Efficacy Of Different Treatments Research Articles

Characterizing post-SSRI sexual dysfunction and its impact on quality of life through an international online survey.

Post-SSRI sexual dysfunction (PSSD) is an underrecognized and poorly understood medical condition characterized by sexual dysfunction that persists despite SSRI discontinuation. We conducted a survey of individuals with PSSD to better characterize this condition and its impact on various quality of life concerns. Surveys were distributed to an online support group for individuals with PSSD. Surveys assessed medications suspected of causing PSSD and symptoms experienced during and after treatment. Respondents reported the trajectory of their condition, the efficacy of different treatments, and the impact of PSSD on their quality of life. 239 survey responses were included in this study. A majority of respondents had a history of SSRI use (92%) compared to only SNRI or atypical antidepressant use (8%). The overall severity of symptoms improved for 45% and worsened or remained the same for 37% of respondents after discontinuing treatment with serotonin reuptake inhibitors. Only 12% of respondents reported being counseled regarding potential sexual dysfunction while taking antidepressants. The majority rated the effect of PSSD on their quality of life as extremely negative (59%) or very negative (23%). PSSD can have an overwhelmingly negative impact on quality of life. Currently, it is unclear why certain individuals develop PSSD and there are no definitive treatments for this condition. Further research of PSSD and greater awareness of this condition is needed among prescribers of serotonin reuptake inhibitors to improve patient care.

LARS: A review of therapeutic options and their efficacy

Therapeutic intervention in sufferers of low anterior resection syndrome (LARS) involves attempts to ameliorate or, more ideally, cure the range of heterogenous symptoms that characterise this debilitating syndrome. Therapeutic interventions can broadly be summarised into: (1) dietary modification/supplementation and pharmacologic agents; (2) pelvic floor rehabilitation; (3) bowel irrigation techniques; (4) neuromodulation; and (5) diverting/defunctioning stoma formation. Measures to improve stool consistency, involving dietary modifications and pharmacological manipulation, are clinically intuitive, but lack a robust evidence-base. Pelvic floor rehabilitation can also be utilized, with demonstrable improvements in incontinence scores and/or quality of life in a systematic review and randomised controlled trial (RCT). However, the relative benefits of individual techniques are difficult to ascertain. Transanal irrigation achieves significant improvement in bowel function, LARS scores and quality of life in a systematic review, including one RCT. Similarly, percutaneous tibial nerve stimulation achieved significant improvements in LARS and symptom scores in one very small RCT comparing it with medical treatment alone. Finally, three systematic reviews reported improvements in symptom severity and quality of life scores following sacral neuromodulation, with success rates of 74% comparable to its use for “de novo” fecal incontinence. Stoma formation is a dramatic but effective solution in resistant cases. Currently, there is a lack of evidence guiding selection and determining efficacy of different interventions in LARS; addressing this remains a key research priority for clinicians given that the burden of bowel dysfunction following low anterior resection remains substantial for a large proportion of patients.

Weight-Loss Strategies for Prevention and Treatment of Hypertension: A Scientific Statement From the American Heart Association.

Hypertension is a major risk factor for cardiovascular and renal diseases in the United States and worldwide. Obesity accounts for much of the risk for primary hypertension through several mechanisms, including neurohormonal activation, inflammation, and kidney dysfunction. As the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed. Lifestyle modification, including diet, reduced sedentariness, and increased physical activity, is usually recommended for patients with obesity; however, the long-term success of these strategies for reducing adiposity, maintaining weight loss, and reducing blood pressure has been limited. Effective pharmacotherapeutic and procedural strategies, including metabolic surgeries, are additional options to treat obesity and prevent or attenuate obesity hypertension, target organ damage, and subsequent disease. Medications can be useful for short- and long-term obesity treatment; however, prescription of these drugs is limited. Metabolic surgery is effective for producing sustained weight loss and for treating hypertension and metabolic disorders in many patients with severe obesity. Unanswered questions remain related to the mechanisms of obesity-related diseases, long-term efficacy of different treatment and prevention strategies, and timing of these interventions to prevent obesity and hypertension-mediated target organ damage. Further investigation, including randomized controlled trials, is essential to addressing these questions, and emphasis should be placed on the prevention of obesity to reduce the burden of hypertensive cardiovascular and kidney diseases and subsequent mortality.

