Early, precise, and safe clinical evaluation of the pharmacodynamic effects of novel agents in the intact human tumor microenvironment.

Introduction: Drug development is systemically inefficient. Research and development costs for novel therapeutics average hundreds of millions to billions of dollars, with the overall likelihood of approval estimated to be as low as 6.7% for oncology drugs. Over half of these failures are due to a lack of drug efficacy. This pervasive and repeated low rate of success exemplifies how preclinical models fail to adequately replicate the complexity and heterogeneity of human cancer. Therefore, new methods of evaluation, early in the development trajectory, are essential both to rule-in and rule-out novel agents with more rigor and speed, but also to spare clinical trial patients from the potentially toxic sequelae (high risk) of testing investigational agents that have a low likelihood of producing a response (low benefit). Methods: The clinical in vivo oncology (CIVO®) platform was designed to change this drug development paradigm. CIVO precisely delivers microdose quantities of up to 8 drugs or combinations directly into patient tumors 4-96 h prior to planned surgical resection. Resected tissue is then analyzed for responses at each site of intratumoral drug exposure. Results: To date, CIVO has been used safely in 6 clinical trials, including 68 subjects, with 5 investigational and 17 approved agents. Resected tissues were analyzed initially using immunohistochemistry and in situ hybridization assays (115 biomarkers). As technology advanced, the platform was paired with spatial biology analysis platforms, to successfully track anti-neoplastic and immune-modulating activity of the injected agents in the intact tumor microenvironment. Discussion: Herein we provide a report of the use of CIVO technology in patients, a depiction of the robust analysis methods enabled by this platform, and a description of the operational and regulatory mechanisms used to deploy this approach in synergistic partnership with pharmaceutical partners. We further detail how use of the CIVO platform is a clinically safe and scientifically precise alternative or complement to preclinical efficacy modeling, with outputs that inform, streamline, and de-risk drug development.

The effects of scaling and root planing plus home oral hygiene maintenance in Stage I/II periodontitis population: A 24-week randomized clinical trial.

OBJECTIVES: To compare the effects of powered and manual toothbrushing following scaling and root planing on bleeding on probing and other clinical indicators of periodontitis. MATERIALS AND METHODS: This was a randomized, examiner-blind, parallel-design, 24-week clinical study. Eligible subjects were 18-75 years of age with Stage I or II periodontitis. All subjects received scaling and root planing (SRP) within 28 days of enrollment. Thereafter, subjects were randomized to twice daily at-home use of either a powered toothbrush (PTB) or a manual toothbrush (MTB). Randomization was balanced for gender and periodontitis stage. No other oral hygiene aids were permitted. Subjects were evaluated every 4 weeks for the following measures: bleeding on probing (BOP), surface plaque (MPI), probing pocket depth (PPD) and clinical attachment level until Week 24. RESULTS: Of 328 randomized subjects, 299 subjects completed the study. For BOP at Week 24, the Least Squares (LS) Mean, standard error (SE) reduction from baseline was 0.24 (0.01) for the PTB group and 0.02 (0.01) for the MTB group, resulting in a statistically significant treatment difference of 0.22 (0.01), p-value < 0.0001. There were also concomitant reductions in MPI and PPD at Week 24, resulting in statistically significant (p-value < 0.0001) LS Mean (SE) treatment differences of 0.86 (0.04) and 0.24 (0.01), for MPI and PPD, respectively. CONCLUSION: When combined with SRP, daily home oral hygiene maintenance including a powered toothbrush significantly reduced clinical symptoms of periodontitis and surface plaque levels compared to a manual toothbrush in a Stage I/II periodontitis population. (ClinicalTrials.gov Identifier: NCT04254770).

Magnetic resonance imaging-guided stereotactic laser ablation therapy for the treatment of pediatric epilepsy: a retrospective multiinstitutional study.

