The protocol of a clinical effectiveness trial comparing standard step-up care, early combination DMARD therapy and early use of TNF inhibitors for the treatment of moderate to severe psoriatic arthritis: the 3-arm parallel group SPEED randomized controlled trial.

Objectives: The aim of the Severe Psoriatic arthritis - Early intervEntion to control Disease trial is to compare outcomes in psoriatic arthritis (PsA) patients with poor prognostic factors treated with standard step-up conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), combination csDMARDs or a course of early biologics. Design: This multicentre UK trial was embedded within the MONITOR-PsA cohort, which uses a trial within cohort design. Methods and analysis: Patients with newly diagnosed PsA and at least one poor prognostic factor (polyarthritis, C-reactive protein >5 mg/dL, health assessment questionnaire >1, radiographic erosions) were randomized equally and open-label to either standard care with 'step-up' csDMARD therapy, initial therapy with combination csDMARDs (methotrexate with either sulfasalazine or leflunomide) or to early biologics induction therapy (adalimumab plus methotrexate). The primary outcome is the PsA disease activity score at week 24. Ethics: Ethical approval for the study was granted by the South Central Research Ethics Committee (ref 18/SC/0107). Discussion: Treatment recommendations for PsA suggest more intensive therapy for those with poor prognostic factors but there are no studies that have previously used prognostic factors to guide therapy. Applying initial intensive therapy has shown improved outcomes in other inflammatory arthritides but has never been tried in PsA. Combination csDMARDs have shown some superiority over single therapies but there are limited data and concerns about side effects. Early use of biologics has also been shown to be superior to methotrexate but these drugs are costly and not usually funded first line. However, if a short course of biologics can rapidly suppress inflammation allowing treatment to be withdrawn and response maintained on methotrexate, this may be a cost-effective model for early use. Trial registration: ClinicalTrials.gov (NCT03739853) and EudraCT (2017-004542-24).

Preliminary evaluation of a smartphone application (DelApp) for identification of delirium in sub-Saharan Africa.

OBJECTIVE: In sub-Saharan Africa, there are no validated screening tools for delirium in older adults, despite the known vulnerability of older people to delirium and the associated adverse outcomes. This study aimed to assess the effectiveness of a brief smartphone-based assessment of arousal and attention (DelApp) in the identification of delirium amongst older adults admitted to the medical department of a tertiary referral hospital in Northern Tanzania. METHOD: Consecutive admissions were screened using the DelApp during a larger study of delirium prevalence and risk factors. All participants subsequently underwent detailed clinical assessment for delirium by a research doctor. Delirium and dementia were identified against DSM-5 criteria by consensus. RESULTS: Complete data for 66 individuals were collected of whom 15 (22.7%) had delirium, 24.5% had dementia without delirium, and 10.6% had delirium superimposed on dementia. Sensitivity and specificity of the DelApp for delirium were 0.87 and 0.62, respectively (AUROC 0.77) and 0.88 and 0.73 (AUROC 0.85) for major cognitive impairment (dementia and delirium combined). Lower DelApp score was associated with age, significant visual impairment (<6/60 acuity), illness severity, reduced arousal and DSM-5 delirium on univariable analysis, but on multivariable logistic regression only arousal remained significant. CONCLUSION: In this setting, the DelApp performed well in identifying delirium and major cognitive impairment but did not differentiate delirium and dementia. Performance is likely to have been affected by confounders including uncorrected visual impairment and reduced level of arousal without delirium. Negative predictive value was nevertheless high, indicating excellent 'rule out' value in this setting.

Pharmacokinetic, sedative, and physiological effects of oral compounded formulations of trazodone alone or in combination with gabapentin in male cats.

