Efficacy and safety of dolutegravir/lamivudine in virologically suppressed female participants: week 48 data from the pooled TANGO and SALSA studies.

OBJECTIVES: Women represent >50% of people with HIV globally but have historically been underrepresented in clinical trials. We evaluated the efficacy and safety of switching to dolutegravir/lamivudine (DTG/3TC) vs continuing their current antiretroviral regimen (CAR) by sex assigned at birth (female and male) in virologically suppressed adults with HIV-1 without prior virological failure in a pooled analysis of two randomized controlled trials. METHODS: This analysis included 48-week data from the phase 3 TANGO and SALSA studies. Primary and key secondary endpoints included proportions of participants with HIV-1 RNA ≥50 and <50 copies/mL at week 48, respectively. Safety was also assessed. RESULTS: Of 1234 participants, 250 (DTG/3TC, n = 133; CAR, n = 117) were female at birth. Week 48 proportions of participants with Snapshot HIV-1 RNA ≥50 copies/mL were similar regardless of sex at birth (DTG/3TC vs CAR: female, <1% [1/133] vs 2% [2/117]; male, <1% [1/482] vs <1% [3/502]). Proportions with HIV-1 RNA <50 copies/mL were high across sexes and treatment groups (DTG/3TC vs CAR: female, 91% [121/133] vs 89% [104/117]; male, 94% [455/482] vs 94% [471/502]). Immunological response with DTG/3TC was slightly higher in female participants. Incidences of adverse events leading to withdrawal and serious adverse events were low and comparable between treatment groups and across sexes. Weight gain was higher with DTG/3TC than with CAR among female participants aged ≥50 years (treatment difference 2.08 kg [95% confidence interval 0.40-3.75]). CONCLUSIONS: Results confirm the robustness of DTG/3TC as a switch option in virologically suppressed females with HIV-1, with outcomes similar to those in males.

The role of area deprivation index in health care disruptions among cancer survivors during the SARS-CoV-2 pandemic.

OBJECTIVE: To examine the associations between demographic/medical and geographic factors with follow-up medical care and health-related quality of life (HRQoL) among cancer survivors during the SARS-CoV-2 pandemic. STUDY DESIGN: Cross-sectional survey. METHODS: An online survey was sent to cancer survivors between May 2020 and January 2021, exploring their experience with SARS-CoV-2, follow-up care, and HRQoL. PolicyMap was used to geocode home addresses. Both geographic and demographic/medical factors were examined for their associations with SARS-CoV-2 experience, follow-up care, and HRQoL (FACT-G7). RESULTS: Geographic data were available for 9651 participants. Patients living in the highest area deprivation index (ADI) neighborhoods (most deprived) had higher odds of avoiding in-person general (odds ratio [OR] = 7.20; 95% confidence interval [CI] = 2.79-18.60), cancer (OR = 8.47; 95% CI = 3.73-19.30), and emergency (OR = 14.2; 95% CI = 5.57-36.30) medical care, as well as lower odds of using telemedicine (OR = 0.61; 95% CI = 0.52-0.73) compared to the lowest ADI group. Race/ethnicity was not associated with follow-up care after controlling for ADI. The effect of ADI on HRQoL was generally in the expected direction, with higher ADI being associated with worse HRQoL. CONCLUSIONS: ADI influenced follow-up medical care more than age, race/ethnicity, or health insurance type. Healthcare providers and institutions should focus on decreasing barriers to in-person and telemedicine health care that disproportionally impact those living in more deprived communities, which are exacerbated by health care disruptions like those caused by the SARS-CoV-2 pandemic.

Efficacy of a mitral regurgitation severity index to predict long-term outcome in dogs with myxomatous mitral valve disease.

