Qualitative Description of Exercise Perceptions and Experiences Among People With Human Immunodeficiency Virus in the High-Intensity Exercise to Attenuate Limitations and Train Habits Study.

BACKGROUND: The benefits of physical activity (PA), specifically exercise, among older adults in general are well known. Yet globally, there is concern regarding limited engagement in PA, increased obesity, and frailty among older people with human immunodeficiency virus related to low levels of PA. METHODS: We conducted in-depth interviews among 30 older, sedentary people with human immunodeficiency virus participating in the ongoing High-Intensity Exercise to Attenuate Limitations and Train Habits (HEALTH study, NCT04550676) between February 2021 and August 2022. A semistructured interview guide, informed by two minds theory, which frames behavior change as an intention-behavior gap between 2 neurocognitive systems, was used to elicit data from participants. Interviews explored general exercise perceptions, self-efficacy for exercise, mobile health intervention tailoring, outcome expectations, and PA goals. Thirty interviews from 33 participants were recorded and transcribed verbatim, and deductive and inductive thematic analysis were used using Dedoose. RESULTS: Physical activity was defined as maintaining daily living activities and addressing health goals. Previous experiences with PA varied among participants and were influenced by chronic illnesses, including human immunodeficiency virus; motivation; work commitments; interest; and social support. Reported barriers to PA included antiretroviral adverse effects, comorbidities, aging, and the COVID-19 pandemic. Changes in health status, body changes, and relationships were identified as benefits of PA. Conversations with healthcare providers supporting exercise goals were perceived to be important but rarely received by the participants. CONCLUSION: Understanding how older people with human immunodeficiency virus perceive PA is crucial to developing tailored strategies and structuring service delivery within the healthcare setting to promote a physically active life.

U.S. Parental Vaccine Hesitancy and the COVID-19 Vaccine: A Scoping Review.

Parental vaccine hesitancy has been a hotly debated issue long before the COVID-19 pandemic. Still, the emergence of a new vaccine during this public health crisis made even pro-vaccine individuals reconsider vaccines for their children. This scoping review was conducted to understand why parents expressed hesitancy towards the COVID-19 vaccine for children under 12 years old. The search included primary sources of evidence published in English from 2020-2022. A final 41 articles met the criteria. Overall, more vaccine-hesitant characteristics were non-white, female, lower education level, lower income, on public insurance, conservative political affiliation, younger age, and rural residence. Concerns affecting confidence in the vaccine were the risk of possible side effects and lack of trust in the development of the emergency approval of the vaccine. School nurses can acknowledge parental fears and provide parents with evidence-based information when communicating with them about vaccinations.

Situational Awareness and Proactive Engagement Predict Higher Time in Range in Adolescents and Young Adults Using Hybrid Closed-Loop.

Background: Adolescents and young adults with type 1 diabetes have high HbA1c levels and often struggle with self-management behaviors and attention to diabetes care. Hybrid closed-loop systems (HCL) like the t:slim X2 with Control-IQ technology (Control-IQ) can help improve glycemic control. The purpose of this study is to assess adolescents' situational awareness of their glucose control and engagement with the Control-IQ system to determine significant factors in daily glycemic control. Methods: Adolescents (15-25 years) using Control-IQ participated in a 2-week prospective study, gathering detailed information about Control-IQ system engagements (boluses, alerts, and so on) and asking the participants' age and gender about their awareness of glucose levels 2-3 times/day without checking. Mixed models assessed which behaviors and awareness items correlated with time in range (TIR, 70-180 mg/dl, 3.9-10.0 mmol/L). Results: Eighteen adolescents/young adults (mean age 18 ± 1.86 years and 86% White non-Hispanic) completed the study. Situational awareness of glucose levels did not correlate with time since the last glucose check (p = 0.8). In multivariable modeling, lower TIR was predicted on days when adolescents underestimated their glucose levels (r = -0.22), received more CGM alerts (r = -0.31), and had more pump engagements (r = -0.27). A higher TIR was predicted when adolescents responded to CGM alerts (r = 0.20) and entered carbohydrates into the bolus calculator (r = 0.49). Conclusion: Situational awareness is an independent predictor of TIR and may provide insight into patterns of attention and focus that could positively influence glycemic outcomes in adolescents. Proactive engagements predict better TIR, whereas reactive engagement predicted lower TIR. Future interventions could be designed to train users to develop awareness and expertise in effective diabetes self-management.

