A temperature model for laser lithotripsy.

OBJECTIVE: To derive and validate a mathematical model to predict laser-induced temperature changes in a kidney during kidney stone treatment. METHODS: A simplified mathematical model to predict temperature change in the kidney for any given renal volume, irrigation flow rate, irrigation fluid temperature, and laser power was derived. We validated our model with matched in vitro experiments. RESULTS: Excellent agreement between the mathematical model predictions and laboratory data was obtained. CONCLUSION: The model obviates the need for repeated experimental validation. The model predicts scenarios where risk of renal tissue damage is high. With real-time knowledge of flow rate, irrigating fluid temperature and laser usage, safety warning levels could be predicted. Meanwhile, clinicians should be aware of the potential risk from thermal injury and take measures to reduce the risk, such as using room temperature irrigation fluid and judicious laser use.

Developing and testing a principle-based fidelity index for peer support in mental health services.

PURPOSE: Evidence suggests that the distinctive relational qualities of peer support-compared to clinical-patient relationships-can be eroded in regulated healthcare environments. Measurement of fidelity in trials of peer support is lacking. This paper reports the development and testing of a fidelity index for one-to-one peer support in mental health services, designed to assess fidelity to principles that characterise the distinctiveness of peer support. METHODS: A draft index was developed using expert panels of service user researchers and people doing peer support, informed by an evidence-based, peer support principles framework. Two rounds of testing took place in 24 mental health services providing peer support in a range of settings. Fidelity was assessed through interviews with peer workers, their supervisors and people receiving peer support. Responses were tested for spread and internal consistency, independently double rated for inter-rater reliability, with feedback from interviewees and service user researchers used to refine the index. RESULTS: A fidelity index for one-to-one peer support in mental health services was produced with good psychometric properties. Fidelity is assessed in four principle-based domains; building trusting relationships based on shared lived experience; reciprocity and mutuality; leadership, choice and control; building strengths and making connections to community. CONCLUSIONS: The index offers potential to improve the evidence base for peer support in mental health services, enabling future trials to assess fidelity of interventions to peer support principles, and service providers a means of ensuring that peer support retains its distinctive qualities as it is introduced into mental health services.

What is the impact of psychiatric decision units on mental health crisis care pathways? Protocol for an interrupted time series analysis with a synthetic control study.

BACKGROUND: The UK mental health system is stretched to breaking point. Individuals presenting with mental health problems wait longer at the ED than those presenting with physical concerns and finding a bed when needed is difficult - 91% of psychiatric wards are operating at above the recommended occupancy rate. To address the pressure, a new type of facility - psychiatric decision units (also known as mental health decision units) - have been introduced in some areas. These are short-stay facilities, available upon referral, targeted to help individuals who may be able to avoid an inpatient admission or lengthy ED visit. To advance knowledge about the effectiveness of this service for this purpose, we will examine the effect of the service on the mental health crisis care pathway over a 4-year time period; the 2 years proceeding and following the introduction of the service. We use aggregate service level data of key indicators of the performance of this pathway. METHODS: Data from four mental health Trusts in England will be analysed using an interrupted time series (ITS) design with the primary outcomes of the rate of (i) ED psychiatric presentations and (ii) voluntary admissions to mental health wards. This will be supplemented with a synthetic control study with the same primary outcomes, in which a comparable control group is generated for each outcome using a donor pool of suitable National Health Service Trusts in England. The methods are well suited to an evaluation of an intervention at a service delivery level targeting population-level health outcome and the randomisation or 'trialability' of the intervention is limited. The synthetic control study controls for national trends over time, increasing our confidence in the results. The study has been designed and will be carried out with the involvement of service users and carers. DISCUSSION: This will be the first formal evaluation of psychiatric decision units in England. The analysis will provide estimates of the effect of the decision units on a number of important service use indicators, providing much-needed information for those designing service pathways. TRIAL REGISTRATION: primary registry: isrctn.com Identifying number: ISRCTN77588384 Link: Date of registration in primary registry: 27/02/2020. PRIMARY SPONSOR: St George's, University of London, Cramner Road, Tooting, SW17 ORE. Primary contact: Joe Montebello.

[The Confusion Assessment Method: Transcultural adaptation of a French version]. / Adaptation transculturelle francophone de la Confusion Assessment Method.

