The Effectiveness of Preventative Interventions to Reduce Mental Health Problems in at-risk Children and Young People: A Systematic Review of Reviews.

Mental health problems are the leading cause of childhood disability worldwide, resulting in poor outcomes for children and young people that persist into adulthood. It is essential that those young people most at risk of developing mental health problems receive effective preventative interventions. Whilst there have been a number of systematic reviews which have examined the effectiveness of secondary prevention interventions for specific groups of children and young people, or to address identified mental health concerns, no review has engaged with the breadth of this literature. We conducted a systematic review of systematic reviews to map this complex field of secondary preventative interventions and identify effective interventions to prevent mental health problems in children and adolescents aged 3-17 years. The review protocol was registered on PROSPERO. We searched five electronic databases from inception to February 2023. The certainty of the evidence was appraised using the AMSTAR 2. We included 49 unique systematic reviews each including between 2 and 249 (mean 34) unique studies; the majority of which were reviews which included only or mostly randomised controlled trials (70%). The reviews examined selective interventions (defined as interventions which are delivered to sub-group populations of young people at increased risk of mental health problems) (n = 22), indicated interventions (defined as interventions which target young people who are found to have pre-clinical symptoms) (n = 15) or a synthesis of both (n = 12). The certainty of the evidence in the reviews was rated as high, (n = 12) moderate (n = 5), low (n = 9) and critically low (n = 23). We found evidence to support both selective and indicated interventions in a range of populations and settings, with most of this evidence available for children and young people in their mid-years (6-10 years) and early adolescence (11-13 years). There was a large body of evidence suggesting that resilience enhancing, cognitive behaviour therapy-based and psychoeducational interventions for children who experience adversity, or those with subclinical externalising problems may offer promise. Early selective interventions for a subpopulation of children and young people who have experienced adversity which combines risk reduction and resilience enhancing approaches directed at children and their families may be effective at reducing mental health problems.

Practitioner perspectives on the nature, causes and the impact of poor mental health and emotional wellbeing on children and young people in contact with children's social care: A qualitative study.

BACKGROUND: Children and young people (CYP) who are in contact with social care are at higher risk of developing mental health difficulties compared to the general population. This has been attributed to their experience of significant childhood adversity. With an increased likelihood of experiencing poorer health outcomes which can persist into adulthood, it is crucial that key factors for their positive mental health development are identified. OBJECTIVE: To identify factors associated with the poor mental health of CYP in contact with social care from the perspective of practitioners working in children's social care and mental health. PARTICIPANTS AND SETTING: Social care and mental health practitioners; three Local Authorities across the North-East of England. METHODS: Four focus groups were conducted with 23 practitioners between April and May 2022. A semi-structured topic guide exploring the nature and associated factors of mental health was used to focus discussion. Data were thematically analysed and informed by the four levels of the socio-ecological model. RESULTS: Individual level risk factors were associated with the CYP's emotional health and included what practitioners described as the 'sense of shame'. Interpersonal level risk factors were most recurrent and included parental factors within the home environment. Community level risk factors consisted of characteristics of settings and institutions that increased the risk of the CYP developing mental health and wellbeing difficulties. Societal level risk factors included broader societal factors such as poverty. Practitioners maintained that certain protective factors possessed or developed by CYP including secure attachments, prevent the development of mental health difficulties. CONCLUSIONS: Our current study provides strong evidence for the interlinkage between multiple levels of risk and their interacting impact on the CYP's mental health and emotional wellbeing. It is imperative that this, and the need to strengthen protective factors, whilst reducing risks are carefully considered for the development of effective support interventions for CYP in contact with social care.

A realist approach to understanding alliancing within Local Government public health and social care service provision.