Neuroimaging correlates of brain injury in Wilson's disease: a multimodal, whole-brain MRI study.

Wilson's disease is an autosomal-recessive disorder of copper metabolism with neurological and hepatic presentations. Chelation therapy is used to 'de-copper' patients but neurological outcomes remain unpredictable. A range of neuroimaging abnormalities have been described and may provide insights into disease mechanisms, in addition to prognostic and monitoring biomarkers. Previous quantitative MRI analyses have focused on specific sequences or regions of interest, often stratifying chronically treated patients according to persisting symptoms as opposed to initial presentation. In this cross-sectional study, we performed a combination of unbiased, whole-brain analyses on T1-weighted, fluid-attenuated inversion recovery, diffusion-weighted and susceptibility-weighted imaging data from 40 prospectively recruited patients with Wilson's disease (age range 16-68). We compared patients with neurological (n = 23) and hepatic (n = 17) presentations to determine the neuroradiological sequelae of the initial brain injury. We also subcategorized patients according to recent neurological status, classifying those with neurological presentations or deterioration in the preceding 6 months as having 'active' disease. This allowed us to compare patients with active (n = 5) and stable (n = 35) disease and identify imaging correlates for persistent neurological deficits and copper indices in chronically treated, stable patients. Using a combination of voxel-based morphometry and region-of-interest volumetric analyses, we demonstrate that grey matter volumes are lower in the basal ganglia, thalamus, brainstem, cerebellum, anterior insula and orbitofrontal cortex when comparing patients with neurological and hepatic presentations. In chronically treated, stable patients, the severity of neurological deficits correlated with grey matter volumes in similar, predominantly subcortical regions. In contrast, the severity of neurological deficits did not correlate with the volume of white matter hyperintensities, calculated using an automated lesion segmentation algorithm. Using tract-based spatial statistics, increasing neurological severity in chronically treated patients was associated with decreasing axial diffusivity in white matter tracts whereas increasing serum non-caeruloplasmin-bound ('free') copper and active disease were associated with distinct patterns of increasing mean, axial and radial diffusivity. Whole-brain quantitative susceptibility mapping identified increased iron deposition in the putamen, cingulate and medial frontal cortices of patients with neurological presentations relative to those with hepatic presentations and neurological severity was associated with iron deposition in widespread cortical regions in chronically treated patients. Our data indicate that composite measures of subcortical atrophy provide useful prognostic biomarkers, whereas abnormal mean, axial and radial diffusivity are promising monitoring biomarkers. Finally, deposition of brain iron in response to copper accumulation may directly contribute to neurodegeneration in Wilson's disease.

Outcomes of Paediatric Cystine Stone Management: Results of a Systematic Review.

PURPOSE OF REVIEW: We wanted to analyse the outcomes of surgical (SWL, URS, PCNL) and medical management of cystine stones in the paediatric population in terms of stone-free status and complication rates, based on all the available literature evidence. RECENT FINDINGS: A systematic review of literature was performed for all studies with paediatric cystine stone management. Twelve studies met the eligibility criteria, of which 4 analysed outcomes of SWL, 2 of URS and 3 of PCNL and 3 focused on the effect of either alkalising agents (potassium citrate, citric acid) or cysteine-binding thiol (CBT) agents (tiopronin, penicillamine). The reported SFR in studies ranged from 50 to 83%, 59 to 100% and 63 to 80.6%, with a complication rate of 2.8-51%, 14-27% and 12.9-15.4% with SWL, URS and PCNL, respectively. Paediatric cystine stones treatment should aim at complete stone clearance, preservation of renal function and prevention of further recurrences. SWL achieves inferior results in case of cystine stones. URS and PCNL are safe and effective procedures in the paediatric population, with a low rate of major complications. Adherence to medical prevention therapies may prolong recurrence-free periods.

