Assertive outreach treatment versus care as usual for the treatment of high-need, high-cost alcohol related frequent attenders: study protocol for a randomised controlled trial.

BACKGROUND: Alcohol-related hospital admissions have doubled in the last ten years to > 1.2 m per year in England. High-need, high-cost (HNHC) alcohol-related frequent attenders (ARFA) are a relatively small subgroup of patients, having multiple admissions or attendances from alcohol during a short time period. This trial aims to test the effectiveness of an assertive outreach treatment (AOT) approach in improving clinical outcomes for ARFA, and reducing resource use in the acute setting. METHODS: One hundred and sixty ARFA patients will be recruited and following baseline assessment, randomly assigned to AOT plus care as usual (CAU) or CAU alone in equal numbers. Baseline assessment includes alcohol consumption and related problems, physical and mental health comorbidity and health and social care service use in the previous 6 months using standard validated tools, plus a measure of resource use. Follow-up assessments at 6 and 12 months after randomization includes the same tools as baseline plus standard measure of patient satisfaction. Outcomes for CAU + AOT and CAU at 6 and 12 months will be compared, controlling for pre-specified baseline measures. Primary outcome will be percentage of days abstinent at 12 months. Secondary outcomes include emergency department (ED) attendance, number and length of hospital admissions, alcohol consumption, alcohol-related problems, other health service use, mental and physical comorbidity 6 and 12 months post intervention. Health economic analysis will estimate the economic impact of AOT from health, social care and societal perspectives and explore cost-effectiveness in terms of quality adjusted life years and alcohol consumption at 12-month follow-up. DISCUSSION: AOT models piloted with alcohol dependent patients have demonstrated significant reductions in alcohol consumption and use of unplanned National Health Service (NHS) care, with increased engagement with alcohol treatment services, compared with patients receiving CAU. While AOT interventions are costlier per case than current standard care in the UK, the rationale for targeting HNHC ARFAs is because of their disproportionate contribution to overall alcohol burden on the NHS. No previous studies have evaluated the clinical and cost-effectiveness of AOT for HNHC ARFAs: this randomized controlled trial (RCT) targeting ARFAs across five South London NHS Trusts is the first. TRIAL REGISTRATION: International standard randomized controlled trial number (ISRCTN) registry: ISRCTN67000214, retrospectively registered 26/11/2016.

Inter-comparison of radon detectors for one to four week measurement periods.

Seven different types of radon detectors (Atmos 12 dpx, RAD7, RStone, Sun Nuclear 1028, Ramon 2.2, Canary and CR-39) were compared for exposure periods of 1, 2, 3 and 4 weeks. The comparison was conducted under two conditions: (a) in a purpose-built radon chamber with an average radon concentration of 2560 Bq m(-3) (b) in a home environment with a radon concentration of 57 Bq m(-3), in both cases measured by the reference detector (Atmos 12 dpx) with a ±10% uncertainty range. In (a) 5 out of 8 detectors recorded radon concentrations within the Atmos uncertainty range and all detectors recorded within ±15%; in (b) 3 out of 9 detectors recorded within the Atmos uncertainty range and 6 out of 9 measured within ±20%, for a 4 week measurement. The results from this study show that radon surveys can be conducted for shorter periods than the recommended 3 months where a rapid indication is needed of whether the radon concentration is above the reference level, such as when assessing the concentration during and after remediation work.

An outdoor radon survey and minimizing the uncertainties in low level measurements using CR-39 detectors.

Long term outdoor radon measurements were recorded in Ireland using CR-39 track etch detectors. A measurement protocol was designed for this study, which was optimized for the relatively low radon concentrations expected outdoors. This protocol included pre-etching the detectors before exposure to allow radon tracks to be more easily distinguished from background. The average outdoor radon concentration for the Republic of Ireland was found to be 5.6 ± 0.7 Bq m(-3). A statistically significant difference between inland and coastal radon concentrations was evident but no difference between mean radon concentrations on the east coast and those on the west coast was observed.

Linking data on women in public family law court proceedings concerning their children to mental health service records in South London.

