A complex case of dysphagia with dual aetiology.

A woman in her early 60s was referred with dysphagia and chest pain to a tertiary referral centre specialising in oesophageal disorders. Cardiac symptom origin and sinister oesophageal pathology had been excluded at her local hospital in NHS Scotland. Under multidisciplinary team oversight, reinvestigation of mucosal pathology and oesophageal motility ultimately uncovered both Type III achalasia and eosinophilic oesophagitis. This case demonstrates the benefit of including provocative testing during high-resolution manometry to reproduce relevant dysphagia and the importance of stopping proton-pump inhibitors long enough to uncover excessive eosinophils which could otherwise be masked. Ultimately, tailored management for both conditions separately was required to achieve symptoms resolution.

5α-Tetrahydrocorticosterone: A topical anti-inflammatory glucocorticoid with an improved therapeutic index in a murine model of dermatitis.

BACKGROUND AND PURPOSE: Glucocorticoids are powerful anti-inflammatory drugs, but are associated with many side-effects. Topical application in atopic dermatitis leads to skin thinning, metabolic changes, and adrenal suppression. 5α-Tetrahydrocorticosterone (5αTHB) is a potential selective anti-inflammatory with reduced metabolic effects. Here, the efficacy and side-effect profile of 5αTHB were compared with hydrocortisone in preclinical models of irritant dermatitis. EXPERIMENTAL APPROACH: Acute irritant dermatitis was invoked in ear skin of male C57BL/6 mice with a single topical application of croton oil. Inflammation was assessed as oedema via ear weight following treatment with 5αTHB and hydrocortisone. Side-effects of 5αTHB and hydrocortisone were assessed following chronic topical steroid treatment (28 days) to non-irritated skin. Skin thinning was quantified longitudinally by caliper measurements and summarily by qPCR for transcripts for genes involved in extracellular matrix homeostasis; systemic effects of topical steroid administration also were assessed. Clearance of 5αTHB and hydrocortisone were measured following intravenous and oral administration. KEY RESULTS: 5αTHB suppressed ear swelling in mice, with ED50 similar to hydrocortisone (23 µg vs. 13 µg). Chronic application of 5αTHB did not cause skin thinning, adrenal atrophy, weight loss, thymic involution, or raised insulin levels, all of which were observed with topical hydrocortisone. Transcripts for genes involved in collagen synthesis and stability were adversely affected by all doses of hydrocortisone, but only by the highest dose of 5αTHB (8× ED50 ). 5αTHB was rapidly cleared from the systemic circulation. CONCLUSIONS AND IMPLICATIONS: Topical 5αTHB has potential to treat inflammatory skin conditions, particularly in areas of delicate skin.

Assessment of Esophageal Motility in Patients With Eosinophilic Esophagitis: A Scoping Review.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated condition causing esophageal symptoms, particularly dysphagia. Despite the important progress in the treatment of EoE, a significant proportion of patients continue to report symptoms that negatively impact quality of life. Esophageal manometry is used to assess motility and function, but is not routinely used in EoE. We aimed to systematically review and describe current literature evaluating esophageal manometry in EoE. Forty-eight studies meeting the criteria were identified, describing 802 patients. Using standard water swallow protocols, the proportion of abnormalities detected was not dissimilar to other populations, apart from disorders of esophago-gastric outflow, which were found in 5%. Twelve studies described pretreatment and posttreatment manometry, with motility normalization after pharmacological therapy reported in 20%. Early, brief panesophageal pressurization was described in a number of studies and was more prevalent in the few studies utilizing additional provocation testing. Reports in the literature regarding temporal relationships between manometric findings and symptoms are variable. Esophageal manometry may be capable of detecting clinically relevant changes to esophageal function in EoE. Possible mechanisms are altered neuromuscular function because of secretory products of EoE and/or fibroinflammatory processes, manifesting as pressurization because of altered esophageal compliance. Some changes may be reversible with therapy. Drawing strong conclusions from the literature is difficult, with bias toward case reports and retrospective observation. Adaptations to assessment protocols to include provocation testing may provide more robust evaluation and detect clinically relevant, subtle changes in esophageal function, earlier within the patient pathway.

Expanding on the use of The International Classification of Functioning, Disability and Health: Examples and resources.