Stress Impact and Care for COVID-19: Pilot Education and Support Course Decreases Burnout Among Nursing Students.

BACKGROUND: Nurses and nursing students have been at the forefront of the fight against COVID-19, often working in conditions that produce stress injuries and burnout. Early recognition and mitigation of stress and emotional trauma help prevent burnout. AIMS: To evaluate the effectiveness of an online 8-hour stress awareness course and associated 1-hour support group in reducing stress and burnout among nursing students. METHODS: We conducted a program evaluation for an online stress awareness pilot course offered to nursing students. The course, and associated support groups led by trained psychiatric mental health nurse practitioner students, included a common language for talking about stress, screening tools for recognizing stress injuries, and strategies for improving self-care. Students completed pre- and post-course surveys. Outcome measures included changes on course learning objectives, level of burnout, health-related locus of control, and experiences of stress and coping. RESULTS: Nursing students (n = 360) enrolled in the course, and 224 (62%) completed pre- and post-course surveys. Sixty percent rated the course excellent or very good. Depression Anxiety and Stress Scales and Impact of Event Scale Revised scores were within established normal ranges. There was a significant increase in all nine course learning objectives (p < .001) and decreased signs of stress (p < .001). Students' level of burnout decreased by odds ratio = 0.58 (95% CI: [0.4, 0.9], p < .006). CONCLUSIONS: Nursing leaders can use psychoeducational strategies to mitigate the impact of stress, build confidence, and support nursing students entering the workforce during these unprecedented times.

Novel predictors of daily fluctuations in glycemia and self-management in adolescents and young adults with type 1 diabetes.

AIMS: To understand morning biopsychosocial factors that predict glycemia, adherence, and goal attainment in adolescents and young adults (AYA) with type 1 diabetes (T1D) on a daily basis. METHODS: Eight-eight AYA (mean 17.6 ± 2.6 years, 54% female, HbA1c 7.9 ± 1.4%, diabetes duration 8.5 ± 4.5 years) with T1D who use Continuous Glucose Monitoring (CGM) completed a 2-week prospective study. Participants chose a self-management goal to focus on during participation. For six days, participants prospectively completed a 25-item Engagement Prediction Survey to assess biopsychosocial factors to predict daily diabetes outcomes and an end-of-day Goal Survey. Lasso and mixed-model regression were used to determine items in the Engagement Prediction Survey most predictive of perceived goal attainment, CGM Time-in-Range (TIR, 70-180 mg/dl), sensor mean glucose, number of insulin boluses and hyperglycemia response (bolus within 30 min of high alert or glucose <200 mg/dl within 2 hours). RESULTS: A 7-item model (including current glucose, planning/wanting to manage diabetes, wanting to skip self-management, feeling good about self, health perception and support needs) explained 16.7% of the daily variance in TIR, 18.6% of mean sensor glucose, 2.1% of the number of boluses, 14% of hyperglycemia response, and 28.7% of goal attainment perceptions. The mean absolute change in day-to-day TIR was 16%, sensor glucose was 30 mg/dl, and the number of boluses was 2. AYA reported more positive Engagement Prediction Survey responses on mornings when they awoke with lower glucose levels. CONCLUSIONS: Morning biopsychosocial state factors predict glycemic and adherence outcomes in AYA with diabetes and could be a novel intervention target for future behavioural interventions.

Cellular miR-150-5p may have a crucial role to play in the biology of SARS-CoV-2 infection by regulating nsp10 gene.