BACKGROUND: Within the current context of continued austerity and post-pandemic recovery, it remains important that Local Government services address the increasing needs of residents as cost-effectively as possible. Alliancing, whereby services work collaboratively focusing on the 'whole-system', has gained popularity as a tool with the potential to support collaborative whole systems approaches. This synthesis aims to identify how alliancing can be successfully operationalised in the commissioning of public health, wider National Health Service (NHS) and social care-related services. METHODS: A realist literature synthesis was undertaken in order to identify underlying generative mechanisms associated with alliancing, the contextual conditions surrounding the implementation and operationalisation of the alliancing approach mechanisms, and the outcomes produced as a result. An iterative approach was taken, using a recent systematic review of the effectiveness of Alliancing, online database searches, and grey literature searches. RESULTS: Three mechanistic components were identified within the data as being core to the successful implementation of alliances in public health and social care-related services within Local Government: (i) Achieving a system-level approach; (ii) placing local populations at the heart of the system; and (iii) creating a cultural shift. Programme theories were postulated within these components. CONCLUSIONS: The alliancing approach offers an opportunity to achieve system-level change with the potential to benefit local populations. The realist synthesis approach taken within this study has provided insights into the necessary contextual and mechanistic factors of the Alliancing approach, above and beyond effectiveness outcomes typically collected through more conventional evaluation methodologies.

Preferences for Delivering Brief Alcohol Intervention to Risky Drinking Parents in Children's Social Care: A Discrete Choice Experiment.

AIMS: Many parents in contact with children's social care services misuse alcohol however do not meet the threshold for specialist alcohol treatment, and typically do not receive appropriate support for their needs. Brief alcohol interventions have been found to be effective in healthcare settings, however, it is unknown whether the brief intervention structure delivered within health settings would transfer well into children's social care. This paper aims to examine the characteristics of brief intervention for alcohol misusing parents which social care practitioners consider to be important and acceptable to implement in this sector. METHODS: We assessed preferences for, and acceptability of, brief alcohol intervention with parents in contact with children's social care using a discrete choice experiment. We recruited 205 children's social care practitioners from London and the North East of England. Data were analysed using mixed logit which accounted for repeated responses. FINDINGS: Six attributes showed statistically significant coefficients, suggesting that a brief intervention with these attributes would encourage implementation. These were: level of alcohol-related risk targeted; intervention recipient; timing of intervention; duration of sessions; number of sessions and intervention structure. The attribute of most importance identified based on the attribute with the largest coefficient in the conditional logit model was risk level. CONCLUSIONS: Brief alcohol interventions delivered to parents in social care should focus on the impact upon children and the wider family, they should be a flexible part of on-going casework and should be more intensive and less structured.

FAB: First UK feasibility trial of a future randomised controlled trial of Family focused treatment for Adolescents with Bipolar disorder.

BACKGROUND: This first mixed-methods UK trial examined the feasibility and acceptability of a future definitive randomised controlled trial (RCT) to evaluate whether Family Focussed Treatment for Adolescents with Bipolar Disorder (FFT-A) UK version can improve family functioning and well-being as part of the management of Paediatric Bipolar Disorder (PBD). METHOD: The trial used a randomised, parallel group, non-blinded design where participants received FFT-A UK (16 sessions over 6 months) immediately or after 12 months (delayed arm). Measures of family functioning, well-being and quality of life of the young person and the main carer (most commonly a parent) were completed at baseline, 6 and 12-months in both arms. Primary outcome measures included rates of eligibility, consent and retention along with estimates of variability in the measures and assessment of the intervention delivery. Qualitative interviews allowed assessment of participants' views about FFT-A and the trial processes. RESULTS: Twenty-seven of 36 young persons with PBD and their families consented; of these, 14 families were randomised to the immediate and 13 to the delayed arm. Two families from the immediate arm withdrew consent and discontinued participation. Quantitative measures were completed by 22 families (88%) at 6-months and 21 families (84%) at 12-months. Qualitative interviews were conducted with 30 participants (9 young people, 15 parents and 6 other family members). Nine families attended 3 post-trial focus groups. CONCLUSION: It was feasible to recruit and retain to this trial. The results highlighted that trial design and measures were acceptable to participants. A benefit in family relationships was reported by participants which they attributed to the intervention in qualitative interviews. Families recommended that future modifications include definitive trial(s) recruiting participants in the age range 15-25 years as it felt this was the age range with maximum need. Trial registration ISRCTN, ISRCTN59769322. Registered 20 January 2014, http://www.isrctn.com/ISRCTN59769322.

