Bilateral accessory flexor indicis muscle: A case study.

Muscular variations within the upper extremities are common and widely documented. They can have a range of implications including nerve compression and misdiagnosis but are often silent. Our report herein describes a bilateral accessory muscle found in the forearm during routine cadaveric dissection. The muscle originates from the medial epicondyle of the humerus between the origins of the flexor digitorum superficialis and flexor carpi radialis muscles. The muscle is digastric, with the distal belly existing as the first lumbrical and the proximal serving as a supernumerary flexor. This functionally atavistic variation could prove clinically relevant for the purposes of donor muscle or tendon tissue as well as surgical complications and compressive neuropathies.

The relevance of false positive acid phosphatase reactions indicative of the presence of seminal fluid from oral and vaginal samples.

The Body Fluid Forum of the Association of Forensic Science Providers recognised concerns raised by forensic practitioners regarding the lack of data to inform on the incidence of significant AP (Acid Phosphatase) reactions from vaginal and oral samples, i.e. those which might be misinterpreted as indicating the presence of semen. This is particularly relevant in the light of appeal court rulings regarding the need for data to support evaluations. This paper presents collaborative data on the nature and incidence of AP reactions from vaginal and oral swabs provided by donors. The results demonstrate that caution is required with mid to strong purple AP reactions from direct testing of oral swabs and with mid purple reactions from vaginal swabs. The use of a Bayesian approach to assist with the provision of opinions regarding the presence of seminal fluid is highlighted.

Background levels of body fluids and DNA on the shaft of the penis and associated underpants in the absence of sexual activity.

This study examines the background of blood, saliva, semen and autosomal DNA on penile swabs and underpants from males in the absence of recent sexual activity. Based on the data collected by the AFSP Body Fluid Forum, the results of this study show that; there is a very low expectation of detecting blood on penile swabs and male underpants; a low expectation of detecting saliva on penile swabs and male underpants; and spermatozoa would be expected in less than a quarter of penile swabs and three quarters of male underpants. As none of the samples had detectable levels of DNA which were suitable for meaningful comparison that did not match the donor or their partner, the expectation of detecting a DNA profile from the cellular background on penile swabs or underpants from a male who has not been involved in recent sexual intercourse is very low. The results of this study are extremely informative when evaluating the significance of blood, saliva, semen and DNA detected on the penile swabs and underpants of males in cases of alleged sexual assault.

Guideline-discordant care among females undergoing groin hernia repair: the importance of sex as a biologic variable.

PURPOSE: Females suffer higher rates of operative recurrence and chronic pain following groin hernia repair. Guidelines recommend minimally invasive (MIS) groin hernia repair as the preferred approach to reduce these adverse outcomes. It is unknown what proportion of females receive MIS hernia repair. Therefore, our goal was to investigate adoption of evidence-based practices in groin hernia repair using sex as a biological variable. METHODS: Retrospective cohort study of adults undergoing elective groin hernia repair (2014-2019) within a statewide quality improvement collaborative. Primary outcome was surgical approach. Multivariable logistic regression was performed to analyze the likelihood of undergoing MIS hernia repair. Secondary outcomes were 30-day adjusted rates of clinical and patient-reported outcomes (PROs). PROs included regret to undergo surgery among patients who completed post-operative surveys. RESULTS: Among 23,723 patients, the majority (90.7%) were males. Compared to males, females less often underwent an MIS surgical approach (37.4% vs 45.1%, p < 0.0001). After adjustment for patient and clinical variables, females remained significantly less likely to undergo MIS groin hernia repair (aOR 0.88, 95% CI 0.80-0.97). Adjusted clinical outcomes were not different between males and females. Among 4325 patients who completed post-operative surveys, adjusted rates of regret to undergo surgery were higher among females (12.9% vs 8.5%, p = 0.003). CONCLUSIONS: Even after adjusting for differences, females were less likely to receive guideline-concordant groin hernia repair and were more likely to regret surgery. Understanding the behaviors of surgeons who treat females with groin hernia may inform quality metrics to promote best practices in this population.

Polygenic Risk Scoring is an Effective Approach to Predict Those Individuals Most Likely to Decline Cognitively Due to Alzheimer's Disease.