The role for circulating miRNAs as biomarkers of the COVID-19 disease remains uncertain. We analysed the circulating miRNA profile in twelve COVID-19 patients with moderate-severe disease. This analysis was conducted by performing next generation sequencing (NGS) followed by real-time polymerase chain reaction (RT-qPCR). Compared with healthy controls, we detected significant changes in the circulating miRNA profile of COVID-19 patients. The miRNAs that were significantly altered in all the COVID-19 patients were miR-150-5p, miR-375, miR-122-5p, miR-494-3p, miR-3197, miR-4690-5p, miR-1915-3p, and miR-3652. Infection assays performed using miRNA mimics in HEK-293 T cells determined miR-150-5p to have a crucial role in SARS-CoV-2 infection and this was based on the following data: (i) miR-150-5p mimic lowered in vitro SARS-CoV-2 infection; (ii) miR-150-5p inhibitor reversed the effects of miR-150-5p mimic on SARS-CoV-2 infection of cells; and (iii) a novel miRNA recognition element (MRE) was identified in the coding strand of SARS-CoV-2 nsp10, the expression of which could be inhibited by miR-150-5p mimic. Our findings identified crucial miRNA footprints in COVID-19 patients with moderate-severe disease. A combination of co-transfection and Western blotting experiments also determined the ability of miR-150-5p to inhibit SARS-CoV-2 infection via directly interacting with MRE in the coding strand of nsp10. Our investigation showed that a sharp decline in the miR-150-5p plasma levels in COVID-19 patients may support enhanced SARS-CoV-2 infection. Furthermore, this study provides insight into one possible mechanism by which COVID-19-induced changes to miR-150-5p levels may promote SARS-CoV-2 infection via modulating nsp10 expression.

Bacillus cytotoxicus-A potentially virulent food-associated microbe.

Bacillus cytotoxicus is a member of the Bacillus cereus group with the ability to grow at high temperatures (up to 52℃) and to synthesize cytotoxin K-1, a diarrhoeagenic cytotoxin, which appears to be unique to this species and more cytotoxic than the cytotoxin K-2 produced by other members of this group. Only a few isolates of this species have been characterized with regard to their cytotoxic effects, and the role of cytotoxin K-1 as a causative agent of food poisoning remains largely unclear. Bacillus cytotoxicus was initially isolated from a food-borne outbreak, which led to three deaths, and the organism has since been linked to other outbreaks all involving plant-based food matrices. Other studies, as well as food-borne incidents reported to the UK Food Standards Agency, detected B. cytotoxicus in insect-related products and in dried food products. With insect-related food becoming increasingly popular, the association with this pathogen is concerning, requiring further investigation and evidence to protect public health. This review summarizes the current knowledge around B. cytotoxicus and highlights gaps in the literature from a food safety perspective.

Predicting optimal use of continuous glucose monitors in adolescents with type 1 diabetes: It's about benefit and burden.

PURPOSE: Youth with type 1 diabetes (T1D) often use Continuous Glucose Monitoring (CGM) devices; however, many do not wear them consistently enough to obtain optimal glycemic benefit. This study aimed to identify demographic and psychosocial predictors of optimal CGM use in adolescents with T1D to inform nurse-led interventions to improve adherence. DESIGN AND METHODS: Cross-sectional survey data from youth (12-19 years) using CGM were analyzed to determine whether perceived benefits/burdens of CGM, self-efficacy, and coping predicted being a "CGM Optimizer" (wearing CGM 6-7 days/week) or "CGM Sub-user." RESULTS: Of 282 adolescents (54% female), 161 were CGM Optimizers and 121 were CGM Sub-Users. Optimizers were younger (15.91 ± 2.17 years vs. 16.79 ± 2.17, p = 0.001), more likely non-Hispanic White (91.9% vs 83.5%, p = 0.029), and more likely to have private insurance (82.0% vs. 69.4%, p = 0.009). Every 1-point increase on Benefits of CGM scale was associated with 2.8 times greater odds of being an Optimizer (OR = 2.82, 95% CI 1.548-5.132, p = 0.001), and every 1-point increase on the Burdens of CGM scale was associated with a 52% decrease in odds (OR = 0.48, 95% CI = 0.283-0.800, p = 0.005), with final logistic regression model (including only these two predictors) explaining 22.3% of variance. CONCLUSION: CGM Optimizing adolescents were more likely to perceive higher benefit and lower burden of CGM. PRACTICAL IMPLICATIONS: Nurse-led interventions to promote benefits of CGM and mitigate burden may help youth increase adherence with CGM to achieve glycemic benefit.

Comorbidity of Lifetime History of Abuse and Trauma With Opioid Use Disorder: Implications for Nursing Assessment and Care.