A qualitative account of young people's experiences of alcohol screening and brief interventions in schools: SIPS Jr-HIGH trial findings.

BACKGROUND: The United Kingdom (UK) has seen a decrease in the number of young people drinking alcohol. However, the UK prevalence of underage drinking still ranks amongst the highest in Western Europe. Whilst there is a wealth of evidence reporting on the effectiveness of both primary, and secondary interventions, there are few reports of the experiences of young people who receive them. METHODS: The present study reports findings from interviews with 33 young people who were involved in an alcohol screening and brief intervention randomized controlled trial in schools in England. All interviews were analysed using inductive applied thematic analysis. RESULTS: Three major themes were identified following the analysis process: 1) drinking identities and awareness of risk; 2) access to support and advice in relation to alcohol use; and 3) appraisal of the intervention and potential impact on alcohol use. CONCLUSIONS: There appeared to be a reluctance from participants to describe themselves as someone who drinks alcohol. Furthermore, those who did drink alcohol often did so with parental permission. There was variation amongst participants as to how comfortable they felt talking about alcohol issues with school staff. Overall participants felt the intervention was useful, but would be better suited to 'heavier' drinkers.

A qualitative exploration of school-based staff's experiences of delivering an alcohol screening and brief intervention in the high school setting: findings from the SIPS JR-HIGH trial.

BACKGROUND: Whilst underage drinking in the UK has been declining in recent years, prevalence is still higher than in most other Western European countries. Therefore, it is important to deliver effective interventions to reduce risk of harm. METHODS: Semi-structured interviews with staff delivering an alcohol screening and brief intervention in the high-school setting. The analysis was informed by normalization process theory (NPT), interviews were open coded and then a framework applied based on the four components of NPT. RESULTS: Five major themes emerged from the analysis. The majority of participants felt that the intervention could be useful, and that learning mentors were ideally suited to deliver it. However, there was a feeling that the intervention should have been targeted at young people who drink the most. CONCLUSIONS: The intervention was generally well received in schools and seen as an effective tool for engaging young people in a discussion around alcohol. However, in the future schools need to consider the level of staffing in place to deliver the intervention. Furthermore, the intervention could focus more on the long-term risks of initiating alcohol consumption at a young age.

Upper limb lymphedema in breast cancer patients in the era of Z0011, sentinel lymph node biopsy and breast conservation.

INTRODUCTION: Surgical techniques in breast cancer (BCa) have seen a dramatic change recently with breast-conserving surgery (BCS) and sentinel lymph node biopsy (SLNB). The ACOSOG-Z0011 trial reported equivalence in outcomes for certain patients with SLN metastases treated with axillary lymph node dissection (ALND) or SLNB alone. Our aim was to investigate changes in lymphedema referral patterns in BCa patients over the last 3 years in a specialist unit and to elucidate effects of SLNB, BCS, and Z0011 trial publication on such patterns. METHODS: A retrospective study was performed over a 3-year period (May 2012-May 2015). Patients were identified using a prospectively maintained lymphedema database and newly referred BCa patients with data availability were included. RESULTS: Overall lymphedema incidence was 11% (19.2% in ALND and 5.1% in SLNB cohort). There was a statistically significant difference in lymphedema referral patterns after Z0011, new referrals reduced by 20% (chi-sq; p = 0.001). Volume of referrals post ALND was reduced by 40% with concomitant 31% rise in those post SLNB alone, reflecting changing surgical patterns. There was a significant change in extent of lymphnode dissection during ALND (p = 0.003). CONCLUSION: The Z0011 trial in association with wider implementation of SLNB has led to significant changes in the lymphedema referral patterns and extent of ALND.

Patient response to physician expressions of uncertainty: a systematic review.