Unraveling the efficacy of different treatments towards suppressing limonin and naringin content of Kinnow juice: An innovative report

Bitterness in juice significantly affects consumer acceptability as well as its shelf life. Juice extracted from Kinnow fruit becomes bitter due to the presence of limonin and naringin. Therefore to remove bitterness from Kinnow juice, different debittering methods have been studied. These methods include hot water treatment, lye treatment (1–2%), Florisil®, β-cyclodextrin (0.5–2.5%) and their optimized treatment (NaOH 1.5% + Florisil® 3% + β-cyclodextrin 2%). Significant effect of treatments on pH, acidity, and TSS (Total soluble solids) was observed. Control (P1) and treated juice samples [lye treated juice (1.5%) (P2); lye treated juice (1.5%) + Florisil® (3%) (P3), and juice from optimized treatment (P4)] were studied for the presence of bioactive compounds and antioxidant properties. The antioxidant profiles of control and treated juice samples were compared using different antioxidant assays. Phenolic compounds in debittered juice (P4) were significantly higher (94.5 mg GAE/100 mL) as compared to control (P1) (90.1 mg GAE/100 mL). HPLC was performed to check the presence of bitter compounds (limonin and naringin) in control and treated juice. A significant decrease in the concentration of limonin (124.45–57.89 μg/mL) and naringin (2.38–1.26 μg/mL) was observed in the selected combined treatment.

Efficacy of Different Interventions to Reduce Pre- or Perioperative Blood Transfusion Rate in Patients with Colorectal Cancer: A Network Meta-Analysis of Randomized Controlled Trials.

Background: The high proportion of blood transfusions before and during surgery carries unnecessary risk and results in poor prognosis in colorectal cancer patients. Different pharmacological interventions (i.e., iron supplement or recombinant erythropoietin) to reduce blood transfusion rates have shown inconclusive results. Methods: This network meta-analysis (NMA) consisted of randomized controlled trials (RCTs) comparing the efficacy of different pharmacologic interventions (i.e., iron supplementation or recombinant erythropoietin) to reduce the blood transfusion rate. NMA statistics were conducted using the frequentist model. Results: Seven RCTs (688 participants) were included in this study. The NMA demonstrated that the combination of high-dose recombinant human erythropoietin and oral iron supplements was associated with the least probability of receiving a blood transfusion [odds ratio = 0.24, 95% confidence intervals (95% CIs): 0.08 to 0.73] and best reduced the amount of blood transfused if blood transfusion was necessary (mean difference = −2.62 U, 95% CI: −3.55 to −1.70 U) when compared to the placebo/control group. None of the investigated interventions were associated with any significantly different dropout rate compared to the placebo/control group. Conclusions: The combination of high-dose recombinant human erythropoietin and oral iron supplements might be considered as a choice for reducing the rate of blood transfusion in patients with colorectal cancer. However, future large-scale RCT with long-term follow-up should be warranted to approve the long-term safety.

EGFR Status Assessment for Better Care of Early Stage Non-Small Cell Lung Carcinoma: What Is Changing in the Daily Practice of Pathologists?

The recent emergence of novel neoadjuvant and/or adjuvant therapies for early stage (I-IIIA) non-small cell lung carcinoma (NSCLC), mainly tyrosine kinase inhibitors (TKIs) targeting EGFR mutations and immunotherapy or chemo-immunotherapy, has suddenly required the evaluation of biomarkers predictive of the efficacy of different treatments in these patients. Currently, the choice of one or another of these treatments mainly depends on the results of immunohistochemistry for PD-L1 and of the status of EGFR and ALK. This new development has led to the setup of different analyses for clinical and molecular pathology laboratories, which have had to rapidly integrate a number of new challenges into daily practice and to establish new organization for decision making. This review outlines the impact of the management of biological samples in laboratories and discusses perspectives for pathologists within the framework of EGFR TKIs in early stage NSCLC.

