Shorter Treatment Duration Research Articles

S3003 Granulomatous Hepatitis as Primary Manifestation of Disseminated Histoplasmosis in an Immunocompetent Host Diagnosed on EUS FNA and Liver Biopsy

Introduction: Disseminated histoplasmosis (DH) presents as primarily lung manifestations with extrapulmonary involvement in immunocompromised hosts. Granulomatous hepatitis as first presentation of DH in an immunocompetent host is uncommon. Case Description/Methods: 25-year-old female presented with one month of fever, fatigue, myalgias, 30-pound weight loss, cough, nausea, vomiting, and epigastric pain. She has lived in the Midwest and southwestern US. Presenting labs: TB 1.9 mg/dL, AP 161 U/L, AST 172 U/L, ALT 463 U/L. Workup was negative for COVID, viral/autoimmune hepatitis, sarcoidosis, tuberculosis, and HIV. CT scan showed suspected gallstones and 9 mm left lower lobe noncalcified nodule. EUS showed a normal common bile duct, gallbladder sludge and enlarged porta hepatis lymph nodes which underwent fine needle aspiration (FNA). She was diagnosed with biliary colic and underwent cholecystectomy, with white plaques noted on the liver surface (A). Liver biopsy/FNA showed necrotizing granulomas (B) and fungal yeast on GMS stain (C). Although histoplasmosis urine and blood antigens were negative, histoplasmosis complement fixation was >1:256. She could not tolerate itraconazole for DH, requiring amphotericin B. She then transitioned to voriconazole, discontinued after 5 weeks due to increasing AP. However, her symptoms resolved with normal transaminases. At one year follow up, she is asymptomatic with normal liver function tests. Discussion: DH is a systemic granulomatous disease caused by Histoplasma capsulatum endemic to Ohio, Mississippi River Valley, and southeastern US. DH more commonly affects immunocompromised hosts with AIDS, immunosuppressants, and organ transplant. Gastrointestinal involvement is common in DH (70-90%) with liver involvement in 90%. However, granulomatous hepatitis as primary manifestation of DH is rare (4% of liver biopsies). Hepatic granulomas are seen in < 20%. Patients may present with nonspecific systemic symptoms. Serum/urine antigens may be negative. Gold standard for diagnosis is identifying yeast on tissue stains. Recommended treatment is amphotericin B followed by 1 year of itraconazole. However, shorter treatment duration may be effective in immunocompetent hosts. This case is unique in that granulomatous hepatitis was the first presentation of DH in our immunocompetent patient diagnosed on EUS FNA and liver biopsy. Clinicians must have a high degree of suspicion for DH in patients with fever of unknown origin especially in endemic areas regardless of immunologic status.Figure 1.: Liver surface, liver biopsy, porta hepatis lymph node FNA.

S775 Major Cardiovascular Adverse Events by Baseline Cardiovascular Risk Stratification in Patients With Ulcerative Colitis Treated With Tofacitinib: Data From the OCTAVE Clinical Program

S775 Major Cardiovascular Adverse Events by Baseline Cardiovascular Risk Stratification in Patients With Ulcerative Colitis Treated With Tofacitinib: Data From the OCTAVE Clinical Program

Review of Hydroxychloroquine Cardiotoxicity: Lessons From the COVID-19 Pandemic.

