The clinical toxicology of sodium hypochlorite

Introduction: Sodium hypochlorite is used as a bleaching and disinfecting agent and is commonly found in household bleach.

Objective: The objective is to review critically the epidemiology, mechanisms of toxicity, clinical features, diagnosis, and management of hypochlorite poisoning.

Methods: PubMed was searched from January 1950 to June 2018 using the terms “Hypochlorite”, “Sodium Hypochlorite”, “Sodium Oxychloride”, “Hypochlorous Acid”, “Bleach”, “Chlorine Bleach”, in combination with the keywords “poisoning”, “poison”, “toxicity”, “ingestion”, “adverse effects”, “overdose”, and “intoxication”. In addition, bibliographies of identified articles were screened for additional relevant studies including non-indexed reports. Non-peer-reviewed sources were also included. These searches produced 110 citations which were considered relevant.

Epidemiology: There is limited information regarding statistical trends on world-wide poisoning from sodium hypochlorite. In the United States of America, poison control center data have shown that enquiries regarding hypochlorite bleaches have ranged from 43,000 to 46,000 per year over the period 2012–2016.

Mechanisms of toxicity: Hypochlorite’s potential to cause toxicity is related to its oxidizing capacity and the pH of the solution. Toxicity arises from its corrosive activity upon contact with mucous membranes and skin.

Features following ingestion: While small accidental ingestions are very unlikely to cause clinically significant toxicity, large ingestions may cause corrosive gastrointestinal injury and systemic effects, including metabolic acidosis, hypernatremia, and hyperchloremia.

Features following dental exposure: Hypochlorite is used extensively by dentists for cleaning root canals and is safe if the solution remains within the root canal. Extrusions into the periapical area can result in severe pain with localized large and diffuse swelling and hemorrhage.

Features following skin exposure: Prolonged or extensive exposure may cause skin irritation and damage to the skin or dermal hypersensitivity. Such exposures can result in either immediate or delayed-type skin reactions. High concentration solutions have caused severe chemical skin burns.

Features following inhalation: Although there are only limited data, inhalation of hypochlorite alone is likely to lead to no more than mild irritation of the upper airways.

Features following ocular exposure: Corneal injuries from ocular exposure are generally mild with burning discomfort and superficial disturbance of the corneal epithelium with recovery within 1 or 2 days. With higher concentration solutions, severe eye irritation can occur.

Diagnosis: The diagnosis can typically be made on the basis of a careful history, including details of the specific product used, its hypochlorite concentration, and the amount involved. As hypochlorite bleach produces a characteristic smell of chlorine, this may provide a diagnostic clue. In severe cases, corrosive injury is suggested on presentation because of hypersalivation, difficulty swallowing, retrosternal pain or hematemesis.

Management: Symptom-directed supportive care is the mainstay of management. Gastrointestinal decontamination is not beneficial. Local corrosive injury is the major focus of treatment in severe cases. Fiberoptic endoscopy and CT thorax/abdomen are complimentary and have been shown to be useful in corrosive injuries in assessing the severity of injury, risk of mortality and risk of subsequent stricture formation and should be performed as soon as possible after ingestion. Dental periapical extrusion injuries should be left open for some minutes to allow bleeding through the tooth and to limit hematoma development in tissue spaces. Once the bleeding has ceased, the canal can be dressed with non-setting calcium hydroxide and sealed coronally.

Conclusions: Accidental ingestion of household bleach is not normally of clinical significance. However, those who ingest a large amount of a dilute formulation or a high concentration preparation can develop severe, and rarely fatal, corrosive injury so prompt supportive care is essential as there is no specific antidote. Treatment primarily consists of symptom-directed supportive care.     

Laparoscopic anterior and posterior native tissue repair: a new pelvic floor approach

Introduction: Traditionally, a cystocele caused by a midline defect of the pelvic fascia is treated by vaginal fascia duplication, also known as anterior colporraphy. The rectocele is managed by suturing the posterior fascia and, frequently, the levator ani muscles. We developed the approach of laparoscopic anterior and posterior fascia repair by native tissue.