Efficacy of Oral Azithromycin versus Doxycycline in the Treatment of Acne Vulgaris

Introduction: Acne vulgaris is one of the most common skin disease affecting adolescence of either sex, globally. Antibiotics like macrolides and tetracycline have been used with good results, studies comparing their efficacy are lacking. The present study compare the efficacy of Azithromycin v/s Doxycycline in acne vulgaris.
 Aims: To compare the efficacy of Azithromycin and Doxycycline in the treatment of acne vulgaris.
 Methods: This is a prospective hospital based comparative study, conducted on 80 patients attending outpatient department of Dermatology, Nepalgunj Medical College Teaching Hospital with acne vulgaris from July 2019 to April 2020. Patient were divided alternately into two groups, Group A received Azithromycin (n=40) and Group B Doxycycline (n=40) and compared the effects of treatment at 6 and 12 weeks. Efficacy assessment was done according to simple acne grading system.
 Results: Acne was predominant in female (62.5%) as compared to male (37.5%). Patient between 16 to 20 years age group were more prone to acne (47.5%). Most of the patients had Grade II acne before treatment in both groups (Azithromycin 52.5%, Doxycycline 55%). After the treatment most of them improve to Grade I at 6 weeks (Azithromycin 50%, Doxycycline 55%) and to Grade zero at 12 weeks (Azithromycin 42.5%, Doxycycline 67.5%).There was no statistically significant difference in treatment efficacy between the two groups at 6 weeks but at 12 weeks efficacy of Doxycycline was significantly better than Azithromycin.
 Conclusion: Both oral Azithromycin and Doxycycline when given for treatment of acne vulgaris the analysis showed good improvement after 6 weeks of treatment but there was no statistically significant difference in the improvement in both groups (p 0.771). However after 12 weeks patient receiving Doxycycline showed statistically significant improvement (p 0.035) in comparison to the patients receiving Azithromycin.

Interventions for the prevention of persistent post-COVID-19 olfactory dysfunction.

Loss of olfactory function is well recognised as a cardinal symptom of COVID-19 infection, and the ongoing pandemic has resulted in a large number of affected individuals with abnormalities in their sense of smell. For many, the condition is temporary and resolves within two to four weeks. However, in a significant minority thesymptoms persist. At present, it is not known whether early intervention with any form of treatment (such as medication or olfactory training) can promote recoveryandprevent persisting olfactory disturbance. OBJECTIVES: To assess the effects (benefits and harms) of interventions that have been used, or proposed, to prevent persisting olfactory dysfunction due to COVID-19 infection. A secondary objective is tokeep the evidence up-to-date, using a living systematic review approach. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane COVID-19 Study Register; Cochrane ENT Register; CENTRAL; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies. The date of the search was 16 December 2020. Randomised controlled trials including participants who had symptoms of olfactory disturbance following COVID-19 infection. Individuals who had symptoms for less than four weeks were included in this review. Studies compared any intervention with no treatment or placebo. DATA COLLECTION AND ANALYSIS: We used standard Cochranemethodological procedures. Our primary outcomes werethe presence of normal olfactory function, serious adverse effects and change in sense of smell. Secondary outcomes were the prevalence of parosmia,change in sense of taste, disease-related quality of life and other adverse effects (including nosebleeds/bloody discharge). We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included one studyof 100 participants, which comparedanintranasal steroid spray to no intervention. Participants in both groupswere also advised to undertake olfactory training for the duration of the trial. Data were identified for only two of the prespecified outcomes for this review, and no data were available for the primary outcome of serious adverse effects. Intranasal corticosteroids compared to no intervention (all using olfactory training) Presence of normal olfactory functionafter three weeksof treatment was self-assessed by the participants, using a visual analogue scale (range 0 to 10, higher scores = better). A score of 10represented "completely normal smell sensation". The evidence is very uncertain about the effect of intranasal corticosteroids on self-rated recovery of sense of smell (estimated absolute effect619 per 1000 compared to 520 per 1000, risk ratio (RR) 1.19, 95% confidence interval (CI) 0.85 to 1.68; 1 study; 100 participants; very low-certainty evidence). Change insense of smellwas not reported, but the self-rated score for sense of smell was reported at the endpoint of the study with the same visual analogue scale(after three weeksof treatment). The median scores at endpoint were 10 (interquartile range (IQR) 9 to 10) for thegroup receiving intranasal corticosteroids, and 10 (IQR 5 to 10) for the group receiving no intervention (1 study; 100 participants; very low-certainty evidence). There is very limited evidence regarding the efficacy of different interventions at preventing persistent olfactory dysfunction following COVID-19 infection. However, wehave identified a small number of additional ongoing studies in this area.As this is a living systematic review, the evidence will be updated regularly to incorporatenew data from these, and other relevant studies, as they become available. For this (first) version of the living review, we identified a single study of intranasal corticosteroids to include in this review, which provided data for only two of our prespecified outcomes. The evidence wasof very low certainty, therefore we were unable to determine whether intranasal corticosteroids may have a beneficial or harmful effect.