OBJECTIVE: The authors of this study evaluated the safety and efficacy of stereotactic laser ablation (SLA) for the treatment of drug-resistant epilepsy (DRE) in children. METHODS: Seventeen North American centers were enrolled in the study. Data for pediatric patients with DRE who had been treated with SLA between 2008 and 2018 were retrospectively reviewed. RESULTS: A total of 225 patients, mean age 12.8 ± 5.8 years, were identified. Target-of-interest (TOI) locations included extratemporal (44.4%), temporal neocortical (8.4%), mesiotemporal (23.1%), hypothalamic (14.2%), and callosal (9.8%). Visualase and NeuroBlate SLA systems were used in 199 and 26 cases, respectively. Procedure goals included ablation (149 cases), disconnection (63), or both (13). The mean follow-up was 27 ± 20.4 months. Improvement in targeted seizure type (TST) was seen in 179 (84.0%) patients. Engel classification was reported for 167 (74.2%) patients; excluding the palliative cases, 74 (49.7%), 35 (23.5%), 10 (6.7%), and 30 (20.1%) patients had Engel class I, II, III, and IV outcomes, respectively. For patients with a follow-up ≥ 12 months, 25 (51.0%), 18 (36.7%), 3 (6.1%), and 3 (6.1%) had Engel class I, II, III, and IV outcomes, respectively. Patients with a history of pre-SLA surgery related to the TOI, a pathology of malformation of cortical development, and 2+ trajectories per TOI were more likely to experience no improvement in seizure frequency and/or to have an unfavorable outcome. A greater number of smaller thermal lesions was associated with greater improvement in TST. Thirty (13.3%) patients experienced 51 short-term complications including malpositioned catheter (3 cases), intracranial hemorrhage (2), transient neurological deficit (19), permanent neurological deficit (3), symptomatic perilesional edema (6), hydrocephalus (1), CSF leakage (1), wound infection (2), unplanned ICU stay (5), and unplanned 30-day readmission (9). The relative incidence of complications was higher in the hypothalamic target location. Target volume, number of laser trajectories, number or size of thermal lesions, or use of perioperative steroids did not have a significant effect on short-term complications. CONCLUSIONS: SLA appears to be an effective and well-tolerated treatment option for children with DRE. Large-volume prospective studies are needed to better understand the indications for treatment and demonstrate the long-term efficacy of SLA in this population.

A Single-Institution Retrospective Study of Patients Treated With Laser-Interstitial Thermal Therapy for Radiation Necrosis of the Brain.

Object Laser-interstitial thermal therapy (LITT) has been proposed as an alternative treatment to surgery for radiation necrosis (RN) in patients treated with stereotactic radiosurgery (SRS) for brain metastases. The present study sought to retrospectively analyze LITT outcomes in patients with RN from SRS. Methods This was a single-institution retrospective study of 30 patients treated from 2011-2018 with pathologically-proven RN after SRS for brain metastases (n=28) or proximally treated extracranial lesions treated with external beam radiotherapy (n=2). Same-day biopsy was performed in all cases. Patients were prospectively followed with Functional Assessment of Cancer Therapy - Brain (FACT-Br), EuroQol-5 Dimension (EQ-5D), Hopkins Verbal Learning Test (HVLT) and clinical history and examination. Adjusted means, standard errors and tests comparing visits to pre-LITT were generated. Kaplan-Meier method was used to estimate time overall survival. Competing risk analysis was used to estimate cumulative incidence of LITT failure. Results In our patient population, median time from radiotherapy to LITT was 13.1 months. Median SRS dose and median LITT treatment target volume were 20 Gy (IQR 18-22) and 3.5 cc (IQR 2.2-4.6), respectively. Seventy-seven percent of our patients tapered off steroids within one month. There were only two instances of RN recurrence after LITT, with recurrence defined as recurrence of symptoms after initial improvement. These recurrences occurred at 1.9 and 3.4 months. The three-, six- and nine-month freedom from recurrence rates were 95.7%, 90.9%, and 90.9%. Median survival in our patient population with pathologically confirmed RN treated with LITT was 2.1 years. Regarding the quality of life questionnaires with which some patients were followed as part of different prospective studies, completion rates were 22/30 for FACT-Br, 16/30 for the EQ-5D and 8/30 for HVLT. Quality of life questionnaire results were overall stable from baseline. Mean FACT-Br scores were stable from baseline (17.9, 16.6, 21.4 and 22.8) to three months (18.8, 15.4, 18.4 and 23.4) (p=0.38, 0.53, 0.09 and 0.59). The mean EQ-5D Aggregate score was stable from baseline (7.1) to one month (7.6) (p=0.25). Mean HVLT-R Total Recall was stable from baseline (20.6) to three months (18.4) (p=0.09). There was a statistically significant decrease in mean Karnofsky Performance Scale (KPS) score from baseline (84) to three-month follow-up (75) (p=0.03). Conclusions LITT represents a safe and durably effective treatment option for RN in the brain. Results demonstrate a median survival of 2.1 years from LITT with only two recurrences, both within four months of treatment and salvageable. Patient-reported outcomes showed no severe declines after LITT. Quality of life questionnaires demonstrated stable well-being and functionality from baseline. LITT should be considered for definitive treatment of RN, especially in cases where patients have significant side effects from standards medical therapies such as steroids or if steroids are minimally effective.