Trazodone and gabapentin are common oral sedatives in cats, used alone or combined, but no pharmacokinetic studies exist for trazodone in this species. The objective of this study was to determine the pharmacokinetics of oral trazodone (T) alone, or in combination with gabapentin (G) in healthy cats. Cats (n = 6) were randomly allocated to receive T (3 mg/kg) intravenously (IV), T (5 mg/kg) orally (PO), or T (5 mg/kg) and G (10 mg/kg) PO with a 1-week washout period between treatments. Heart rate, respiratory rate, indirect blood pressure, and level of sedation were assessed, and venous blood samples were collected serially over 24 h. Analysis of plasma trazodone concentration was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oral T administration resulted in a bioavailability of 54.9(7-96)%, and 17.2(11-25)% when administered with G. Tmax 0.17 (0.17-0.5) and 0.17 (0.17-0.75) h; Cmax 1.67 ± 0.91 and 1.22 ± 0.54 µg/mL, AUC 5.23 (2.0-18.76) and 2.37 (1.17-7.80) h*µg/mL; T1/2 5.12 ± 2.56 and 4.71 ± 1.07 h; for T and TG, respectively. Sedation was significant when compared to baseline in all groups from 20 or 45 min to 8 h indicating some lag between peak plasma concentration and sedative effects. Physiological variables remained within normal limits. This study concludes that oral trazodone is rapidly absorbed in healthy cats. Addition of gabapentin did not result in more profound sedation, showing no clinical advantage of combining these drugs in this study population.

Persistent hypersomnia following repetitive mild experimental traumatic brain injury: Roles of chronic stress and sex differences.

Traumatic brain injury (TBI) is often more complicated than a single head injury. An extreme example of this point may be military service members who experience a spectrum of exposures over a prolonged period under stressful conditions. Understanding the effects of complex exposures can inform evaluation and care to prevent persistent symptoms. We designed a longitudinal series of non-invasive procedures in adult mice to evaluate the effects of prolonged mild stress and head injury exposures. We assessed anxiety, depression, and sleep-wake dysfunction as symptoms that impact long-term outcomes after mild TBI. Unpredictable chronic mild stress (UCMS) was generated from a varied sequence of environmental stressors distributed within each of 21 days. Subsequently, mice received a mild blast combined with closed-head mild TBI on 5 days at 24-h intervals. In males and females, UCMS induced anxiety without depressive behavior. A major finding was reproducible sleep-wake dysfunction through 6- to 12-month time points in male mice that received UCMS with repetitive blast plus TBI events, or surprisingly after just UCMS alone. Specifically, male mice exhibited hypersomnia with increased sleep during the active/dark phase and fragmentation of longer wake bouts. Sleep-wake dysfunction was not found with TBI events alone, and hypersomnia was not found in females under any conditions. These results identify prolonged stress and sex differences as important considerations for sleep-wake dysfunction. Furthermore, this reproducible hypersomnia with impaired wakefulness is similar to the excessive daytime sleepiness reported in patients, including patients with TBI, which warrants further clinical screening, care, and treatment development.

Limbic Responses Following Shock Wave Exposure in Male and Female Mice.

Blast traumatic brain injury (bTBI) presents a serious threat to military personnel and often results in psychiatric conditions related to limbic system dysfunction. In this study, the functional outcomes for anxiety- and depressive-like behaviors and neuronal activation were evaluated in male and female mice after exposure to an Advanced Blast Simulator (ABS) shock wave. Mice were placed in a ventrally exposed orientation inside of the ABS test section and received primary and tertiary shock wave insults of approximately 15 psi peak pressure. Evans blue staining indicated cases of blood-brain barrier breach in the superficial cerebral cortex four, but not 24 h after blast, but the severity was variable. Behavioral testing with the elevated plus maze (EPM) or elevated zero maze (EZM), sucrose preference test (SPT), and tail suspension test (TST) or forced swim test (FST) were conducted 8 days-3.5 weeks after shock wave exposure. There was a sex difference, but no injury effect, for distance travelled in the EZM where female mice travelled significantly farther than males. The SPT and FST did not indicate group differences; however, injured mice were less immobile than sham mice during the TST; possibly indicating more agitated behavior. In a separate cohort of animals, the expression of the immediate early gene, c-Fos, was detected 4 h after undergoing bTBI or sham procedures. No differences in c-Fos expression were found in the cerebral cortex, but female mice in general displayed enhanced c-Fos activation in the paraventricular nucleus of the thalamus (PVT) compared to male mice. In the amygdala, more c-Fos-positive cells were observed in injured animals compared to sham mice. The observed sex differences in the PVT and c-Fos activation in the amygdala may correlate with the reported hyperactivity of females post-injury. This study demonstrates, albeit with mild effects, behavioral and neuronal activation correlates in female rodents after blast injury that could be relevant to the incidence of increased post-traumatic stress disorder in women.