Wnt/β-catenin inhibitor ICG-001 enhances the antitumor efficacy of radiotherapy by increasing radiation-induced DNA damage and improving tumor immune microenvironment in hepatocellular carcinoma

Background and purposeRadiotherapy (RT) has a promising anti-tumor effect depending on its effects on both cancer cells and tumor immune microenvironment (TIME). As one of the most common alterations in hepatocellular carcinoma (HCC), wnt/β-catenin pathway activation, has been reported to induce radioresistance and suppressive TIME. In this study, we aim to explore the effect of wnt/β-catenin inhibitor ICG-001 on radiosensitivity and RT-related TIME of HCC and the underlying mechanism. Materials and methodsC57BL/6 and nude mouse tumor models were used to evaluate the efficacy of different treatments on tumor growth, recurrence and mice survival. Flow cytometry was performed to assess tumor infiltrating lymphocytes (TILs). DNA damage response (DDR) and radioresistance was investigated by colony formation assays, γ-H2AX and micronuclei measurements. ResultsThe addition of ICG-001 to RT exhibited better anti-tumor and survival-prolong efficacy in C57BL/6 than nude mice. TILs analysis revealed that ICG-001 plus RT boosted the infiltration and IFN-γ production of TIL CD8+ T cells, meanwhile reduced the number of Tregs. Moreover, mechanistic study demonstrated that ICG-001 increased the radiation-induced DDR of HCC cells by suppressing p53, thus leading to stronger activation of cGAS/STING pathway. Utilization of cGAS/STING pathway inhibitors impaired the therapeutic effect of combination therapy. Furthermore, combination therapy led to stronger immunologic memory and tumor relapse prevention. ConclusionsOur findings showed that ICG-001 displayed both local and systematic effects by increasing radiosensitivity and improving immunity in HCC, which indicated that ICG-001 might be a potential synergetic treatment for radiotherapy and radioimmunotherapy in HCC patients.