Magnetic resonance-guided stereotactic laser ablation therapy for the treatment of pediatric brain tumors: a multiinstitutional retrospective study.

OBJECTIVE: This study aimed to assess the safety and efficacy of MR-guided stereotactic laser ablation (SLA) therapy in the treatment of pediatric brain tumors. METHODS: Data from 17 North American centers were retrospectively reviewed. Clinical, technical, and radiographic data for pediatric patients treated with SLA for a diagnosis of brain tumor from 2008 to 2016 were collected and analyzed. RESULTS: A total of 86 patients (mean age 12.2 ± 4.5 years) with 76 low-grade (I or II) and 10 high-grade (III or IV) tumors were included. Tumor location included lobar (38.4%), deep (45.3%), and cerebellar (16.3%) compartments. The mean follow-up time was 24 months (median 18 months, range 3-72 months). At the last follow-up, the volume of SLA-treated tumors had decreased in 80.6% of patients with follow-up data. Patients with high-grade tumors were more likely to have an unchanged or larger tumor size after SLA treatment than those with low-grade tumors (OR 7.49, p = 0.0364). Subsequent surgery and adjuvant treatment were not required after SLA treatment in 90.4% and 86.7% of patients, respectively. Patients with high-grade tumors were more likely to receive subsequent surgery (OR 2.25, p = 0.4957) and adjuvant treatment (OR 3.77, p = 0.1711) after SLA therapy, without reaching significance. A total of 29 acute complications in 23 patients were reported and included malpositioned catheters (n = 3), intracranial hemorrhages (n = 2), transient neurological deficits (n = 11), permanent neurological deficits (n = 5), symptomatic perilesional edema (n = 2), hydrocephalus (n = 4), and death (n = 2). On long-term follow-up, 3 patients were reported to have worsened neuropsychological test results. Pre-SLA tumor volume, tumor location, number of laser trajectories, and number of lesions created did not result in a significantly increased risk of complications; however, the odds of complications increased by 14% (OR 1.14, p = 0.0159) with every 1-cm3 increase in the volume of the lesion created. CONCLUSIONS: SLA is an effective, minimally invasive treatment option for pediatric brain tumors, although it is not without risks. Limiting the volume of the generated thermal lesion may help decrease the incidence of complications.

Nurse-led care is preferred over GP-led care of gout and improves gout outcomes: results of Nottingham Gout Treatment Trial follow-up study.

OBJECTIVES: To explore patient satisfaction, gout knowledge, medication adherence and flares among participants receiving nurse-led or general practitioner (GP)-led care of gout in the Nottingham Gout Treatment Trial phase-II (NGTT-II). METHODS: A total of 438 participants of NGTT-II were sent a questionnaire enquiring about gout knowledge, satisfaction with health-care practitioner, urate-lowering treatment being undertaken, and gout flares ⩾1 year after their final visit. Nurse-led care participants were asked about their preference for receiving gout treatment from either a GP or a nurse. RESULTS: Completed questionnaires were returned by 82% of participants. Participants previously receiving nurse-led care reported greater satisfaction with health-care practitioner (P < 0.001), had better gout knowledge (P = 0.02), were more likely to be taking urate-lowering treatment [adjusted relative risk (95% CI) 1.19 (1.09, 1.30)], and self-reported fewer flares in the previous 12 months [median (inter-quartile range) 0 (0-0) vs 1 (0-3), P < 0.001] than those receiving GP-led care. Of participants receiving nurse-led care, 41-63% indicated preference for receiving gout treatment from a nurse, while only 5-20% indicated preference for receiving treatment from GPs. CONCLUSION: The results of this study favour nurse-led care, involving individualized patient education and engagement and a treat-to-target strategy, in terms of patient acceptability, long-term adherence, and flares. Further research is required to evaluate the feasibility of implementing such a model of care in clinical practice.