INTRODUCTION: Maternal mental health problems and substance misuse are key risk factors for child neglect or abuse and court-mandated placement into care. Linkage between mental health records and family court data could raise awareness about parent mental health needs and inform approaches to address them. OBJECTIVES: To evaluate data linkage between administrative family court data and electronic mental health records for a population-based mental health service for 1.3 million people in South London. METHODS: We deterministically linked administrative family court data for women (n=5463) involved in care proceedings in South London with service user records from the South London and Maudsley NHS Mental Health Trust (SLaM). We restricted the cohort to women involved in proceedings between 2007 and 2019, in local authorities where SLaM solely provides secondary/tertiary mental health services and the Improving Access to Psychological Therapies (IAPT) (n=3226). We analysed the associations between match status and sociodemographic/case characteristics using multivariable logistic regression. RESULTS: Two-thirds (2317/3226; 66%) of women linked to a SLaM service user record at some point; most (91%) who linked accessed secondary/tertiary mental health services, indicating serious mental illness. Accounting for possible missed matches, we estimated that 70-83% of women accessed SLaM services at some point. Older women at index proceedings (>35yrs OR: 0.69, 95%CI: 0.54-0.88vs <25yrs) and Black women or women from other ethnic groups (Black ethnic groups 0.65, 0.50-0.83; other ethnicity 0.59, 0.43-0.81 vs White ethnic groups) had lower odds of linking. Odds of linking were higher for women with an infant in proceedings (1.42, 1.18-1.71), or with curtailed/terminated parental responsibility (1.44, 1.20-1.73). CONCLUSION: Our linkage supports growing evidence of a high burden of mental health problems and substance misuse among women whose children enter care in England, compared to the general population. Research using this linkage should inform strategies to address the considerable mental health needs of vulnerable women and their children.

Mobile telephone delivered contingency management for encouraging adherence to supervised methadone consumption: feasibility study for an RCT of clinical and cost-effectiveness (TIES).

BACKGROUND: Prescription methadone or buprenorphine enables people with opioid use disorder to stop heroin use safely while avoiding withdrawal. To ensure methadone is taken as prescribed and to prevent diversion onto the illicit market, people starting methadone take their daily dose under a pharmacist's supervision. Many patients miss their daily methadone dose risking withdrawal, craving for heroin and overdose due to loss of heroin tolerance. Contingency management (CM) can improve medication adherence, but remote delivery using technology may be resource-light and cost-effective. We developed an innovative way to deliver CM by mobile telephone. Software monitors patients' attendance and supervised methadone consumption through an internet self-login at the pharmacy and sends reinforcing text messages to patients' mobile telephones. A linked system sends medication adherence reports to prescribers and provides early warning alerts of missed doses. A pre-paid debit card system provides financial incentives. METHODS: A cluster randomised controlled trial design was used to test the feasibility of conducting a future trial of mobile telephone CM to encourage adherence to supervised methadone in community pharmacies. Each cluster (drug service/3 allied pharmacies) was randomly allocated to provide patient's presenting for a new episode of opiate agonist treatment (OAT) with either (a) mobile telephone text message CM, (b) mobile telephone text message reminders, or (c) no text messages. We assessed acceptability of the interventions, recruitment, and follow-up procedures. RESULTS: Four drug clinics were approached and three recruited. Thirty-three pharmacists were approached and 9 recruited. Over 3 months, 173 individuals were screened and 10 enrolled. Few patients presented for OAT and high numbers were excluded due to receiving buprenorphine or not attending participating pharmacies. There was 96% consistency in recording medication adherence by self-login vs. pharmacy records. In focus groups, CM participants were positive about using self-login, the text messages, and debit card. Prescribers found weekly reporting, time saving, and allowed closer monitoring of patients. Pharmacists reported that the tablet device was easy to host. CONCLUSION: Mobile telephone CM worked well, but a planned future trial will use modified eligibility criteria (existing OAT patients who regularly miss their methadone/buprenorphine doses) and increase the number of participating pharmacies. TRIAL REGISTRATION: The trial is retrospectively registered, ISRCTN 58958179 .

Microwave hearing: evidence for thermoacoustic auditory stimulation by pulsed microwaves.

