Clinical trial: predictive factors for response to gut-directed hypnotherapy for refractory irritable bowel syndrome, a post hoc analysis.

BACKGROUND: Gut-directed hypnotherapy is effective for patients with irritable bowel syndrome (IBS). Despite its considerable evidence base, gut-directed hypnotherapy is not widely available and remains a limited resource. This emphasises the need to select patients who are most likely to benefit. AIM: To determine whether baseline patient characteristics were predictive of response to gut-directed hypnotherapy in patients with IBS METHODS: We conducted a secondary analysis of outcomes of 448 patients with refractory Rome III IBS who participated in a randomised study confirming non-inferiority of 6 compared to 12 sessions of gut-directed hypnotherapy. We compared baseline patient characteristics, including age, sex, IBS subtype, quality of life and IBS-Symptom Severity Scale (IBS-SSS), non-colonic symptom score and Hospital Anxiety and Depression (HAD) score between responders and non-responders. We defined response as ≥50-point decrease in IBS-SSS or ≥30% reduction in pain severity scores. RESULTS: Overall, 76.3% achieved ≥50-point decrease in IBS-SSS. Responders had a higher baseline non-colonic symptom score (p = 0.005). Those who achieved ≥30% improvement in abdominal pain scores (59.8%) had higher baseline IBS-SSS (p = 0.03), and lower baseline HAD-depression score (p = 0.012). Fifty-four patients (12%) dropped out of gut-directed hypnotherapy. Compared to completers, dropouts had higher baseline HAD-anxiety score (p = 0.034). CONCLUSIONS: These data suggest that patients with a higher burden of gastrointestinal and extraintestinal symptoms are most likely to benefit from gut-specific behavioural intervention for refractory IBS. Clinical assessment of gastrointestinal, somatic and psychological symptom profiles may play a role in selecting patients for gut-directed hypnotherapy.

Improving access to gut-directed hypnotherapy for irritable bowel syndrome in the digital therapeutics' era: Are mobile applications a "smart" solution?

Gut-directed hypnotherapy (GDH) is a highly effective brain-gut behavioral therapy which is recommended in international guidelines for the treatment of irritable bowel syndrome (IBS). There is increasing recognition of the value of GDH as part of integrated care alongside medical and dietary approaches. This has led to recent innovations to widen access to GDH to meet the increasing demand. Recent advances include streamlined courses of individualized GDH, group therapy, and remote delivery. In this issue of Neurogastroenterology and Motility, Peters et al. retrospectively report outcomes of smartphone app-delivered GDH in a population with self-reported IBS. While adherence was low, those that completed smart phone-delivered GDH-achieved symptom benefit. This mini-review summarizes the current evidence-base for available modalities of GDH and discusses the current and future utility and development of mobile health applications in the digital therapeutics' era.

Patient satisfaction after remotely delivered gut-directed hypnotherapy for irritable bowel syndrome during the COVID-19 era: implications for future practice.

OBJECTIVE: Gut-directed hypnotherapy (GDH) is an evidence-based treatment for irritable bowel syndrome (IBS). Adoption of remote GDH has been accelerated by the COVID-19 pandemic. We aimed to evaluate patient experience and satisfaction following remote GDH. DESIGN: On completing 12 sessions of remote GDH via Skype using the Manchester protocol, patients with refractory IBS completed a feedback form on their experience. The proportion reporting positive outcomes (≥30% improvement in global IBS symptoms or abdominal pain, satisfaction, recommendation to family/friends) were compared by patient factors (age, gender, proximity, preferences). RESULTS: Of 52 patients completing the feedback form, 27 (52%) indicated that they would have opted for remote over face-to-face GDH, regardless of the pandemic situation. On a five-point scale (5=easy), patients rated the platform easy-to-use (mean 4.5±0.8) without impairment of communication (mean rating 4.6±0.8). Following remote GDH, 30/52 (58%) reported ≥30% global IBS symptom improvement, and 24/52 (46%) reported ≥30% pain reduction. 90% would recommend remote GDH to others. Only 39% felt they would have benefitted more from face to face. Those who would have chosen remote GDH regardless of the pandemic were more likely to be satisfied (p=0.01). Age, gender and proximity did not influence outcomes, satisfaction and likelihood of recommending remote GDH to others. Difficulties during remote sessions were infrequent in both those that were satisfied, and those that would have preferred face to face. CONCLUSION: These data support the need to continue developing remote GDH in the post-COVID era but suggest that there is still a role for face-to-face GDH, with patient choice being an important factor.