INTRODUCTION: The Confusion Assessment Method (CAM) is a validated key tool in clinical practice and research programs to diagnose delirium and assess its severity. There is no validated French version of the CAM training manual and coding guide (Inouye SK). The aim of this study was to establish a consensual French version of the CAM and its manual. METHODS: Cross-cultural adaptation to achieve equivalence between the original version and a French adapted version of the CAM manual. RESULTS: A rigorous process was conducted including control of cultural adequacy of the tool's components, double forward and back translations, reconciliation, expert committee review (including bilingual translators with different nationalities, a linguist, highly qualified clinicians, methodologists) and pretesting. A consensual French version of the CAM was achieved. CONCLUSION: Implementation of the CAM French version in daily clinical practice will enable optimal diagnosis of delirium diagnosis and enhance communication between health professionals in French speaking countries. Validity and psychometric properties are being tested in a French multicenter cohort, opening up new perspectives for improved quality of care and research programs in French speaking countries.

Psychological treatments for early psychosis can be beneficial or harmful, depending on the therapeutic alliance: an instrumental variable analysis.

BACKGROUND: The quality of the therapeutic alliance (TA) has been invoked to explain the equal effectiveness of different psychotherapies, but prior research is correlational, and does not address the possibility that individuals who form good alliances may have good outcomes without therapy. METHOD: We evaluated the causal effect of TA using instrumental variable (structural equation) modelling on data from a three-arm, randomized controlled trial of 308 people in an acute first or second episode of a non-affective psychosis. The trial compared cognitive behavioural therapy (CBT) over 6 weeks plus routine care (RC) v. supportive counselling (SC) plus RC v. RC alone. We examined the effect of TA, as measured by the client-rated CALPAS, on the primary trial 18-month outcome of symptom severity (PANSS), which was assessed blind to treatment allocation. RESULTS: Both adjunctive CBT and SC improved 18-month outcomes, compared to RC. We showed that, for both psychological treatments, improving TA improves symptomatic outcome. With a good TA, attending more sessions causes a significantly better outcome on PANSS total score [effect size -2.91, 95% confidence interval (CI) -0.90 to -4.91]. With a poor TA, attending more sessions is detrimental (effect size +7.74, 95% CI +1.03 to +14.45). CONCLUSIONS: This is the first ever demonstration that TA has a causal effect on symptomatic outcome of a psychological treatment, and that poor TA is actively detrimental. These effects may extend to other therapeutic modalities and disorders.

The effect of psychiatric decision unit services on inpatient admissions and mental health presentations in emergency departments: an interrupted time series analysis from two cities and one rural area in England.

AIMS: High-quality evidence is lacking for the impact on healthcare utilisation of short-stay alternatives to psychiatric inpatient services for people experiencing acute and/or complex mental health crises (known in England as psychiatric decision units [PDUs]). We assessed the extent to which changes in psychiatric hospital and emergency department (ED) activity were explained by implementation of PDUs in England using a quasi-experimental approach. METHODS: We conducted an interrupted time series (ITS) analysis of weekly aggregated data pre- and post-PDU implementation in one rural and two urban sites using segmented regression, adjusting for temporal and seasonal trends. Primary outcomes were changes in the number of voluntary inpatient admissions to (acute) adult psychiatric wards and number of ED adult mental health-related attendances in the 24 months post-PDU implementation compared to that in the 24 months pre-PDU implementation. RESULTS: The two PDUs (one urban and one rural) with longer (average) stays and high staff-to-patient ratios observed post-PDU decreases in the pattern of weekly voluntary psychiatric admissions relative to pre-PDU trend (Rural: -0.45%/week, 95% confidence interval [CI] = -0.78%, -0.12%; Urban: -0.49%/week, 95% CI = -0.73%, -0.25%); PDU implementation in each was associated with an estimated 35-38% reduction in total voluntary admissions in the post-PDU period. The (urban) PDU with the highest throughput, lowest staff-to-patient ratio and shortest average stay observed a 20% (-20.4%, CI = -29.7%, -10.0%) level reduction in mental health-related ED attendances post-PDU, although there was little impact on long-term trend. Pooled analyses across sites indicated a significant reduction in the number of voluntary admissions following PDU implementation (-16.6%, 95% CI = -23.9%, -8.5%) but no significant (long-term) trend change (-0.20%/week, 95% CI = -0.74%, 0.34%) and no short- (-2.8%, 95% CI = -19.3%, 17.0%) or long-term (0.08%/week, 95% CI = -0.13, 0.28%) effects on mental health-related ED attendances. Findings were largely unchanged in secondary (ITS) analyses that considered the introduction of other service initiatives in the study period. CONCLUSIONS: The introduction of PDUs was associated with an immediate reduction of voluntary psychiatric inpatient admissions. The extent to which PDUs change long-term trends of voluntary psychiatric admissions or impact on psychiatric presentations at ED may be linked to their configuration. PDUs with a large capacity, short length of stay and low staff-to-patient ratio can positively impact ED mental health presentations, while PDUs with longer length of stay and higher staff-to-patient ratios have potential to reduce voluntary psychiatric admissions over an extended period. Taken as a whole, our analyses suggest that when establishing a PDU, consideration of the primary crisis-care need that underlies the creation of the unit is key.

