Polymicrobial abscess following ovariectomy in a mouse.

BACKGROUND: Ovariectomy is a common procedure in laboratory rodents used to create a post-menopausal state. Complications including post-surgical abscess are rarely reported, but merit consideration for the health and safety of experimental animals. CASE PRESENTATION: A female C57/black6 mouse was ovariectomized as part of a cohort study. At Day 14 post-surgery, she developed a visible swelling on the right side, which 7 days later increased in size over 24 h, leading to euthanasia of the animal. Gross pathology was consistent with abscess. A core of necrotic tissue was present in the uterine horn. Abscess fluid and affected tissue were collected for Gram stain and bacteriological culture. The abscess core and fluid yielded three distinct types of bacterial colonies identified by 16S ribosomal RNA sequencing as Streptococcus acidominimus, Pasteurella caecimuris, and a novel species in the genus Gemella. CONCLUSIONS: This is the first report of polymicrobial abscess in a rodent as a complication of ovariectomy, and the first description of a novel Gemella species for which we have proposed the epithet Gemella muriseptica. This presentation represents a potential complication of ovariectomy in laboratory animals.

Understanding the effectiveness and mechanisms of a social prescribing service: a mixed method analysis.

BACKGROUND: Evidence of the effectiveness of social prescribing is inconclusive causing commissioning challenges. This research focusses on a social prescribing scheme in Northern England which deploys 'Wellbeing Coordinators' who offer support to individuals, providing advice on local groups and services in their community. The research sought to understand the outcomes of the service and, in addition, the processes which supported delivery. METHODS: Quantitative data was gathered from service users at the point they entered the service and also at the point they exited. Qualitative interviews were also undertaken with service users to gather further understanding of the service and any positive or negative outcomes achieved. In addition, a focus group discussion was also conducted with members of social prescribing staff to ascertain their perspectives of the service both from an operational and strategic perspective. RESULTS: In total, 342 participants provided complete wellbeing data at baseline and post stage and 26 semi-structured qualitative interviews were carried out. Improvements in participants' well-being, and perceived levels of health and social connectedness as well as reductions in anxiety was demonstrated. In many cases, the social prescribing service had enabled individuals to have a more positive and optimistic view of their life often through offering opportunities to engage in a range of hobbies and activities in the local community. The data on reductions in future access to primary care was inconclusive. Some evidence was found to show that men may have greater benefit from social prescribing than women. Some of the processes which increased the likelihood of success on the social prescribing scheme included the sustained and flexible relationship between the service user and the Wellbeing Coordinator and a strong and vibrant voluntary and community sector. CONCLUSIONS: Social prescribing has the potential to address the health and social needs of individuals and communities. This research has shown a range of positive outcomes as a result of service users engaging with the service. Social prescribing should be conceptualised as one way to support primary care and tackle unmet needs.

Neonatal pain and stress disrupts later-life pavlovian fear conditioning and sensory function in rats: Evidence for a two-hit model.

Early life trauma has been linked to increased risks for anxiety, depression, and chronic pain. We used rodent models of acute and inflammatory neonatal pain to explore effects on fear conditioning and somatosensory function. Hindpaw needle pricks or handling on postnatal days (PNDs) 1-7 caused lasting impacts on affective and somatosensory function when assessed at later ages, PNDs 24 (postweaning), 45 (adolescence), or 66 (adulthood). First, auditory, but not contextual, freezing was mildly disrupted regardless of age. Second, a profound postfear conditioning tactile hypersensitivity was observed in neonatally stressed, postweaning rats. In the absence of fear conditioning, the mechanical hypersensitivity was not observed, consistent with a two-hit model of psychopathology. Injections of 2% α-carrageenan did not have the same lasting impact but was slightly protective against observed effects of neonatal vehicle injections. Basal and elicited corticosterone levels postweaning were not altered by neonatal pain or handling. These data demonstrate that neonatal adversity can have lasting impacts on affective and somatosensory function that differs regardless of age.

Voluntary exercise blocks ongoing pain and diminishes bone remodeling while sparing protective mechanical pain in a rat model of advanced osteoarthritis pain.