Purpose of ReviewThe coronavirus disease 2019 (COVID-19) pandemic has popularized the usage of hydroxychloroquine and chloroquine (HCQ/CQ) as treatments for COVID-19. Previously used as anti-malarial and now commonly used in rheumatologic conditions, preliminary in vitro studies have demonstrated these medications also have anti-viral properties. Retinopathy and neuromyopathy are well recognized complications of using these treatments; however, cardiotoxicity is under-recognized. This review will discuss the implications and cardiotoxicity of HCQ/CQ, their mechanisms of action, and their utility in COVID-19.Recent FindingsEarly clinical trials demonstrated a modest benefit of HCQ in COVID-19, causing a push for the usage of it. However, further large multi-center randomized control centers, demonstrated no benefit, and even a trend towards worse outcomes. The predominant cardiac complication observed with HCQ in COVID-19 was cardiac arrhythmias and prolonging of the QT interval. However, with chronic usage of HCQ/CQ, the development of heart failure (HF) and cardiomyopathy (CM) can occur.SummaryAlthough, most adverse cardiac events related to HCQ/CQ usage in COVID-19 were secondary to conduction disorders given the short duration of treatment, HCQ/CQ can cause CM and HF, with chronic usage. Given the insufficient evidence, HCQ/CQ usage in COVID-19 is not routinely recommended, especially with novel therapies now being developed and used. Additionally, usage of HCQ/CQ should prompt initial cardiac evaluation with ECG, and yearly monitoring, with consideration for advanced imaging if clinically warranted. The diagnosis of HCQ/CQ cardiomyopathy is important, as prompt cessation can allow for recovery when these changes are still reversible.

A neuropsychological approach in a paediatric acquired brain injury unit under the public health system

IntroductionPaediatric acquired brain injury (ABI) causes cognitive and behavioural difficulties and alters the course of child development. The ABI unit at Hospital Infantil Universitario Niño Jesús is the first within the public Spanish health system to provide comprehensive coverage to these patients and their families. ObjectiveThis study aims to show the working methodology followed with patients and their families, and to describe the clinical characteristics of the patients treated and the outcomes of treatment. PatientsFifty-three patients aged between 3 months and 16 and a half years received treatment. The conditions treated were brain tumours, stroke, traumatic brain injury, damage secondary to epilepsy surgery, and hypoxia. MethodsAll patients were evaluated at admission and at discharge. Treatments were adapted to each patient’s difficulties and their severity, as well as to the patient’s age. Families received individual and group therapy. ResultsOlder age was associated with better cognitive recovery and shorter duration of treatment. Different conditions show differential impact on intelligence quotient and developmental quotient scores at the beginning of treatment, with hypoxia and encephalitis being associated with greatest severity. Intelligence quotient and developmental quotient scores and visual memory and attention scores at discharge improved significantly after the faceted neuropsychological treatment with respect to scores registered at admission. ConclusionsThe care of patients with ABI should include neuropsychological rehabilitation programmes and provide emotional support to the family so that they may actively participate in the recovery of the child or adolescent.

Host-directed therapies in pulmonary tuberculosis: Updates on anti-inflammatory drugs.

Tuberculosis (TB) is a lethal disease and remains one of the top ten causes of mortality by an infectious disease worldwide. It can also result in significant morbidity related to persistent inflammation and tissue damage. Pulmonary TB treatment depends on the prolonged use of multiple drugs ranging from 6 months for drug-susceptible TB to 6–20 months in cases of multi-drug resistant disease, with limited patient tolerance resulting from side effects. Treatment success rates remain low and thus represent a barrier to TB control. Adjunct host-directed therapy (HDT) is an emerging strategy in TB treatment that aims to target the host immune response to Mycobacterium tuberculosis in addition to antimycobacterial drugs. Combined multi-drug treatment with HDT could potentially result in more effective therapies by shortening treatment duration, improving cure success rates and reducing residual tissue damage. This review explores the rationale and challenges to the development and implementation of HDTs through a succinct report of the medications that have completed or are currently being evaluated in ongoing clinical trials.

Drug resistant tuberculosis: Implications for transmission, diagnosis, and disease management.