The Effects of Use of a Powered and a Manual Home Oral Hygiene Regimen on Plaque and Gum Health in an Orthodontic Population.

OBJECTIVES: The objective of this study was to compare the effect of two home use oral hygiene regimens on plaque, gingivitis, and gingival bleeding on subjects undergoing orthodontic treatment with fixed appliances. METHODS: This was a randomized, parallel, single-center clinical trial. Eligible study subjects fit the following profile: age 12-65 years; nonsmoker; plaque score of = 2.0 per Bonded Bracket Index (BBI) on dentition with fixed orthodontic hardware; minimum of 10 orthodontic brackets in each arch or on all teeth from first molar to first molar; presenting with mild to moderate gingivitis, defined as a score of = 1 on at least 20 sites per Gingival Bleeding Index (GBI). Subjects with advanced periodontal disease or gingival recession were not eligible. Eligible subjects were randomized to one of two home use oral hygiene regimens: manual toothbrush plus string floss (used with a threading device) for interdental cleaning (MTF regimen); or Philips Sonicare EasyClean power toothbrush with InterCare brush head and AirFloss Pro powered device, used with BreathRx mouthrinse for interdental cleaning (Sonicare Orthodontic Regimen or SOR). All subjects brushed twice daily with standard fluoridated dentifrice and performed interdental cleaning once daily. Efficacy and safety examinations were performed at Baseline and following three and six weeks of home use of the study products, and included assessments of BBI, GBI, Modified Gingival Index (MGI), and Modified Plaque Index (MPI). RESULTS: Of 228 enrolled subjects, 223 were included in the primary analysis. For the primary endpoint, reduction in BBI score following three weeks of product use, the overall least squares (LS) mean (95% CI) reduction was 0.89 (0.84, 0.95) for SOR and 0.06 (0.01, 0.12) for MTF. Expressed as percent reduction (95% CI) from Baseline, this was 33.1% (31.1%, 35.2%) for SOR and 2.01% (-0.06%, 4.07%) for MTF. The differences between regimens were statistically significant, p < 0.0001. Statistically significant differences between regimens were observed in BBI following six weeks of product use, and also for all other efficacy variables (GBI, MGI, MPI) at Week 3 and Week 6. CONCLUSIONS: The powered oral hygiene regimen was significantly more effective than a manual regimen in reducing plaque on bracketed and non-bracketed teeth, and in reducing gingival bleeding and gingival inflammation in orthodontic subjects following three weeks of use and persisting following six weeks of use. All products were safe on oral tissues and fixed orthodontic appliances.

A Comparison of the Effects of a Powered and Manual Toothbrush on Gingivitis and Plaque: A Randomized Parallel Clinical Trial.