Material and methods: The methods were based on anterior and posterior exposure of pelvic fascia similar to the preparation of an extended sacral colpopexy. The fascia was compressed and narrowed by absorbable woven sutures, size 1. Twenty-seven patients were followed up for 6–13?months. All patients received additional apical fixation by pectopexy.

Results: In the examination group, 13 patients underwent anterior laparoscopic fascia repair and 23 had posterior repair. We detected one apical and one posterior relapse, and also one in the anterior repair group. The patient with the apical relapse reported pain and de novo urgency. Anatomical reconstruction was achieved in all other patients.

Summary: Laparoscopic anterior and posterior native tissue repair appears to be a feasible method for the treatment of midline cystocele and rectocele. No new risks were observed. The technique leaves no scar in the vagina and is well accepted.

Abbreviations: POPQ: Pelvic Organ Prolapse Quantification System; FDA: Food and Drug Association; US: United States; Fig: Figure; ICIQ: International Consultation on Incontinence Questionnaire     

Quantitative real-time PCR for differential diagnostics of parvovirus B19 infection in acute liver failure patients

Background: Human Parvovirus B19 (B19V) is a common pathogen worldwide. After primary infection, B19V-DNA may permanently persist in non-erythroid tissues, including the liver of patients with acute liver failure (ALF).

Objective: To validate a real-time PCR (qPCR) for the quantification of B19V-DNA, in order to establish a differential diagnosis for B19V infection in ALF patients.

Methods: The qPCR techniques were based on Sybr Green® and TaqMan® methodologies. To evaluate the quality parameters of both methods, samples from patients with or without B19V infection were tested. The diagnostic utility of qPCR in the detection B19V-DNA in patients with ALF was evaluated by testing archived serum and hepatic tissue explants from 10 patients.

Results: The Sybr Green® methodology showed 97% efficiency, the limits of detection and quantification were 62.6 and 53,200 copies/mL, respectively. The TaqMan® methodology showed 95% efficiency, the limits of detection and quantification were 4.48 and 310 copies/mL, respectively. A false positive result was found only with the Sybr Green® methodology. Among ALF patients without defined etiology, three (30%) were positive for B19V DNA in serum and liver.

Conclusion: The qPCR methods validated here were effective in clarifying uncommon cases of B19V-related ALF and are fit for differential diagnosis of ALF causes.     

Glucose status and depressive symptoms: a cohort study of elderly people in northwest Finland

Objective: To assess the association between depressive symptoms and impaired glucose metabolism in the elderly population in arctic latitudes.

Design: A population-based study. Setting. Community.

Subjects: The study population consisted of 1,830 subjects born between the years 1915 and 1958 in the northernmost part of Finland, the Muonio-Enontekiö district, who participated in a health survey during 1974–1984. In 2014, a health questionnaire was sent to 1,037 subjects, and 757 participants (73%) answered it. Those (n?=?629) living in the Muonio-Enontekiö district undergone a clinical examination in 2014 and 2015 including blood collections.

Main outcome measures: Depressive symptoms defined by the Beck Depression Inventory II (BDI II) with a cut-off point of 14. Different diabetic states based on WHO’s classification criteria defined by fasting plasma glucose and ADA’s criteria by glycosylated haemoglobin (HbA1c) values.

Results: According to logistic regression analysis, depressive symptoms (BDI-II ≥ 14) were associated statistically significantly with previously known type 2 diabetes, the odds ratio (OR) being 4.33 (95% CI 1.53–14.14). Regarding prediabetic fasting glucose/HbA1c values, the corresponding OR was 2.94 (95% CI 1.17–8.94). The prevalence of depressive symptoms (BDI-II ≥ 14) was 7.1%, (men 9.7% and women 5.4%) and 13.7% (men 9.9% and women 17.0%) in subjects living in Muonio-Enontekiö district and in those who had moved away from there, respectively.

Conclusions: The association of depressive symptoms between prediabetes and diabetes seems to be present also in the northernmost latitudes of the world.     

Brief report: Bereaved parents informing research design: The place of a pilot study

Background: Risk minimization in research with bereaved parents is important. However, little is known about which research methods balance the sensitivity required for bereaved research participants and the need for generalizable results.

Aim: To explore parental experiences of participating in mixed method bereavement research via a pilot study.