BACKGROUND: Opioid use disorder (OUD) is a public health crisis and is challenging to treat. Previous research has shown correlations between OUD, abuse/trauma, and chronic pain. AIMS: The purpose of this study was to investigate history of lifetime sexual, physical, and/or emotional abuse among participants in a medication-assisted treatment (MAT) program for OUD, and to investigate associations between abuse history and chronic pain. METHODS: This is a secondary analysis of intake data from a 2-year, nonexperimental cohort treatment program of patients with OUD in rural Colorado. De-identified data were provided by 476 adult MAT patients using the Adult Addiction Severity Index (ASI-6). The ASI-6 includes three yes/no questions about history of abuse (emotional, physical, and sexual), with separate scoring for "past 30 days" and "lifetime" abuse. RESULTS: Lifetime history among MAT program for OUD patients was 23% for sexual abuse, 43% for physical abuse, and 58% for emotional abuse. History of physical abuse was significantly associated with having a chronic pain diagnosis, χ2 = 4.49, p = .03, and also with higher reported pain levels, t(460) = 2.71, p = .007. CONCLUSION: Lifetime history of physical abuse was associated with OUD and chronic pain, yet standard pain assessments do not assess these factors. In health care settings, the implementation of standardized trauma-informed screening tools, prompt recognition of abuse/trauma history, and adjunct psychological interventions may reduce stigma, reduce opioid use escalation, and help patients overcome OUD.

Distribution of High-Sensitivity Troponin Taken Without Conventional Clinical Indications in Critical Care Patients and Its Association With Mortality.

OBJECTIVES: To describe the distribution of high-sensitivity troponin in a consecutive cohort of patients in critical care units, regardless of clinical indication, and its association with clinical outcomes. DESIGN: Prospective observational study. SETTING: Single-center teaching hospital. PATIENTS: Consecutive patients admitted to two adult critical care units (general critical care unit and neuroscience critical care unit) over a 6-month period. INTERVENTIONS: All patients had high-sensitivity troponin tests performed at admission and tracked throughout their critical care stay, regardless of whether the supervising team felt there was a clinical indication. The results were not revealed to patients or clinicians unless clinically requested. MEASUREMENTS AND MAIN RESULTS: There were 1,033 patients in the study cohort (general critical care unit 750 and neuroscience critical care unit 283). The median high-sensitivity troponin was 21 ng/L (interquartile range, 7-86 ng/L), with 560 patients (54.2%) above the upper limit of normal as defined by the manufacturer. Admission high-sensitivity troponin concentrations above the upper limit of normal in general critical care unit and neuroscience critical care unit were associated with increasing age, comorbidity, markers of illness severity, and the need for organ support. On adjusted analysis, the high-sensitivity troponin concentration remained an independent predictor of critical care mortality in general critical care unit and neuroscience critical care unit. CONCLUSIONS: High-sensitivity troponin elevation, taken outside the context of conventional clinical indications, was common in the critically ill. Such elevations were associated with increasing age, comorbidity, illness severity, and the need for organ support. Admission high-sensitivity troponin concentration is an independent predictor of critical care mortality and as such may represent a novel prognostic biomarker at admission.

Plasma Neurofilament Light as a Biomarker of Neurological Involvement in Wilson's Disease.

BACKGROUND: Outcomes are unpredictable for neurological presentations of Wilson's disease (WD). Dosing regimens for chelation therapy vary and monitoring depends on copper indices, which do not reflect end-organ damage. OBJECTIVE: To identify a biomarker for neurological involvement in WD. METHODS: Neuronal and glial-specific proteins were measured in plasma samples from 40 patients and 38 age-matched controls. Patients were divided into neurological or hepatic presentations and those with recent neurological presentations or deterioration associated with non-adherence were subcategorized as having active neurological disease. Unified WD Rating Scale scores and copper indices were recorded. RESULTS: Unlike copper indices, neurofilament light (NfL) concentrations were higher in neurological than hepatic presentations. They were also higher in those with active neurological disease when controlling for severity and correlated with neurological examination subscores in stable patients. CONCLUSION: NfL is a biomarker of neurological involvement with potential use in guiding chelation therapy and clinical trials for novel treatments. © 2020 University College London. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Risk of UTI in kidney stone formers: a matched-cohort study over a median follow-up of 19 years.

