Weight change following diagnosis with psychosis: a retrospective cohort study in Greater Manchester, UK.

INTRODUCTION: Weight gain in the months/years after diagnosis/treatment of severe enduring mental illness (SMI) is a major predictor of future diabetes, dysmetabolic profile and increased risk of cardiometabolic diseases. There is limited data on the longer-term profile of weight change in people with a history of SMI and how this may differ between individuals. We here report a retrospective study on weight change over the 5 years following an SMI diagnosis in Greater Manchester UK, an ethnically and culturally diverse community, with particular focus on comparing non-affective psychosis (NAP) vs affective psychosis (AP) diagnoses. METHODS: We undertook an anonymised search in the Greater Manchester Care Record (GMCR). We reviewed the health records of anyone who had been diagnosed for the first time with first episode psychosis, schizophrenia, schizoaffective disorder, delusional disorder (non-affective psychosis = NAP) or affective psychosis (AP). We analysed body mass index (BMI) change in the 5-year period following the first prescription of antipsychotic medication. All individuals had taken an antipsychotic agent for at least 3 months. The 5-year follow-up point was anywhere between 2003 and 2023. RESULTS: We identified 9125 people with the diagnoses above. NAP (n = 5618; 37.3% female) mean age 49.9 years; AP (n = 4131; 60.5% female) mean age 48.7 years. 27.0% of NAP were of non-White ethnicity vs 17.8% of AP individuals. A higher proportion of people diagnosed with NAP were in the highest quintile of social disadvantage 52.4% vs 39.5% for AP. There were no significant differences in baseline BMI profile. In a subsample with HbA1c data (n = 2103), mean HbA1c was higher in NAP at baseline (40.4 mmol/mol in NAP vs 36.7 mmol/mol for AP). At 5-year follow-up, there was similarity in both the overall % of individuals in the obese ≥ 30 kg/m2 category (39.8% NAP vs 39.7% AP), and % progressing from a normal healthy BMI transitioned to obese/overweight BMI (53.6% of NAP vs 55.6% with AP). 43.7% of those NAP with normal BMI remained at a healthy BMI vs 42.7% with AP. At 5-year follow-up for NAP, 83.1% of those with BMI ≥ 30 kg/m2 stayed in this category vs 81.5% of AP. CONCLUSION: The results of this real-world longitudinal cohort study suggest that the changes in BMI with treatment of non-affective psychosis vs bipolar disorder are not significantly different, while 43% maintain a healthy weight in the first 5 years following antipsychotic prescription.

Lumbar microdiscectomy and post-operative activity restrictions: a protocol for a single blinded randomised controlled trial.

BACKGROUND: Lumbar microdiscectomy is the most commonly performed spinal surgery procedure, with over 300,000 cases performed annually in the United States alone. Traditionally, patients were advised to restrict post-operative activity as this was believed to reduce the risk of disc reherniation and progressive instability. However, this practice would often delay patients return to work. In contemporary practice many surgeons do not restrict patient post-operative activity due to the perception this practice is unnecessary. We describe a randomised controlled trial to assess the impact of activity restrictions on clinical outcome following lumbar discectomy. METHODS/DESIGN: The lumbar microdiscectomy and post-operative activity restriction trial is a multi-centre, randomised, controlled single blinded trial. Two hundred ten patients due to undergo single level lumbar microdiscectomy without a history of previous spine surgery, infection or fracture are randomised to be advised either restricted or unrestricted activity for a period of 30 days following lumbar microdiscectomy. Actual adherence with trial allocation will be monitored bioelectronically via a wearable device. Outcome assessment at follow up will occur at 1, 3, 6 and 12 months. The primary outcome will be a composite endpoint comprising changes in Visual Analogue Scale (Leg and Back), Oswestry Disability Index and the absence of intervertebral disc reherniation or secondary intervention. DISCUSSION: This randomised controlled trial will directly compare post-operative protocols of activity restrictions and no restrictions following lumbar discectomy with adherence monitored bioelectronically. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12616001360404 (retrospectively registered 30/09/2016).

Competency Development to Support Safe Nurse Practitioner Prescribing of Controlled Drugs and Substances in British Columbia.