Most physiotherapists today are familiar with the abbreviation ICF and know that it stands for the International Classification of Functioning, Disability and Health; the title of the World Health Organization's international standard for describing health and health related states. Most universities in South Africa and globally have adopted the framework of the ICF in their curricula especially in promoting clinical reasoning, however, translating that knowledge for recording and monitoring has been slow in coming. Less well known, is how the ICF is and can be used and how it can inform physiotherapy practice, research, education and administration. Our article outlines the importance of the ICF to physiotherapy and recommends resources to facilitate expanded ICF use by physiotherapists. Examples are given of how to use coding and the importance of aggregating data and concluding with resources that can assist with the expanded use. Sufficient evidence and resources are available to support the expanded use of the ICF for data collection and clinical coding. Clinical implications: The aggregation of data can be used for the monitoring of universal health coverage especially in the context of National Health Insurance implementation.

20 Years of ICF-International Classification of Functioning, Disability and Health: Uses and Applications around the World.

The International Classification of Functioning Disability and Health (ICF) was approved in 2001 and, since then, several studies reported the increased interest about its use in different sectors. A recent overview that summarizes its applications is lacking. This study aims to provide an updated overview about 20 years of ICF application through an international online questionnaire, developed by the byline authors, and sent to each World Health Organization Collaborating Centers of the Family of International Classifications (WHO-FIC CCs). Data was collected during October 2020 and December 2021 and descriptive content analyses were used to report main results. Results show how, in most of the respondent countries represented by WHO-FIC CCs, ICF was mainly used in clinical practice, policy development and social policy, and in education areas. Despite its applications in different sectors, ICF use is not mandatory in most countries but, where used, it provides a biopsychosocial framework for policy development in health, functioning and disability. The study provides information about the needs related to ICF applications, that can be useful to organize targeted intervention plans. Furthermore, this survey methodology can be re-proposed periodically to monitor the use of the ICF in the future.

Inter-rater agreement when linking stroke interventions to the extended international classification of functioning, disability and health core set for stroke.

PURPOSE: To uncover the factors that influence inter-rater agreement when extracting stroke interventions from patient records and linking them to the relevant categories in the Extended International Classification of Functioning, Disability and Health Core Set for Stroke. METHOD: Using 10 patient files, two linkers independently extracted interventions and linked the target of the intervention to relevant functions in the ICF. The percentage agreement of extracted interventions and the ICF codes was calculated. Non-matching interventions and codes were further analysed to determine the reasons for poor agreement. RESULTS: A total of 518 interventions were extracted, with 44.01% agreement between the two linkers. Of the non-agree codes and interventions, 43.79% were due to mismatched ICF codes and 56.20% were due to mismatched interventions. Differences were due to linkers (a) extracting interventions from different parts of the patient note (b) differences in interpreting the target of the intervention, and (c) choosing a different code with similar meaning. CONCLUSION: Greater reliability when linking interventions to ICF codes can be achieved by; health services using a consistent progress note that uses ICF language, recording the intervention aim, linkers knowing the aims of each discipline's interventions and using multiple reliability checks and analysis to inform the linking method.Implications for rehabilitationLinking intervention targets to the ICF and to the ICHI is an emerging research field.Development of trustworthy inter-rater reliability methods is needed to achieve its potential to demonstrate the equity, quality and effectiveness of interventions.Independent linking of patient notes to the ICF can identify factors that impact inter-rater reliability.When writing patient notes, health professionals should use a consistent format that identifies the functional target of the intervention using ICF terms.

Remodeling of the ICF: A commentary.

Since its publication in 2001 the International Classification of Functioning, Disability and Health (ICF) has attracted debate about the content and the model presented. After almost 20 years use, regular updating since 2008 and with the prospect of a new edition in 2020 there is increasing interest in the ICF as a tool to meet contemporary information requirements. Information on functioning is important across not only health systems, but all areas where change in functioning is important: education, employment, and social welfare for example. This commentary responds to the issues raised in a commentary by Mitra & Shakespeare in 2019 and supports review of the ICF in the current context by informing users and providers of data on human functioning how they might engage in the maintenance, updating, and modernisation of the ICF.

Characterization of Phosphopeptide Positional Isomers on the Transcriptional Co-activator TAZ.

The transcriptional co-activator with the PDZ binding motif (TAZ) is a critical regulator of numerous cellular processes such as cell differentiation, development, proliferation, and cell growth. Aberrant expression and activity of TAZ are also featured in many human malignancies. A hallmark of TAZ biology is its cytoplasmic retention mediated by 14-3-3 isoforms in response to phosphorylation of Ser89 by members of the LATS family of kinases. Following the observation that TAZ is a highly phosphorylated protein even when Ser89 is mutated, high-resolution mass spectrometry employing data-independent acquisition and ion mobility separation was conducted to elucidate additional TAZ phosphorylation sites that may play a role in regulating this critical transcriptional rheostat. Numerous phosphorylation sites on TAZ were identified, including several novel modifications. Of notable interest was the identification of positional phosphoisomers on a phosphopeptide containing Ser89. Optimized use of a so-called wideband enhancement acquisition technique yielded higher-quality fragmentation data that confirmed the detection of Ser93 as the positional phosphoisomer partner of Ser89 and identified diagnostic fragment ions for the phosphorylation events. Functional analysis indicated that Ser93 phosphorylation reduces the level of 14-3-3 association and increases the level of nuclear translocation, indicating this phosphorylation event attenuates the 14-3-3-mediated TAZ cytoplasmic retention mechanism. These findings suggest that the biological activities of TAZ are likely dynamically regulated by multisite phosphorylation.