BACKGROUND: There is a clear need for simple and effective tests to identify individuals who are most likely to develop Alzheimer's Disease (AD) both for the purposes of clinical trial recruitment but also for improved management of patients who may be experiencing early pre-clinical symptoms or who have clinical concerns. OBJECTIVES: To predict individuals at greatest risk of progression of cognitive impairment due to Alzheimer's Disease in individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) using a polygenic risk scoring algorithm. To compare the performance of a PRS algorithm in predicting cognitive decline against that of using the pTau/Aß1-42 ratio CSF biomarker profile. DESIGN: A longitudinal analysis of data from the Alzheimer's Disease Neuroimaging Initiative study conducted across over 50 sites in the US and Canada. SETTING: Multi-center genetics study. PARTICPANTS: 515 subjects who upon entry to the study were diagnosed as cognitively normal or with mild cognitive impairment. MEASUREMENTS: Use of genotyping and/or whole genome sequencing data to calculate polygenic risk scores and assess ability to predict subsequent cognitive decline as measured by CDR-SB and ADAS-Cog13 over 4 years. RESULTS: The overall performance for predicting those individuals who would decline by at least 15 ADAS-Cog13 points from a baseline mild cognitive impairment in 4 years was 72.8% (CI:67.9-77.7) AUC increasing to 79.1% (CI: 75.6-82.6) when also including cognitively normal participants. Assessing mild cognitive impaired subjects only and using a threshold of greater than 0.6, the high genetic risk participant group declined, on average, by 1.4 points (CDR-SB) more than the low risk group over 4 years. The performance of the PRS algorithm tested was similar to that of the pTau/Aß1-42 ratio CSF biomarker profile in predicting cognitive decline. CONCLUSION: Calculating polygenic risk scores offers a simple and effective way, using DNA extracted from a simple mouth swab, to select mild cognitively impaired patients who are most likely to decline cognitively over the next four years.

Correlates of infection with Helicobacter pylori positive and negative cytotoxin-associated gene A phenotypes among Arab and Jewish residents of Jerusalem.

We examined the prevalence and correlates of Helicobacter pylori (H. pylori) infection according to cytotoxin-associated gene A (CagA) phenotype, a main virulence antigen, among the ethnically diverse population groups of Jerusalem. A cross-sectional study was undertaken in Arab (N = 959) and Jewish (N = 692) adults, randomly selected from Israel's national population registry in age-sex and population strata. Sera were tested for H. pylori immunoglobulin G (IgG) antibodies. Positive samples were tested for virulence IgG antibodies to recombinant CagA protein, by enzyme-linked immunosorbent assay. Multinomial regression models were fitted to examine associations of sociodemographic factors with H. pylori phenotypes. H. pylori IgG antibody sero-prevalence was 83.3% (95% confidence interval (CI) 80.0%-85.5%) and 61.4% (95% CI 57.7%-65.0%) among Arabs and Jews, respectively. Among H. pylori positives, the respective CagA IgG antibody sero-positivity was 42.3% (95% CI 38.9%-45.8%) and 32.5% (95% CI 28.2%-37.1%). Among Jews, being born in the Former Soviet Union, the Middle East and North Africa, vs. Israel and the Americas, was positively associated with CagA sero-positivity. In both populations, sibship size was positively associated with both CagA positive and negative phenotypes; and education was inversely associated. In conclusion, CagA positive and negative infection had similar correlates, suggesting shared sources of these two H. pylori phenotypes.

Oral reserpine administration in horses results in low plasma concentrations that alter platelet biology.

BACKGROUND: Reserpine is a popular drug in the equine industry for long-term tranquilisation. Clinical observations revealed that blood from horses receiving oral reserpine was hypercoagulable. No studies have documented the pharmacokinetics of orally administered reserpine nor the effects of reserpine on platelets in horses. OBJECTIVES: To evaluate the pharmacokinetics of oral reserpine in horses and the effects of clinically relevant concentrations of reserpine on platelet functionality in vitro. STUDY DESIGN: Experimental controlled study. METHODS: The pharmacokinetics of oral reserpine (2.5 mg/horse, once) were determined in six healthy adult horses. Plasma samples were collected and concentrations of reserpine were determined by UPLC-MS/MS. Using this data, the in vitro effects of reserpine on platelets were examined. Aggregation, adhesion and releasate assays for serotonin and thromboxane B2 were performed on platelets exposed to varying concentrations of reserpine (0.01-10 ng/mL), aspirin (negative control) and saline (unexposed control). RESULTS: Oral reserpine administration demonstrated low plasma concentrations with a Cmax of 0.2 ± 0.06 ng/mL and a prolonged half-life of 23.6 ± 6.24 h. Simulations over a dose range of 2-8 µg/kg predicted Cmax at steady state between 0.06-0.9 ng/mL. Platelets exposed to these reserpine concentrations in vitro displayed increased aggregation and adhesion compared to unexposed or aspirin-exposed platelets as well as compared to higher concentrations of reserpine. These functional changes correlated with lower concentrations of serotonin and higher concentrations of thromboxane B2 in the platelet suspension supernatant. MAIN LIMITATIONS: This study used a small number of horses and only in vitro platelet experiments. CONCLUSIONS: Oral reserpine demonstrates low plasma concentrations and a prolonged half-life in horses. At these concentrations, reserpine causes significant changes in platelet function, most likely due to serotonin release and re-uptake which primes platelets for activation and thromboxane B2 release. These findings suggest that clinicians should harvest blood for biological processing prior to the onset of reserpine administration.