PURPOSE: To describe risk of UTI in Stone formers comparing to non-stone formers. METHODS: Retrospective cohort study using electronic records for patients across southern England. Stone formers referred to a tertiary referral centre in Southern England, comparator patients were age and sex matched with 3:1 ratio from same database. Those with no documentation were excluded. UTI defined using ICD-10 codes. Risk of UTI presented as hazard ratio with 95% confidence interval, generated using cox regression. Sample size calculated using 80% power and significance set at 0.05. RESULTS: Eight hundred and nineteen stone formers were included after 1000 records were screened for inclusion, with 2477 age and sex matched non-stone formers extracted from the same database. Sample size was calculated at 287 per group. Stone formers were at significantly increased risk of developing a UTI (HR 5.67; 95% CI 4.52-7.18, p < 0.001). Median follow-up was 19 years (IQR: 15-22). CONCLUSIONS: Kidney stone formers are at increased risk of developing urinary tract infections.

Associations between demographics and quality of life in children in the first year of cancer treatment.

Symptom distress and decreased quality of life (QOL) among children with cancer are well documented. Research is emerging on the child's voice in QOL-symptom reports, but existing QOL questionnaires are burdensome and objective biologic markers are lacking. We examined children's symptoms and QOL from parent and child perspectives and compared the results to one biologic marker (body posture). A cross-sectional secondary analysis of prospective data from children receiving creative arts therapy explored potential associations among demographics with and between QOL measures (PedsQL, Faces Scale, posture). Children (n = 98) ranged in age from 3 to 17 years (M = 7.8) and were in the first year of cancer treatment. No significant associations were found among the child's sex, race/ethnicity, socioeconomic status (SES), or distance from hospital, and total PedsQL. Older age was associated with worse total PedsQL, pain, nausea, worry, and posture (all P < 0.05). Greater worry (ß = 0.51) and worse posture (ß = 0.41) were the QOL variables most strongly correlated with older age. Poorer posture was associated with worse child PedsQL (total score, nausea, treatment anxiety, cognitive) and parent PedsQL (pain, nausea). Worse scores on the Faces Scale, PedsQL, and posture were all correlated (r = 0.21-0.39, all P < 0.05). Interventions to improve QOL could target nausea, worry, and older patients. Accuracy and interpretation of symptom distress in children are problematic. The Faces Scale and posture may be suitable, readily obtained measures of QOL in pediatric oncology that hold promise.

Discontinuation of Transmission Precautions for COVID-19 Patients: Polymerase Chain Reaction Diagnostics, Patient Delays, and Cycle Threshold Values.

BACKGROUND: The decision of when it is safe to discontinue transmission-based precautions for SARS-CoV-2 coronavirus disease 2019 (COVID-19) hospitalized patients has been controversial. The Centers for Disease Control and Prevention offered reverse transcriptase polymerase chain reaction (PCR) diagnostic test- or symptom-based guidelines. METHODS: A retrospective chart review of Vidant Health system, Eastern North Carolina, was conducted. Length of stay, days in isolation unit, and date appropriate for discharge or isolation discontinuation based on the symptom-based strategy were recorded. RESULTS: Of 196 COVID hospitalized patients, 34 had repeated COVID PCR tests 3 or more days from their first positive test result. Half of these patients experienced delays in release from transmission-based precautions because of repeated positive PCR test results and use of the test-based approach. This resulted in an additional 166 days of hospitalization, costing an estimated $415,000. Furthermore, 2 subjects had a combined 16-day delay in necessary medical procedures. Most of the COVID PCR platforms yield quantitative results in the form of cycle threshold (Ct) values, the number of cycles needed to detect the genome. These values have also been used to assess whether patients are likely to remain contagious. None of our patients who met the criteria for symptom-based strategy for transmission-based precaution discontinuation had positive PCR test results with Ct values lower than 25, but 4 had Ct values lower than 30. CONCLUSIONS: Concerns surround immunocompromised patients and those treated with steroids who might be delayed or incapable of stopping viral replication and thus remain contagious. Our results suggest that clinicians use all available data including Ct values to evaluate the safety of discontinuation of transmission precautions.