BACKGROUND: The consequences of uncertainty are extensive with the potential to influence a multitude of issues such as patient expectations, diagnosis, treatment decisions, patient confidence and satisfaction and ultimately patient compliance. AIMS: To review the relevant literature pertaining to physician expressions of uncertainty and its effects on patients. METHODS: A search was conducted in July 2016 of electronic databases; PsycINFO, PsycARTICLES, MEDLINE and Embase. Key search terms included uncertainty, physician uncertainty, patient attitude, patient confidence and patient satisfaction. Other sources were obtained from reference lists. The eligibility of studies and data extracted were cross-checked with inclusion and exclusion criteria. RESULTS: The search yielded 14 studies and 4 were included for review. These studies yielded mixed results. In some studies patients preferred disclosure of uncertainty while in others such disclosure was negatively associated with patient confidence and satisfaction. This is at odds with the belief of theorists that uncertainty disclosure to patients is the crux of a successful doctor-patient relationship. The studies were, however, united in so far as the way in which the uncertainty was communicated to the patient was pivotal to patient responses to uncertainty. CONCLUSIONS: Uncertainty is a ubiquitous feature of medicine and more research should examine how physician's expressions of uncertainty affect patients.

Can a theoretical framework help to embed alcohol screening and brief interventions in an endoscopy day-unit?

INTRODUCTION AND AIMS: The National Institute for Health Care and Excellence recommend that alcohol screening and brief intervention (ASBI) should be routinely implemented in secondary care. This study used theoretical frameworks to understand how health professionals can be supported to adapt their behaviour and clinical practice. DESIGN AND METHODS: Staff training and support was conducted using theoretical frameworks. A 12-week study, delivering ASBI was carried out as part of routine practice in an endoscopy day-unit. Anonymised patient data were collected using the Alcohol Use Disorders Identification Tool (AUDIT) and whether patients received a brief intervention. Staff completed the Shortened Alcohol and Alcohol Problems Perceptions Questionnaire at three time points and took part in a focus group both pre and post study. RESULTS: For staff, levels or role adequacy, role legitimacy, motivation to discuss alcohol, security in their role, job satisfaction and commitment to working with patients who drink increased during the time of the study. 1598 individual patients were seen in the department in the timeframe. Of these, 1180 patients were approached (74%); 18% (n=207) of patients were AUDIT positive. DISCUSSION: This study has shown that it is possible to reach a high number of patients in a busy hospital out-patient department and deliver ASBI by working with staff using theoretical frameworks for training. Embedding evidence-based public health interventions into routine clinical environments is complex. The social system in which professionals operate requires consideration alongside individual professionals' real and perceived barriers and facilitators to change.

AESOPS: a randomised controlled trial of the clinical effectiveness and cost-effectiveness of opportunistic screening and stepped care interventions for older hazardous alcohol users in primary care.