BACKGROUND: Predicting progression of myxomatous mitral valve disease (MMVD) in dogs can be challenging. HYPOTHESIS/OBJECTIVES: The mitral regurgitation severity index (MRSI) will predict time to congestive heart failure (CHF) and all-cause death in dogs with MMVD. ANIMALS: Eight hundred sixty-nine client-owned dogs. METHODS: Retrospective study pooling data from 4 previous samples including dogs with MMVD stage B2 or C. MRSI was calculated as: (heart rate [HR]/120) × left atrium-to-aorta ratio (LA:Ao) × (age in years/10) × 100. Alternative MRSI formulas substituting radiographic measures of left atrial size were also calculated. Cox proportional hazard modeling and time-dependent receiver-operator characteristic curves quantified prognostic performance. RESULTS: For Stage B2 pooled samples, MRSI > 156 was predictive of time to CHF (median 407 vs 1404 days; area under the curve [AUC] 0.68; hazard ratio 3.02 [95% CI 1.9-4.9]; P < .001). MRSI > 173 was predictive of all-cause death (median survival 868 vs 1843 days; AUC 0.64; hazard ratio 4.26 [95% CI 2.4-7.5]; P < .001). MRSI showed superior predictive value compared to the individual variables of HR, LA:Ao, and age. Variations of the MRSI equation substituting radiographic vertebral left atrial size for LA:Ao were also significantly predictive of outcome in stage B2. MRSI was not consistently predictive of outcome in Stage C. CONCLUSIONS AND CLINICAL IMPORTANCE: MRSI was predictive of outcome (onset of CHF and all-cause death) in MMVD Stage B2, demonstrating utility as a useful prognostic tool. Echocardiographic LA:Ao can be effectively replaced by radiographically determined LA size in the MRSI formula.

Heterogeneity of quality of life in the later stages of first-episode psychosis recovery.

PURPOSE: First-episode psychosis (FEP) is characterised by wide heterogeneity in terms of symptom presentation and illness course. However, the heterogeneity of quality of life (QoL) in FEP is not well understood. We investigated whether subgroups can be identified using participants' responses on four QoL domains (physical health, psychological, social relationships, and environmental) 18-months into the recovery phase of FEP. We then examined the discriminant validity of these subgroups with respect to clinical, cognitive, and functioning features of FEP. METHOD: Demographic and clinical characteristics, QoL, cognition, and functioning were assessed in 100 people with FEP at the 18-month follow-up of a randomised controlled trial of Individual Placement Support, which aims to facilitate vocational recovery. QoL was measured using the World Health Organisation's QoL-BRIEF. A two-stage clustering approach using Ward's method and Squared Euclidean Distance with a k-means confirmation was conducted. Multinomial logistic regressions were used to establish external validity. RESULTS: Three QoL subgroups emerged: a 'good' subgroup with relatively high QoL across all domains (31%), an 'intermediate' subgroup with relatively low psychological QoL (48%) and a 'poor' subgroup with markedly low social relationship QoL (21%). Negative symptoms, depressive symptoms, social/occupational functioning, and social inclusion at follow-up predicted subgroup membership. Sensitivity analysis found similar results. CONCLUSION: Although some individuals with FEP have QoL comparable to individuals without mental ill health, QoL can remain concerningly low despite treatment efforts. Future research on interventions that target factors associated with poor QoL, such as low social inclusion, is required to counteract prolonged poor QoL in FEP.

Prevalence of aldosterone breakthrough in dogs receiving renin-angiotensin system inhibitors for proteinuric chronic kidney disease.

BACKGROUND: The influence of aldosterone breakthrough (ABT) on proteinuria reduction during renin-angiotensin system (RAS) inhibition for spontaneous proteinuric chronic kidney disease (CKDP ) has not been determined in dogs. OBJECTIVES: Determine whether ABT occurs in dogs with CKDP and if it is associated with decreased efficacy in proteinuria reduction during RAS inhibitor treatment. ANIMALS: Fifty-six client-owned dogs with CKDP and 31 healthy client-owned dogs. METHODS: Prospective, multicenter, open-label clinical trial. Dogs were treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker alone or in combination at the attending clinician's discretion and evaluated at 5 time points over 6 months. Healthy dogs were used to determine the urine aldosterone-to-creatinine ratio cutoff that defined ABT. The relationship of ABT (present at ≥50% of visits) and proteinuria outcome (≥50% reduction in urine protein-to-creatinine ratio from baseline at ≥50% of subsequent visits) was evaluated. Mixed effects logistic regression was used to evaluate the relationship between clinical variables and outcomes (either successful proteinuria reduction or ABT). RESULTS: Thirty-six percent (20/56) of dogs had successful proteinuria reduction. Between 34% and 59% of dogs had ABT, depending on the definition used. Aldosterone breakthrough was not associated with proteinuria outcome. Longer duration in the study was associated with greater likelihood of successful proteinuria reduction (P = .002; odds ratio, 1.6; 95% confidence interval [CI], 1.2-2.2). CONCLUSIONS AND CLINICAL IMPORTANCE: Aldosterone breakthrough was common in dogs receiving RAS inhibitors for CKDp but was not associated with proteinuria outcome.

Anatomical variations of the superficial ulnar artery: case series observed on historical specimens prepared by Ludwik Karol Teichmann.