Experience and clinical efficacy of gut-directed hypnotherapy in an Asian population with refractory irritable bowel syndrome.

Background and Aim: Recent studies have highlighted the high worldwide prevalence of irritable bowel syndrome (IBS) and disparities in its management between ethnic groups. For instance, gut-directed hypnotherapy (GDH), one of the most effective evidence-based treatments for IBS, is not recommended in Asian countries partly due to lack of population-specific outcome data. In this context, we evaluated the outcomes of GDH in an Asian population. Methods: Consecutive British Asian patients with refractory IBS who received 12-sessions of GDH using the Manchester protocol were included. Patients were treated by a team including a therapist able to speak several Asian languages. All patients prospectively completed the following questionnaires before and after GDH: IBS symptom severity score (IBS-SSS), hospital anxiety and depression scale (HADS), non-colonic symptom score, and the quality-of-life (QOL) score. The primary outcome measure was response to GDH defined by ≥50-point reduction in IBS-SSS. Pre- and post-treatment data were compared statistically. Results: Forty-four Asian patients with IBS (age 49 ± 13 years; 29 [66%] female; baseline IBS-SSS: 332.8 ± 94.6) completed GDH. Overall, 37 of 44 (84%) achieved a ≥50-point reduction in IBS-SSS and 25 of 44 (57%) achieved ≥30% reduction in abdominal pain scores. Following GDH, there were also significant mean improvements in IBS-SSS (-132.1, P < 0.0001), non-colonic symptom score (P < 0.0001), QOL score (P < 0.0001), HADS-anxiety (P < 0.0001), and HADS-depression (P < 0.0001), compared with baseline. Conclusion: Regardless of the ethnicity of the therapist, GDH was highly effective with similar response rates to outcomes in other IBS populations, supporting the development of GDH in Asian countries.

The effectiveness of mRNA-1273 vaccine against COVID-19 caused by Delta variant: A systematic review and meta-analysis.

We aimed to perform meta-analyses to summarize the overall effectiveness of the mRNA-1273 vaccine against COVID-19 caused by the Delta variant from real-world studies. A systematic literature search with no language restriction was performed in electronic databases to identify eligible observational studies that reported the effectiveness of the mRNA-1273 vaccine to prevent reverse transcription-polymerase chain reaction (RT-PCR) confirmed COVID-19 caused by Delta variant of SARS-CoV-2 (B.1.617.2). A random-effects meta-analysis model was used to estimate the pooled odds ratio (OR) at a 95% confidence interval (CI), and the vaccine effectiveness was indicated as (pooled OR - 1)/OR. Five studies were included for this systematic review and meta-analysis. The meta-analysis revealed that the administration of mRNA-1273 vaccine protected against RT-PCR confirmed COVID-19 caused by Delta variant ≥21 days post first dose, with pooled vaccine effectiveness of 66% (95% CI: 65%-67%), as well as ≥14 days after the second dose, with pooled vaccine effectiveness of 91% (95% CI: 84%-95%). In conclusion, the mRNA-1273 vaccine offers a substantial protection rate against RT-PCR confirmed COVID-19 caused by the Delta variant upon full vaccination, although with slightly reduced effectiveness relative to other strains of SARS-CoV-2.

Gut-focused hypnotherapy for children and adolescents with irritable bowel syndrome.

OBJECTIVE: Severe irritable bowel syndrome (IBS) in school children and adolescents often leads to stigmatisation, social withdrawal, disrupted education and psychological distress. While there are few effective treatment options for IBS in this age group, gut-focused hypnotherapy (GFH) has shown promise in several trials. Unfortunately, GFH is not widely available, and clinical data outside of trials are scarce. Here, we evaluated outcomes from GFH in patients with IBS, aged ≤18 years, from a tertiary referral centre. DESIGN/METHOD: Consecutive patients aged ≤18 years with severe IBS received 12 sessions of GFH, at weekly intervals, using the Manchester Protocol. Clinical outcomes data, including IBS Symptom Severity Score (IBS-SSS), Hospital Anxiety and Depression Scale (HADS), Non-colonic Symptom Score and Quality-of-Life (QoL) score, were collected prospectively, and compared pre-GFH and post-GFH. Clinical response was defined as ≥50 point reduction in IBS-SSS. RESULTS: 32 young patients fulfilling Rome III diagnostic criteria for IBS (median age 16 (range 8-18) years, n=23/32 (72%) female individuals) completed GFH. At baseline, the mean duration of IBS was 5.9±0.9 years, and the mean IBS-SSS was 313±14. After GFH, 28/32 (88%) responded, with a mean overall reduction in IBS-SSS -159±16 (p<0.0001), and 24/32 (75%) achieved ≥30% reduction in abdominal pain scores. GFH also improved: non-colonic symptoms (p<0.0001), HADS-anxiety (p<0.0001), HADS-depression (p=0.0002) and QoL Scores (p<0.0001). CONCLUSION: GFH is highly effective in children and adolescents with IBS. Early intervention with GFH in childhood IBS may reduce the subsequent burden of this problem in adults.