OBJECTIVES: To compare the effect of a powered and a manual toothbrush on gingivitis and plaque following two and four weeks of home use. METHODS: This was a randomized, parallel-design, single-blind clinical trial. Eligible participants were generally healthy non-smoking manual toothbrush users aged 18-65 years, with a plaque score of = 1.8 per Lobene and Soparkar Modified Plaque Index (MPI) following a 3-6 hour plaque accumulation period, and mild to moderate gingivitis defined as a Gingival Bleeding Index (GBI) = 1 on at least 20 sites. Subjects with advanced periodontal disease, xerostomia, excessive gingival recession, uncontrolled diabetes, and heavy deposits of calculus or rampant decay were excluded. Enrolled participants were randomly dispensed either a Philips Sonicare powered toothbrush used with the InterCare brush head (PTB) or an American Dental Association (ADA) reference manual toothbrush (MTB). Efficacy and safety variables were assessed at Baseline, and at two and four weeks following twice-daily product home use. The primary endpoint of the study was reduction of gingivitis per the Modified Gingival Index (MGI) after four weeks of home use. RESULTS: All 148 randomized subjects (74 per group) completed the study. A statistically significant difference in MGI reduction was observed between the two study groups (p < 0.001). The least square (LS) mean and standard error reduction from Baseline was 0.72 (0.04) for the PTB group compared to 0.09 (0.04) for the MTB group. Expressed as percent reduction from Baseline, the LS mean values were 35.77% (2.19%) and 4.22% (2.19%) for PTB and MTB, respectively. Statistically significant differences were also observed for MGI reduction at Week 2, as well as for MPI and GBI reduction at Weeks 2 and 4. CONCLUSIONS: The powered toothbrush was statistically significantly superior to a manual toothbrush in reducing gingival inflammation, gingival bleeding, and plaque following two and four weeks of home use.

A 3 months clinical evaluation comparing two professional bleaching systems of 25% and 40% hydrogen peroxide and extended treatment outcome using a power versus a manual toothbrush.

OBJECTIVES: To assess two professional tooth bleaching products: Philips Zoom WhiteSpeed (PZW) and Ultradent Opalescence Boost PF (UOB); and to assess bleaching maintenance after use of Philips Sonicare power toothbrush (SDC) or manual toothbrush (MTB). METHODS: There was a randomized, parallel clinical trial. Eligible subjects were 18-75 years, with VITA Classical shade (VCS) of A3 on anterior teeth. Subjects were randomized to bleaching with PZW or UOB. Tooth color and shade were assessed using VITA EasyShade (VES), VCS, and VITA Bleachedguide (VBG). Subjects returned on Days 7 and 30. On Day 30, participants were dispensed either SDC or MTB for home use until Day 90. RESULTS: A total of 135 subjects completed the study. For the primary endpoint, ΔE at Day 7, a significantly larger reduction was observed for PZW than UOB (P value = .0059). Significant differences in shade were also observed at Day 7 for VCS (P value = 0.0106), and VBG (P value = .0489). On Day 90, the SDC was statistically superior to MTB in maintaining shade per VBG and VCS, but not ΔE. CONCLUSIONS: At Day 7, PZW showed statistically greater change in overall color and shade than UOB. The SDC maintained tooth shade significantly better than MTB. Both bleaching regimens were safe. CLINICAL SIGNIFICANCE: The outcomes confirm the bleaching efficacy advantage of a lower H2 O2 dose-LED accelerated professional tooth bleaching system, compared to a higher-dose H2 O2 approach. The safety assessments via clinical intraoral exam and daily logged use of subjects' desensitizing agents, and the incidence and severity of reported sensitivity, provide evidence that both professional products are safe for use. Finally, powered tooth brushing may confer an advantage to manual tooth brushing in maintaining tooth shade-change results following professional whitening.

Implication of nurse intervention on engagement with urate-lowering drugs: A qualitative study of participants in a RCT of nurse led care.

OBJECTIVES: To explore patient perception of the role of a nurse-led complex package of care in facilitating engagement with urate-lowering therapies (ULTs) in the management of gout. METHODS: Thirty people who had participated in a randomised controlled trial investigating the effect of a nurse-led complex package of care for gout, were purposively sampled and interviewed between 18-26 months after the end of the trial. Interviews were recorded, transcribed and analysed using a modified grounded-theory approach. Data were managed using Nvivo. STATA v15 was used to describe summary statistics. RESULTS: Participants described their views and experiences of engaging with a nurse-led intervention designed to provide holistic assessment, individualised patient education, and involvement in shared decision-making for the long-term management of gout. The analysis revealed key themes in how nurse-led intervention facilitated engagement with ULT, namely by proving improved knowledge and understanding of gout and its treatment, involvement of patients in decision-making about treatment, and increased confidence about benefits from treatment. However, some treatment uncertainty and concern remained and one participant free of gout flares discontinued ULT, while another halved the dose after the end of the trial. CONCLUSIONS: This study reports data on patient experience of engaging with ULT to manage gout after receiving nurse-led care. It demonstrates that shared decision-making and the joint efforts of fully informed practitioners and patients persuades patients to engage with ULTs, and that experiencing the benefits of curative treatment motivates them to maintain adherence.

Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial.

BACKGROUND: In the UK, gout management is suboptimum, with only 40% of patients receiving urate-lowering therapy, usually without titration to achieve a target serum urate concentration. Nurses successfully manage many diseases in primary care. We compared nurse-led gout care to usual care led by general practitioners (GPs) for people in the community. METHODS: Research nurses were trained in best practice management of gout, including providing individualised information and engaging patients in shared decision making. Adults who had experienced a gout flare in the previous 12 months were randomly assigned 1:1 to receive nurse-led care or continue with GP-led usual care. We assessed patients at baseline and after 1 and 2 years. The primary outcome was the percentage of participants who achieved serum urate concentrations less than 360 µmol/L (6 mg/dL) at 2 years. Secondary outcomes were flare frequency in year 2, presence of tophi, quality of life, and cost per quality-adjusted life-year (QALY) gained. Risk ratios (RRs) and 95% CIs were calculated based on intention to treat with multiple imputation. This study is registered with www.ClinicalTrials.gov, number NCT01477346. FINDINGS: 517 patients were enrolled, of whom 255 were assigned nurse-led care and 262 usual care. Nurse-led care was associated with high uptake of and adherence to urate-lowering therapy. More patients receiving nurse-led care had serum urate concentrations less than 360 µmol/L at 2 years than those receiving usual care (95% vs 30%, RR 3·18, 95% CI 2·42-4·18, p<0·0001). At 2 years all secondary outcomes favoured the nurse-led group. The cost per QALY gained for the nurse-led intervention was £5066 at 2 years. INTERPRETATION: Nurse-led gout care is efficacious and cost-effective compared with usual care. Our findings illustrate the benefits of educating and engaging patients in gout management and reaffirm the importance of a treat-to-target urate-lowering treatment strategy to improve patient-centred outcomes. FUNDING: Arthritis Research UK.

Supplemental Vitamins and Minerals for CVD Prevention and Treatment.

The authors identified individual randomized controlled trials from previous meta-analyses and additional searches, and then performed meta-analyses on cardiovascular disease outcomes and all-cause mortality. The authors assessed publications from 2012, both before and including the U.S. Preventive Service Task Force review. Their systematic reviews and meta-analyses showed generally moderate- or low-quality evidence for preventive benefits (folic acid for total cardiovascular disease, folic acid and B-vitamins for stroke), no effect (multivitamins, vitamins C, D, ß-carotene, calcium, and selenium), or increased risk (antioxidant mixtures and niacin [with a statin] for all-cause mortality). Conclusive evidence for the benefit of any supplement across all dietary backgrounds (including deficiency and sufficiency) was not demonstrated; therefore, any benefits seen must be balanced against possible risks.

Bidirectional association between disturbed sleep and neuropathic pain symptoms: a prospective cohort study in post-total joint replacement participants.

BACKGROUND: Disturbed sleep is strongly correlated with chronic pain. The aim of this study was to examine the association between sleep disturbance and incident joint pain focusing on neuropathic-like pain symptoms. METHODS: A total of 423 individuals who had undergone total joint replacement (TJR) for osteoarthritis were assessed at the mean time of 3.6 years post-surgery and again at 5.9 years post-TJR, using the Medical Outcomes Survey sleep subscale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and painDETECT questionnaire instruments. Cox hazard ratios (HRs) and 95% confidence intervals (CIs) were computed adjusting for age, body mass index, sex, and use of hypnotic and analgesic medication. RESULTS: The presence of neuropathic pain symptoms predicted incidence of disturbed sleep after adjustment for covariates and pain severity (adjusted HR [aHR] 2.01, 95% CI: 1.00-4.10; p<0.05). There was no association between joint pain and incidence of disturbed sleep when individuals with neuropathic pain symptoms at the baseline visit were excluded (aHR 1.11, 95% CI: 0.47-2.67). Disturbed sleep at baseline predicted incident neuropathic joint pain symptoms (aHR 2.75, 95% CI: 1.21-6.26; p<0.016) but had no effect on incidence of joint pain when all types of pain were considered together (aHR 0.63, 95% CI: 0.30-1.39). CONCLUSION: These data suggest a causal bidirectional link between sleep disturbance and joint pain with neuropathic features but not with other types of joint pain.