Design: A convergent parallel mixed method design assessing bereaved parents’ experience of research participation.

Setting/participants: Eleven parents whose child was treated for cancer at The Royal Children’s Hospital, Brisbane completed the questionnaire/interview being piloted (n?=?8 mothers; n?=?3 fathers; >6 months and <6 years bereaved). Of these, eight parents completed the pilot study evaluation questionnaire, providing feedback on their experience of participation.

Results: Participants acknowledged the importance of bereaved parents being central to research design and the development of bereavement programs. Sixty-three per cent (n?=?5/8) of parents described completion of the questionnaire as ‘not at all/a little bit’ of a burden. Seventy-five per cent (n?=?6/8) of parents opting into the telephone interview described participation as ‘not at all/a little bit’ of a burden. When considering the latest timeframes for participation in bereavement research 63% (n?=?5/8) of parents indicated ‘no endpoint.’ Findings from the pilot study enabled important adjustments to be made to a large-scale future study.

Conclusions: As a research method, pilot studies may be utilized to minimize harm and maximize the potential benefits for vulnerable research participants. A mixed method approach allows researchers to generalize findings to a broader population while also drawing on the depth of the lived experience.     

Diagnosing depression in primary care: a Rasch analysis of the major depression inventory

Objective: This study aims to assess the measurement properties of the Major Depression Inventory (MDI) in a clinical sample of primary care patients.

Design: General practitioners (GPs) handed out the MDI to patients aged 18–65 years on clinical suspicion of depression.

Setting: Thirty-seven general practices in the Central Denmark Region participated in the study.

Patients: Data for 363 patients (65% females, mean age: 49.8 years, SD: 17.7) consulting their GP were included in the analysis.

Main outcome measures: The overall fit to the Rasch model, individual item and person fit, and adequacy of response categories were tested. Statistical tests for local dependency, unidimensionality, differential item functioning, and correct targeting of the scale were performed. The person separation reliability index was calculated. All analyses were performed using RUMM2030 software.

Results: Items 9 and 10 demonstrated misfit to the Rasch model, and all items demonstrated disordered response categories. After modifying the original six-point to a five-point scoring system, ordered response categories were achieved for all 10 items. The MDI items seemed well targeted to the population approached. Model fit was also achieved for core symptoms of depression (items 1–3) and after dichotomization of items according to diagnostic procedure.

Conclusion: Despite some minor problems with its measurement structure, the MDI seems to be a valid instrument for identification of depression among adults in primary care. The results support screening for depression based on core symptoms and dichotomization of items according to diagnostic procedure.

• Key points

• The Major Depression Inventory (MDI) is widely used for screening, diagnosis and monitoring of depression in general practice.

• This study demonstrates misfit of items 9 and 10 to the Rasch model and a need to modify the scoring system

• The findings support screening for depression based on core symptoms and dichotomization of items according to diagnostic procedure.

• Minor problems with measurement structure should be addressed in future revisions of the MDI.

     

Reference-less MR thermometry on pre-clinical thiel human cadaver for liver surgery with MRgFUS

Purpose: Reference-less MR thermometry can be a promising technique for temperature mapping during liver treatment with Magnetic Resonance-guided Focused Ultrasound (MRgFUS), as it is more robust to breathing motion than Proton Resonance Frequency MR thermometry. However, there is a lack of a pre-clinical model for repeatable testing of reference-less thermometry. The purpose of this work was to verify the explanted Thiel embalmed human liver and whole Thiel embalmed human cadaver for application of a custom made reference-less thermometry algorithm during MRgFUS sonication.

Material and methods: Phase maps were generated during sonication as an input to the algorithm. A square Region-of-Interest (ROI) was designed around the heated area. The ROI was interpolated using a two-dimensional polynomial to the surrounding phase map to calculate the background phase.

Results: Using the phase information from the images, the temperature rise was measured. Validation of the methodology showed accordance of temperatures with actual temperatures.

Conclusions: The explanted liver and the whole cadaver constitute a promising and feasible model to study reference-less techniques for thermometry during MRgFUS, before clinical trials.     