Avoiding the Banality of Evil in Times of COVID-19: Thinking Differently with a Biopsychosocial Perspective for Future Health and Social Policies Development.

The COVID-19 pandemic provides the opportunity to re-think health policies and health systems approaches by the adoption of a biopsychosocial perspective, thus acting on environmental factors so as to increase facilitators and diminish barriers. Specifically, vulnerable people should not face discrimination because of their vulnerability in the allocation of care or life-sustaining treatments. Adoption of biopsychosocial model helps to identify key elements where to act to diminish effects of the pandemics. The pandemic showed us that barriers in health care organization affect mostly those that are vulnerable and can suffer discrimination not because of severity of diseases but just because of their vulnerability, be this age or disability and this can be avoided by biopsychosocial planning in health and social policies. It is possible to avoid the banality of evil, intended as lack of thinking on what we do when we do, by using the emergence of the emergency of COVID-19 as a Trojan horse to achieve some of the sustainable development goals such as universal health coverage and equity in access, thus acting on environmental factors is the key for global health improvement.

Toward a Harmonized WHO Family of International Classifications Content Model.

An overarching WHO-FIC Content Model will allow uniform modeling of classifications in the WHO Family of International Classifications (WHO-FIC) and promote their joint use. We provide an initial conceptualization of such a model.

Systematic review and meta-analysis: is bowel preparation still necessary in small bowel capsule endoscopy?

INTRODUCTION: Optimal bowel preparation for small bowel capsule endoscopy(SBCE) is controversial. This meta-analysis aimed to investigate the effects of laxatives in SBCE. METHODS: A comprehensive literature search was conducted for studies investigating the use of laxatives in SBCE. The primary outcome was diagnostic yield(DY) for SB findings; secondary outcomes SB visualization quality(SBVQ) and completion rate(CR). Pooled odds ratios(ORs) with 95% confidence intervals(CIs) and number needed to treat(NNT) were calculated. RESULTS: Forty studies (4380 patients with laxatives, 2185 without) were included. Laxative use did not improve DY of SB findings overall (OR 1.11 (95%CI 0.85-1.44)) or for significant SB findings (OR 1.10 (95%CI 0.76-1.60)). However, SBVQ improved with the use of laxatives (OR 1.60 (95%CI 1.08-2.06)), NNT 14. The OR for completed SBCE was 1.30 (95%CI 0.95-1.78). Patients given polyethylene glycol(PEG) had lower DY than sodium phosphate(NaP). SBVQ improved more with NaP (NNT 7) than PEG (NNT 53). CONCLUSIONS: Laxatives do not significantly improve DY or CR in SBCE, but do improve SBQV. The use of laxatives may be beneficial in patients likely to have subtle findings. There are significant differences in methodology/definitions between studies, hence the need for standardized visualization scoring and recording of SBCE findings.

Interventions to increase engagement with rehabilitation in adults with acquired brain injury: A systematic review.

Rehabilitation in adults with acquired brain injury is often hampered by a lack of client engagement with the rehabilitation process, leading to frustration, withdrawal of services and poorer recovery. Motivation, apathy and awareness are potential mechanisms underlying engagement, but few studies have suggested potential intervention techniques. A systematic review of the literature was carried out to identify and evaluate interventions designed to increase rehabilitation engagement in adults with acquired brain injury. Database searches used the following terms: rehabilitation, brain injury, and compliance/engagement/adherence in PsychInfo, Medline, Cinahl, Embase, AMED, Web of Knowledge, PsycBite, Cochrane clinical trials, and clinicaltrials.org. Hand searches were conducted of reference lists and relevant journals. Fifteen studies were included in the review. Intervention techniques fell into two broad categories: behavioural modification techniques and cognitive/meta-cognitive skills. Contingent reward techniques were most effective at increasing adherence and compliance, while interventions enabling clients' active participation in rehabilitation appeared to increase engagement and motivation. The review highlighted methodological and measurement inconsistencies in the field and suggested that interventions should be tailored to clients' abilities and circumstances.

