxicity in the setting of MRD compared to overt disease are changing clinical practice and challenging investigators to redefine treatment failure, the role of disease surveillance in remission, and clinical trial eligibility in the era of MRD.

Early non-response to certolizumab pegol in rheumatoid arthritis predicts treatment failure at one year. Data from a randomised phase III clinical trial

ObjectivesTo compare different early clinical criteria of non-response determined at three months as predictors of clinical failure at one year in patients with rheumatoid arthritis starting therapy with certolizumab pegol. MethodsData were derived from a randomised Phase III clinical trial in patients with rheumatoid arthritis who failed to respond to methotrexate monotherapy. Patients included in this post-hoc analysis were treated with certolizumab pegol (400mg qd reduced to 200mg qd after one month) and with methotrexate. The study duration was twelve months. Response at three months was determined with the American College of Rheumatology-50, Disease Assessment Score-28 ESR, Health Assessment Questionnaire and the Clinical Disease Activity Index. The performance of these measures at predicting treatment failure at twelve months defined by the American College of Rheumatology-50 criteria was determined, using the positive predictive values as the principal evaluation criterion. ResultsThree hundred and eighty two patients were available for analysis and 225 completed the twelve-month follow-up. At Week 52, 149 (38.1%) patients met the American College of Rheumatology-50 response criterion. Positive predictive values ranged from 81% for a decrease in Health Assessment Questionnaire- Disability index score since baseline >0.22 to 95% for a decrease in Disease Assessment Score-28 score since baseline≥1.2. Sensitivity was≤70% in all cases. Performance of these measures was similar irrespective of the definition of treatment failure at 12months. ConclusionsSimple clinical measures of disease activity can predict future treatment failure reliably and are appropriate for implementing treat-to-target treatment strategies in everyday practice.

Should viral load thresholds be lowered?: Revisiting the WHO definition for virologic failure in patients on antiretroviral therapy in resource-limited settings.

The World Health Organization (WHO) guidelines on antiretroviral therapy (ART) define treatment failure as 2 consecutive viral loads (VLs) ≥1000 copies/mL. There is, however, little evidence supporting 1000 copies as an optimal threshold to define treatment failure. Objective of this study was to assess the correlation of the WHO definition with the presence of drug-resistance mutations in patients who present with 2 consecutive unsuppressed VL in a resource-limited setting.In 10 nurse-led clinics in rural Lesotho children and adults on first-line ART for ≥6 months received a first routine VL. Those with plasma VL ≥80 copies/mL were enrolled in a prospective study, receiving enhanced adherence counseling (EAC) and a follow-up VL after 3 months. After a second unsuppressed VL genotypic resistance testing was performed. Viruses with major mutations against ≥2 drugs of the current regimen were classified as "resistant".A total of 1563 adults and 191 children received a first routine VL. Of the 138 adults and 53 children with unsuppressed VL (≥80 copies/mL), 165 (116 adults; 49 children) had a follow-up VL after EAC; 108 (74 adults; 34 children) remained unsuppressed and resistance testing was successful. Ninety of them fulfilled the WHO definition of treatment failure (both VL ≥1000 copies/mL); for another 18 both VL were unsuppressed but with <1000 copies/mL. The positive predictive value (PPV) for the WHO failure definition was 81.1% (73/90) for the presence of resistant virus. Among the 18 with VL levels between 80 and 1000 copies/mL, thereby classified as "non-failures", 17 (94.4%) harbored resistant viruses. Lowering the VL threshold from 1000 copies/mL to 80 copies/mL at both determinations had no negative influence on the PPV (83.3%; 90/108).The current WHO-definition misclassifies patients who harbor resistant virus at VL below 1000 c/mL as "nonfailing." Lowering the threshold to VL ≥80 copies/mL identifies a significantly higher number of patients with treatment-resistant virus and should be considered.

World Gastroenterology Organisation Global Guidelines: GERD Global Perspective on Gastroesophageal Reflux Disease.

PROBIOTICS—THE CONCEPTHistory and DefinitionsA century ago, Elie Metchnikoff (a Russian scientist, Nobel laureate, and professor at the Pasteur Institute in Paris) postulated that lactic acid bacteria (LAB) offered health benefits capable of promoting longevity. He suggested that “intestinal autoint

Late outcomes after the Cox maze IV procedure for atrial fibrillation

ObjectiveThe Cox maze IV procedure (CMPIV) has been established as the gold standard for surgical ablation; however, late outcomes using current consensus definitions of treatment failure have not been well described. To compare to reported outcomes of catheter-based ablation, we report our institutional outcomes of patients who underwent a left-sided or biatrial CMPIV at 5 years of follow-up. MethodsBetween January 2002 and September 2014, data were collected prospectively on 576 patients with AF who underwent a CMPIV (n = 532) or left-sided CMPIV (n = 44). Perioperative variables and long-term freedom from AF, with and without AADs, were compared in multiple subgroups. ResultsFollow-up at any time point was 89%. At 5 years, overall freedom from AF was 93 of 119 (78%), and freedom from AF off AADs was 77 of 177 (66%). No differences were found in freedom from AF, with or without AADs, at 1, 2, 3, 4, and 5 years for patients with paroxysmal AF (n = 204) versus with persistent/longstanding persistent AF (n = 305), or for those who underwent standalone versus a concomitant CMP. Duration of preoperative AF and hospital length of stay were the best predictors of failure at 5 years. ConclusionsThe outcomes of the CMPIV remain good at late follow-up. The type of preoperative AF or the addition of a concomitant procedure did not affect late success. The results of the CMPIV remain superior to those reported for catheter ablation and other forms of surgical AF ablation, especially for patients with persistent or longstanding AF.