BACKGROUND: This report presents a series of cases representing variant origin and course of the ulnar artery, namely the superficial ulnar artery (SUA), observed during the review of collection of historical specimens prepared in the 19th century by the prominent Polish anatomist Ludwik Karol Teichmann and his collaborators, exhibited in the Anatomy Museum of Jagiellonian University Medical College. RESULTS: Three distinct variants of the SUA were found on anatomical specimens of the upper limb with arteries injected by using Teichmann's method. In case no. 1, the SUA originated from the brachial artery slightly above the interepicondylar line of the humerus. This aberrant vessel gave off the common interosseous artery in the upper half of the cubital fossa and then ran superficially to the bicipital aponeurosis and over the muscles arising from the medial epicondyle of the humerus. The cases no. 2 and 3 involved two similar variants of the superficial artery in which the common interosseous artery arose from the radial artery. In the unique case no. 4, the SUA arose from the radial artery. CONCLUSIONS: The SUA shows diverse anatomy regarding its topography and blood supply territory. Orthopaedic, hand, and plastic surgeons should be aware of anatomic variations of the SUA both in planning and in conducting surgeries of the upper limb.

Myxomatous mitral valve disease in Miniature Schnauzers and Yorkshire Terriers: 134 cases (2007-2016).

OBJECTIVE: To characterize features of myxomatous mitral valve disease (MMVD) in Miniature Schnauzers and Yorkshire Terriers. ANIMALS: 69 Miniature Schnauzers and 65 Yorkshire Terriers, each with MMVD. PROCEDURES: Medical record data for each dog were collected; the study period was January 2007 through December 2016. If available, radiographic data were evaluated, and a vertebral heart scale score was assigned for each dog. Statistical analysis was performed with Student t and Fisher exact tests. RESULTS: Compared with Yorkshire Terriers, the prevalence of MMVD was significantly higher in Miniature Schnauzers and affected dogs were significantly younger at the time of diagnosis. Miniature Schnauzers were significantly more likely to have mitral valve prolapse and syncope, compared with Yorkshire Terriers. Yorkshire Terriers were significantly more likely to have coughing and have had previous or current treatment with cardiac medications, compared with Miniature Schnauzers. There was no statistical difference between breeds with regard to abnormally high vertebral heart scale scores or radiographic evidence of congestive heart failure. CONCLUSIONS AND CLINICAL RELEVANCE: With regard to MMVD, features of the disease among Miniature Schnauzers and Yorkshire Terriers were similar, but there were also a few discernable differences between these 2 breeds and from historical findings for dogs with MMVD of other breeds. Clinical signs at the time of diagnosis differed between the 2 breeds, which may have reflected concurrent breed-specific conditions (sick sinus syndrome or airway disease [eg, tracheal collapse]). Future work should include prospective studies to provide additional information regarding the natural progression of MMVD in these dog breeds.

Reducing pain through distraction therapy in small acute paediatric burns.

INTRODUCTION: The majority of patients who sustained small (low % total body surface area [TBSA]) burns are assessed in an outpatient setting. This can be a traumatic experience, particularly, for paediatric patients. During the initial assessment pharmacological and non-pharmacological adjuncts, such as distraction therapy, can be employed to provide an environment that may reduce and minimise distress. In this study, we investigated whether distraction therapy reduces objective pain scores during the outpatient assessment of small acute burns in children. METHODS: Two cohorts of patients were formed. In the first group (group A), the children received analgesia and routine nursing care. In the second group (group B), the children received specialist distraction therapy in addition to the same analgesia and nursing care. We recorded patient demographics, TBSA, anatomical sites and mechanism of burn. The Wong Baker™ visual analogue scale (VAS) was used to convert perceived pain, as reported by the patient or parent, into a numerical value at three set intervals during the consultation. RESULTS: 50 patients were recruited with 32 patients in group A and 18 in group B. A larger TBSA positively correlated with higher pain scores (p < 0.05). At the start of the consultation the mean pain score without distraction therapy was 1.55 and with specialist distraction therapy was 0.33 (p < 0.05). The mean peak pain score during dressing change without distraction therapy was 6.80 and with specialist distraction was 4.47 (p < 0.05). At the end of the procedure, the mean pain score was 2.12 without distraction therapy and with specialist distraction 1.75. CONCLUSION: This study of pain scores in small acute paediatric burns has shown that distraction therapy provided by a qualified play specialist can reduce maximal pain by over 2 points on the Wong-Baker™ VAS. Consideration should be given to ensure that distraction therapy is available at all times during initial consultations for children who have sustained small burns.