Microbotanical residues for the study of early hominin tools.

More than 2 million years ago in East Africa, the earliest hominin stone tools evolved amidst changes in resource base, with pounding technology playing a key role in this adaptive process. Olduvai Gorge (now Oldupai) is a famed locality that remains paramount for the study of human evolution, also yielding some of the oldest battering tools in the world. However, direct evidence of the resources processed with these technologies is lacking entirely. One way to obtain this evidence is through the analysis of surviving residues. Yet, linking residues with past processing activities is not simple. In the case of plant exploitation, this link can only be established by assessing site-based reference collections inclusive of both anthropogenic and natural residues as a necessary first step and comparative starting point. In this paper, we assess microbotanical remains from rock clasts sourced at the same quarry utilized by Oldowan hominins at Oldupai Gorge. We mapped this signal and analysed it quantitatively to classify its spatial distribution objectively, extracting proxies for taxonomic identification and further comparison with freestanding soils. In addition, we used blanks to manufacture pounding tools for blind, controlled replication of plant processing. We discovered that stone blanks are in fact environmental reservoirs in which plant remains are trapped by lithobionts, preserved as hardened accretions. Tool use, on the other hand, creates residue clusters; however, their spatial distribution can be discriminated from purely natural assemblages by the georeferencing of residues and statistical analysis of resulting patterns. To conclude, we provide a protocol for best practice and a workflow that has the advantage of overcoming environmental noise, reducing the risk of false positive, delivering a firm understanding of residues as polygenic mixtures, a reliable use of controls, and most importantly, a stronger link between microbotanical remains and stone tool use.

Effect of 15° Reverse Trendelenburg Position on Arterial Oxygen Tension during Isoflurane Anesthesia in Horses.

Lower than expected arterial oxygen tension (PaO2) continues to be an unresolved problem in equine anesthesia. The aim of this randomized, crossover, and prospective study using six adult horses is to determine if a 15° reverse Trendelenburg position (RTP) increases PaO2 during inhalation anesthesia. Under constant-dose isoflurane anesthesia, dorsally recumbent horses were positioned either horizontally (HP) or in a 15° RTP for 2 h. Lungs were mechanically ventilated (15 mL/kg, 6 breaths/min). Arterial carbon dioxide tension (PaCO2), PaO2, inspired oxygen fraction (FiO2), and end-tidal carbon dioxide tension (EtCO2) were determined every 30 min during anesthesia. Indices of dead-space ventilation (Vd/Vt), oxygenation (P-F ratio), and perfusion (F-shunt) were calculated. Dobutamine and phenylephrine were used to support mean arterial pressure (MAP). Data are presented as median and range. In one horse, which was deemed an outlier due to its thoracic dimensions and body conformation, indices of oxygenation worsened in RTP compared to HP (median PaO2 438 vs. 568 mmHg; P-F ratio 454 vs. 586 mmHg, and F-shunt 13.0 vs. 5.7 mmHg). This horse was excluded from calculations. In the remaining five horses they were significantly better with RTP compared to HP. Results in remaining five horses showed that PaO2 (502, 467-575 vs. 437, 395-445 mmHg), P-F ratio (518, 484-598 vs. 455, 407-458 mmHg), and F-shunt (10.1, 4.2-11.7 vs. 14.2, 13.8-16.0 mmHg) were significantly different between RTP and HP (p = 0.03). Other variables were not significantly different. In conclusion, the 15° RTP resulted in better oxygenation than HP in dorsally recumbent, isoflurane-anesthetized horses, although worsening of oxygenation may occur in individual horses. A study detailing the cardiovascular consequences of RTP is necessary before it can be recommended for clinical practice.

Measuring Anxiety-Like Behaviors in Rodent Models of Traumatic Brain Injury.