Acoustic transients can be thermally generated in water by pulsed microwave energy. The peak pressure level of these transients, measured within the audible frequency band as a function of the microwave pulse parameters, is adequate to explain the "clicks" heard by people exposed to microwave radiation.

Low frequency electric field induced changes in the shape and motility of amoebas.

Perpendicular and parallel elongation of the giant amoeba, Chaos chaos (Chaos carolinensis), have been observed in alternating electric fields over a wide frequency range (from about 1 hertz to about 10 megahertz). The characteristics change as a function of frequency. Simple dielectric forces may be important in the production of these effects.

Calcium as a coagonist of inositol 1,4,5-trisphosphate-induced calcium release.

Inositol 1,4,5-trisphosphate (IP3)-induced calcium release from intracellular stores is a regulator of cytosolic-free calcium levels. The subsecond kinetics and regulation of IP3-induced calcium-45 release from synaptosome-derived microsomal vesicles were resolved by rapid superfusion. Extravesicular calcium acted as a coagonist, potentiating the transient IP3-induced release of calcium-45. Thus, rapid elevation of cytosolic calcium levels may trigger IP3-induced calcium release in vivo. Extravesicular calcium also produced a more slowly developing, reversible inhibition of IP3-induced calcium-45 release. Sequential positive and negative feedback regulation by calcium of IP3-induced calcium release may contribute to transients and oscillations of cytosolic-free calcium in vivo.

Expression of the Alzheimer amyloid precursor gene transcripts in the human brain.

An alternate form of the Alzheimer amyloid protein precursor mRNA that encodes a protease inhibitor domain has recently been reported. Oligonucleotide probes that differentiate between the two mRNAs are used to describe the expression of each amyloid precursor transcript in the human brain. RNA blot analyses show that one of the mRNAs is expressed selectively in the nervous system, that the two messages display different regional distributions in the adult human brain, and that the expression of the two mRNAs is differentially affected in Down's syndrome brain and in Alzheimer's disease frontal cortex. In situ hybridization shows that the two transcripts display the same laminar distribution in the adult cortex but that the transcripts differ significantly in their levels of expression in pyramidal cells of the hippocampus.

Local calcium release in dendritic spines required for long-term synaptic depression.

We have used rats and mice with mutations in myosin-Va to evaluate the range and function of IP3-mediated Ca2+ signaling in dendritic spines. In these mutants, the endoplasmic reticulum and its attendant IP3 receptors do not enter the postsynaptic spines of parallel fiber synapses on cerebellar Purkinje cells. Long-term synaptic depression (LTD) is absent at the parallel fiber synapses of the mutants, even though the structure and function of these synapses otherwise appear normal. This loss of LTD is associated with selective changes in IP3-mediated Ca2+ signaling in spines and can be rescued by photolysis of a caged Ca2+ compound. Our results reveal that IP3 must release Ca2+ locally in the dendritic spines to produce LTD and indicate that one function of dendritic spines is to target IP3-mediated Ca2+ release to the proper subcellular domain.

Positive reinforcement targeting abstinence in substance misuse (PRAISe): Study protocol for a Cluster RCT & process evaluation of contingency management.

There are approximately 256,000 heroin and other opiate users in England of whom 155,000 are in treatment for heroin (or opiate) addiction. The majority of people in treatment receive opiate substitution treatment (OST) (methadone and buprenorphine). However, OST suffers from high attrition and persistent heroin use even whilst in treatment. Contingency management (CM) is a psychological intervention based on the principles of operant conditioning. It is delivered as an adjunct to existing evidence based treatments to amplify patient benefit and involves the systematic application of positive reinforcement (financial or material incentives) to promote behaviours consistent with treatment goals. With an international evidence base for CM, NICE recommended that CM be implemented in UK drug treatment settings alongside OST to target attendance and the reduction of illicit drug use. While there was a growing evidence base for CM, there had been no examination of its delivery in UK NHS addiction services. The PRAISe trial evaluates the feasibility, acceptability, clinical and cost effectiveness of CM in UK addiction services. It is a cluster randomised controlled effectiveness trial of CM (praise and financial incentives) targeted at either abstinence from opiates or attendance at treatment sessions versus no CM among individuals receiving OST. The trial includes an economic evaluation which explores the relative costs and cost effectiveness of the two CM intervention strategies compared to TAU and an embedded process evaluation to identify contextual factors and causal mechanisms associated with variations in outcome. This study will inform UK drug treatment policy and practice. Trial registration ISRCTN 01591254.