Brief Report: Monosodium Urate Monohydrate Crystal Deposits Are Common in Asymptomatic Sons of Patients With Gout: The Sons of Gout Study.

OBJECTIVE: To estimate the prevalence and distribution of asymptomatic monosodium urate monohydrate (MSU) crystal deposition in sons of patients with gout. METHODS: Patients with gout were mailed an explanatory letter with an enclosed postage-paid study packet to mail to their son(s) age ≥20 years old. Sons interested in participating returned a reply form and underwent telephone screening. Subsequently, they attended a study visit at which blood and urine samples were obtained and musculoskeletal ultrasonography was performed, with the sonographer blinded with regard to the subject's serum urate level. Images were assessed for double contour sign, intraarticular or intratendinous aggregates/tophi, effusion, and power Doppler signal. Logistic regression was used to examine associations. Adjusted odds ratios (ORadj ) and 95% confidence intervals (95% CIs) were calculated. RESULTS: One hundred thirty-one sons (mean age 43.8 years, mean body mass index 27.1 kg/m2 ) completed assessments. The serum urate level was ≥6 mg/dl in 64.1%, and 29.8% had either a double contour sign or intraarticular aggregates/tophi in ≥1 joint. All participants with MSU deposition had involvement of 1 or both first metatarsophalangeal joints. Intratendinous aggregates were present in 21.4% and were associated with intraarticular MSU crystal deposits (ORadj 2.96 [95% CI 1.17-7.49]). No participant with a serum urate level of ≤5 mg/dl had MSU crystal deposition seen on ultrasonography, and 24.2% of those with serum urate levels between 5 and 6 mg/dl had ultrasonographic MSU deposition. MSU crystal deposition was associated with increasing serum urate levels (ORadj 1.61 [95% CI 1.10-2.36] for each increase of 1 mg/dl). CONCLUSION: Asymptomatic sons of patients with gout frequently have hyperuricemia and MSU crystal deposits. In this study MSU crystal deposits were present in participants with serum urate levels of ≥5 mg/dl. Evaluation of subjects without a family history of gout is needed to determine whether the threshold for MSU crystal deposition is also lower in the general population.

First validation of the gout activity score against gout impact scale in a primary care based gout cohort.

OBJECTIVES: To validate the gout activity score (GAS) against the gout impact scale in a primary care based gout cohort. METHODS: This was a single-centre cross-sectional study. People with gout who participated in previous research at academic rheumatology, University of Nottingham, UK, and consented for participation in future studies were mailed a questionnaire in September 2015. Those returning completed questionnaires were invited to attend for a study visit at which blood was collected and musculoskeletal examination was performed. The Gout Assessment Questionnaire, which contains the gout impact scale (GIS), and short form (SF) 36v2 questionnaires were completed. The GAS3-step-c score was calculated. Spearman's correlation coefficient was calculated to examine correlation between GAS and SF-36 v2, and GIS. Statistical analyses were performed using PASW v22. RESULTS: One hundred and two (93% men) of the 150 participants who were mailed a questionnaire attended the study visit. Their mean (SD) age, body mass index, serum uric acid and GAS were 67.94 (9.93) years, 29.96 (4.57) kg/m2, 5.25 (1.75) mg/dl, and 2.99 (0.74) respectively. There was moderate correlation between GAS and gout concern overall, unmet gout treatment need, and gout concern during an attack components of GIS (r=0.306 to 0.453), but no to poor correlation between GAS and summary scores and scales of SF-36 v2 (r=-0.090 to -0.251). CONCLUSION: This first study to validate GAS against the GIS found moderate correlation. However, this study did not examine the predictive validity of GAS, and prospective studies are needed before GAS can be used widely.

Amplified hearing device use in acute care settings for patients with hearing loss: A feasibility study.