Pharmacotherapy in COVID-19 patients: a review of ACE2-raising drugs and their clinical safety.

The COVID-19 pandemic is caused by the severe acute-respiratory-syndrome-coronavirus-2 that uses ACE2 as its receptor. Drugs that raise serum/tissue ACE2 levels include ACE inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs) that are commonly used in patients with hypertension, cardiovascular disease and/or diabetes. These comorbidities have adverse outcomes in COVID-19 patients that might result from pharmacotherapy. Increasing ACE2 could potentially increase the risk of infection, severity or mortality in COVID-19 or it might be protective as it forms angiotensin-(1-7) which exhibits anti-inflammatory/anti-oxidative effects and prevents diabetes- and/or hypertension-induced end-organ damage. Thus, there existed clinical uncertainty. Here, we review studies implicating 15 classes of drugs in increasing ACE2 levels in vivo and the available literature on the clinical safety of these drugs in COVID-19 patients. Further, in a re-analysis of clinical data from a meta-analysis of 9 studies, we show that ACEIs/ARBs usage was not associated with an increased risk of all-cause mortality. Literature suggests that ACEIs/ARBs usage generally appears to be clinically safe though their use in severe COVID-19 patients might increase the risk of acute renal injury. For definitive clarity, further clinical and mechanistic studies are needed in assessing the safety of all classes of ACE2 raising medications.

Rising Events and Improved Outcomes of Gastrointestinal Bleed With Shock in USA: A 12-year National Analysis.

OBJECTIVE: Limited information is available based on single-center studies on trends of incidence and outcomes in gastrointestinal (GI) bleed with shock. METHODS: We analyzed data from 2002 to 2013 National Inpatient Sample. Using ICD-9 codes we identified 6.4 million hospital discharges of GI bleed from National Inpatient Sample database. Events were analyzed based on type of GI bleed, in-hospital mortality, hemodynamic status, and use of blood products. RESULTS: GI bleed with shock results in higher hospital mortality (20.77% with shock vs. 2.6% without shock). Between 2002 and 2013, there has been an increase in the percentage of upper and lower GI bleed with shock (1.35% to 4.92% and 1.49% to 3.06%) along with a reduction in mortality in both upper GI bleed with shock (26.9% to 13.8%) and lower GI bleed with shock (54.7% to 19.7%). Consistent with the rise in GI bleed with shock was an increase in blood product utilization. Packed red blood cell (pRBC) transfusion was associated with reduction in mortality in both nonvariceal upper GI bleed with shock (18.3% without pRBC vs. 13.9% receiving pRBC) and lower GI bleed with shock (36.05% without pRBC vs. 22.13% receiving pRBC), but did not affect mortality in variceal upper GI bleed with shock (31.79% vs. 32.22%). CONCLUSIONS: GI bleed with shock carries a higher mortality and have been steadily increasing from 2002 to 2013. pRBC transfusion was associated in improved mortality in GI bleed with shock except variceal bleed.

A Scoping Review of the Quality and the Design of Evaluations of Mobile Health, Telehealth, Smart Pump and Monitoring Technologies Performed in a Pharmacy-Related Setting.

Background: There is currently a need for high quality evaluations of new mobile health, telehealth, smart pump and monitoring technologies undertaken in a pharmacy-related setting. We aim to evaluate the use of these monitoring technologies performed in this setting. Methods: A systematic searching of English articles that examined the quality and the design of technologies conducted in pharmacy-related facilities was performed using the following databases: MEDLINE and Cumulative index to Nursing and Allied Health Literature (CINAHL) to identify original studies examining the quality and the design of technologies and published in peer-reviewed journals. Extraction of articles and quality assessment of included articles were performed independently by two authors. Quality scores over 75% are classed as being acceptable using a "relatively conservative" quality benchmark. Scores over 55% are included using a "relatively liberal" cut-off point. Results: Screening resulted in the selection of 40 formal evaluations. A substantial number of studies (32, 80.00%) were performed in the United States, quantitative in approach (33, 82.50%) and retrospective cohort (24, 60.00%) in study design. The most common pharmacy-related settings were: 22 primary care (55.00%); 10 hospital pharmacy (25.00%); 7 community pharmacy (17.50%); one primary care and hospital pharmacy (2.50%). The majority of the evaluations (33, 82.50%) reported clinical outcomes, six (15.00%) measured clinical and economic outcomes, and one (2.50%) economic only. Twelve (30.00%) quantitative studies and no qualitative study met objective criteria for "relatively conservative" quality. Using a lower "relatively liberal" benchmark, 27 quantitative (81.82%) and four qualitative (57.41%) studies met the lower quality criterion. Conclusion: Worldwide, few evaluations of mobile health, telehealth, smart pump and monitoring technologies in pharmacy-related setting have been published.Their quality is often below the standard necessary for inclusion in a systematic review mainly due to inadequate study design.