BACKGROUND: There is clear evidence of the detrimental impact of hazardous alcohol consumption on the physical and mental health of the population. Estimates suggest that hazardous alcohol consumption annually accounts for 150,000 hospital admissions and between 15,000 and 22,000 deaths in the UK. In the older population, hazardous alcohol consumption is associated with a wide range of physical, psychological and social problems. There is evidence of an association between increased alcohol consumption and increased risk of coronary heart disease, hypertension and haemorrhagic and ischaemic stroke, increased rates of alcohol-related liver disease and increased risk of a range of cancers. Alcohol is identified as one of the three main risk factors for falls. Excessive alcohol consumption in older age can also contribute to the onset of dementia and other age-related cognitive deficits and is implicated in one-third of all suicides in the older population. OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of a stepped care intervention against a minimal intervention in the treatment of older hazardous alcohol users in primary care. DESIGN: A multicentre, pragmatic, two-armed randomised controlled trial with an economic evaluation. SETTING: General practices in primary care in England and Scotland between April 2008 and October 2010. PARTICIPANTS: Adults aged ≥ 55 years scoring ≥ 8 on the Alcohol Use Disorders Identification Test (10-item) (AUDIT) were eligible. In total, 529 patients were randomised in the study. INTERVENTIONS: The minimal intervention group received a 5-minute brief advice intervention with the practice or research nurse involving feedback of the screening results and discussion regarding the health consequences of continued hazardous alcohol consumption. Those in the stepped care arm initially received a 20-minute session of behavioural change counselling, with referral to step 2 (motivational enhancement therapy) and step 3 (local specialist alcohol services) if indicated. Sessions were recorded and rated to ensure treatment fidelity. MAIN OUTCOME MEASURES: The primary outcome was average drinks per day (ADD) derived from extended AUDIT--Consumption (3-item) (AUDIT-C) at 12 months. Secondary outcomes were AUDIT-C score at 6 and 12 months; alcohol-related problems assessed using the Drinking Problems Index (DPI) at 6 and 12 months; health-related quality of life assessed using the Short Form Questionnaire-12 items (SF-12) at 6 and 12 months; ADD at 6 months; quality-adjusted life-years (QALYs) (for cost-utility analysis derived from European Quality of Life-5 Dimensions); and health and social care resource use associated with the two groups. RESULTS: Both groups reduced alcohol consumption between baseline and 12 months. The difference between groups in log-transformed ADD at 12 months was very small, at 0.025 [95% confidence interval (CI)--0.060 to 0.119], and not statistically significant. At month 6 the stepped care group had a lower ADD, but again the difference was not statistically significant. At months 6 and 12, the stepped care group had a lower DPI score, but this difference was not statistically significant at the 5% level. The stepped care group had a lower SF-12 mental component score and lower physical component score at month 6 and month 12, but these differences were not statistically significant at the 5% level. The overall average cost per patient, taking into account health and social care resource use, was £488 [standard deviation (SD) £826] in the stepped care group and £482 (SD £826) in the minimal intervention group at month 6. The mean QALY gains were slightly greater in the stepped care group than in the minimal intervention group, with a mean difference of 0.0058 (95% CI -0.0018 to 0.0133), generating an incremental cost-effectiveness ratio (ICER) of £1100 per QALY gained. At month 12, participants in the stepped care group incurred fewer costs, with a mean difference of -£194 (95% CI -£585 to £198), and had gained 0.0117 more QALYs (95% CI -0.0084 to 0.0318) than the control group. Therefore, from an economic perspective the minimal intervention was dominated by stepped care but, as would be expected given the effectiveness results, the difference was small and not statistically significant. CONCLUSIONS: Stepped care does not confer an advantage over minimal intervention in terms of reduction in alcohol consumption at 12 months post intervention when compared with a 5-minute brief (minimal) intervention. TRIAL REGISTRATION: This trial is registered as ISRCTN52557360. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 25. See the HTA programme website for further project information.

Correlation of the virological response to short-term maraviroc monotherapy with standard and deep-sequencing-based genotypic tropism prediction methods.

Genotypic tropism testing methods are emerging as the first step before prescription of the CCR5 antagonist maraviroc (MVC) to HIV-infected patients in Europe. Studies validating genotypic tests have included other active drugs that could have potentially convoluted the effects of MVC. The maraviroc clinical test (MCT) is an in vivo drug sensitivity test based on the virological response to a short-term exposure to MVC monotherapy. Thus, our aim was to compare the results of genotypic tropism testing methods with the short-term virological response to MVC monotherapy. A virological response in the MCT was defined as a ≥ 1-log(10) decrease in HIV RNA or undetectability after 8 days of drug exposure. Seventy-three patients undergoing the MCT were included in this study. We used both standard genotypic methods (n = 73) and deep sequencing (n = 27) on MCT samples at baseline. For the standard methods, the most widely used genotypic algorithms for analyzing the V3 loop sequence, geno2pheno and PSSM, were used. For deep sequencing, the geno2pheno algorithm was used with a false-positive rate cutoff of 3.5. The discordance rates between the standard genotypic methods and the virological response were approximately 20% (including mostly patients without a virological response). Interestingly, these discordance rates were similar to that obtained from deep sequencing (18.5%). The discordance rates between the genotypic methods (tropism assays predictive of the use of the CCR5 coreceptor) and the MCT (in vivo MVC sensitivity assay) indicate that the algorithms used by genotypic methods are still not sufficiently optimized.