Evaluation of the economic burden of kidney stone disease in the UK: a retrospective cohort study with a mean follow-up of 19 years.

OBJECTIVE: To estimate the cost of kidney stone disease (KSD) in England. PATIENTS AND METHODS: We conducted a retrospective cohort study of patients with KSD, referred to a metabolic stone clinic between 1990 and 2007 using electronic records of patients with KSD in a tertiary referral centre, to determine cost using UK National Health Service (NHS) tariff, with subsequent extrapolation to the entire England population. Those with no documentation and <5 years follow-up were excluded. The outcome measure was calculation of cost (as per 2018 NHS tariff) presented as lower and higher estimates for: per episode; total within the cohort; and estimation of initial, 5-,10- and 15-year costs for the cohort and total population in England. Linear regression was used to examine for significant predictors of per episode and total cost. RESULTS: A total of 781 patients were included in the study after 1000 records were screened for inclusion, with a mean follow-up of 19 years. The mean (SD) overall costs per episode were between £1277 (1724) and £2887 (2492). Total initial costs for the cohort were between £950 842 and £2 336 442, rising to between £1.43 million and £3.02 million at 15 years of follow-up. Estimated cost in 2010 in England alone was between £190 million and £324 million. CONCLUSION: KSD is a costly disease, comparable to the combined cost of prostate and bladder cancer in UK.

A Glaucoma-Specific Brief Motivational Interviewing Training Program for Ophthalmology Para-professionals: Assessment of Feasibility and Initial Patient Impact.

Our objective was to test the feasibility of, fidelity to, and initial impact of a brief, glaucoma-specific motivational interviewing (MI) training program for ophthalmic para-professionals. This prospective, mixed-methods study had two components, one for staff and one for patients. Staff fidelity to MI principles was graded through audio-recorded encounters after initial and final training sessions. After training, patients graded staff for adherence to autonomy supportive care. Semi-structured interviews with para-professionals elicited feedback about the training and about their ability to implement MI in the clinic. The impact on patient satisfaction with staff communication, eye drop instillation self-efficacy, and overall health activation was assessed using a survey pre- and post-training. Para-professionals met two of three program goals for MI skills and improved in their overall scores for MI fidelity. Para-professionals noted lack of time in the clinic as a significant barrier to implementing counseling. Patient satisfaction with staff communication increased after the training (p = 0.04) among patients who rated their staff above the mean for providing autonomy supportive care. The intervention did not improve patients' eye drop instillation self-efficacy or overall health activation. Training para-professional staff in brief, glaucoma-specific MI techniques is feasible and may improve patient satisfaction, though dedicated time in clinic is needed to implement MI counseling into glaucoma practice.

Biomarkers for diagnosis of Wilson's disease.