Mobility of water bound to biological membranes. A proton NMR relaxation study.

Water proton nuclear magnetic resonance relaxation measurements have been obtained for aqueous suspensions of red cell membranes. These data support a model in which water molecules are exchanging rapidly between a bound phase with restricted motions and a free phase with dynamic properties similar to liquid water. From this model and these data, estimates are obtained for the relaxation time for bound phase water. Possible relaxation mechanisms for bound phase water are discussed and some support is found for an intermolecular interaction modulated by translational motions characterized by a diffusion constant of 10(-9) cm2/s.

Use of circumferential tangential cryostat sections of the intestine in the diagnosis of Hirschsprung's disease.

Technical and staining methods are described for making tangential sections using a specially prepared chuck surface in a cryostat. The method gives a rapid definitive diagnosis of Hirschsprung's disease in children.

Ultrastructural changes in the rabbit lens induced by microwave radiation.

Rabbits were irradiated with 2450-MHz continuous microwave energy. Effects of the radiation on the ocular lens were assessed by slit-lamp biomicroscopic examination of the eye. Two lenses were selected for electron microscopy, one that was severely damaged and one that appeared unaffected by the radiation. There were prominent ultrastructural changes in both lenses.

Ascorbic acid changes in cultured rabbit lenses after microwave irradiation.

Whole body exposure of rabbits to microwave radiation causes a decrease in ascorbic acid in the lens. In our study, rabbit lenses maintained in culture medium (37 degrees C) were exposed to either pulsed or continuous wave S-band radiation for 10-15 min at power densities between 0 and 200 mW/cm-2. Total ascorbic acid was measured in selected lenses 1-3 days after irradiation. The temperature of the culture medium was measured during irradiation. Matched control lenses were exposed to similar time-temperature environments, but without microwave irradiation. Ascorbic acid decreased significantly in lenses exposed to microwave radiation. No differences were found, however, between irradiated and control lenses subjected to identical time-temperature conditions. At a given average power density, the time-temperature variation was independent of modulation. A decrease in ascorbic acid is apparently a direct thermal effect of microwave radiation in rabbit lens culture.

Randomized trial of supervised injectable versus oral methadone maintenance: report of feasibility and 6-month outcome.

AIM: To assess the feasibility of a randomized clinical trial of supervised injectable versus oral methadone maintenance and to assess medium-term treatment outcomes. DESIGN: Randomized clinical trial of supervised injectable versus supervised oral methadone maintenance treatment (MMT). Trial participants were dependent illicit opiate injectors allocated at intake to supervised injectable or oral methadone maintenance treatment. SETTING: Specialist addictions treatment centre in South London. SUBJECTS: Forty dependent illicit opiate injectors seeking methadone maintenance treatment. INTERVENTIONS: Daily supervised injectable and oral methadone maintenance, delivered at the treatment centre. MAIN OUTCOME MEASURES: Frequency of illicit heroin use and frequency of illicit drug injecting during 30 days before intake to treatment and prior to 6-month follow-up. SECONDARY OUTCOME MEASURES: frequency of use of illicit methadone, crack cocaine, benzodiazepines and alcohol, physical and psychological health symptoms and acquisitive crime. RESULTS: Injectable and oral MMT were both generally acceptable to the study participants: there was a high level of agreement to enter the randomized trial, and subsequent retention in treatment was good. The average number of days of illicit heroin use reduced from 22.2 to 7.6 for the injectable MMT group and from 22.4 to 8.7 for the oral MMT group. The average number of days of illicit injecting reduced from 25.7 to 10.8 days for the injectable group and from 20.1 to 11.9 days for the oral group. Patients' physical and psychological health symptoms and involvement in acquisitive crime also reduced in both groups. Treatment satisfaction ratings at follow-up were higher among patients in the injectable MMT group. The ratio for the actual medication costs between injectable and oral MMT was 6.8:1, and for the direct operational costs was 4.7:1. There was some evidence of a differential patient response with greater reductions in heroin use occurring among patients who were daily illicit injectors and had poorer psychological and physical health (at entry) who were allocated to injectable MMT. CONCLUSIONS: Conduct of the trial has demonstrated that it is feasible to implement supervised injectable methadone maintenance treatment in the context of (although separate from) a specialist oral methadone maintenance service. Patients assigned to receive either supervised injectable or oral MMT had broadly equivalent, positive during-treatment outcomes at 6-month follow-up. Future studies should seek to identify patient characteristics which are linked to good outcome in injectable MMT. Practical evidence-based guidance to physicians about determining which patients are more suitable for injectable MMT is urgently needed.