ABSTRACT: Exercise is the most common treatment recommended by healthcare providers for the treatment of musculoskeletal pain. We examined whether voluntary running wheel exercise improves pain and bone remodeling in rats with monosodium iodoacetate-induced unilateral knee joint pain. During acquisition of wheel running before osteoarthritis (OA) treatment, rats separated into 2 groups characterized by either high or low levels of voluntary wheel running as indicated by distance and peak speed. After the induction of knee joint OA, all rats showed diminished voluntary wheel running throughout the study. Voluntary wheel running failed to alter evoked nociceptive responses evaluated as weight asymmetry or hind paw tactile thresholds at any timepoint of the study. By contrast, relief of ongoing pain was demonstrated by conditioned place preference produced by lidocaine injection into the monosodium iodoacetate-treated knee in high but not low-running rats. Both high and low voluntary runners showed diminished trabecular bone loss compared with sedentary controls. These observations indicate that both high-intensity and low-intensity exercise is beneficial in protecting against bone remodeling in advanced OA. The data suggest that similar to clinical observation, bone remodeling does not correlate with pain. In addition, these results suggest that higher intensity exercise may relieve persistent ongoing OA pain while maintaining movement-evoked nociception. The relief of ongoing pain can potentially offer significant improvement in quality of life, whereas preservation of responses to movement-evoked pain may be especially important in protecting the joint from damage because of overuse.

Effect of a multi-faceted rapid response system re-design on repeat calling of the rapid response team.

BACKGROUND: Repeat Rapid Response Team (RRT) calls are associated with increased in-hospital mortality risk and pose an organisation-level resource burden. Use of Non-Technical Skills (NTS) at calls has the potential to reduce potentially preventable repeat calling. NTS are usually improved through training, although this consumes time and financial resources. Re-designing the Rapid Response System (RRS) to promote use of NTS may provide a feasible alternative. METHODS: A pre-post observational study was undertaken to assess the effect of an RRS re-design that aimed to promote use of NTS during RRT calls. The primary outcome was the proportion of admissions each month subject to repeat RRT calling, and the average number of repeat calls per admission each month was the secondary outcome of interest. Univariate and multivariable interrupted time series analyses compared outcomes between the two study phases. RESULTS: The proportion of admissions with repeat calls each month increased across both phases of the study period, but the increase was lower in the post re-design phase (change in regression slope -0.12 (standard error 0.07) post versus pre re-design). The multivariable model predicted a 6% reduction (95% confidence interval -15.1-3.1; P = 0.19) in the proportion of admissions having repeat calls at the end of the post redesign phase study compared to the predicted proportion in the absence of the re-design. The average number of calls per admission was also predicted to decrease in the post re-design phase, with an estimated difference of -0.07 calls per admission (equivalent to one fewer repeat call per 14 patients who had RRT calls) at the end of the post re-design phase (95% confidence interval -0.23-0.08, P = 0.35). CONCLUSION: This study of an RRS re-design showed modest, but not statistically significant, reductions in the proportion of admissions with repeat calls and the mean number of repeat calls per admission. Given the economic and workforce capacity issues that all health care systems now face, even small improvements in the RRS may have lasting impact across the organisation. For the potential interest of RRS managers, this paper presents a pragmatic, low-cost initiative intended to enhance communication and cooperation at RRT calls.

Reasons for Repeat Rapid Response Team Calls, and Associations with In-Hospital Mortality.

BACKGROUND: Previous publications noted increased mortality risk in patients subject to repeat rapid response team (RRT) calls. These patients were examined as a homogenous group, but there may be many reasons for repeat calls. Those potentially preventable by the rapid response system have not been investigated. METHODS: In a retrospective cohort study, patients with potentially preventable repeat calls were classified into two categories: type 1 (patients who had a repeat call following an initial call that ended despite the patient still triggering RRT calling criteria [T1-PRC]) and type 2 (patients with a repeat call within 24 hours of an initial call and for the same reason [T2-PRC]). In-hospital mortality for these patients and for those with repeat calls for all other reasons (ORC) were compared to patients with only a single call during their admission (SC). RESULTS: Mortality occurred in 31 (43.7%) T1-PRC, 13 (15.1%) T2-PRC, 56 (28.9%) ORC, and 289 (13.9%) SC patients. Univariate odds ratios (ORs), in comparison to SC patients, were 4.81 (95% confidence interval [CI]: 2.96-7.81; p < 0.001), 1.10 (95% CI: 0.60-2.02; p = 0.75), and 2.52 (95% CI: 1.80-3.52; p < 0.001), respectively. Mortality effects persisted for the T1-PRC and ORC groups after adjustment for patient, admission, and initial call characteristics with ORs of 4.07 (95% CI: 2.36-7.01; p < 0.001) and 2.29 (95% CI: 1.57-3.34; p < 0.001), respectively. CONCLUSION: This study found that repeat calls following an initial call that ended with ongoing breach of predefined calling criteria were strongly associated with increased mortality. This highlights the risk to patients when the RRT leaves reversible clinical deterioration unresolved at the end of a call.