The objective of this study was to assess the feasibility of using amplified hearing devices (AHD) in acute care settings for patients with hearing loss. Secondary objectives include patient and nurse satisfaction, and nursing perceived productivity. Twenty-five adult hard of hearing patients and 15 nurses were evaluated. Patients with a perceived hearing handicap were identified through the Hearing Handicap for the Elderly Screening Version. Patient and staff nurse surveys were used to assess for satisfaction with using the AHD. Nurses were surveyed to evaluate whether they felt the AHD made patient communication more efficient and effective. Twenty-four patients expressed satisfaction with the AHD and would use it in future hospitalizations. Nurses also reported satisfaction, perceived improvement of patient communication and decreased time spent communicating with patients. Results demonstrate the feasibility of using an AHD in acute care inpatient settings where elderly hard of hearing patients are common.

Neuropathic pain-like symptoms and pre-surgery radiographic severity contribute to patient satisfaction 4.8 years post-total joint replacement.

AIM: To investigate a comprehensive range of factors that contribute to long-term patient satisfaction post-total joint replacement (TJR) in people who had undergone knee or hip replacement for osteoarthritis. METHODS: Participants (n = 1151) were recruited from Nottinghamshire post-total hip or knee replacement. Questionnaire assessment included medication use, the pain-DETECT questionnaire (PDQ) to assess neuropathic pain-like symptoms (NP) and TJR satisfaction measured on average 4.8 years post-TJR. Individual factors were tested for an association with post-TJR satisfaction, before incorporating all factors into a full model. Data reduction was carried out using LASSO and receiver operator characteristic (ROC) curve analysis was used to quantify the contribution of variables to post-TJR satisfaction. RESULTS: After data reduction, the best fitting model for post-TJR satisfaction included various measures of pain, history of revision surgery, smoking, pre-surgical X-ray severity, WOMAC function scores and various comorbidities. ROC analysis of this model gave AUC = 0.83 (95%CI: 0.80-0.85). PDQ scores were found to capture much of the variation in post-TJR satisfaction outcomes: AUC = 0.79 (0.75-0.82). Pre-surgical radiographic severity was associated with higher post-TJR satisfaction: ORsatisfied = 2.06 (95%CI: 1.15-3.69), P = 0.015. CONCLUSION: These results highlight the importance of pre-surgical radiographic severity, post-TJR function, analgesic medication use and NP in terms of post-TJR satisfaction. The PDQ appears to be a useful tool in capturing factors that contribute to post-TJR satisfaction.

Triggers of acute attacks of gout, does age of gout onset matter? A primary care based cross-sectional study.

OBJECTIVES: To determine the proportion of people with gout who self-report triggers of acute attacks; identify the commonly reported triggers, and examine the disease and demographic features associated with self-reporting any trigger(s) of acute attacks of gout. METHODS: Individuals with gout were asked to fill a questionnaire enquiring about triggers that precipitated their acute gout attacks. Binary logistic regression was used to compute odds ratio (OR) and 95% confidence intervals (CI) to examine the association between having ≥1 self-reported trigger of acute gout and disease and demographic risk factors and to adjust for covariates. All statistical analyses were performed using STATA. RESULTS: 550 participants returned completed questionnaires. 206 (37.5%) reported at least one trigger of acute attacks, and less than 5% reported >2 triggers. Only 28.73% participants reported that their most recent gout attack was triggered by dietary or lifestyle risk factors. The most frequently self-reported triggers were alcohol intake (14.18%), red-meat or sea-food consumption (6%), dehydration (4.91%), injury or excess activity (4.91%), and excessively warm or cold weather (4.36% and 5.45%). Patients who had onset of gout before the age of 50 years were significantly more likely to identify a trigger for precipitating their acute gout attacks (aOR (95%CI) 1.73 (1.12-2.68) after adjusting for covariates. CONCLUSION: Most people with gout do not identify any triggers for acute attacks, and identifiable triggers are more common in those with young onset gout. Less than 20% people self-reported acute gout attacks from conventionally accepted triggers of gout e.g. alcohol, red-meat intake, while c.5% reported novel triggers such as dehydration, injury or physical activity, and weather extremes.