The validity of suspected blood indicator software in capsule endoscopy: a systematic review and meta-analysis.

INTRODUCTION: Software tools have been developed as capsule endoscopy (CE) reading aids. The suspected blood indicator (SBI) tags possible areas of haemorrhage in the gastrointestinal (GI) tract. This meta-analysis aims to investigate the diagnostic accuracy of SBI in CE. Areas covered: A systematic literature search was conducted for studies on the use of SBI in CE. Sensitivity, specificity and diagnostic odds ratio (DOR) of SBI in diagnosing GI bleeding was evaluated. 2040 patients from 16 studies underwent 2049 CE examinations. The overall sensitivity of SBI for bleeding or potentially bleeding lesions was 0.553, specificity 0.578, DOR 12.354. The sensitivity of SBI for active bleeding was 0.988, specificity 0.646, DOR 229.89. Expert commentary: Currently, SBI has limited validity in CE reading. However, in active GI bleeding, it has good sensitivity, supporting its use in the acute setting.

Brain serotonin signaling does not determine sexual preference in male mice.

It was reported recently that male mice lacking brain serotonin (5-HT) lose their preference for females (Liu et al., 2011, Nature, 472, 95-100), suggesting a role for 5-HT signaling in sexual preference. Regulation of sex preference by 5-HT lies outside of the well established roles in this behavior established for the vomeronasal organ (VNO) and the main olfactory epithelium (MOE). Presently, mice with a null mutation in the gene for tryptophan hydroxylase 2 (TPH2), which are depleted of brain 5-HT, were tested for sexual preference. When presented with inanimate (urine scents from male or estrous female) or animate (male or female mouse in estrus) sexual stimuli, TPH2-/- males show a clear preference for female over male stimuli. When a TPH2-/- male is offered the simultaneous choice between an estrous female and a male mouse, no sexual preference is expressed. However, when confounding behaviors that are seen among 3 mice in the same cage are controlled, TPH2-/- mice, like their TPH2+/+ counterparts, express a clear preference for female mice. Female TPH2-/- mice are preferred by males over TPH2+/+ females but this does not lead to increased pregnancy success. In fact, if one or both partners in a mating pair are TPH2-/- in genotype, pregnancy success rates are significantly decreased. Finally, expression of the VNO-specific cation channel TRPC2 and of CNGA2 in the MOE of TPH2-/- mice is normal, consistent with behavioral findings that sexual preference of TPH2-/- males for females is intact. In conclusion, 5-HT signaling in brain does not determine sexual preference in male mice. The use of pharmacological agents that are non-selective for the 5-HT neuronal system and that have serious adverse effects may have contributed historically to the stance that 5-HT regulates sexual behavior, including sex partner preference.

Mice genetically depleted of brain serotonin do not display a depression-like behavioral phenotype.

Reductions in function within the serotonin (5HT) neuronal system have long been proposed as etiological factors in depression. Selective serotonin reuptake inhibitors (SSRIs) are the most common treatment for depression, and their therapeutic effect is generally attributed to their ability to increase the synaptic levels of 5HT. Tryptophan hydroxylase 2 (TPH2) is the initial and rate-limiting enzyme in the biosynthetic pathway of 5HT in the CNS, and losses in its catalytic activity lead to reductions in 5HT production and release. The time differential between the onset of 5HT reuptake inhibition by SSRIs (minutes) and onset of their antidepressant efficacy (weeks to months), when considered with their overall poor therapeutic effectiveness, has cast some doubt on the role of 5HT in depression. Mice lacking the gene for TPH2 are genetically depleted of brain 5HT and were tested for a depression-like behavioral phenotype using a battery of valid tests for affective-like disorders in animals. The behavior of TPH2(-/-) mice on the sucrose preference test, tail suspension test, and forced swim test and their responses in the unpredictable chronic mild stress and learned helplessness paradigms was the same as wild-type controls. While TPH2(-/-) mice as a group were not responsive to SSRIs, a subset responded to treatment with SSRIs in the same manner as wild-type controls with significant reductions in immobility time on the tail suspension test, indicative of antidepressant drug effects. The behavioral phenotype of the TPH2(-/-) mouse questions the role of 5HT in depression. Furthermore, the TPH2(-/-) mouse may serve as a useful model in the search for new medications that have therapeutic targets for depression that are outside of the 5HT neuronal system.

Rehabilitation treatment taxonomy and the international classification of health interventions.

This commentary provides some reactions to the rehabilitation treatment taxonomy project in relation to work already underway to develop an International Classification of Health Interventions. This commentary also includes some comments in response to questions posed by the authors.