Females have greater susceptibility to develop ongoing pain and central sensitization in a rat model of temporomandibular joint pain.

Temporomandibular joint osteoarthritis (TMJOA) is a prevalent source of temporomandibular joint disorder (TMD). Women are more commonly diagnosed with TMD and are more likely to seek care at tertiary orofacial pain clinics. Limited knowledge regarding mechanisms underlying temporomandibular joint (TMJ) pain impairs development of improved pain management strategies. In a rat model of unilateral TMJOA, monosodium iodoacetate (MIA) produces joint pathology in a concentration-dependent manner. Unilateral MIA produces alterations in meal patterns in males and females without altering overnight time spent eating or weight across 2 weeks. Monosodium iodoacetate (80 mg/mL)-treated males develop ongoing pain within 2 weeks after MIA injection. Females develop ongoing pain at a 5-fold lower MIA concentration (16.6 mg/m). Monosodium iodoacetate (80 mg/mL)-treated males show spread of tactile hypersensitivity across the face during the first week after injection and then to the fore paws and hind paws during the second week after injection, indicating development of central sensitization. At the lower dose, female rats demonstrate a similar spread of tactile hypersensitivity, whereas male rats do not develop ongoing pain or spread of tactile hypersensitivity outside the area of the ipsilateral temporomandibular joint. These observations indicate that females have a higher susceptibility to development of ongoing pain and central sensitization compared with male rats that is not due to differences in MIA-induced joint pathology. This model of TMJOA pain can be used to explore sex differences in pain processes implicated in development of neuropathic pain, ongoing pain, and central sensitization, allowing for development of individualized strategies for prevention and treatment of TMD joint pain.

The relative efficacy of imatinib, dasatinib and nilotinib for newly diagnosed chronic myeloid leukemia: a systematic review and network meta-analysis.

OBJECTIVES: Dasatinib 100 mg daily and nilotinib 600/800 mg daily have been compared to imatinib as first line treatments for CML in two recent randomised studies. However, no head to head evidence exists of the relative efficacy of dasatinib and nilotinib. METHODS: We conducted a systematic literature review and used the data extracted to perform an indirect comparison meta-analysis of the three interventions. RESULTS: Data from eight clinical studies (3,520 individuals) were included, all of which were of good quality (low risk of bias). At six months, the odds of complete cytogenetic response (CCyR) for dasatinib and nilotinib were approximately three times those for imatinib (range 2.77 to 3.06, all values not significant). At twelve months datatinib and nilotinib were significantly better than imatinib for both CCyR and major molecular response (MMR) (CCyR odds range 2.06 to 2.41, MMR odds range 2.09 to 2.87). At eighteen months dasatinib and nilotinib were again significantly better in terms of CCyR than imatinib (response odds 1.55 to 2.01). When dasatinib and nilotinib were compared to each other, for both clinical endpoints at all time points the response odds were not significantly different. CONCLUSIONS: On the basis of a systematic review of the current literature base, dasatinib 100 mg, nilotinib 600 mg and nilotinib 800 mg should be viewed as equivalent in terms of complete cytogenetic and major molecular response.

Sulthiame in refractory paediatric epilepsies: an experience of an 'old' antiepileptic drug in a tertiary paediatric neurology unit.

PURPOSE: Sulthiame is an old antiepileptic drug primarily used in a few European countries for the treatment of benign epilepsy of childhood with central temporal spikes. Other studies suggest that it might be effective in children and adults with a range of refractory seizure types. METHODS: A retrospective case note review was undertaken to evaluate the efficacy and safety of sulthiame as adjunctive therapy in children with refractory epilepsies. RESULTS: Twenty patients (10 female) were evaluated, aged 10.7 (range 2.1-17) years. The median duration of treatment with sulthiame was 18 (range 2-37) months. Fifty five percent of patients showed at least a 50% reduction in seizure frequency and two patients were seizure-free at the end of follow-up. Patients with focal seizures responded best. Seven patients reported side effects, leading to withdrawal of the drug in two (10%). CONCLUSION: Sulthiame was reasonably effective and well-tolerated in a heterogeneous group of 20 children with refractory epilepsies. Although an 'old' antiepileptic drug it should be considered in a similar population.