The link between childhood trauma and dissociation in frequent users of classic psychedelics and dissociatives

Background: Childhood trauma severity is associated with the level of subsequent substance use as well as with the self-reported severity of dissociation. Classic psychedelics and dissociatives target neurotransmitter systems thought to be involved in the onset of dissociative symptoms and may evoke severe and long-lasting symptoms of depersonalization in some users. However, it is currently unclear whether drug use puts people with a history of childhood trauma at higher risk of developing dissociative symptoms.

Objectives: The current study investigates whether the one-year prevalence of substance use significantly moderates the link between childhood trauma and the severity of depersonalization.

Methods: Participants (n = 297, of which 80.2% were active users) filled out an online self-report questionnaire including the Childhood Trauma Questionnaire (CTQ), the Cambridge Depersonalisation Scale (CDS), and information about their substance use.

Results: Results indicate that childhood trauma and substance use are significant individual predictors of dissociation scores in this sample, but no moderation of substance use on the link between childhood trauma and depersonalization was established.

Conclusions: It is hypothesized that the quality (particularly the context) of the experience of substance use rather than the sheer quantity may be responsible for the manifestation of depersonalization.     

Recommendations to improve opioid use disorder outcomes in countries of the Middle East

Background: Progress has been made in treatment of opioid use disorder (OUD) in the Middle East; current clinical practice often differs from standards of care elsewhere.

Aim: describe treatment approaches in selected countries to inform recommendations for improving care.

Methods: Evidence describing approaches to OUD care was collected and analyzed in a structured, comparative manner. Recommendations were developed based on experts’ clinical experience in the region.

Results: Care differs across countries assessed: Egypt, KSA, UAE, Oman, Kuwait, and Bahrain. Detoxification programs are the common treatment approach in Egypt, KSA, Oman, and Bahrain; integrated programs with opioid agonist therapy (OAT): UAE, Kuwait. Fear of misuse and diversion risk commonly limits access to OAT. Problems with sourcing medicines may limit treatment options. There is limited data on treatment needs or provision. Recommendations: develop effective policy and expert-led consensus on best practice for OUD in the region including integrated treatment programs, provide support for specialists and centers, include innovative medication choices with low diversion risk, promote collaborative work, coordinate data collection, and sharing.

Conclusions: There is important unmet need for OUD in the region and opportunity to improve services through collaboration to support change. Therapy options with reduced diversion risk may address barriers to care.     

Reference values for cardiopulmonary exercise testing in healthy subjects – an updated systematic review

Introduction: Reference values for cardiopulmonary exercise testing (CPET) parameters provide the comparative basis for answering important questions concerning the normalcy of exercise responses in patients, and significantly impacts the clinical decision-making process.

Areas covered: The aim of this study was to provide an updated systematic review of the literature on reference values for CPET parameters in healthy subjects across the life span.

A systematic search in MEDLINE, Embase, and PEDro databases were performed for articles describing reference values for CPET published between March 2014 and February 2019.

Expert opinion: Compared to the review published in 2014, more data have been published in the last five years compared to the 35 years before. However, there is still a lot of progress to be made. Quality can be further improved by performing a power analysis, a good quality assurance of equipment and methodologies, and by validating the developed reference equation in an independent (sub)sample. Methodological quality of future studies can be further improved by measuring and reporting the level of physical activity, by reporting values for different racial groups within a cohort as well as by the exclusion of smokers in the sample studied. Normal reference ranges should be well defined in consensus statements.     

Determining the best approach to reduce the impact of exercise-induced atrial fibrillation: prevention,screening, or symptom-based treatment?

Introduction: Regular endurance exercise over the course of many years appears to increase the risk of atrial fibrillation (AF). These data challenge the notion that the benefits of physical activity have no appreciable limits. The incidence of exercise-induced AF is expected to increase as a consequence of the popularity of extreme endurance sports. Actions to reduce its impact are warranted.

Areas covered: This review focuses on exercise-induced AF and reviews the existing data regarding the prevention, screening, and treatment of this disease, with the aim of elucidating the best options for this group of patients.

Expert commentary: To date, strategies to deal with exercise-induced AF are unsatisfactory. Improved knowledge of AF pathology and better classification schemes are needed to address current pitfalls.     