Sensitivity of Sickness Impact Profile items to measure change over time in a low-back pain patient group.

The purpose of this study was to identify Sickness Impact Profile (SIP) items that are most sensitive to change in patients with low-back pain. Seventy-six patients with low-back pain were administered the SIP at their initial visit and after discharge from physiotherapy treatment. A formal item reduction was performed to identify the most sensitive items. An item was considered sensitive if it showed change in 20% of the patients and had an item-corrected total SIP score correlation greater than 0.30. Twenty items were identified. Seven of the 20 items identified in this study appear on the Roland-Morris disability questionnaire. Also, only 50% of the items identified are from the physical subscale of the SIP.

Excessive alcohol consumption and drinking expectations among clients in methadone maintenance.

Excessive alcohol consumption and related problems are common among clients in methadone maintenance treatment (MMT), yet relatively little is known about the psychological and social determinants of alcohol-related attitudes and behaviors during treatment. This study reports on the prevalence of alcohol dependence, patterns of alcohol consumption and preliminary findings about clients' beliefs that they will change their drinking behavior in the future. Data were gathered from personal interviews with 66 clients attending a MMT program in South London (some 80.5% of the eligible caseload). Forty-one percent of the overall sample met DSM-IV criteria for alcohol dependence in the past 12 months. Among clients who reported drinking in the past month (n = 50), 54% were classified as dependent, and these clients reported consuming an average of 23.5 UK standard units of absolute alcohol (188g/6.58 ounces) on a typical drinking day in the past month. Exploratory analyses suggested that expectations to change drinking behavior were predicted by subjective norms (social pressures), perceived functions of alcohol use, past drinking levels and current dose of methadone. Clinicians engaged in alcohol problems assessment and counseling during MMT could usefully examine these influences to strengthen treatment provision.

Physical impairments and functional limitations: a comparison of individuals 1 year after total knee arthroplasty with control subjects.

BACKGROUND AND PURPOSE: The purpose of this study was to examine the physical impairments and functional limitations of individuals with total knee arthroplasty (TKA), as compared with individuals with no diagnosed knee disease (control subjects). SUBJECTS: Twenty-nine individuals 1 year following TKA (13 women, 16 men) and 40 age- and gender-matched control subjects (18 women, 22 men) were assessed. METHODS: Walking speed, stair-climbing ability, knee torque (in newton-meters), and total work performed during 15 repeated contractions were evaluated. RESULTS: Walking speeds for men with TKA were 13% and 17% slower at normal and fast speeds, respectively. Their stair-climbing ability was even more compromised (51% slower). Walking speeds for women with TKA were 17% and 18% slower at normal and fast speeds, respectively. Similarly, their stair-climbing time was more compromised (43% slower). Men with TKA were 37% to 39% weaker and performed 36% to 37% less total work of their knee extensors compared with the control subjects. Similarly, women with TKA had knee extensor strength deficits of 28% to 29% and performed 24% less total work. CONCLUSION AND DISCUSSION: One year after TKA, marked physical impairments and functional limitations persisted. [Walsh M, Woodhouse LJ, Thomas SG, Finch E. Physical impairments and functional limitations: a comparison of individuals 1 year after total knee arthroplasty with control subjects.