Therapeutic Efficacy of Mcl-1 Antagonism in Large Granular Lymphocyte Leukemia

Introduction: Large granular lymphocyte (LGL) leukemia is a spectrum of rare clonal lymphoproliferative disorders, all of which involve expansion of large granular lymphocytes. Immunosuppressive regimens using methotrexate or cyclophosphamide are utilized as front-line treatments in LGL leukemia but are not curative nor are they effective in all patients. The aggressive LGL variants have no effective treatment and are refractory to conventional chemotherapy. The lack of effective and targeted therapies results from an incomplete picture of survival mechanisms that contribute to the pathogenesis of leukemic LGLs.We have previously reported that STAT3 is constitutively active in LGL leukemia cells and up to 40% of patients harbor activating mutations in STAT3 within the leukemic clone. We have also reported that the pro-survival Bcl-2-family protein Mcl-1 is upregulated in LGL leukemia patients. Additionally, we have identified MCL1 as a transcriptional target of STAT3 in leukemic LGLs. Recently, novel small molecule inhibitors of Mcl-1 have been identified including marinopyrrole A (maritoclax) and its derivative KS18. These inhibitors effectively induced apoptosis in Mcl-1-dependent cells and suppressed the growth of Mcl-1-dependent hematologic cancer xenografts in nude mice without apparent toxicity. Thus, this study further investigates the role of Mcl-1 in LGL leukemia and the potential therapeutic application of the Mcl-1 antagonists maritoclax and KS18.Results: Knockdown of Mcl-1 in human-derived LGL leukemia cell lines (TL1 and NKL) resulted in decreased cell viability by MTS assay and increased apoptosis by flow cytometry in Mcl-1 siRNA versus scramble siRNA-transfected cells (NKL and TL-1 cells: p < 0.001). Treatment with maritoclax or KS18 decreased cell proliferation and increased apoptosis in NKL, TL1 and RNK16 (rat-derived LGL leukemia cell line) cells (Maritoclax, EC50: 2.45, 1.43 and 1.23 μM respectively) (KS18, EC50: 1.30, 0.60 and 0.31 μM respectively). Ex vivo treatment with maritoclax and KS18 induced selective apoptosis in PBMCs from LGL leukemia patients (NK-LGL, n = 6; T-LGL, n = 12) but not normal donor PBMCs (n = 4) (Maritoclax and KS18, p < 0.0001). Importantly, there was no significant difference in treatment efficacy in patient cells with wild-type STAT3 (n = 9) versus mutant STAT3 (Y640F, n = 5; D661Y, n = 3). We then proceeded to mechanistic studies of Mcl-1 antagonism. Both maritoclax and KS18 induced selective and dose-dependent Mcl-1 degradation by western blot in NKL, TL1, RNK16 and PBMCs from LGL leukemia patients. We further delineated that this effect was proteasome dependent as it is reversible by pre-treatment with MG132, a proteasome inhibitor.Preclinical in vivo studies were then conducted in Fisher F344 rats that were transplanted with primary leukemic LGL cells and monitored for signs of leukemia through serial CBC and body weight measurements. Leukemic rats developed progressive anemia, thrombocytopenia and leukocytosis and significant weight loss. Rats were treated with vehicle or KS18 (2.5 or 5.0 mg/kg i.p. daily) upon detection of leukemic features. In non-leukemic KS18-treated rats, there were no observed toxicities and there was no difference in survival or weight gain versus vehicle-treated non-leukemic rats. However, leukemic KS18-treated rats exhibited findings consistent with tumor lysis syndrome, including sudden death associated with severely increased serum LDH and increased apoptosis in heart and spleen tissues. At necropsy, leuk/KS18 rats exhibited significantly decreased infiltration and elevated apoptosis of leukemic cells in heart and spleen tissues. Conversely, in leuk/veh rats, spleen tissue lacked normal histologic structure with red pulp replaced almost completely by leukemia cells. Ex vivo KS18 treatment also decreased the viability of PBMC and spleen cells from leukemic animals (p < 0.0001). These data indicate that Mcl-1 is a promising therapeutic target as evidenced by potent therapeutic efficacy of KS18 in LGL cell lines and primary patient material and in an aggressive rat model of LGL leukemia. Further studies are required in order to optimize drug dose, timing and concentrations of KS18 in order to prevent potential tumor lysis syndrome and optimize therapeutic benefit. DisclosuresGru:Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Identifying treatment effects using trimmed means when data are missing not at random.

Patients often discontinue from a clinical trial because their health condition is not improving or they cannot tolerate the assigned treatment. Consequently, the observed clinical outcomes in the trial are likely better on average than if every patient had completed the trial. If these differences between trial completers and non-completers cannot be explained by the observed data, then the study outcomes are missing not at random (MNAR). One way to overcome this problem-the trimmed means approach for missing data due to study discontinuation-sets missing values as the worst observed outcome and then trims away a fraction of the distribution from each treatment arm before calculating differences in treatment efficacy (Permutt T, Li F. Trimmed means for symptom trials with dropouts. Pharm Stat. 2017;16(1):20-28). In this paper, we derive sufficient and necessary conditions for when this approach can identify the average population treatment effect. Simulation studies show the trimmed means approach's ability to effectively estimate treatment efficacy when data are MNAR and missingness due to study discontinuation is strongly associated with an unfavorable outcome, but trimmed means fail when data are missing at random. If the reasons for study discontinuation in a clinical trial are known, analysts can improve estimates with a combination of multiple imputation and the trimmed means approach when the assumptions of each hold. We compare the methodology to existing approaches using data from a clinical trial for chronic pain. An R package trim implements the method. When the assumptions are justifiable, using trimmed means can help identify treatment effects notwithstanding MNAR data.

Modeling Subtypes of Automatically Reinforced Self-Injurious Behavior with the Evolutionary Theory of Behavior Dynamics.