Time since intercourse (TSI) data from a large-scale casework study of penile-vaginal penetration allegations using Sperm Elution​™.

Time since intercourse (TSI) expectations are dependent on the method used to recover spermatozoa from vaginal swabs. TSI data following Sperm Elution™ is presented from a large scale study of 2269 cases of penile-vaginal penetration sexual assault allegations analysed by Cellmark Forensic Services and is compared to published TSI data generated using two different water-based elution methods Sperm Elution recovered spermatozoa in 32% of cases analysed where the alleged offence had occurred 3-4 days previously, significantly above the level detected using other elution methods. The improvements afforded by Sperm Elution in the ability to generate clearly distinguishable male DNA profiles from samples containing low levels of spermatozoa, and the recovery of further spermatozoa from swabs previously subjected to water-based elution methods are also discussed.

DNA transfer through nonintimate social contact.

The UK and Ireland Association of Forensic Science Providers' (AFSP) Body Fluid Forum (BFF) set out to assist in the interpretation of sexual offence cases where semen is absent on vaginal swabs but female DNA is present on penile swabs or male underwear, and the issue to be addressed is whether or not sexual intercourse occurred. This study aims to investigate the frequency and amount of female DNA transferred to the penis and underwear of males following staged nonintimate social contact with females and to compare the findings with the amount of female DNA transferred to the penis and subsequently to the underwear of a male who had engaged in unprotected sexual intercourse with a female. In this study, no matching female DNA was detected on the inside front of the 44 items of male underwear used in this research following staged contact of a nonintimate nature and subsequent secondary transfer to the penis. After sexual intercourse, full profiles matching the female participant were found on the inside front of the males underwear with maximum peak heights in the range between 1898 and 3157 rfu. It was possible to demonstrate that DNA can occasionally transfer to the waistband and outside front of underwear worn by a male following staged nonintimate social contact. Data obtained in this study suggest that a matching female DNA profile below a peak height of 1000 rfu on the waistband of a male's underwear might be explained by nonintimate social contact with secondary transfer of female DNA from the male's hands.

Psychotropic prescribing patterns among adolescents in Northern Ireland presenting with psychotic symptoms during a 5-year period.

OBJECTIVE: To report new prescriptions of psychotropic medications among adolescents presenting with new onset psychotic symptoms during a 5-year period. METHODS: The Northern Ireland Early Onset Psychosis Study is a naturalistic longitudinal observational study of patients with an early onset first psychotic episode. All patients aged <18 years presenting to specialist mental health services across Northern Ireland with new onset psychotic symptoms between 2001 and 2006 were recruited (n=113). Clinical case notes were analysed retrospectively for details of subsequent treatment with psychotropic medications. RESULTS: A total of 100 patients (88.5%) were prescribed some form of psychotropic medication. Over three-quarters of patients received an antipsychotic as their first medication. Risperidone (45.8%), olanzapine (24.0%) and chlorpromazine (12.5%) were the most commonly prescribed first-line antipsychotic medications. Of a total of 160 antipsychotic prescriptions, 81 (50.6%) were off-label. Prescriptions were most likely to have been deemed off-label owing to medications not being licensed in under-18s (71.6% of off-label prescriptions) but other reasons were medications being used outside licensed age ranges (23.5%) and outside licensed indications (4.9%). CONCLUSIONS: This is the first study examining psychotropic prescribing patterns in a complete sample of all children and adolescents presenting with early onset psychotic episodes in a single geographical area. The observation of risperidone as the most commonly prescribed antipsychotic was in keeping with previous studies in child and adolescent populations. Rates of off-label prescribing were lower than previously observed although our study was the first to investigate off-label prescribing solely in children and adolescents presenting with psychotic symptoms.