Drug resistant tuberculosis contributes significantly to the global burden of antimicrobial resistance, often consuming a large proportion of the healthcare budget and associated resources in many endemic countries. The rapid emergence of resistance to newer tuberculosis therapies signals the need to ensure appropriate antibiotic stewardship, together with a concerted drive to develop new regimens that are active against currently circulating drug resistant strains. Herein, we highlight that the current burden of drug resistant tuberculosis is driven by a combination of ongoing transmission and the intra-patient evolution of resistance through several mechanisms. Global control of tuberculosis will require interventions that effectively address these and related aspects. Interrupting tuberculosis transmission is dependent on the availability of novel rapid diagnostics which provide accurate results, as near-patient as is possible, together with appropriate linkage to care. Contact tracing, longitudinal follow-up for symptoms and active mapping of social contacts are essential elements to curb further community-wide spread of drug resistant strains. Appropriate prophylaxis for contacts of drug resistant index cases is imperative to limit disease progression and subsequent transmission. Preventing the evolution of drug resistant strains will require the development of shorter regimens that rapidly eliminate all populations of mycobacteria, whilst concurrently limiting bacterial metabolic processes that drive drug tolerance, mutagenesis and the ultimate emergence of resistance. Drug discovery programs that specifically target bacterial genetic determinants associated with these processes will be paramount to tuberculosis eradication. In addition, the development of appropriate clinical endpoints that quantify drug tolerant organisms in sputum, such as differentially culturable/detectable tubercle bacteria is necessary to accurately assess the potential of new therapies to effectively shorten treatment duration. When combined, this holistic approach to addressing the critical problems associated with drug resistance will support delivery of quality care to patients suffering from tuberculosis and bolster efforts to eradicate this disease.

Visceral Leishmaniasis: Epidemiology, Diagnosis, and Treatment Regimens in Different Geographical Areas with a Focus on Pediatrics.

Visceral Leishmaniasis (VL) is a vector-borne disease caused by an intracellular protozoa of the genus Leishmania that can be lethal if not treated. VL is caused by Leishmania donovani in Asia and in Eastern Africa, where the pathogens’ reservoir is represented by humans, and by Leishmania infantum in Latin America and in the Mediterranean area, where VL is a zoonotic disease and dog is the main reservoir. A part of the infected individuals become symptomatic, with irregular fever, splenomegaly, anemia or pancytopenia, and weakness, whereas others are asymptomatic. VL treatment has made progress in the last decades with the use of new drugs such as liposomal amphotericin B, and with new therapeutic regimens including monotherapy or a combination of drugs, aiming at shorter treatment duration and avoiding the development of resistance. However, the same treatment protocol may not be effective all over the world, due to differences in the infecting Leishmania species, so depending on the geographical area. This narrative review presents a comprehensive description of the clinical picture of VL, especially in children, the diagnostic approach, and some insight into the most used pharmacological therapies available worldwide.

Assessing the proportion of patients with hepatitis C treated before and after initiation of an ambulatory pharmacist-led hepatitis C program: A retrospective analysis

BackgroundIn a community with rates of hepatitis C virus (HCV) 10 times greater than the national average, a pharmacist-led HCV clinic creates a unique opportunity to make an extensive impact on a large population. This study aimed to describe the impact of an ambulatory pharmacist-led HCV clinic on successful HCV treatment initiation. ObjectivesThe primary objective was to determine HCV treatment initiation before and after introduction of a pharmacist-led HCV clinic. Secondary objectives include identifying benefits of the clinic through barriers that exist pre-and postclinic, average time to HCV treatment initiation, and current and last known points of care in the treatment process. Practice descriptionThe ambulatory program was established in 2018 with a collaborative practice agreement with gastroenterologists in the health system, allowing for providers to refer patients to the pharmacy clinic for HCV medication initiation and monitoring. Practice innovationThrough maintaining relations with providers, the local health department, and emergency department staff, pharmacists aimed to connect more patients to HCV treatment. Clinical pharmacists work with patients to refer them to specialty pharmacies, ensuring quick treatment start and financial coverage. Evaluation methodsA single-center, retrospective chart review was conducted to assess treatment initiation in patients with a positive HCV antibody in 2016 (preclinic) or 2019 (postclinic). ResultsA statistically significant difference was found for the proportion of patients that started treatment before versus after clinic initiation (P < 0.001). For secondary objectives, a statistically significant difference was found between the number of patients who completed the treatment process in 2016 and those in 2019 (P < 0.001). The average time from diagnosis to treatment initiation was reduced from 66.75 weeks ± SD 13.22 in 2016 to 22.87 weeks ± SD 4.19 in 2019. ConclusionAn ambulatory pharmacist-led HCV clinic results in a higher proportion of patients starting treatment for hepatitis C, better linkage to care, and shorter treatment duration.