Assessing leg health in chickens using a force plate and gait scoring: how many birds is enough?

Meat chickens from experimental flocks were tested repeatedly from three to six weeks of age using gait score (GS) and force plate (FP) techniques, and the findings were related to postmortem results for leg health. This initial study indicated that five weeks was the optimal age to test birds using the FP to indicate abnormalities and pathologies. Birds (n=492) with a range of walking styles were then selected at five weeks of age from three commercial flocks, gait scored and tested using a FP. A subsample of these birds (n=191) was examined postmortem, and relationships between leg abnormalities and pathologies, GS and FP results were investigated. Models of leg abnormalities and pathologies with GS or FP measurements as covariates left much variation unexplained; hence, the number of birds that would need to be tested using these methods to assess the flock prevalence of leg abnormalities or pathologies is high.

Conflicting perspectives compromising discussions on cardiopulmonary resuscitation.

Healthcare professionals, patients and their relatives are expected to discuss resuscitation together. This study aims to identify the differences in the knowledge base and understanding of these parties. Questionnaires examining knowledge and opinion on resuscitation matters were completed during interviews of randomly selected doctors, nurses and the general public. 70% doctors, 24% nurses and 0% of a public group correctly estimated survival to discharge following in-hospital resuscitation attempts. Deficiencies were identified in doctor and nurse knowledge of ethics governing resuscitation decisions. Public opinion often conflicts with ethical guidelines. Public understanding of the nature of cardiopulmonary arrests and resuscitation attempts; and of the implications of a 'Do Not Attempt Resuscitation (DNAR)' order is poor. Television medical dramas are the primary source of resuscitation knowledge. Deficiencies in healthcare professionals' knowledge of resuscitation ethics and outcomes may compromise resuscitation decisions. Educational initiatives to address deficiencies are necessary. Parties involved in discussion on resuscitation do not share the same knowledge base reducing the likelihood of meaningful discussion. Public misapprehensions surrounding resuscitation must be identified and corrected during discussion.

Multilocus phylogenetic diversity of Fusarium avenaceum pathogenic on lisianthus.

Fusarium avenaceum is a globally distributed fungus commonly isolated from soil and a wide range of plants. Severe outbreaks of crown and stem rot of the flowering ornamental, lisianthus (Eustoma grandiflorum), have been attributed to F. avenaceum. We sequenced portions of the translation elongation factor 1-alpha (tef) and beta-tubulin (benA) protein coding genes as well as partial intergenic spacer (IGS) regions of the nuclear ribosomal genes in 37 Fusarium isolates obtained from lisianthus and other host plants. Isolates that were previously identified morphologically as F. acuminatum were included as an outgroup. Phylogenetic analyses of tef, benA, and IGS sequences showed that F. avenaceum isolates were an exclusive group with strong bootstrap support and no significant incongruence among gene genealogies. Isolates from lisianthus were scattered within this clade and did not form distinct groups based on host species or locality. Pathogenicity tests of F. avenaceum isolates obtained from several other hosts showed an ability to cause disease on lisianthus, suggesting that F. avenaceum may be pathogenic on lisianthus regardless of its phylogenetic origin. These findings have management implications and suggest that any host that supports F. avenaceum may serve as a source of inoculum for lisianthus growers.

Use of an admission early warning score to predict patient morbidity and mortality and treatment success.