The subtypes of automatically reinforced self-injurious behavior (ASIB) delineated by Hagopian and colleagues (Hagopian et al., 2015; 2017) demonstrated how functional-analysis (FA) outcomes may predict the efficacy of various treatments. However, the mechanisms underlying the different patterns of responding obtained during FAs and corresponding differences in treatment efficacy have remained unclear. A central cause of this lack of clarity is that some proposed mechanisms, such as differences in the reinforcing efficacy of the products of ASIB, are difficult to manipulate. One solution may be to model subtypes of ASIB using mathematical models of behavior in which all aspects of the behavior can be controlled. In the current study, we used the evolutionary theory of behavior dynamics (ETBD; McDowell, 2019) to model the subtypes of ASIB, evaluate predictions of treatment efficacy, and replicate recent research aiming to test explanations for subtype differences. Implications for future research related to ASIB are discussed.

Effects of molecular markers on the treatment decision and prognosis of colorectal cancer: a narrative review.

To summarize the effects of molecular markers on the treatment decision and prognosis of colorectal cancer. Colorectal cancer is a highly heterogeneous disease. Even colorectal cancers of the same pathological type and clinical stage may have significant differences in treatment efficacy and prognosis. There are three main molecular mechanisms for the occurrence and development of colorectal cancer: chromosomal instability (CIN) pathway, microsatellite instability (MSI), and CpG island methylate phenotype (CIMP). There are multiple molecular markers distributed on each pathway. We performed a literature search on the PubMed database for studies published in English (from the date of initiation of the database to the year of 2020) using the following subject terms: "colon cancer", "rectal cancer", "colorectal cancer", "molecular markers", "biomarkers", "treatment strategies", and "prognosis". The different expression states of molecular markers have a significant impact on the treatment decision and prognosis of colorectal cancer. Main colorectal cancer molecular markers include MSI and some important genes. Individualized treatments for tumors with different molecular phenotypes have improved the treatment effectiveness for colorectal cancer. The rational use of molecular markers is valuable for treatment decision-making and the prognosis of patients with colorectal cancer.

Toward understanding COVID-19 pneumonia: a deep-learning-based approach for severity analysis and monitoring the disease

We report a new approach using artificial intelligence (AI) to study and classify the severity of COVID-19 using 1208 chest X-rays (CXRs) of 396 COVID-19 patients obtained through the course of the disease at Emory Healthcare affiliated hospitals (Atlanta, GA, USA). Using a two-stage transfer learning technique to train a convolutional neural network (CNN), we show that the algorithm is able to classify four classes of disease severity (normal, mild, moderate, and severe) with the average Area Under the Curve (AUC) of 0.93. In addition, we show that the outputs of different layers of the CNN under dominant filters provide valuable insight about the subtle patterns in the CXRs, which can improve the accuracy in the reading of CXRs by a radiologist. Finally, we show that our approach can be used for studying the disease progression in a single patient and its influencing factors. The results suggest that our technique can form the foundation of a more concrete clinical model to predict the evolution of COVID-19 severity and the efficacy of different treatments for each patient through using CXRs and clinical data in the early stages of the disease. This use of AI to assess the severity and possibly predicting the future stages of the disease early on, will be essential in dealing with the upcoming waves of COVID-19 and optimizing resource allocation and treatment.

P603 Patient characteristics and adverse effects in biologic treatment of Crohn’s Disease and Ulcerative Colitis: A nationwide Danish cohort study years 2015–2018