Direct to consumer genetic testing: a systematic review of position statements, policies and recommendations.

In healthcare settings, genetic tests to determine whether an individual had inherited a genetic mutation are ordered by a health professional, and the results are interpreted and conveyed to the patient by that person. However, direct to consumer genetic testing (DTCGT) has enabled individuals to purchase genetic tests and receive results without the intervention of a health professional. To inform a set of guidelines for consumers and health professionals, we undertook a systematic review of position statements, policies and recommendations on the use of DTCGT. We performed a search of seven databases and the Internet for relevant documents. The search terms were 'direct to consumer' and 'genetic test', and documents in English published from 2002 to 2011 were included. The search retrieved 314 items, of which 14 were eligible for review. Five themes were derived from thematic analysis: motivation for use, potential benefits, potential harms, recommendations to guide consumers and need for research. The authors of these documents described more potential harms than benefits, but, although some stated that direct to consumer testing should be actively discouraged, others supported consumer rights to make autonomous choices. Further research into the impact of direct to consumer testing on health services and consumers is required to inform policies.

Out of the silence: towards grassroots and trauma-informed support for people who have experienced sexual violence and abuse.

To experience sexual violence and abuse is to experience silence. This commentary explores some of the ways in which psychiatry reinforces the silencing of sexual violence survivors. We argue that current psychiatric responses to sexual violence typically constitute iatrogenic harm including through: a failure to provide services that meet survivors' needs, a failure to believe or validate disclosures; experiences of medicalisation and diagnoses which can delegitimise people's own knowledge and meaning; 'power over' relational approaches which can prevent compassionate responses and result in staff having to develop their own coping strategies; and poorly addressed and reported experiences of sexual violence within psychiatric settings. We argue that these multiple forms of silencing have arisen in part because of biomedical dominance, a lack of support and training in sexual violence for staff, inconsistent access to structured, reflective supervision, and the difficulties of facing the horror of sexual violence and abuse. We then describe community-based and grassroots responses, and consider the potential of trauma-informed approaches. Whilst this paper has a UK focus, some aspects will resonate globally, particularly given that Western psychiatry is increasingly being exported around the globe.

Characterization of keratocalmin, a calmodulin-binding protein from human epidermis.

Using affinity-purified calmodulin-binding proteins from human epidermis we have developed a monoclonal IgM antibody, ROC 129.1, to a human desmosomal calcmodulin-binding protein. This antibody reacts with a submembranous 250-kD protein from human keratinocytes and stains human epidermis in a "cell-surface pattern". Permeability studies indicated that the epitope with which this monoclonal reacts is on the inner surface of the cell membrane. Immunoelectronmicroscopy localized the antigen to the desmosome. The epitope is restricted to stratified squamous epithelia and arises between 8-12 wk of fetal development. This desmosomal calmodulin-binding protein, which we have termed keratocalmin, may be involved in the calcium-regulated assembly of desmosomes.

Endothelin- and oxytocin-induced calcium signaling in cultured human myometrial cells.