Clinical efficacy of a benazepril and spironolactone combination in dogs with congestive heart failure due to myxomatous mitral valve disease: The BEnazepril Spironolactone STudy (BESST).

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS), when chronically activated, is harmful and RAAS-suppressive drugs are beneficial in the treatment of congestive heart failure (CHF). Mineralocorticoid receptor antagonists are widely used in the treatment of CHF in people. HYPOTHESIS/OBJECTIVES: To determine if a mineralocorticoid receptor antagonist (spironolactone) is beneficial and safe in CHF due to myxomatous mitral valve disease (MMVD) of varying severity, we hypothesized that, when combined with furosemide, a combination product (S+BNZ) containing the ACE inhibitor (ACE-I), benazepril, and spironolactone, would be superior to benazepril alone. ANIMALS: Five hundred and sixty-nine client-owned dogs, with MMVD and CHF (ACVIM Stage C) of ≤10-days' duration. METHODS: After initial stabilization, dogs were randomized into a positive-controlled, double-blind, multicenter trial, to receive furosemide plus S+BNZ or furosemide plus benazepril. The primary outcome variable was the percentage of dogs reaching cardiac endpoint before Day 360. Cardiac endpoint was defined as cardiac death or euthanasia, recurrence of pulmonary edema, necessity for nonauthorized cardiac drug(s) or a furosemide dosage >8 mg/kg/d. RESULTS: A significantly lower percentage of dogs treated with S+BNZ reached the primary outcome variable by Day 360 (OR = 0.56; 95% CI, 0.32-0.98; P = .04) and risk of dying or worsening from cardiac causes, was significantly reduced (HR = 0.73; 95% CI = 0.59-0.89, P = .002) vs benazepril alone. Adverse events, potentially associated with treatment, were rare and equal between groups. CONCLUSION AND CLINICAL IMPORTANCE: The combination of S+BNZ is effective, safe, and superior to benazepril alone, when used with furosemide for the management of mild, moderate or severe CHF caused by MMVD in dogs.

COVID-19 infection in patients with intestinal failure: UK experience.

BACKGROUND: The direct effect of the coronavirus disease 2019 (COVID-19) pandemic on patients with intestinal failure (IF) has not been described. METHODS: We conducted a nationwide study of UK IF centers to evaluate the infection rates, presentations, and outcomes in patients with types 2 and 3 IF. RESULTS: A total of 45 patients with IF contracted COVID-19 between March and August 2020; this included 26 of 2191 (1.2%) home parenteral nutrition (HPN)-dependent adults and 19 of 298 (6.4%) adults hospitalized with type 2 IF. The proportion of patients receiving nursing care for HPN administration was higher in those with community-acquired COVID-19 (66.7%) than the proportion in the entire HPN cohort (26.1%; P < .01). Two HPN-dependent and 1 hospitalized patient with type 2 IF died as a direct consequence of the virus (6.7% of 45 patients with types 2 or 3 infected). CONCLUSION: This is the first study to describe the outcomes of COVID-19 in a large cohort of patients requiring long-term PN. Methods to reduce hospital and community nosocomial spread would likely be beneficial.

Unusual formation of the musculocutaneous and median nerves: a case report refined by intraneural dissection and literature review.

This report presents a detailed anatomical investigation of an upper limb specimen showing an atypical formation of the musculocutaneous nerve (MCN) and median nerve (MN). The study was refined by intraneural dissection, which supplements earlier descriptions of similar anatomical variations and allows for revision of the accepted classification. The case described in this report was an incidental finding during routine dissection of a fixed isolated upper limb. Intraneural dissection revealed partial fusion between the MCN and aberrant bundles of the MN. Those aberrant bundles joined the main steam of the MN at the level at which the MCN branched off as an independent nerve. The procedure allowed the aberrant fibres of the MN to be differentiated from the MCN. The presence of separate bundles in a territory corresponding to the MCN was confirmed, although those bundles and the aberrant MN bundles were covered by a common epineurium. The aberrant MN bundles running within the MCN did not contribute to innervation of the forearm muscles. They rejoined the main nerve trunk in the arm. A comprehensive understanding of the diverse anatomical variations of the upper limb nerves could be crucial for the safety and success of surgical procedures, especially procedures for reconstructing the brachial plexus or its branches.

Clinical utility of liver biopsies in dogs undergoing splenectomy.