In 2012, Canada passed legislation giving nurse practitioners (NPs) authority to prescribe controlled drugs and substances. Steps toward safe implementation by the nursing regulatory body in British Columbia included development of controlled drugs and substances prescribing competencies for use in educating and authorizing NPs for this new scope. In this article, we discuss the development and refinement of the competencies, specifically their application to nursing regulation in British Columbia. Methods include incorporation of the Competency Outcome Performance Assessment Model as a guiding theoretical framework. Over two meetings in 2014, a small representative panel of health professionals completed face and content validation of 17 initial competencies using a visual Likert-type scale ranking process (1-5, unnecessary to essential) with Google Docs for real-time comparative refinement. The resulting 10 competency statements provide the foundation for outcome indicator development which will be used in NP education and the regulatory body's regulation and remediation processes. Finally, we describe the policy process applied to implement competencies for NP controlled drugs and substances prescribing and the subsequent challenges of implementation of controlled drugs and substances authority in British Columbia. The article concludes with an overview of lessons learned that may be beneficial to health professions regulatory bodies introducing or expanding prescribing scope for NPs.

First episode psychosis and weight gain a longitudinal perspective in Cheshire UK: a comparison between individuals with nonaffective versus affective psychosis.

Early weight gain following initiation of antipsychotic treatment predicts longer-term weight gain, with attendant long-term consequences including premature cardiovascular events/death. An important question is whether there is a difference in weight change over time between people with affective versus nonaffective psychosis. Here we describe the results of a real-world analysis of the BMI change in the months postdiagnosis with affective versus nonaffective psychosis. Methods: We undertook an anonymised search across one Primary Care Network in Cheshire, UK with a total population of 32 301 individuals. We reviewed the health records of anyone who had been diagnosed over a 10-year period between June 2012 and June 2022 for the first time with first episode nonaffective psychosis versus psychosis associated with depression or bipolar affective disorder (affective psychosis). Results: The overall % change in BMI was +8% in nonaffective psychosis individuals and +4% in those with a diagnosis of affective psychosis - however, the distribution was markedly skewed for nonaffective psychosis patients. Using caseness as >30% increase in BMI; affective = 4% cases and nonaffective = 13% cases, there was a three-fold difference in terms of increase in BMI. In regression analysis, the r2 linking the initial BMI to % change in BMI was 0.13 for nonaffective psychosis and 0.14 for affective psychosis. Conclusion: The differences observed here in the distribution of weight change over time between individuals with affective versus nonaffective psychosis may relate to underlying constitutional differences. The phenotypic and genetic factors underlying this difference remain to be defined.

Clinical management of the alcohol withdrawal syndrome.

Up to half of individuals with a history of long-term, heavy alcohol consumption will experience the alcohol withdrawal syndrome (AWS) when consumption is significantly decreased or stopped. In its most severe form, AWS can be life-threatening. Medically assisted withdrawal (MAW) often forms the first part of a treatment pathway. This clinical review discusses key elements of the clinical management of MAW, necessary adjustments for pregnancy and older adults, likely outcome of an episode of MAW, factors that might prevent completion of the MAW process and ways of overcoming barriers to ongoing treatment of alcohol use disorder. The review also discusses the use of benzodiazepines in MAW. Although there is clear evidence for their use, benzodiazepines have been associated with abuse liability, blunting of cognition, interactions with depressant drugs, craving, delirium, dementia and disrupted sleep patterns. Because glutamatergic activation and glutamate receptor upregulation contribute to alcohol withdrawal, anti-glutamatergic strategies for MAW and other potential treatment innovations are also considered.

Relationship between herniated intervertebral disc fragment weight and pain in lumbar microdiscectomy patients.

OBJECTIVE: The relationship between lumbar disc herniation (LDH) size and the severity of preoperative pain and its impact on postoperative recovery is incompletely understood. This study was conducted to investigate the association between herniated disc fragment weight and pain before and after microdiscectomy. METHODS: A consecutive series of patients from an ongoing randomised controlled trial (ACTRN12616001360404) were included in this study. Included patients were aged between 18 and 75, had a clinical diagnosis of radiculopathy, and MRI evidence of a concordant single-level lumbar disc herniation. All patients underwent standard microdiscectomy without aggressive discectomy or curettage of the endplates. Disc fragment weight was measured intraoperatively. RESULTS: A total of 122 patients with a mean age of 49.5 ± 12.8 years, were included. The median weight of disc fragment was 0.545 g (95% CI 0.364 - 0.654 g). There was no relationship between disc weight and the duration of symptoms (p = 0.409) severity of preoperative leg pain (p = 0.070) or preoperative back pain (p = 0.884). Disc fragment weight was demonstrated to have no correlation with clinically significant postoperative leg pain improvement (p = 0.535) or back pain (p = 0.991). Additional LDH factors, including radiological percentage of canal compromise (p = 0.714), herniation classification (p = 0.462), and vertebral level (p = 0.788) were also shown to have no effect on leg pain outcomes. CONCLUSIONS: Disc fragment weight had no effect on the severity of pain at presentation or after microdiscectomy. Patients benefit from surgery equally, regardless of the size of LDH.