Hepatitis prevention project in the Korean American community in Killeen, Texas.

Educational efforts related to viral hepatitis have the potential to increase awareness and identify chronically infected individuals and can lead to successful vaccination strategies. However, in underserved semirural communities, such as the Korean American community in Killeen, Texas, these outreach activities are lacking. The GanYum ("hepatitis" in Korean) Prevention Project aimed to evaluate thoughts/behaviors, assess vulnerability, and educate Korean Americans on hepatitis B and C. Two outreach events were held at a Korean church and a Korean market (O'Mart) to provide education, screening, and outreach about viral hepatitis. Ninety-six patients were screened at two events. Five patients were found to be positive for hepatitis B surface antigen and were referred to their primary care physicians and the liver clinic at Scott & White Healthcare in Temple, Texas. Fifty-one patients (53%) were found to be immune to hepatitis B, and 40 patients (42%) were hepatitis B vulnerable. We demonstrated that the prevalence of chronic hepatitis B in Koreans in our study is similar to the previously documented prevalence (5%). Our educational efforts were successful in changing perceptions regarding the modes of transmission and exacerbating factors of chronic viral hepatitis and encouraged participants to seek care for their liver diseases, if needed. We found that both venues (the church and Korean market) were appropriate to screen and educate participants; churches seemed to have a more engaged audience.

Screening for hepatitis B in patients with lymphoma.

Chronic hepatitis B virus (HBV) infection can be reactivated during lymphoma chemotherapy, specifically with rituximab. In 2008, the Centers for Disease Control and Prevention and, in 2010, the American Society of Clinical Oncology made recommendations that anyone who received cytotoxic or immunosuppressive therapy should be tested for serologic markers of HBV infection. In our study, we wanted to determine the screening rates for HBV infection at our institution and if simply adding a checkbox onto the rituximab order would improve HBV screening. We performed a retrospective chart review of two cohorts of lymphoma patients at Scott & White Health Clinic. Cohort 1 included patients from 1993 to 2008. Cohort 2 included patients who received rituximab after an institutionwide protocol (rituximab order checkbox) was initiated in 2011. A total of 452 patients treated for lymphoma were reviewed. Only 15 of the 404 Cohort 1 patients received HBV screening (3.7%; 95% confidence interval, 2.1%-6.1%). Screening rates were statistically higher if baseline liver laboratory values were elevated (P < 0.0001). HBV was also checked more frequently if patients' liver function tests became elevated while on chemotherapy, 85.7% (12/14). Of the 48 patients in Cohort 2, 33 patients (68.7%) received HBV screening. No patients in either cohort had a positive HBV surface antigen or developed reactivation of HBV during chemotherapy. The addition of a checkbox on the rituximab order form significantly increased our screening for HBV infection in lymphoma patients initiating chemotherapy.

A comparative drug utilisation study of the treatment of diabetes in Malaysia and Australia.

BACKGROUND: Once a disease of developed countries, type 2 diabetes mellitus (T2DM) has become widespread worldwide. For people with T2DM, achievement of therapeutic outcomes demands the rational and quality use of medicine. AIMS: The primary aim of this study was to examine the prevalence of diabetes and prescribing patterns of anti-diabetic medications in Australia and Malaysia. METHODS: The most recent, publicly available, statistical reports (2004-2008) on the use of medicines published in Australia and in Malaysia were evaluated. Defined daily doses (DDDs/1,000 population/day) were derived from the reports and used to rank and compare individual drug use. RESULTS: There was an increasing trend in the prevalence of diabetes in Australia, although there is a greater predicted increase in prevalence for Malaysia. While drugs used for the treatment of diabetes were not the most highly used drugs in Australia, their use increased during the study period, from 42.64 to 48.61 DDD/1,000/day. Anti-diabetic drugs were the most frequently dispensed class of drugs in Malaysia. Although the total consumption of anti-diabetic drugs in Malaysia decreased between 2006 and 2007 (from 40.30 to 39.72), this was followed by a marked increase to 46.69 in 2008. There was a marked reduction in the dispensing of insulin in Malaysia from 2004 to 2007 (7.77 to 3.23). CONCLUSION: The use of drugs to treat diabetes does not reflect the usage patterns found in Australia. Effective drug use reviews are required to ensure impartial access in middle- and low-income countries.