OBJECTIVE: To determine the prevalence of neoplasia detected on liver biopsy obtained at the time of splenectomy in dogs with splenic masses. MATERIALS AND METHODS: Retrospective study of medical records of dogs with splenic masses from which liver biopsies were taken following splenectomy. RESULTS: Malignant splenic neoplasia was detected in 50 of 113 (44.2%) of the dogs undergoing splenectomy. Neoplastic liver disease was detected on biopsy from 1 of 40 (2.5%) dogs with a grossly normal liver and from 20 of 69 (28.9%) dogs with a grossly abnormal liver. Dogs with a grossly abnormal liver had a ~ 16 times (95% CI: 2.5-170) higher chance of being diagnosed with liver neoplasia on biopsy. Haemoabdomen was also associated with an increased likelihood of liver neoplasia on biopsy at the time of splenectomy. CLINICAL SIGNIFICANCE: A liver biopsy taken from grossly normal liver is a low-yield diagnostic test but liver biopsy is recommended following splenectomy if the liver appears abnormal at surgery.

Treatment of dogs with severe heartworm disease.

Fortunately, the majority of dogs diagnosed with heartworm infection are asymptomatic (or have only mild symptoms such as intermittent cough) and go through adulticide therapy without complication. Complications occurring with heartworm infection and during its treatment most often directly reflect the pulmonary vascular and parenchymal injury inflicted by Dirofilaria immitis. Clinical signs may include exercise intolerance, frequent cough, hemoptysis, tachypnea, and dyspnea. Severe manifestations such as heart failure and caval syndrome may prove fatal. Acute hypersensitivity reactions after initiation of macrocyclic lactone preventive therapy in microfilaremic dogs or after melarsomine injection during adulticide therapy do occur, but are uncommon. This article reviews complications associated with heartworm infection.

Non-Arsenical heartworm adulticidal therapy using topical moxidectin-imidacloprid and doxycycline: A prospective case series.

This prospective case series evaluated the adulticidal efficacy of topical 10 % moxidectin/2.5 % imidacloprid (M/I; Advantage Multi®, Bayer, Shawnee Mission, KS, USA) and doxycycline in dogs with naturally occurring heartworm infection (HWI). Twenty-two dogs with HWI whose owners declined melarsomine were treated with M/I at the preventive dosage twice monthly for 90 days then monthly thereafter and doxycycline (median [interquartile range; IQR] dosage 12.6 [12.0-16.1] mg/kg/day) for the first 15 days. Although strict activity restriction was not imposed, owners were asked to prevent their dogs from exercising strenuously. This protocol was referred to as the MOXY protocol. Antigen testing was performed every 30-60 days, until dogs had 'no antigen detected' (NAD). Twenty-one of the 22 dogs ultimately converted to NAD by 434 days (median [IQR]), 234 (179-303). One dog remained positive 701 days after MOXY initiation and was considered a treatment failure. All sera which converted to NAD on HW antigen testing were retested after heat-treatment. Twelve dogs had NAD on the heat-treated test on the same day as having their first NAD on the conventional test. Six of 9 dogs testing positive after heat-treatment were retested and all 6 had NAD on a heat-treated test within 2-3 months. Microfilaremia was cleared in all 8 dogs re-tested. Four dogs required treatment for cough, thought due to heartworm (HW) death, an average of 89 days after initiation of MOXY. This cough was most likely due to pneumonitis with heartworm-pulmonary thromboembolism. One dog required hospitalization for 24 -h and recovered fully with corticosteroid therapy and supportive care and 2 dogs were treated in an outpatient fashion with steroids. The MOXY protocol was tolerated and 96 % (21/22) of dogs converted to NAD, though 2 dogs required greater than 1 year to achieve this result. Nonaresenical-adulticide therapy may result in pneumonitis and heartworm-pulmonary thromboembolism at unpredictable times, potentially months after initiation of macrocyclic lactone therapy and exercise restriction should be considered when using a nonarsenical protocol. Although not currently recommended by the American Heartworm Society (AHS), non-arsenical strategies are in use and the goal of this study was to evaluate the efficacy, duration of therapy, and safety of an accelerated dosing protocol of M/I with doxycycline.

Potential cost-effectiveness of a maternal Group B streptococcal vaccine in The Gambia.