Public perception of Invisalign® clear aligner treatment: A cross-sectional survey-based study

Objectives: The demand for clear aligner treatment has increased in recent years. Thus, this study investigated public knowledge regarding Invisalign clear aligner treatment. Material and Methods: A web-based survey was administered through different social media platforms covering different aspects of Invisalign treatment, namely: Treatment efficiency, patient discomfort, appliance esthetic attractiveness, oral hygiene maintenance, and treatment aesthetic results. Participants were also asked to outline their perception of Invisalign treatment cost. A Likert-type scale was used to rank the participant responses. Data were analyzed with the Chi-square test and Bonferroni correction for multiple comparisons. Results: Out of 934 eligible adult participants, 19.6% were aware of Invisalign. Most of the Invisalign-familiar respondents were unaware of its cost (27.9%) but agree it is generally better (49.7%), requires fewer visits (38.2%), results in shorter treatment duration (39.4%) and reduced teeth discomfort (35%), more esthetically attractive (64%), yields easier oral hygiene maintenance (55.2%), and produces superior esthetic results (43.7%) than traditional braces. In addition, males and average-income participants were more likely to believe that Invisalign treatment produces superior esthetic results than traditional braces (P = 0.0002 and P = 0.002, respectively). Average-income participants also believed that Invisalign treatment was generally better (P &lt; 0.0001). While participants in the age-range 55–64 years strongly believe, it is cheaper (P &lt; 0.0001) than traditional braces. Conclusion: This study highlighted the lack of public knowledge about Invisalign treatment. The results also indicated the importance of ensuring public access to reliable information backed up by high-quality evidence.

Can quarantine plant-parasitic nematodes within wastes be managed by useful tools in a circular economy approach?

Seen as an integral part of sustainable development, circular economy represents a model of production and consumption notably based on the limitation of both resource wastage and environmental impact. Laboratories and commercial companies working on plant pathogens, in particular quarantine species, must effectively disinfect their waste to avoid disseminating these organisms. The methods used for waste disinfection can however incur high energy costs or pose environmental and human health hazards. Here, we tested the effectiveness of five disinfection methods — chlorination, heat treatment, composting, mesophilic methanation and waste stabilization ponds — on plant-parasitic nematodes belonging to the genera Globodera and Meloidogyne. For the widely used chlorination and heat treatment methods, we showed that they can be very effective in inactivating nematodes at relatively low chlorine doses and temperatures (60 °C–3 min and 50 °C–30 min), respectively. For the three other disinfection methods tested, initially designed for waste recycling, we obtained different levels of efficiency. Composting and mesophilic methanation (based on cattle or pig slurry) both led to the complete elimination of nematodes, even for short treatment durations. However, waste stabilization ponds showed contrasting results, ranging from virtually no effect to high levels of inactivation of nematodes. Our study demonstrates that it is possible to use more environmentally friendly disinfection methods to control plant-parasitic nematodes. In particular, this finding paves the way towards the treatment of infected plant materials using composting or methanation, providing that disinfection is still reached under other (real-life) treatment conditions, especially with other kinds of waste. Both composting and methanation recycle and thus valorize infected waste; they are viable alternatives to landfilling or incineration, thereby demonstrating the usefulness of a circular economy approach.

Engaging Patients and Caregivers in an Early Health Economic Evaluation: Discerning Treatment Value Based on Lived Experience.