Anxiety is a common complaint following acquired traumatic brain injury (TBI). However, the measurement of dysfunctional anxiety behavioral states following experimental TBI in rodents is complex. Some studies report increased anxiety after TBI, whereas others find a decreased anxiety-like state, often described as increased risk-taking behavior or impulsivity. These inconsistencies may reflect a lack of standardization of experimental injury models or of behavioral testing techniques. Here, we review the most commonly employed unconditioned tests of anxiety and discuss them in a context of experimental TBI. Special attention is given to the effects of repeated testing, and consideration of potential sensory and motor confounds in injured rodents. The use of multiple tests and alternative data analysis methods are discussed, as well as the potential for the application of common data elements (CDEs) as a means of providing a format for documentation of experimental details and procedures of each published research report. CDEs may improve the rigor, reproducibility, as well as endpoint for better relating findings with clinical TBI phenotypes and the final goal of translation. While this may not resolve all incongruities in findings across laboratories, it is seen as a way forward for standardized and universal data collection for improvement of data quality and sharing, and advance therapies for neuropsychiatric symptoms that often present for decades following TBI.

Targeting Soluble Epoxide Hydrolase and Cyclooxygenases Enhance Joint Pain Control, Stimulate Collagen Synthesis, and Protect Chondrocytes From Cytokine-Induced Apoptosis.

Objective: To determine the symptomatic and disease-modifying capabilities of sEH and COX inhibitors during joint inflammation. Methods: Using a blinded, randomized, crossover experimental design, 6 adult healthy horses were injected with lipopolysaccharide (LPS; 3 µg) from E. coli in a radiocarpal joint and concurrently received the non-selective cyclooxygenase (COX) inhibitor phenylbutazone (2 mg/kg), the sEH inhibitor t-TUCB (1 mg/kg) or both (2 mg/kg phenylbutazone and 0.1, 0.3, and 1 mg/kg t-TUCB) intravenously. There were at least 30 days washout between treatments. Joint pain (assessed via inertial sensors and peak vertical forces), synovial fluid concentrations of prostanoids (PGE2, TxB2), cytokines (IL-1ß, IL-6, TNF-α) and biomarkers of collagen synthesis (CPII) and degradation (C2C) were measured at pre-determined intervals over a 48-h period. The anti-apoptotic effect of COX and sEH inhibitors was determined via ELISA technique in primary equine chondrocytes incubated with TNF-α (10 ng/ml) for 24 h. Apoptosis was also determined in chondrocytes incubated with sEH-generated metabolites. Results: Combined COX and sEH inhibition produced significantly better control of joint pain, prostanoid responses, and collagen synthesis-degradation balance compared to each compound separately. When administered separately, pain control was superior with COX vs. sEH inhibition. Cytokine responses were not different during COX and/or sEH inhibition. In cultured chondrocytes, sEH inhibition alone or combined with COX inhibition, but not COX inhibition alone had significant anti-apoptotic effects. However, sEH-generated metabolites caused concentration-dependent apoptosis. Conclusions: Combined COX and sEH inhibition optimize pain control, attenuate loss of articular cartilage matrix during joint inflammation and cytokine-induced chondrocyte apoptosis.

Comprehensively addressing postpartum maternal health: a content and image review of commercially available mobile health apps.

BACKGROUND: The United States is currently facing a maternal morbidity and mortality crisis, with the highest rates of any resource-rich nation. In efforts to address this, new guidelines for postpartum care suggest that mobile health (mHealth) apps can help provide complementary clinical support for new mothers during the postpartum period. However, to date no study has evaluated the quality of existing mHealth tools targeted to this time period in terms of sufficiency of maternal health information, inclusivity of people of color, and app usability. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were used to review the peripartum apps from the Apple and Google Play stores in either the Health/Fitness, Medical, or Education categories. Apps were evaluated for extent and quality of maternal health information and inclusivity of people of color using an a priori coding scheme. App usability was evaluated using the Mobile Application Rating Scale (MARS) score. RESULTS: Of the 301 apps from the Apple and Google Play stores, 25 met criteria for final evaluation. Of the 30 maternal health topics coded for, the median number addressed by apps was 19.5 (65%). Peripartum behaviors were more frequently addressed than peripartum outpatient care topics and peripartum acute health risks. The coverage of maternal health information and inclusivity of people of color in app imagery both correlated positively with the MARS usability score of the app. Only 8 apps (32%) portrayed greater than 24% images of people of color- the percent of non-white Americans according to 2019 census estimates. There was no correlation between MARS usability score and number of app users, as estimated by number of ratings for the app available on the app store. In addition, apps with evidence-based maternal health information had greater MARS engagement, information, and aesthetics scores. However, presence of evidence-based information did not correlate with greater numbers of app users. CONCLUSIONS: Current commercially available peripartum apps range widely in quality. Overall current app offerings generally do not provide adequate maternal health information and are not optimally accessible to the target users in terms of inclusivity of women of color or app usability. Apps delivering evidence-based information and more usable design are more likely to meet these standards but are not more likely to be downloaded by users.