OBJECTIVE: To estimate neonatal health benefits and healthcare provider costs of a theoretical Group B streptococcal (GBS) hexavalent maternal vaccination programme in The Gambia, a low-income setting in West Africa. METHODS: A static decision analytic cost-effectiveness model was developed from the healthcare provider perspective. Demographic data and acute care costs were available from studies in The Gambia undertaken in 2012-2015. Further model parameters were taken from United Nations and World Health Organisation sources, supplemented by data from a global systematic review of GBS and literature searches. As vaccine efficacy is not known, we simulated vaccine efficacy estimates of 50-90%. Costs are reported in US dollars. Cost-effectiveness thresholds of one (US$473, very cost effective) and three (US$1420, cost effective) times Gambian GDP were used. RESULTS: Vaccination with a hexavalent vaccine would avert 24 GBS disease cases (55%) and 768 disability adjusted life years compared to current standard of care (no interventions to prevent GBS disease). At vaccine efficacy of 70%, the programme is cost-effective at a maximum vaccine price per dose of 12 US$ (2016 US$), and very cost-effective at a maximum of $3/dose. The total costs of vaccination at $12 is $1,056,962 for one annual cohort of Gambian pregnant women. One-way sensitivity analysis showed that GBS incidence was the most influential parameter on the cost effectiveness ratio. CONCLUSION: The introduction of a hexavalent vaccine would considerably reduce the current burden of GBS disease in The Gambia but to be cost-effective, the vaccine price per dose would need to be $12/dose or less.

When does shared decision making is adopted in psychiatric clinical practice? Results from a European multicentric study.

To identify factors associated with the use of shared decision making in routine mental health care in a large multicenter European study. Data have been collected within the study "Clinical decision making and outcome in routine care for people with severe mental illness" (CEDAR), which is a naturalistic, longitudinal, observational study carried out in six European countries. Patients with a severe mental illness attending outpatient units and their treating clinicians have been recruited. Clinicians' Clinical Decision Making (CDM) styles have been explored through the Clinical Decision Making Style Scale. Patients' clinical and social outcomes have been assessed through validated assessment instruments. The sample consisted of 588 patients and 213 professionals. Professionals were mainly psychiatrists (35.7%), nurses (21.6%), support workers, social workers or occupational therapists (24.9%), psychologists (9.9%) or trainees in psychiatry (4.7%). In the majority of cases, clinicians adopted a shared CDM style. Shared CDM was more frequently adopted with patients with psychotic disorders, with a better quality of life and social functioning. At multivariate analyses, the likelihood of adopting shared decision making increased in patients with higher levels of interpersonal relationships' skills (p < 0.05) and global functioning (p < 0.01). On the contrary, being a trainee in psychiatry reduced the likelihood of adopting shared CDM (p < 0.008). Shared decision making has been adopted mainly when patients have a better functioning and less severe clinical symptomatology and by less trained clinicians, differently from national and international recommendations. More efforts should be made to implement interventions to promote shared CDM, with a specific focus for trainees in psychiatry.

Age-related neurochemical and behavioural changes in D409V/WT GBA1 mouse: Relevance to lewy body dementia.

Heterozygous mutations in GBA1, the gene which encodes the lysosomal enzyme glucocerebrosidase (GCase), are a strong genetic risk factor for the development of Lewy body dementia (LBD). Until this point however, recapitulation of the symptoms and pathology of LBD has been limited to a homozygous GBA1 mouse model which genetically and enzymatically reflects the lysosomal storage disorder Gaucher's disease. This study reports for the first time cognitive impairment by two independent behavioural tests in heterozygous GBA1 mutant mice (D409V/WT) which demonstrate significant cognitive impairment by the age of 12 months. Furthermore, reductions in GBA1 GCase enzyme activity within the brain reflects levels seen in sporadic and GBA1 mutant LBD patients. While there is no overt deposition of Lewy bodies within the hippocampus, alterations to cholinergic machinery and glial proliferation are evident, both pathological features of LBD. Interestingly, we also describe the novel finding of significantly reduced GBA2 GCase enzyme activity specifically within the hippocampus. This suggests that reduced GBA1 GCase enzyme activity dis-equilibrates the finely balanced glycosphingolipid metabolism pathway and that reductions in GBA2 GCase enzyme could contribute to the pathological and behavioural effects seen. Overall, this study presents evidence to suggest that pathological hallmarks associated with LBD specifically affecting brain regions intrinsically linked with cognition are present in the D409V/WT mice. In the absence of Lewy body deposition, the D409V/WT mice could be considered an early pre-clinical model of LBD with potential for drug discovery. Since few robust pre-clinical models of LBD currently exist, with further characterization, the mouse model described here may contribute significantly to developments in the LBD field.