Traditionally, economic evaluations have engaged clinicians and policymakers; however, patients and their caregivers have insight that can ensure that the economic evaluation process appropriately reflects disease consequences and adequately addresses their priorities related to treatment. We aimed to identify patient priorities to inform an early economic evaluation of chimeric antigen receptor T-cell therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukemia. We conducted two online group discussions of four participants each, involving patients with experience of hematological cancer and a caregiver. We used an adapted version of the nominal group technique, a consensus-building discussion approach, to generate focused qualitative data. Patients and a caregiver acknowledged both the costs directly related to clinical care, such as the out-of-pocket cost of drugs, and the indirect treatment costs, such as the cost of transport, accommodation, and food. The emotional and physical toll of treatment and the influence of treatment on employment and education were additional costs emphasized by participants. Treatment benefits prioritized by participants included the efficacy of treatment, manageable side effects, improved quality of life, accessibility of treatment, and short treatment duration. Engaging patients and caregivers in an early economic evaluation could help identify additional costs and benefits of therapies that are not typically recognized in economic evaluations but have the potential to increase the commercial viability of novel therapies. This research also demonstrates how patients and caregivers can be engaged at different levels in the development of early economic evaluation models.

Effect of maxillary and mandibular extrusion arches on dentoskeletal changes in adults with anterior open bite: a quantitative analysis.

To quantify dentoskeletal changes accompanying the use of extrusion arches during the treatment of anterior open bite (AOB) in adults. A total of 23 adult patients with an AOB of -3.05 mm ± 1.27 mm were treated with upper and lower extrusion arches after the alignment phase. Lateral cephalograms were taken before placement of the extrusion arch, immediately after closure of the open bite (T2), and at the end of orthodontic treatment (T3). Data were statistically analyzed using repeated-measures analysis of variance and the Bonferroni post hoc test for pairwise comparisons (α = 0.05). Successful closure of AOB, with an overall change in overbite of 4.73 ± 1.93 mm, was achieved in an average of 3.8 months and remained stable at T3. Upper and lower incisors were significantly extruded by 2.05 mm ± 0.72 mm and 2.54 mm ± 1.63 mm, respectively, and significantly retroclined by 6.36° ± 1.63° and 8.45° ± 3.83°, respectively, with a resultant increase in the interincisal angle of 12.80° ± 2.09°. Statistically significant intrusion and mesial tipping (P < .001) of the maxillary and mandibular first molars were observed at T2. Dentoskeletal changes remained stable at T3, except for a significant reduction of the mesial tipping of the maxillary and mandibular first molars. The combined use of maxillary and mandibular extrusion arches resulted in significant favorable dentoskeletal changes that led to the successful closure of AOB during a short duration of treatment.

Effect of Ozone Treatment on the Contents of Selected Bioactive Phytochemicals in Leaves of Alligator Plant Kalanchoe daigremontiana

The study investigated the effect of ozone treatment applied to Kalanchoe daigremontiana plants on the contents of selected phytochemicals and on markers of oxidative stress in the leaves. For this purpose, alligator plants were exposed to the gaseous ozone applied at a rate of 5 and 10 ppm for 1, 5, and 10 min. Subsequently, tests were performed to assess the ozone-treated plants for the ability to produce reactive oxygen species (ROS), and for the activation of superoxide dismutase (SOD) and catalase (CAT), i.e., enzymes responsible for the decomposition of ROS. Measurements were also carried out to determine antioxidant potential, total contents of polyphenols, and vitamin C in plants as well as their mechanical properties. The findings show that the use of controlled conditions of ozone treatment (10 ppm; 1 min) resulted in increased contents of selected bioactive compounds (enhancement of total polyphenols 79%, enhancement of antioxidant potential ABTS 55.6% and DPPH 65.8%) in the ozone-treated raw material, with no phytotoxic effects of the process observed. It was shown that a short duration of ozone treatment is related to the increased activity of SOD (max 44%) and CAT (max 18.8%), which contributes to the lower production of ROS in cells of Kalanchoe daigremontiana.

Neurocognitive performance and quality of life of older adults with HIV on antiretroviral treatment in Northern Thailand.