Perceived sources of stress among Malaysian dental students.

OBJECTIVE: The study objectives were to identify the stress levels and to explore the impact of students' year of study and gender on the perceived sources of stress among Malaysian dental students. METHODS: This was a cross-sectional study involving dental students from year one to year five from private and public universities in Malaysia. The study was formally approved by the Research and Ethics Committee, International Medical University Malaysia. Dental Environment Stress (DES) questionnaire was used for data collection and the gathered data were analyzed using SPSS® version 18. The Kruskal-Wallis and the Mann-Whitney U tests were used to compare stress items across various academic years and universities. RESULTS: A total of five hundred and twenty nine (529) students participated in this study. Fear of failing the course at the end of year exams (mean stress level=5.57); concerns regarding completion of clinical work (mean=5.30); and examination results and grades (mean=5.27) were found as top stressors among dental students. Female students had higher stress scores than males with respect to personal issues, academic performance, educational environment and learning of clinical skills. Students from public universities had higher stress scores than their counterparts from private universities. CONCLUSIONS: The Malaysian dental students reported higher levels of stress. Present study identified stressors affecting dental students' academic life, and highlights the importance of stress management programs and other measures to minimize the impact of stress on both academic and personal lives of the students.

Crystal structure and interaction of phycocyanin with ß-secretase: A putative therapy for Alzheimer's disease.

Alzheimer's disease (AD) represents a neurological disorder, which is caused by enzymatic degradation of an amyloid precursor protein into short peptide fragments that undergo association to form insoluble plaques. Preliminary studies suggest that cyanobacterial extracts, especially the light-harvesting protein phycocyanin, may provide a means to control the progression of the disease. However, the molecular mechanism of disease control remains elusive. In the present study, intact hexameric phycocyanin was isolated and crystallized from the cyanobacterium Leptolyngbya sp. N62DM, and the structure was solved to a resolution of 2.6 A. Molecular docking studies show that the phycocyanin αß-dimer interacts with the enzyme ß-secretase, which catalyzes the proteolysis of the amyloid precursor protein to form plaques. The molecular docking studies suggest that the interaction between phycocyanin and ß-secretase is energetically more favorable than previously reported inhibitor-ß-secretase interactions. Transgenic Caenorhabditis elegans worms, with a genotype to serve as an AD-model, were significantly protected by phycocyanin. Therefore, the present study provides a novel structure-based molecular mechanism of phycocyanin-mediated therapy against AD.

Multi-disciplinary approach for management of refractory benign occlusive esophageal strictures.

BACKGROUND: Benign occlusive esophageal strictures create substantial morbidity and have poor surgical outcomes. Various endoscopic techniques have been described to manage these strictures. The challenge remains to maintain adequate long-term esophageal patency and to limit the need for serial endoscopic dilations. Little has been reported regarding the management of these benign occlusive strictures. METHODS: We report a case series describing the management of technically challenging benign occlusive esophageal strictures. Three patients with occlusive esophageal strictures of differing etiologies were treated using a variety of endoscopic methodologies. RESULTS: The first patient sustained a caustic oropharyngeal injury resulting in a proximal esophageal stricture which was treated by using a combined antegrade retrograde dilation (CARD) with argon plasma coagulation (APC) and needle knife dissection resulting in the successful recanalization and patency of his stricture. A second patient developed an esophageal stricture following radiotherapy, and was treated with a CARD procedure and serial balloon dilations in combination with APC to successfully achieve esophageal luminal patency. The final patient acquired an occlusive esophageal stricture after treatment for thyroid cancer which was treated with endoscopic needle knife dissection followed by serial balloon dilations to successfully manage this stricture. CONCLUSIONS: Occlusive esophageal strictures pose a difficult challenge to gastroenterologists and little has been reported with regards to their endoscopic management. Using the CARD technique, needle knife dissection and APC, individually or in combination, luminal patency of occlusive esophageal strictures can be accomplished safely with good results.