Transcatheter aortic valve replacement and cardiac conduction

Introduction: Conduction abnormalities after transcatheter aortic valve replacement (TAVR) account for a high percentage of post-TAVR complications.

Areas covered: The etiology of conduction abnormalities is closely tied to cardiac anatomy (length of membranous septum, degree of calcification, location of left bundle within the membranous septum), baseline conduction abnormalities (preprocedure right bundle branch block), and procedural variables (type of valve, depth of implant). Management of new high-grade AV block and new left bundle branch block varies by institution in the absence of consensus guidelines.

Expert opinion: Authors describe the incidence, etiology, outcomes, and management of conduction abnormalities related to aortic stenosis and TAVR.     

Potential effect of opium addiction on lipid profile and blood glucose concentration in type 2 diabetic patients in Iran

Background: Diabetes is one of the most common chronic diseases in the world. People believe that opium improves blood glucose and lipid profiles in these patients and controversial studies show the effect of consumption of opium in controlling these indices. Accordingly, this study aimed to compare the serum levels of blood indices such as fasting blood glucose (FBS), Hemoglobin A1c (HbA1c) and lipid profile in opium users and non-users in type ΙΙ diabetic patients.

Methods: In this cross-sectional study, among type II diabetic patients referred to the Diabetes Clinic of Birjand 45 opium users and 135 non-users were selected and entered the study by the convenience sampling method.

Results: The results of this study showed that the mean serum levels of FBS, HbA1c, and serum lipid profiles were not significantly different between the two groups of opium users and non-users, but the levels of triglyceride (TG) were significantly 0.18 unit higher in the opium users, compared to non-opium users.

Conclusion: According to the results, the use of opium does not affect the indices of blood glucose, HbA1c and serum lipid profiles except triglyceride in diabetic patients. The general belief that opioid use reduces biochemical indices does not seem to be correct.

Abbreviations: FBS: fasting blood sugar; HbA1c: Hemoglobin A1c; LDL: low-density lipoprotein; HDL: High-density lipoproteins; HDL-C: High-density lipoproteins-cholesterol; BMI: Body mass index; IQR: Inter quartile range; TG: triglyceride; TC: total cholesterol; NS: non-significant; S: significant; ATN: Acute tubular necrosis     

Histopathological differences of experimental aneurysms treated with bare platinum,fibered, and bioactive coils

Purpose: To evaluate the histopathological features of experimental aneurysms embolized with bare platinum, fibered, and bioactive coils.

Material and methods: Twelve experimental aneurysms were constructed in three swine. The aneurysms were divided into four groups and were embolized using a bare platinum coil alone (P group, n?=?2), a bioactive coil alone (B group, n?=?2), a combination of fibered and bare platinum coils (F/P group, n?=?4) and a combination of fibered and bioactive coils (F/B group, n?=?4). Histopathological data for all aneurysms recorded at 63?days were analyzed in terms of neointima formation, fibrosis, foreign-body giant-cell infiltration, and organization.

Results: Fibrosis was significantly greater in group B compared with that in group F/P (p?=?.02). Inflammation with foreign-body giant-cell infiltration was significantly greater in groups F/P and F/B compared with that in groups P and B (p?=?.007).

Conclusion: The present study revealed that the embolic effect of fibered coils was not a thrombus but instead was a foreign-body response in the chronic phase.     

Anti-IL17 therapies for psoriasis

Introduction: Interleukin-17 (IL-17) is a proinflammatory cytokine considered to play a significant role in the immunopathogenesis of plaque psoriasis. As a result, focus in clinical trials has undergone a shift towards disease specific targets, with the goals of more effective treatment and reduction in the incidence of serious adverse events.

Areas covered: Two monoclonal antibodies targeting IL-17A (secukinumab, ixekizumab) and one against the IL-17 receptor (brodalumab) are approved for the treatment of moderate-to-severe plaque psoriasis. Herein, the clinical efficacy, safety and tolerability of each is reviewed by summarizing the existing literature (found via PubMed database).