Cost-Effectiveness of Offering Cervical Cancer Screening with HPV Self-Sampling among African-American Women in the Mississippi Delta.

BACKGROUND: African-American women in the United States have an elevated risk of cervical cancer incidence and mortality. In the Mississippi Delta, cervical cancer disparities are particularly stark. METHODS: We conducted a micro-costing study alongside a group randomized trial that evaluated the efficacy of a patient-centered approach ("Choice" between self-collection at home for HPV testing or current standard of care within the public health system in Mississippi) versus the current standard of care ["Standard-of-care screening," involving cytology (i.e., Pap) and HPV co-testing at the Health Department clinics]. The interventions in both study arms were delivered by community health workers (CHW). Using cost, screening uptake, and colposcopy adherence data from the trial, we informed a mathematical model of HPV infection and cervical carcinogenesis to conduct a cost-effectiveness analysis comparing the "Choice" and "Standard-of-care screening" interventions among un/underscreened African-American women in the Mississippi Delta. RESULTS: When each intervention was simulated every 5 years from ages 25 to 65 years, the "Standard-of-care screening" strategy reduced cancer risk by 6.4% and was not an efficient strategy; "Choice" was more effective and efficient, reducing lifetime risk of cervical cancer by 14.8% and costing $62,720 per year of life saved (YLS). Screening uptake and colposcopy adherence were key drivers of intervention cost-effectiveness. CONCLUSIONS: Offering "Choice" to un/underscreened African-American women in the Mississippi Delta led to greater uptake than CHW-facilitated screening at the Health Department, and may be cost-effective. IMPACT: We evaluated the cost-effectiveness of an HPV self-collection intervention to reduce disparities.

Treating to target in psoriatic arthritis: assessing real-world outcomes and optimising therapeutic strategy for adults with psoriatic arthritis-study protocol for the MONITOR-PsA study, a trials within cohorts study design.

BACKGROUND: The Tight Control of psoriatic arthritis (TICOPA) trial confirmed improved clinical outcomes with a treat to target (T2T) strategy in psoriatic arthritis (PsA). This consisted of 4-weekly review and escalation of 'step up' therapy (single disease modifying therapy (DMARD), combination DMARDs and then biologics) based on remission criteria. Based on this, a T2T approach is supported by European PsA treatment recommendations. However, it is not commonly implemented in routine care primarily due to feasibility and cost concerns. In the TICOPA trial, the same treatment regime was used for all participants regardless of their disease profile. Despite the recognition of PsA as a highly heterogeneous condition, no studies have tailored which drugs are used depending on disease severity. The cohort will establish real world outcomes for the T2T approach in PsA and also form the basis of a trials within cohorts (TWiCs) design to test alternative therapeutic approaches within embedded clinical trials providing an evidence base for treatment strategy in PsA. METHODS: The Multicentre Observational Initiative in Treat to target Outcomes in Psoriatic Arthritis (MONITOR-PsA) cohort will apply a T2T approach within routine care. It will recruit newly diagnosed adult patients with PsA starting systemic therapies. The cohort is observational allowing routine therapeutic care within NHS clinics but a T2T approach will be supported when monitoring treatment within the cohort. Eligible participants will be adults (≥18 years) with active PsA with ≥ 1 tender or swollen joints or enthesis who have not previously had treatment with DMARDs for articular disease. DISCUSSION: This study is the first TWiC designed to support a fully powered randomised drug trial. The results from the observational cohort will be compared with those observed in the TICOPA trial investigating the clinical effectiveness and health care costs of the pragmatic T2T approach. Nested trials will provide definitive RCT evidence establishing the optimal management of PsA within the T2T approach. The TWiCs design allows robust generalizability to routine healthcare, avoids disappointment bias, aids recruitment and in future will allow assessment of longer-term outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03531073 . Retrospectively registered on 21 May 2018.