Abstract Background Biological therapies have demonstrated effectiveness in the treatment of Crohn’s Disease (CD) and Ulcerative Colitis (UC), but comparative analyses of the various treatments remain limited. Methods Using Danish national registries, we performed a nationwide cohort study including all bio-naïve individuals diagnosed with UC or CD initiating treatment with infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ), golimumab (GOL), or ustekinumab (UST) during 2015–2018. The hazard ratios (HR) of hospitalization, surgery, and start of corticosteroid therapy were explored using Cox regression adjusted for health-related and socio-economic parameters at treatment initiation. Results More than 90% of 1,836 CD and 1,886 UC patients had IFX as first-line treatment. Patients with ADA, VDZ, UST or GOL as first-line treatment were older at diagnosis and start of biologic treatment. A larger proportion were women, had higher education, and had previously had IBD surgery. We observed a higher risk of all-cause hospitalization (HR: 1.56 (95% CI: 1.16; 2.10)) among CD patients with ADA as first-line treatment compared to IFX. No risk difference was observed of IBD hospitalization, IBD related surgery, or use of corticosteroids between ADA- and IFX-treated CD patients. We observed no risk difference between ADA- and IFX-treated UC patients for any outcomes. For both CD and UC patients, analyses of VDZ were based on very low number of cases and the results were inconclusive. Analyses of GOL and UST were not possible because of low numbers. Second-line treatment with VDZ compared to ADA among CD patients previously treated with IFX showed no risk difference of all-cause hospitalization (1.32 (0.91; 1.92)), IBD hospitalization (1.27 (0.68; 2.35)), IBD related surgery (1.41 (0.69; 2.85)), or use of corticosteroids (0.70 (0.27; 1.82)). Among UC patients, second-line VDZ was associated with an increased risk of IBD related surgery (1.94 (1.01; 3.71)), but not of all-cause hospitalization (0.77 (0.48; 1.24)), IBD hospitalization (0.75 (0.38; 1.46)), or corticosteroid use (0.92 (0.37; 2.28)) compared to ADA. Conclusion We observed increased risk of hospitalization among CD patients treated with ADA compared to IFX, and increased risk of IBD-related surgery in UC patients receiving VDZ as second line treatment compared to ADA. The differences in key baseline characteristics patients initiating biologic treatment with ADA, VDZ, UST or GOL compared to IFX might reflect differences in disease state, that justify deviations from treatment guideline. It should be further investigated if the associations are an effect of differences in treatment efficacy and safety or confounding by differences in disease state at treatment start.

Current Intervention Treatments for Food Addiction: A Systematic Review.

Research on the concept of food addiction (FA) has steadily grown and, based on a widely used self-report, FA is estimated to affect between 16–20% of the adult population. However, there are few interventions available for people with self-reported FA, and their efficacy is unclear. The primary aim of the review was to examine the efficacy of different interventions, including behavioural/lifestyle, medication and surgical approaches, for reducing symptoms and/or changing diagnosis of FA among adolescents and adults. A secondary aim was to examine the influence of sex as a moderator of intervention effects. A systematic search was performed from 2008–2020 to identify studies that used the YFAS to assess the effectiveness of interventions on FA. Nine studies were identified (n = 7 adults, n = 2 adolescents) including a total of 812 participants (range 22–256) with an average of 69% females per study. The types of interventions included medications (n = 3), lifestyle modification (n = 3), surgical (n = 2) and behavioural (n = 1), with FA being assessed as a secondary outcome in all studies. Five studies in adults reported a significant reduction in FA symptoms or diagnosis from pre to post-intervention, two when compared to a control group and three in the intervention group only. Efficacious interventions included: medication (combination of naltrexone and bupropion, as well as pexacerfont), bariatric surgery and lifestyle modification. No significant changes in FA were reported in adolescent studies. Given few studies were identified by the review, there is insufficient evidence to provide clear recommendations for practice; however, some interventions show potential for reducing self-reported FA outcomes in adults. Future research should explore the longer-term efficacy of interventions and the effectiveness of treatments with sufficient sample sizes.

Use of circulating tumor DNA in colorectal cancer patients to assess tumor burden and response to therapy: An observational study.

3528 Background: Residual disease after treatment for colorectal cancer (CRC) poses a risk for recurrence but imaging and CEA are limited in their capacity to detect residual disease. A simple test is needed for assessing treatment response. This study determined whether levels of methylated BCAT1/IKZF1 DNA in blood correlate with tumor burden and whether post-treatment levels inform efficacy of different treatments for CRC. Methods: Patients with primary CRC had blood collected prior to treatment (n = 282, 59.9% males, median age 68.5y). Cell free DNA (cfDNA) was extracted from plasma and assayed for methylation in BCAT1 and IKZF1. Detection of methylation in either gene deemed a sample positive; levels were expressed as %methylation (average methylation/average cfDNA). Positive patients had additional samples collected post-treatment for early stage CRC (surgery, n = 31), advanced/metastatic CRC (surgery + adjuvant chemotherapy, n = 15), and rectal cancer (neoadjuvant therapy, surgery +/- chemotherapy, n = 6), or following mid-therapy suspension of treatment in advanced CRC (n = 24). Tumor size was expressed as the maximum diameter of the primary (assessed surgically or by MRI). Results: Pretreatment results increased with CRC stage. Positivity by stage was: I, 23.7% (14/59); II, 62.1% (54/87); III, 68.6% (70/102); IV, 85.3% (29/34). Level by stage: I, 0.0%; II, 0.06%; III, 0.07%; IV, 4.07%, p &lt; 0.001). Pretreatment levels correlated significantly with tumor size (r = 0.372, p &lt; 0.001). Post-treatment blood was collected a median 2.4mo (IQR 1.7-3.9) after therapy completion. Positivity decreased after completing treatment (Table), with 88.4% of cases (46/52) becoming ctDNA negative. All cases with complete treatment had a reduction in biomarker levels, whereas in those with incomplete therapy, 54.5% (12/22) remained positive and the pre- and post-treatment levels were not significantly different. Of those positive after treatment, 13 had a further blood sample: 8 had become ctDNA negative and all but one remained disease free. Five remained positive and all had further suspected or confirmed disease. Conclusions: Levels of methylated BCAT1 and IKZF1 DNA in blood correlated with tumor burden; levels became undetectable in the majority of patients following completion of planned curative intent treatment. The methylated ctDNA blood test aids monitoring of responses to therapy and identification of those cases with residual cancer who might benefit from ongoing therapy.[Table: see text]