BACKGROUND: Early warning scores (EWS) are used to identify physiological deterioration in patients. Studies to date have primarily focused on the correlation between trends in serially recorded EWS of inpatients and clinical outcomes. This study examined the predictive value of an EWS calculated immediately on presentation to hospital for acute medical patients. METHOD: A prospective study of 225 consecutive medical admissions. Pulse, systolic blood pressure, respiratory rate, oxygen saturation and neurological status were used to calculate an EWS. Patients were divided into four score categories based on their EWS. The primary endpoints examined were intensive care unit (ICU)/coronary care unit (CCU) admission, death, cardiac arrest and length of hospital stay. RESULTS: For each rise in score category there was an increased risk of admission to ICU (odds ratio (OR) 3.35, CI 1.52 to 7.40, p = 0.003), admission to CCU (OR 1.82, CI 1.07 to 3.09, p = 0.027), death (OR 2.19, CI 1.41 to 3.39, p = 0.000) and reaching the combined endpoint of CCU/ICU admission or death (OR 2.19, CI 1.41 to 3.39, p = 0.000). The higher the score the longer the length of hospital admission (p = 0.04). A decrease in EWS between first presentation to hospital and transfer to the ward was associated with a decreased risk of reaching the combined endpoint of CCU or ICU admission or death (OR 2.56, CI 1.11 to 5.89, p = 0.028). DISCUSSION: Higher admission EWS correlate with increased risk of CCU/ICU admission, death and longer hospital stays independent of patient age. An improvement in serial EWS within 4 h of presentation to hospital predicts improved clinical outcomes. The EWS is a potential triage tool in the emergency department for acute medical patients.

Comparative validity of seven scoring systems for the instrumental activities of daily living scale in rural elders.

Lawton and Brody's eight-item Instrumental Activities of Daily Living (IADL) scale is used often with elderly patients but scored in several different ways. We scored the IADL with seven popular procedures ranging from relatively simple to complex (Guttman scores, summed and Rasch scores from dichotomous, trichotomous, and polytomous items) in a sample of rural elders (N = 231). We compared the IADL scales' prediction of concurrent cognitive functioning, depressive symptoms, psychosocial functioning, and health care use (medications, outpatient visits, inpatient days). Validity coefficients ranged from small to large among outcome variables but were highly consistent across IADL scoring procedures. Consequently, researchers and clinicians may prefer to use simpler IADL scoring procedures with this population.

Comparison of atazanavir with lopinavir/ritonavir in patients with prior protease inhibitor failure: a randomized multinational trial.

OBJECTIVES: To compare change from baseline in HIV RNA and fasting low-density lipoprotein (LDL) cholesterol levels in protease inhibitor (PI)-experienced patients receiving unboosted atazanavir 400 mg once daily versus lopinavir 400 mg boosted with ritonavir 100 mg twice daily, with two nucleoside reverse transcriptase inhibitors (NRTIs). Secondary objectives included virologic response, CD4 cell count changes, other lipid changes, safety, and tolerability. METHODS: Randomized, open-label, multinational, 48-week study in patients with one PI-regimen failure, HIV RNA > or = 1000 copies/mL, and CD4 count > or = 50 cells/mm3. RESULTS: Three hundred patients were randomized; 290 treated (144 atazanavir, 146 lopinavir/ritonavir). Lopinavir/ritonavir resulted in a significantly greater reduction in HIV RNA than unboosted atazanavir (-2.02 vs -1.59 log10 copies/mL, p < 0.001) at week 48. Secondary efficacy endpoints also favored lopinavir/ritonavir; the differences in efficacy between regimens were also observed in secondary analyses comparing those subjects who were susceptible and those subjects who were resistant to their respective PIs at baseline. However, both regimens were equally effective in subjects who had no baseline NRTI mutations. From baseline to week 48, atazanavir resulted in either no change or decreases in fasting LDL cholesterol, total cholesterol, and fasting triglycerides (-6%, -2%, and +1%), whereas lopinavir/ritonavir resulted in increases (+3%, +12%, and +53%) (p < 0.05, all between-treatment comparisons). Fewer patients were administered lipid-lowering therapy in the atazanavir arm (6% vs 20% for lopinavir/ritonavir). Both regimens were safe and well tolerated. CONCLUSIONS: While both treatments demonstrated good antiviral efficacy, relatively greater antiviral suppression was observed with lopinavir/ritonavir. In those patients with no NRTI mutations at baseline, both regimens demonstrated comparable virologic suppression. Atazanavir-treated patients demonstrated a superior lipid profile and required less frequent lipid-lowering treatment.