The demonstration that endothelin (ET) induces rat uterine contraction, coupled with the observation that ET is present in human amniotic fluid, suggests that the myometrium may be an important target organ for this hormone. We show that in quiescent human myometrial cells ET produced a dose-dependent increase in cytosolic free Ca2+ (Cai2+), which was markedly attenuated when the cells were studied in Ca2(+)-free media. Preincubation with nicardipine, diltiazem, or verapamil reduced the ET-evoked Cai2+ transient by 30, 40, and 65%, respectively. The presence of voltage sensitive Ca2+ channels was demonstrated by Mn2+ quenching of fura-2. Activation of the Na+/H+ antiport could not be demonstrated with ET stimulation. In nonquiescent cells, the ET-evoked Cai2+ transient was significantly reduced, while the response to oxytocin was retained. This is at least partially explained by a reduction in Bmax (maximal binding capacity) for ET (mean +/- SEM) from 3,506 +/- 268 binding sites/cell in quiescent cells to 2,411 +/- 300 binding sites/cell, as well as 72% increase in Kd (equilibrium dissociation constant), in the nonquiescent cells. We conclude that, in human myometrial cells, ET and oxytocin modulate Cai2+ through independent receptors and propose that ET, like oxytocin, is an important endogenous modulator of uterine contractility.

An association of lower serum citrulline levels within 30 days of acute rejection in patients following small intestine transplantation.

INTRODUCTION: In a prospective protocol we studied whether serum citrulline level within 30 days of an acute rejection was predictive of the episode. METHODS: An acute rejection episode was defined as the date of occurrence of any biopsy-proven rejection in which treatment was initiated until two successive biopsies showed no further rejection. We compared the mean citrulline level based on values determined within 30 days of the start of an acute rejection episode with the mean citrulline level measured on the same patient during a rejection-free period. Serum citrulline measurements were available immediately prior to the occurrence of rejection for 22 patients who experienced 37 episodes. RESULTS: For the 12 episodes of mild rejection, the mean serum citrulline level +/- SE (standard error) was 15.0 + 2.3 micromol/L prior to rejection and 18.8 +/- 2.4 micromol/L during the rejection-free periods. A paired t test of the mean differences was not significant (P = 17). For the 25 episodes of moderate or severe rejection, the mean serum citrulline level was 12.4 +/- 1.1 micromol/L before rejection and 18.8 +/- 2.0 micromol/L during the rejection-free periods. A paired t test of the mean difference was statistically significant (P = .002). CONCLUSIONS: Although further study of citrulline as a marker for the early detection of acute rejection episodes is needed, our hope is that its use will help to prevent some of these early episodes from evolving into full-blown moderate or severe grades of rejection.

Modulation of epidermal growth factor receptors by retinoic acid in ME180 cells.

Retinoic acid (RA) increases epidermal growth factor (EGF) receptors in many cells; in ME180 cells, a human epidermoid carcinoma, RA resulted in a dose- and time-dependent reduction of EGF binding. In RA-treated ME180 cells, binding was 41% of the control. The reduction of EGF binding was due to a decrease in the number of receptors, from 8.7 x 10(4) to 3.6 x 10(4) per cell. The difference was present 8 h after the addition of RA and was reversible 3 days after its removal. Scatchard analysis indicated that RA did not change the binding affinity of EGF (Kd = 1 nM). Also, RA did not alter the rate of EGF internalization or the down-regulation induced by exogenous EGF. Flow-cytometric analysis revealed that RA did not alter the cell cycle. Soluble cell membrane extracts were prepared in a Tris buffer with protease inhibitors, immunoprecipitated, electrophoresed, and immunoblotted with an antiserum to EGF receptors. The EGF receptor band of Mr 170,000 was decreased in RA-treated cells. These results suggest that RA reduces the synthesis of EGF receptors in ME180 cells.

Endogenous substrates for epidermal transglutaminase.

Potential in vivo substrates for epidermal transglutaminase have been isolated and partially characterized in human stratum corneum and new born rat epidermis. [14C]Putrescine and dansylcadaverine were incorporated into epidermal proteins in vitro. Two high molecular weight proteins incorporated the labels in both the rat ahd human homogenates. One of the proteins was too large to enter a 4% sodium dodecyl sulfate-polyacrylamide spacer gel; the other was seen at the interface between the spacer gel and a 10% sodium dodecyl sulphate-polyacrylamide running gel. These proteins were present in a buffer extract, sodium dodecyl sulphate-dithiothreitol extract and NaOH extract. The labels were also incorporated into protein in the insoluble pellet remaining after the afore-mentioned extractions. The incorporation of putrescine and dansylcadaverine was time dependent, and was inhibited by known inhibitors of epidermal transglutaminase. The two high molecular weight proteins had similar amino acid composition, characterized by high glycine, glutamic acid, serine and aspartic acid. The amino acid composition was similar to, although not identical with, the amino acid composition of alpha-keratin proteins. Epidermal homogenates incubated in the presence of transglutaminase showed progressive insolubilization of the protein. This cross-linking was inhibited by putrescine. [14C]Glycine, [14C]histidine and [4C]proline were incorporated into epidermal proteins in newborn rats in vivo. The glycine-labelled protein became progressively more insoluble when incubated in vitro in the presence of transglutaminase. In vitro incubation with transglutaminase had no effect on the histidine-and proline-labelled proteins.