IntroductionWith virologic suppression and longer life expectancy, older adults with HIV (OAHIV) are at risk for neurocognitive impairment (NCI). This study investigated neurocognitive performance, quality of life (QOL) and the association between OAHIV determinants.MethodsThis cross‐sectional study was conducted in OAHIV aged ≥ 50 years on antiretroviral treatment at community hospitals in Northern Thailand between September and November 2020. The Montreal Cognitive Assessment Thai Version (MoCA‐T) and the Thai‐validated Medical Outcomes Study HIV (MOS‐HIV) were used. NCI was defined as MoCA‐T scores <25: 16–24 for amnestic mild cognitive impairment (aMCI) and <16 for dementia. For QOL, higher scores meant better QOL; a physical health summary T‐score ≥50 was defined as good QOL.ResultsOverall, 269 OAHIV were enrolled; 59% were female and 99% had virologic suppression. The current median age was 61.8 years (interquartile range [IQR] 58.9–65.7). The median duration of antiretroviral treatment was 10.5 years (IQR 8.5–13.5). The current median CD4 count (234 tested) was 484 cells/mm3 (IQR 339–634), and 99% had plasma HIV RNA <40 copies/ml (229 tested). The median MoCA‐T score was 20.0 (IQR 16.3–23.0). There were 234 OAHIV (87.3%) with NCI: 182 (67.9%) with aMCI and 52 (19.4%) with dementia. A hundred and ninety (70.6%) had good QOL. Bivariate analysis revealed no correlation between MoCA‐T scores and QOL. Multivariable linear regression analysis revealed that MoCA‐T score was associated with older age (r = –0.144, p = 0.002), lower education (r = 0.629, p < 0.001), lower income (r = 0.797, p = 0.040) and shorter treatment duration (r = 0.189, p = 0.006).ConclusionsThe vast majority of OAHIV with virologic suppression had NCI. Approximately two‐thirds had a mild impairment and one‐fifth had dementia. Neurocognitive performance and QOL were not correlated. Addressing mild NCI would enable more targeted monitoring. Early intervention and support could minimize functional impairment with increased age.

Effect of Ozone Treatment Intensity on Pasting Property, Protein Composition, and Steamed Bread Quality of Ozone-Treated Wheat Flour

Wheat flours were treated with ozone gas at low- and high-intensity conditions (0.61 and 3.82 g/h) for different durations (short: 5 min; long: 30 min), and the ozone-treated flours were evaluated in quality properties, including pH, protein component, water molecular mobility of dough, pasting property, and steamed bread quality. At both conditions, ozone treatment decreased the pH of wheat flour. Long duration of high-intensity treatment aroused significant increase in insoluble polymeric protein (IPP) content of wheat flour, but other treatments did not significantly change the IPP content. Dough of ozone-treated flour had higher water molecular mobility than that of native flour. Short duration of low-intensity treatment did not significantly change most pasting viscosity parameters of wheat flour, but other treatments increased the peak viscosity, breakdown viscosity, and setback viscosity. Steamed bread of ozone-treated flour had lower specific volume and pore uniformity than that of native flour. Long duration of high-intensity treatment of flour increased the hardness and chewiness of the steamed bread product, but other treatment showed opposite effect. Among the four ozone treatments, long duration of high-intensity treatment aroused the greatest change in pH, IPP, water molecular mobility of dough, and the quality of steamed bread, while short duration of low-intensity treatment had the minimum effect. Long duration of low-intensity treatment was close to the short duration of high-intensity treatment in quality attributes of wheat flour and the total ozone yield. These results suggested that the quality of wheat flour gradually changed with the increase of total ozone yield, and overozonization would greatly deteriorate the quality of wheat flour.

A comprehensive review on disposition kinetics and dosage of oral administration of Andrographis paniculata, an alternative herbal medicine, in co-treatment of coronavirus disease.