BACKGROUND: Wilson's disease, first described by Samuel Wilson in 1912, is an autosomal recessive metabolic disorder resulting from mutations in the ATP7B gene. The disease develops as a consequence of copper accumulating in affected tissues. There is no gold standard for the diagnosis of Wilson's disease, which is often delayed due to the non-specific clinical features and the need for a combination of clinical and laboratory tests for diagnosis. This delay may in turn affect clinical outcome and has implications for other family members in terms of diagnosis. The Leipzig criteria were established to help standardise diagnosis and management. However, it should be emphasised that these criteria date from 2003, and many of these have not been formally evaluated; this review examines the evidence behind biochemical testing for Wilson's disease. OBJECTIVES: To determine the diagnostic accuracy of three biochemical tests at specified cut-off levels for Wilson's disease. The index tests covered by this Cochrane Review are caeruloplasmin, 24-hour urinary copper and hepatic copper content. These tests were evaluated in those with suspected Wilson's disease and appropriate controls (either healthy or those with chronic liver disease other than Wilson's). In the absence of a gold standard for diagnosing Wilson's disease, we have used the Leipzig criteria as a clinical reference standard. To investigate whether index tests should be performed in all individuals who have been recommended for testing for Wilson's disease, or whether these tests should be limited to subgroups of individuals. SEARCH METHODS: We identified studies by extensive searching of, e.g. the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, the Web of Science and clinical trial registries (29 May 2019). Date of the most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Inborn Errors of Metabolism Register: 29 May 2019. SELECTION CRITERIA: We included prospective and retrospective cohort studies that assessed the diagnostic accuracy of an index test using the Leipzig criteria as a clinical reference standard for the diagnosis of Wilson's disease. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed and extracted data and assessed the methodological quality of each included study using the QUADAS-2 tool. We had planned to undertake meta-analyses of the sensitivity, specificity at relevant cut-offs for each of the biochemical tests for Wilson's, however, due to differences in the methods used for each biochemical index test, it was not possible to combine the results in meta-analyses and hence these are described narratively. MAIN RESULTS: Eight studies, involving 5699 participants (which included 1009 diagnosed with Wilson's disease) were eligible for inclusion in the review. Three studies involved children only, one adults only and the four remaining studies involved both children and adults. Two evaluated participants with hepatic signs and six with a combination of hepatic and neurological signs and symptoms of Wilson's disease, as well as pre-symptomatic individuals. The studies were of variable methodological quality; with high risk if bias for participant selection and the reference standard used being of greatest methodological concern. Key differences between studies include differences in assay methodology, different cut-off values for diagnostic thresholds, different age and ethnicity groups. Concerns around study design imply that diagnostic accuracy figures may not transfer to populations outside of the relevant study. INDEX TEST: caeruloplasmin Five studies evaluated various thresholds of caeruloplasmin (4281 participants, of which 541 had WD). For caeruloplasmin a cut-off of 0.2 g/L as in the Leipzig criteria achieved a sensitivity of 77.1% to 99%, with variable specificity of 55.9% to 82.8%. Using the cut-off of 0.1 g/L of the Leipzig criteria seemed to lower the sensitivity overall, 65% to 78.9%, while increasing the specificity to 96.6% to 100%. INDEX TEST: hepatic copper Four studies evaluated various thresholds of hepatic copper (1150 participants, of which 367 had WD). The hepatic copper cut-off of 4 µmol/g used in the Leipzig criteria achieved a sensitivity of 65.7% to 94.4%, with a variable specificity of 52.2% to 98.6%. INDEX TEST: 24-hour urinary copper Three studies evaluated various thresholds of 24-hour urinary copper (268 participants, of which 101 had WD). For 24-hour urinary copper, a cut-off of 0.64 to 1.6 µmol/24 hours used in the Leipzig criteria achieved a variable sensitivity of 50.0% to 80.0%, with a specificity of 75.6% to 98.3%. AUTHORS' CONCLUSIONS: The cut-offs used for caeruloplasmin, 24-hour urinary copper and hepatic copper for diagnosing Wilson's disease are method-dependent and require validation in the population in which such index tests are going to be used. Binary cut-offs and use of single-test strategies to rule Wilson's disease in or out is not supported by the evidence in this review. There is insufficient evidence to inform testing in specific subgroups, defined by age, ethnicity or clinical subgroups.

Outcomes and Long-term Follow-up of Patients with Cystine Stones: a Systematic Review.

PURPOSE OF REVIEW: Cystine stone patients can be difficult to manage with frequent recurrences. We performed a systematic review with a view to assessing interventions, compliance and their long-term outcomes. RECENT FINDINGS: Ten retrospective observational studies (253 patients) assessed the outcomes and long-term follow-up of cystine stone patients. The mean length of follow-up was 9.6 years (range 3.5-21.8 years). The overall mean number of surgical procedures/patient was 5.7 (range 2-9.8/patient) with the overall mean number of surgical procedures/patient/year at 0.59 (range 0.22-1.32/patient/year). While open surgery has decreased over the last decade and PCNL has been stable, there seems to be a rise of RIRS during this period. Patients with cystine stones need periodic interventions for stone recurrences despite medical management, with limited data showing the impact on renal function. While the management is individualised, wide variability exists with often poor and incomplete patient data.