Skin sulfhydryl oxidase. Purification and some properties.

A sulfhydryl-oxidizing enzyme has been found in skin of young rats and a method for purifying the enzyme over 600-fold has been developed. Enzymatic activity was assayed either by its ability to oxidize dithiothreitol of by measuring its ability to renature reductively denatured ribonuclease A. Skin sulfhydryl oxidase catalyzed the oxidation of various thiols: dithiothreitol, dithioerythritol, D-penicillamine, and L-cysteine. Glutathione and 2-mercaptoethanol were very poor substrates for the enzyme. The enzyme also reactivated reductively denatured ribonuclease A, with neither the presence of a thiol nor prior reduction of the enzyme being necessary. The molecular weight of the enzyme was estimated to be 66 000 +/- 2000, and the isoelectric point was determined to be at pH 4.65. Alkylating reagents alone had some inhibiting effect on skin sulfhydryl oxidase; when the enzyme was preincubated with thiols which were substrates, inhibition by alkylating reagents was greatly increased. After preincubation with dithiothreitol, treatment of the enzyme with alkylating reagents or N-ethylmaleimide caused significant inhibition; preincubation with a poor substrate, reduced glutathione, did not enhance inhibition by alkylating reagents or N-ethylmaleimide.

The polypeptide composition of epidermal prekeratin.

An alpha-fibrous protein, prekeratin, has been isolated from cow snout epidermis with citrate buffer, pH 2.65. Using acrylamide electrophoresis with 0.1% sodium dodecyl sulfate, prekeratin can be shown to contain three polypeptide chains of different molecular weights. The two faster migrating components are very similar with a mol. wt of about 47,000 while the slower one has a mol. wt of about 58,000. Chromatography on a number of molecular sieve and exchange resins does not separate the components, but use of Sepharose 2B with 0.1 M Tris, pH 9.0, containing 10% propanol gives two peaks of protein. The first and major peak contains all three components while the second has only the two with the faster mobility. The two more rapidly migrating components and the slower one were isolated by acrylamide electrophoresis, and the latter has an amino acid composition more compatible with a non-helical protein. Enzymatic digestion with tosyl-L-phenylalanine chloromethylketone-treated (TPCK-)trypsin shows that the component of mol. wt 58,000 is more susceptible to hydrolysis than the other two. These data suggest that prekeratin is not homogenous in composition and consists of several interacting polypeptide chains. One of these components would appear to be non-helical in structure.

Computer-assisted cognitive therapy for depression: maintaining efficacy while reducing therapist time.

OBJECTIVE: The aim of this investigation was to compare the efficacy of computer-assisted cognitive therapy against standard cognitive therapy and a control group without treatment for outpatients with nonpsychotic major depressive disorder. METHOD: Medication-free participants (N=45) with major depressive disorder were randomly assigned to cognitive therapy (N=15), computer-assisted cognitive therapy (N=15), or a wait list (N=15). Both active treatments consisted of nine sessions over 8 weeks. Therapist time was reduced after the first visit for computer-assisted cognitive therapy, with 25-minute sessions rather than 50-minute sessions. Assessments were completed pretreatment, after 4 and 8 weeks of therapy, and 3 and 6 months posttreatment. RESULTS: Computer-assisted cognitive therapy and standard cognitive therapy were superior to the wait list control group for treatment of depression and did not differ from each other on the primary outcome variables. Very large between-group effect sizes were observed. Improvement in depression for both computer-assisted cognitive therapy and standard cognitive therapy was maintained at the 3- and 6-month follow-up evaluations. Computer-assisted cognitive therapy had more robust effects, relative to being wait-listed, than standard cognitive therapy in reducing measures of cognitive distortion and in improving knowledge about cognitive therapy. CONCLUSIONS: A multimedia, computer-assisted form of cognitive therapy with reduced therapist contact was as efficacious as standard cognitive therapy. Computer-assisted therapy could decrease costs and improve access to cognitive therapy for depression.