Initial evaluation of a canine stifle arthrotomy post-operative pain model.

Most models of acute post-operative orthopedic pain involve the injection of a clinically irrelevant pro-inflammatory agent. The ideal model should, however, be clinically relevant and allow full functional recovery of enrolled animals after research is completed. This study explored the validity of a model employing arthrotomy and objectively measured limb use. Six purpose-bred Beagles underwent arthrotomies on each stifle with a washout period in between. Using a randomized crossover design, each dog received placebo and an extended-release buprenorphine (ER-Bup) preparation. Static and dynamic ground reaction forces (GRFs) were measured prior to and for 72 h following surgery using a pressure sensitive walkway (PSW). GRFs for each hind limb were compared using difference (delta), and symmetry indices (SI). The effects of surgery and of treatment were analyzed using repeated measures ANCOVA. The results indicated significantly decreased limb use compared to baseline for placebo, and significantly increased limb use in the ER-Bup group over placebo at all times for % bodyweight distribution (%BWdistrib), peak vertical force (PVF) and vertical impulse (VI). There was a significant treatment by time interaction for velocity (P = 0.03) and %BWdistrib (P = 0.01, 0.003). Overall, the data show that reduced limb use was present for at least 72 h following arthrotomy. In addition, the use of the ER-Bup analgesic decreased lameness, confirming the validity of this approach as a model of post-operative pain. Subjective assessments did not detect the pain-inducing effects of arthrotomy or pain-alleviating effects of treatment, and subjective measures of procedural pain in research dogs need to be developed.

TRIM25 has a dual function in the p53/Mdm2 circuit.

P53 is an important tumor suppressor that, upon activation, induces growth arrest and cell death. Control of p53 is thus of prime importance for proliferating cells, but also for cancer therapy, where p53 activity contributes to the eradication of tumors. Mdm2 functionally inhibits p53 and targets the tumor suppressor protein for degradation. In a genetic screen, we identified TRIM25 as a novel regulator of p53 and Mdm2. TRIM25 increased p53 and Mdm2 abundance by inhibiting their ubiquitination and degradation in 26 S proteasomes. TRIM25 co-precipitated with p53 and Mdm2 and interfered with the association of p300 and Mdm2, a critical step for p53 polyubiquitination. Despite the increase in p53 levels, p53 activity was inhibited in the presence of TRIM25. Downregulation of TRIM25 resulted in an increased acetylation of p53 and p53-dependent cell death in HCT116 cells. Upon genotoxic insults, TRIM25 dampened the p53-dependent DNA damage response. The downregulation of TRIM25 furthermore resulted in massive apoptosis during early embryogenesis of medaka, which was rescued by the concomitant downregulation of p53, demonstrating the functional relevance of the regulation of p53 by TRIM25 in an organismal context.

CD44 functions in Wnt signaling by regulating LRP6 localization and activation.

Wnt reception at the membrane is complex and not fully understood. CD44 is a major Wnt target gene in the intestine and is essential for Wnt-induced tumor progression in colorectal cancer. Here we show that CD44 acts as a positive regulator of the Wnt receptor complex. Downregulation of CD44 expression decreases, whereas CD44 overexpression increases Wnt activity in a concentration-dependent manner. Epistasis experiments place CD44 function at the level of the Wnt receptor LRP6. Mechanistically, CD44 physically associates with LRP6 upon Wnt treatment and modulates LRP6 membrane localization. Moreover, CD44 regulates Wnt signaling in the developing brain of Xenopus laevis embryos as shown by a decreased expression of Wnt targets tcf-4 and en-2 in CD44 morphants.

Evaluation of the effect of orally administered acid suppressants on intragastric pH in cats.