Coronavirus disease 2019 (COVID-19) is a present global health crisis that is driving the investigation of alternative phytomedicines for antiviral purposes. The evidence suggests that Andrographis paniculata crude or extract is a promising candidate for treating symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review aims to consolidate the available reports on the disposition kinetics of andrographolide, a main active component of A. paniculata. The second objective of this review is to summarize the available reports on an appropriate oral dosage for the use of andrographolide in upper respiratory tract infections (URTIs) and other viral infectious diseases. The data were collected from the literature on absorption, distribution, biotransformation, and excretion of andrographolide, and information was also obtained from scientific databases about the use of A. paniculata. The finding of this review on pharmacokinetics indicates that andrographolide is slightly absorbed into the blood circulation and exhibits poor oral bioavailability, whereas its distribution process is unrestricted. In the termination phase, andrographolide preferentially undergoes biotransformation partly through phase I hydroxylation and phase II conjugation, and it is then eliminated via the renal excretion and hepatobiliary system. The key summary of the recommended dosage for andrographolide in uncomplicated URTI treatment is 30 mg/day for children and 60 mg/day for adults. The dose for adult patients with pharyngotonsillitis could be increased to 180 mg/day, but not exceed 360 mg/day. Co-treatment with A. paniculata in concert with the standard supportive care for influenza reduced the severity of symptoms, shortened treatment duration, and decreased the risk of developing post-influenza complications. The recommended starting dose for use in patients with mild COVID-19 is 180 mg/day of andrographolide, based on the dose used in patients experiencing a URTI with inflammation. This review is not only applicable for evaluating the appropriate doses of andrographolide for antiviral treatments but also encourages future research evaluating the effectiveness of these recommended dosages during the COVID-19 pandemic.

Management of intra-thoracic anastomotic leakages after esophagectomy: updated systematic review and meta-analysis of endoscopic vacuum therapy versus stenting

Despite a significant decrease of surgery-related mortality and morbidity, anastomotic leakage still occurs in a significant number of patients after esophagectomy. The two main endoscopic treatments in case of anastomotic leakage are self-expanding metal stents (SEMS) and the endoscopic vacuum therapy (EVT). It is still under debate, if one method is superior to the other. Therefore, we performed a systematic review and meta-analysis of the existing literature to compare the effectiveness and the related morbidity of SEMS and EVT in the treatment of esophageal leakage. We systematically searched for studies comparing SEMS and EVT to treat anastomotic leak after esophageal surgery. Predefined endpoints including outcome, treatment success, endoscopy, treatment duration, re-operation rate, intensive care and hospitalization time, stricture rate, morbidity and mortality were assessed and included in the meta-analysis. Seven retrospective studies including 338 patients matched the inclusion criteria. Compared to stenting, EVT was significantly associated with higher healing (OR 2.47, 95% CI [1.30 to 4.73]), higher number of endoscopic changes (pooled median difference of 3.57 (95% CI [2.24 to 4.90]), shorter duration of treatment (pooled median difference − 11.57 days; 95% CI [− 17.45 to − 5.69]), and stricture rate (OR 0.22, 95% CI [0.08 to 0.62]). Hospitalization and intensive care unit duration, in-hospital mortality rate, rate of major and treatment related complications, of surgical revisions and of esophago-tracheal fistula failed to show significant differences between the two groups. Our analysis indicates a high potential for EVT, but because of the retrospective design of the included studies with potential biases, these results must be interpreted with caution. More robust prospective randomized trials should further investigate the potential of the two procedures.

Insights into current physical, chemical and hybrid technologies used for the treatment of wastewater contaminated with pharmaceuticals

The purpose of this article is to review the current physical, chemical and hybrid technologies practices employed in the removal of pharmaceuticals from liquid effluents originating from various resources including municipal waste, hospitals discharge with a focus on pharmaceutical manufacturing industry. Pharmaceutical pollutants are mostly persistent organic compounds that are not easily removed by conventional wastewater treatment processes. The literature reviewed shows that advanced oxidation processes are able to degrade these persistent pharmaceuticals. However, the oxidation may also introduce toxic oxidation intermediates/by-products if these processes are not properly monitored and operated. Physical treatments, like carbon adsorption and membrane filtration, can provide a barrier that prevents both parent compounds and toxic intermediates passing into treated wastewater. However, these processes are phase changing technologies in which contaminants are transferred from one phase to another hence, the retentate water and absorbent require further treatment, and properly managed disposal. The combination of different processes can be an ideal treatment scheme, for the retention and degradation of both parent and transformation compounds. Through hybrid technologies, the advantages of the methods are combined, leading to a maximization of contaminants removal. The review highlights the importance of installing combined wastewater treatment processes to reduce the amounts of pharmaceutical residues before the wastewater enters the environment. The use of advanced oxidation process, either as a pre-treatment or as a post-treatment combined with biological, adsorption, or filtration process is recommended as a promising option. Nevertheless, the optimum treatment methods for the pharmaceuticals-containing wastewater depends on the quality and quantity of wastewater, as well as on the pharmaceutical compounds residues and their hazardous effects. • Evidence of pharmaceuticals including antibiotics in aquatic environment. • Physicochemical processes have high removal efficiency and short treatment duration. • AOPs and their combination with physicochemical processes are promising options. • Hybrid technology can provide a solution for pharmaceutical wastewater treatment.