Hippocampal-Dependent Cognitive Dysfunction following Repeated Diffuse Rotational Brain Injury in Male and Female Mice.

Cognitive dysfunction is a common, often long-term complaint following acquired traumatic brain injury (TBI). Cognitive deficits suggest dysfunction in hippocampal circuits. The goal of the studies described here is to phenotype in both male and female mice the hippocampal-dependent learning and memory deficits resulting from TBI sustained by the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) device-a model that delivers both a contact-concussion injury as well as unrestrained rotational head movement. Mice sustained either sham procedures or four injuries (0.7 J, 24-h intervals). Spatial learning and memory skills assessed in the Morris water maze (MWM) approximately 3 weeks following injuries were significantly impaired by brain injuries; however, slower swimming speeds and poor performance on visible platform trials suggest that measurement of cognitive impairment with this test is confounded by injury-induced motor and/or visual impairments. A separate experiment confirmed hippocampal-dependent cognitive deficits with trace fear conditioning (TFC), a behavioral test less dependent on motor and visual function. Male mice had greater injury-induced deficits on both the MWM and TFC tests than female mice. Pathologically, the injury was characterized by white matter damage as observed by silver staining and glial fibrillary acidic protein (astrogliosis) in the optic tracts, with milder damage seen in the corpus callosum, and fimbria and brainstem (cerebral peduncles) of some animals. No changes in the density of GABAergic parvalbumin-expressing cells in the hippocampus, amygdala, or parietal cortex were found. This experiment confirmed significant sexually dimorphic cognitive impairments following a repeated, diffuse brain injury.

Behavioral and Myelin-Related Abnormalities after Blast-Induced Mild Traumatic Brain Injury in Mice.

In civilian and military settings, mild traumatic brain injury (mTBI) is a common consequence of impacts to the head, sudden blows to the body, and exposure to high-energy atmospheric shockwaves from blast. In some cases, mTBI from blast exposure results in long-term emotional and cognitive deficits and an elevated risk for certain neuropsychiatric diseases. Here, we tested the effects of mTBI on various forms of auditory-cued fear learning and other measures of cognition in male C57BL/6J mice after single or repeated blast exposure (blast TBI; bTBI). bTBI produced an abnormality in the temporal organization of cue-induced freezing behavior in a conditioned trace fear test. Spatial working memory, evaluated by the Y-maze task performance, was also deleteriously affected by bTBI. Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) analysis for glial markers indicated an alteration in the expression of myelin-related genes in the hippocampus and corpus callosum 1-8 weeks after bTBI. Immunohistochemical and ultrastructural analyses detected bTBI-related myelin and axonal damage in the hippocampus and corpus callosum. Together, these data suggest a possible link between blast-induced mTBI, myelin/axonal injury, and cognitive dysfunction.

Given a choice between self-sampling at home for HPV testing and standard of care screening at the clinic, what do African American women choose? Findings from a group randomized controlled trial.

The goals of this study were to: (1) evaluate adherence to cervical cancer screening using a patient-centered approach that provided a choice of self-sampling at home for human papillomavirus (HPV) testing or standard of care screening at the local health department ('Choice') versus only standard of care screening at the local health department ('SCS') among un/under-screened African-American women; and (2) examine whether women given a choice were more likely to choose and adhere to self-sampling for HPV testing. We conducted a group randomized trial among un/under-screened African-American women in the Mississippi Delta, with "town" as the unit of randomization (12 towns). Both interventions (i.e., 'Choice' versus 'SCS') were delivered by Community Health Workers (CHWs) through a door-to-door approach. A total of 335 women were enrolled in the study from 2016 to 2019. The 'Choice' arm had a significantly (p = 0.005) higher adherence to screening compared to the 'SCS' arm after adjusting for the cluster effect and other relevant behavioral variables. Participants in the 'Choice' arm were 5.62 (95% CI 1.71-18.44) times more likely to adhere to cervical cancer screening compared to participants in the 'SCS' arm. Women in the 'Choice' arm were significantly more likely to choose (76%) and adhere to self-sampling at home for HPV testing (48% adherence) compared to standard of care screening at the local health department (7.5% adherence). A theory-driven, CHW-led intervention can effectively promote cervical cancer screening among un/under-screened African-American women in a rural setting when women are provided with a choice between two screening modalities. Clinical Trials Registration: NCT03713710.