BACKGROUND: Acid suppressant drugs are a mainstay of treatment for cats with gastrointestinal erosion and ulceration. However, clinical studies have not been performed to compare the efficacy of commonly PO administered acid suppressants in cats. HYPOTHESIS/OBJECTIVES: To compare the effect of PO administered famotidine, fractionated omeprazole tablet (fOT), and omeprazole reformulated paste (ORP) on intragastric pH in cats. We hypothesized that both omeprazole formulations would be superior to famotidine and placebo. ANIMALS: Six healthy adult DSH colony cats. METHODS: Utilizing a randomized, 4-way crossover design, cats received 0.88-1.26 mg/kg PO q12h fOT, ORP, famotidine, and placebo (lactose capsules). Intragastric pH monitoring was used to continuously record intragastric pH for 96 hours beginning on day 4 of treatment. Plasma omeprazole concentrations at steady state (day 7) were determined by high performance liquid chromatography (HPLC) with ultraviolet detection. Mean percentage time that intragastric pH was ≥ 3 and ≥ 4 were compared among groups using ANOVA with a posthoc Tukey-Kramer test (α = 0.05). RESULTS: The mean percentage time ± SD that intragastric pH was ≥ 3 was 68.4 ± 35.0% for fOT, 73.9 ± 23.2% for ORP, 42.8 ± 18.6% for famotidine, and 16.0 ± 14.2% for placebo. Mean ± SD plasma omeprazole concentrations were similar in cats receiving fOT compared to those receiving ORP and in a range associated with acid suppression reported in other studies. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest that both omeprazole formulations provide superior acid suppression in cats compared to famotidine or placebo. Fractionated enteric-coated OT is an effective acid suppressant despite disruption of the enteric coating.

Feline musculoskeletal pain index: responsiveness and testing of criterion validity.

BACKGROUND: Progress in establishing if therapies provide relief to cats with degenerative joint disease (DJD)-associated pain is hampered by a lack of validated owner-administered assessment methods. HYPOTHESIS: That an appropriately developed subjective owner-completed instrument (Feline Musculoskeletal Pain Index-FMPI) to assess DJD-associated impairment would have responsiveness and criterion validity. ANIMALS: Twenty-five client-owned cats with DJD-associated pain. METHODS: FMPI responsiveness (ability to detect the effect of an analgesic treatment) and validity (correlation with an objective measure) were explored through a stratified, randomized, double blinded, placebo-controlled, crossover 10-week clinical study. Meloxicam was administered to effect pain relief. A linear mixed model, backward stepwise regression, and Pearson correlations were used to assess responsiveness and criterion validity with the assumption that the NSAID would increase activity. RESULTS: Positive responses of cats to placebo (P = .0001) and meloxicam treatment (P = .0004) were detected; however, the instrument did not detect any difference between placebo and meloxicam (linear mixed model), even for the high impairment cases. Percent meloxicam target dose administered, temperament, and total baseline FMPI score were covariates that most affected FMPI scores. Controlling for significant covariates, most positive effects were seen for placebo treatment. Positive treatment effects on activity were detected, but only for the cases designated as most highly impaired. CONCLUSIONS AND CLINICAL IMPORTANCE: Neither responsiveness nor criterion validity were detected by the inclusion criteria for cases in this study. The data suggest that further work is indicated to understand factors affecting activity in cats to optimize inclusion criteria.

Ronidazole pharmacokinetics in cats following delivery of a delayed-release guar gum formulation.

Ronidazole (RDZ) is the only known effective treatment for feline diarrhea caused by Tritrichomonas foetus. This study aimed to develop guar gum-coated colon-targeted tablets of RDZ and to determine the pharmacokinetics of this delayed-release formulation in cats. Guar gum-coated tablets were administered orally once to five healthy cats (mean dose 32.3 mg/kg). The tablets were then administered once daily for 5 days to four cats (mean dose 34.5 mg/kg), and absorption studies repeated on day 5. Plasma was collected and analyzed for RDZ concentration, and pharmacokinetic noncompartmental and deconvolution analysis were performed on the data. There was negligible RDZ release until after 6 h, and a delayed peak plasma concentration (mean Cmax 28.9 µg/mL) at approximately 14.5 h, which coincides with colonic arrival in cats. Maximum input rate (mg/kg per hour) occurred between 6 and 16 h. This delayed release of ronidazole from guar gum-coated tablets indicates that release of RDZ may be delayed to deliver the medication to a targeted area of the intestine. Repeated dosing with guar gum tablets to steady-state did not inhibit drug bioavailability or alter the pharmacokinetics. Such targeted RDZ drug delivery may provide improved efficacy and reduce adverse effects in cats.

Acid phosphatase screening - wetting test paper or wetting fabric and test paper?

Detecting and locating semen stains is addressed by identifying the associated acid phosphatase activity of semen. The recovery of semen stains is critical as it can, via DNA testing, address the possible source(s) of the semen and may aid in the interpretation of a case. The purpose of these experiments, carried out on behalf of the Body Fluids Forum, was to consider whether wetting the test paper alone or wetting the semen stained fabric and the test paper affected the detection and location of the semen stains on various fabric types, or the subsequent recovery of spermatozoa from these fabrics. It became evident that the preferred approach varied depending on the fabric type being tested but that more often than not, wetting both the fabric and the test paper had a detrimental effect on the recovery of spermatozoa.