Effectiveness of Delivering Dialectical Behavioral Therapy Techniques by Email in Patients With Borderline Personality Disorder: Nonrandomized Controlled Trial.

BackgroundBorderline personality disorder is a debilitating and prevalent mental health disorder, with often inaccessible treatment options. Electronically delivered dialectical behavioral therapy could be an efficacious and more accessible intervention.ObjectiveWe aimed to evaluate the efficacy of electronic delivery of dialectical behavioral therapy in the treatment of individuals with symptoms of borderline personality disorder.MethodsStudy participants diagnosed with borderline personality disorder were offered either an email-based or in-person group format dialectical behavioral therapy skill-building program. During each session, participants were provided with both the material and feedback regarding their previous week’s homework. Electronically delivered dialectical behavioral therapy protocol and content were designed to mirror in-person content. Participants were assessed using the Self-Assessment Questionnaire (SAQ) and Difficulties in Emotion Regulation Scale (DERS).ResultsThere were significant increases in SAQ scores from pre- to posttreatment in the electronic delivery group (F1,92=69.32, P<.001) and in-person group (F1,92=60.97, P<.001). There were no significant differences observed between the groups at pre- and posttreatment for SAQ scores (F1,92=.05, P=.83). There were significant decreases in DERS scores observed between pre- and posttreatment in the electronic delivery group (F1,91=30.15, P<.001) and the in-person group (F1,91=58.18, P<.001). There were no significant differences observed between the groups for DERS scores pre- and posttreatment (F1,91=.24, P=.63). There was no significant difference in treatment efficacy observed between the 2 treatment arms (P<.001).ConclusionsDespite the proven efficacy of in-person dialectical behavioral therapy in the treatment of borderline personality disorder, there are barriers to receiving this treatment. With the prevalence of internet access continuing to rise globally, delivering dialectical behavioral therapy with email may provide a more accessible alternative to treatment for individuals with borderline personality disorder without sacrificing the quality of care.Trial RegistrationClinicalTrials.gov NCT04493580; https://clinicaltrials.gov/ct2/show/NCT04493580

Genomic factors underlying sex differences in trauma-related disorders

Post-traumatic stress disorder (PTSD) is a devastating illness with treatment that is effective in only approximately half of the population. This limited rate of response highlights the necessity for research into underlying individual biological mechanisms that mediate development and progression of this disease, allowing for identification of patient-specific treatments. PTSD has clear sex differences in both risk and symptom patterns. Thus, one approach is to characterize trauma-related changes between men and women who exhibit differences in treatment efficacy and response to trauma. Recent technological advances in sequencing have identified several genomic loci and transcriptional changes that are associated with post-trauma symptomatology. However, although the diagnosis of PTSD is more prevalent in women, the genetic factors underlying sex differences remain poorly understood. Here, we review recent work that highlights current understanding and limitations in the field of sex differences in PTSD and related symptomatology.

Efficacy of vision-based treatments for children and teens with amblyopia: a systematic review and meta-analysis of randomised controlled trials

ObjectiveTo identify differences in efficacy between vision-based treatments for improving visual acuity (VA) of the amblyopic eye in persons aged 4–17 years old.Data sourcesOvid Embase, PubMed (Medline), the Cochrane Library,...