Owner evaluation of quality of life and mobility in osteoarthritic cats treated with amantadine or placebo.

OBJECTIVES: The aim of the study was to determine if amantadine improves owner-identified mobility impairment and quality of life associated with osteoarthritis in cats. METHODS: Using a blinded, placebo-controlled, randomized, crossover design, 13 healthy client-owned cats with clinical and radiographic evidence of osteoarthritis and owner-identified mobility impairment were studied. Cats received 5 mg/kg amantadine or placebo q24h PO for 3 weeks each with no washout period in between. Locomotor activity was continuously assessed with a collar-mounted activity monitor system, and owners chose and rated two mobility-impaired activities using a client-specific outcome measures (CSOM) questionnaire on a weekly basis. Locomotor activity on the third treatment week was analyzed with two-tailed paired t-tests. The CSOM scores were analyzed using a mixed-effect model and the Bonferroni post-hoc test. Owner-perceived changes in quality of life were compared between treatments using the χ2 test. Statistical significance was set at P <0.05. RESULTS: Mean ± SD activity counts during the third week of each treatment were significantly lower with amantadine (240,537 ± 53,880) compared with placebo (326,032 ± 91,759). CSOM scores assigned by the owners were significantly better with amantadine on the second (3 ± 1) and third (3 ± 1) weeks compared with placebo (5 ± 2 and 5 ± 1, respectively). A significantly greater proportion of owners reported improvement in quality of life with amantadine compared with placebo. CONCLUSIONS AND RELEVANCE: Amantadine significantly decreased activity, but improved owner-identified impaired mobility and owner-perceived quality of life in cats with osteoarthritis. Amantadine appears to be an option for the symptomatic treatment of osteoarthritis in cats.

Clinical effectiveness of symptomatic therapy compared with standard step-up care for the treatment of low-impact psoriatic oligoarthritis: the two-arm parallel group randomised POISE feasibility study.

INTRODUCTION: In psoriatic arthritis (PsA), treatment recommendations support first-line use of disease-modifying antirheumatic drugs (DMARDs). There are few treatment strategy trials, and no previous studies have investigated tailored treatment choice by disease severity. Studies in oligoarthritis (<5 inflamed joints) are limited but have suggested that some can be managed without DMARDs, preventing unnecessary side effects. This study aimed to assess the feasibility and acceptability of a study comparing standard DMARD treatment against symptomatic therapy in patients with mild psoriatic oligoarthritis. METHODS: This trial was embedded within the MONITOR-PsA cohort, which uses a Trials Within Cohorts (TWiCs) design. Patients with newly diagnosed psoriatic oligoarthritis, with low disease activity (PASDAS ⩽ 3.2) and the absence of poor prognostic factors [C reactive protein (CRP) < 5 mg/dL, HAQ < 1, no radiographic erosions] were randomised open-label to either standard care with 'step-up' DMARD therapy or to symptomatic therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) and local corticosteroid injections to inflamed joints. Key outcomes were the proportion of eligible cohort patients, consent and study completion rate. RESULTS: Over the 15-month study period, only one eligible patient was randomised. Although oligoarthritis patients represented 45% of patients in this early PsA cohort, the majority did not have mild disease (24% raised CRP, 51% moderate disease activity, 13% radiographic damage and/or poor function). Of those meeting trial inclusion criteria, many patients refused treatment in the observational cohort prior to an invitation into the trial as they did not wish to be treated with DMARDs. CONCLUSION: The study was not feasible as designed. Oligoarthritis represents around half of initial PsA presentations, but the majority starting therapy have high-impact disease. A small proportion have mild oligoarticular disease but many are not keen on treatment with DMARDs, given the potential side effects of these medications. Further research is needed to support evidence-based treatment in this subgroup. TRIAL REGISTRATION NUMBER: - ClinicalTrials.gov (NCT03797872) and EudraCT (2018-001085-42).