Expert commentary: The development and approval of the IL-17 inhibitor agents secukinumab, ixekizumab, and brodalumab has expanded psoriatic treatment with effective options, validating the importance of the pro-inflammatory role of IL-17 psoriatic pathophysiology. Biologic treatment options for psoriasis will continue to grow, especially IL-17 and IL-23 related agents, with an increasing specificity of agents to be available in the future.     

A standing posture support device that reduces laparoscopic surgeons’ occupational lower limb stress

Background: We developed a surgical knee rest (SKR) that can be used to decrease the stress placed on the lower half of the body when surgeons work in the standing position. We tested the effectiveness of this device in the context of laparoscopic surgery.

Material and methods: Five healthy, right-handed male surgeons participated, and we recorded surface electromyography (sEMG) signals from the two heads of the left and right gastrocnemius (Gc) muscles during laparoscopic resections of colorectal cancer. The outcome variable was the percentage of maximum Gc muscle effort generated, reported as percent maximal isometric voluntary contraction (%MVC), and this variable was compared between surgeries performed with and without use of the SKR. Assessment covered the first 100?min of surgery, subdivided into two 50-min periods.

Results: Mean %MVC of the left Gc muscle for the full 100-min test period was significantly decreased when the SKR was used (p?=?.027, vs. SKR not used). Notably, mean %MVC of both Gc muscles was significantly decreased during the first 50?min of surgery (p?=?.008 and p?=?.0046).

Conclusion: The SKR is useful for decreasing physical stress incurred by laparoscopic surgeons when working in the standing position.     

Effect of cholinergic crisis on the potency of different emergency anaesthesia protocols in soman-poisoned rats

Background: In a military or terrorist scenario, combination of organophosphorus compounds (OP) poisoning with physical trauma requiring surgical treatment and thus general anaesthesia are possible. Previous in vitro studies showed an altered potency of relevant anaesthetics during cholinergic crisis. Hence, it is not clear, which anaesthetics are suitable to achieve the necessary stage of surgical anaesthesia in OP poisoning.

Methods: In the present study, different anaesthetic regimens (ketamine-midazolam, propofol-fentanyl, thiopental-fentanyl), relevant in military emergency medicine, were examined in soman-poisoned rats. Clinical signs and cardiovascular variables were recorded continuously. Blood samples for acetylcholinesterase (AChE) activity were drawn. After euthanasia or death of the animals, brain and diaphragm were collected for cholinesterase assays.

Results: Propofol-fentanyl and thiopental-fentanyl resulted in surgical anaesthesia throughout the experiments. With ketamine-midazolam, surgical anaesthesia without respiratory impairment could not be achieved in pilot experiments (no soman challenge) and was therefore not included in the study. Soman-poisoned and control animals required a comparable amount of propofol-fentanyl or thiopental-fentanyl. In combination with atropine, significantly less propofol was needed. Survival rate was higher with thiopental compared to propofol. Atropine improved survival in both groups. Blood and tissue AChE activities were strongly inhibited after soman administration with and without atropine treatment.

Discussion: The current in vivo study did not confirm concerns of altered potency of existing anaesthetic protocols for the application of propofol or thiopental with fentanyl due to soman poisoning. Despite severe cholinergic crisis, sufficient anaesthetic depth could be achieved in all animals.

Conclusion: Further experiments in in vivo models closer to human pharmaco- and toxicokinetics (e.g., swine) are required for confirmation of the initial findings and for improving extrapolation to humans.     

Bioengineering and regeneration of gastrointestinal tissue: where are we now and what comes next?

Introduction: The field of tissue engineering and regenerative medicine has been applied to the gastrointestinal (GI) tract for a couple decades. Several achievements have been accomplished that provide promising tools for treating diseases of the GI tract.

Areas covered: The work described in this review covers the traditional aspect of using cells and scaffolds to replace parts of the tract. Several studies investigated different types of biomaterials and different types of cells. A more recent approach involved the use of gut-derived organoid units that can differentiate into all gut cell layers. The most recent approach introduced the use of organ-on-a-chip concept to understand the physiology and pathophysiology of the GI system.

Expert opinion: The different approaches tackle the diseases of the GI tract from different perspectives. While all these different approaches provide a promising and encouraging future for this field, the translational aspect is yet to be studied.