Esophageal impedance baselines in infants before and after placebo and proton pump inhibitor therapy.

BACKGROUND: Esophageal impedance monitoring records changes in conductivity. During esophageal rest, impedance baseline values may represent mucosal integrity. The aim of this study was to assess the influence of acid suppression on impedance baselines in a placebo-controlled setting. METHODS: Impedance recordings from 40 infants (0-6 months) enrolled in randomized placebo-controlled trials of proton pump inhibitor (PPI) were retrospectively analyzed. Infants underwent 24 h pH-impedance monitoring prior to and after 2 weeks of double blind therapy with placebo or a PPI. Typical clinical signs of gastro-esophageal reflux (GER) were recorded and I-GERQ-R questionnaire was completed. KEY RESULTS: Median (IQR) impedance baseline increased on PPI treatment (from 1217 (826-1514) to 1903 (1560-2194) Ω, P < 0.001) but not with placebo (from 1445 (1033-1791) to 1650 (1292-1983) Ω, P = 0.13). Baselines before treatment inversely correlate with the number of GER, acid GER, weakly acid GER, acid exposure, and symptoms. The change in baseline on treatment inversely correlates with acid exposure and acid GER. Patients with initial low baselines have no improved symptomatic response to treatment. CONCLUSIONS & INFERENCES: Impedance baselines are influenced by GER and increase significantly more with PPI therapy than with placebo. Clinical impact of this observation remains undefined as targeting therapy at infants with low baselines does not improve symptomatic response to treatment.

Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort.

The hereditary sensory and autonomic neuropathies (HSAN, also known as the hereditary sensory neuropathies) are a clinically and genetically heterogeneous group of disorders, characterised by a progressive sensory neuropathy often complicated by ulcers and amputations, with variable motor and autonomic involvement. To date, mutations in twelve genes have been identified as causing HSAN. To study the frequency of mutations in these genes and the associated phenotypes, we screened 140 index patients in our inherited neuropathy cohort with a clinical diagnosis of HSAN for mutations in the coding regions of SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 (TRKA) and NGFB. We identified 25 index patients with mutations in six genes associated with HSAN (SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 and NGFB); 20 of which appear to be pathogenic giving an overall mutation frequency of 14.3%. Mutations in the known genes for HSAN are rare suggesting that further HSAN genes are yet to be identified. The p.Cys133Trp mutation in SPTLC1 is the most common cause of HSAN in the UK population and should be screened first in all patients with sporadic or autosomal dominant HSAN.

Dose reduction of meloxicam in dogs with osteoarthritis-associated pain and impaired mobility.

BACKGROUND: Progressive nonsteroidal anti-inflammatory drug (NSAID) dose reduction appears logical; however, there is no evidence-based medicine indicating that efficacy is maintained as dose is reduced. OBJECTIVE: To determine if NSAID dose can be reduced and pain relief and mobility can be maintained in dogs with osteoarthritis (OA). ANIMALS: Client-owned dogs (n = 59) with OA-associated impaired mobility and pain. METHODS: Prospective, randomized, blinded study. After 14 days wash-out, dogs were randomized to reducing dose (RDG) (n = 30) or maintenance dose (MDG) (n = 29). MDG received standard dose meloxicam. RDG received a reducing dose from D28 onward, reducing to 0% of maintenance for the final 2 weeks. Assessments were at D14, 28, 42, 56, 70, 84, 98 and 112 using subjective owner assessments, accelerometry (AM), and standing percent body weight distribution (%BW). A Kaplan-Meier survival curve described how dogs dropped out because of insufficient pain control. A Log-rank test compared the groups. RESULTS: More dogs in RDG (13) dropped out because of owner-evaluated insufficient pain control compared with MDG (5) (P = .029; odds ratio: 3.67; median dropout time: 84 days in each group). For the dogs that did not drop out (n = 41), there were no significant differences between groups in owner assessments (P > .2 for each), %BW placed on the index limb (P = .750), or accelerometer-measured activity (P = .14). CONCLUSION AND CLINICAL RELEVANCE: Dose reduction is a less effective means of pain control compared with maintained dosing. However, NSAID dose reduction with maintained efficacy is possible, but success appears to be individual dog dependent.