Efficacy of intravaginal electrical stimulation with different treatment frequency in women with refractory idiopathic overactive bladder

ABSTRACTObjective The aim of this study is to evaluate the effect of intravaginal electrical stimulation (IVES) therapies with different treatment frequencies (two or five days in a week) added to bladder training (BT) on incontinence-related quality of life (QoL) and clinical parameters in women with refractory idiopathic overactive bladder (OAB).Material and Methods Fifty-two women with refractory idiopathic OAB were randomized into two groups as follows: Group 1 (n:26) received BT and IVES, two times in a week, for 10 weeks and Group 2 (n:26) received BT and IVES five times in a week, for 4 weeks. IVES was performed 20 minutes in a day, a total of 20 sessions for both groups. Women were evaluated for incontinence severity (24h pad test), pelvic floor muscles strength (perineometer), 3-day voiding diary (frequency of voiding, nocturia, incontinence episodes, and the number of pads), symptom severity (OAB-V8), quality of life (IIQ-7), treatment success (positive response rate), cure/improvement rate and treatment satisfaction (Likert scale).Results There was no statistically significant differences in all parameters between the two groups at the end of the treatment. It was found that the treatment satisfaction scores, cure/improvement and positive response rates were not significantly different between two groups (p>0.05).Conclusion We concluded that the application of IVES twice a week or 5 times a week added to BT were both effective on incontinence-related QoL and clinical parameters in women with refractory idiopathic OAB. These two IVES frequencies had similar clinical efficacy and patient satisfaction with a slight difference between them; 5 times per week IVES has a shorter treatment duration.

A PROSPECTIVE INTERVENTIONAL STUDY TO COMPARE THE TREATMENT OUTCOMES IN PATIENTS WITH TWO DIFFERENT FRACTIONATION SCHEDULE OF WHOLE BRAIN RADIOTHERAPY WITH MULTIPLE BRAIN METASTASES

Purpose of study : To compare the treatment outcomes in patients with brain metastasis treated with two different fractionation schedules of whole brain radiotherapy. A prospective randomised study was carried out on newly diagnosed cancer patients with MRIMaterials and methods: diagnosis of brain metastasis. Patients with multiple bm with Eastern Cooperative Oncology Group performance status 0-4 were included. In Arm A, patients received whole brain radiotherapy (WBRT) of total dose 30 GY , 3Gy/fraction/10# over 2 weeks ,whereas , in Arm-B patients received total dose of 20 GY in 4Gy/fraction/5# over 1 week. Assessment of improvement in clinical symptoms was done using BARTHEL'S ADJUSTED DAILY LIVE (ADL)14 Score before treatment, just after treatment and 6 week of treatment and improvement was analysed. At three months follow up , radiological response was carried out by MRI scan of brain. Acute toxicities were assessed during treatment and follow up ( up to 90 days post EBRT ) using clinical status, laboratory investigations and radiological test and graded according to RTOG/EORTC criteria. Results: Signicant improvement in terms of ADL score was observed in both arms , however when both arms were compared , no signicant difference was found out. There was no statistically signicant difference in response or morbidity between the two treatment arms. In theConclusions: palliative setting short duration of treatment with minimum discomfort to the patient is desirable. 20 Gy in 5 fractions is equally effective as 30 Gy in 10 fractions, with slight advantage in terms of toxicity. Thus 20 Gy in 5 fractions can be preferred in brain metastasis patients, especially those with poor performance status.