Childbirth experiences of women with obstetric fistula in Tanzania and Uganda and their implications for fistula program development.

INTRODUCTION AND HYPOTHESIS: authors sought evidence from the testimonies of women living with fistula regarding local risk factors for fistula and the impact of fistula on women's lives. METHODS: one hundred thirty-seven women recruited from health facilities and at the community level in Tanzania and Uganda were interviewed using quantitative and qualitative methods, including participatory approaches. RESULTS: women of all ages and parities endured fistula. The testimonies illustrated that physical, socio-economic and cultural constraints, as well as health system failures, led to fistula, and the condition imposed harsh consequences on women's lives. Constraints included deficient maternal health services and personnel, delays in seeking and accessing care, and limited fistula repair services. Women endured severe social stigma and severe economic hardships. CONCLUSIONS: participants' testimonies expand current understanding of women's experience of fistula and point to recommendations that could improve maternal health care, reduce women's risk of fistula, and improve the lives of women living with the condition.

Duraplasty in Traumatic Thoracic Spinal Cord Injury: Impact on Spinal Cord Hemodynamics, Tissue Metabolism, Histology, and Behavioral Recovery Using a Porcine Model.

After acute traumatic spinal cord injury (SCI), the spinal cord can swell to fill the subarachnoid space and become compressed by the surrounding dura. In a porcine model of SCI, we performed a duraplasty to expand the subarachnoid space around the injured spinal cord and evaluated how this influenced acute intraparenchymal hemodynamic and metabolic responses, in addition to histological and behavioral recovery. Female Yucatan pigs underwent a T10 SCI, with or without duraplasty. Using microsensors implanted into the spinal cord parenchyma, changes in blood flow (ΔSCBF), oxygenation (ΔPO2), and spinal cord pressure (ΔSCP) during and after SCI were monitored, alongside metabolic responses. Behavioral recovery was tested weekly using the Porcine Injury Behavior Scale (PTIBS). Thereafter, spinal cords were harvested for tissue sparing analyses. In both duraplasty and non-animals, the ΔSCP increased ∼5 mm Hg in the first 6 h post-injury. After this, the SCP appeared to be slightly reduced in the duraplasty animals, although the group differences were not statistically significant after controlling for injury severity in terms of impact force. During the first seven days post-SCI, the ΔSCBF or ΔPO2 values were not different between the duraplasty and control animals. Over 12 weeks, there was no improvement in hindlimb locomotion as assessed by PTIBS scores and no reduction in tissue damage at the injury site in the duraplasty animals. In our porcine model of SCI, duraplasty did not provide any clear evidence of long-term behavioral or tissue sparing benefit after SCI.

Novel Application of the Pfirrmann Disc Degeneration Grading System to 9.4T MRI: Higher Reliability Compared to 3T MRI.

STUDY DESIGN: Reliability study. OBJECTIVE: To evaluate the applicability and reliability of 9.4T magnetic resonance imaging (MRI) in the assessment of degenerative disc disease compared with 3T MRI. SUMMARY OF BACKGROUND DATA: MRI is a reliable indicator of biochemical changes in the intervertebral disc (IVD) including hydration status, proteoglycan content, and disc degeneration compared with anatomical and histological studies. High-field 9.4T MRI has been shown to provide superior resolution and anatomical detail. However, it has not been tested against current standard MRI techniques. METHODS: Disc degeneration was initiated in 36 skeletally mature ewes 6 months prior to necropsy via validated surgical IVD injury models using either scalpel injury or drill-bit injury techniques at lumbar spine levels L2/3 and L3/4 with L1/2, L4/5, and L5/6 serving as control discs. All ex vivo IVDs were examined with 9.4T MRI and 3T MRI. All scans were analyzed using the Pfirrmann grading system by four independent observers. Intra- and interobserver reliability was assessed using kappa statistics and Spearman correlation. RESULTS: Inter- and intraobserver agreement for 9.4T MRI was excellent, both at κ 0.91 (P < 0.001). Comparatively, 3T interobserver reliability demonstrated substantial agreement at κ 0.61 (P < 0.001). Complete agreement was obtained in 92.7% to 100% of discs at 9.4T compared with 69.7% to 83.1% at 3T. A difference of one grade or more occurred in 6.7% at 9.4T and 39.3% at 3T. 9.4T MRI scored 97.3% of discs as grade 1 to 2 compared with 71.3% at 3T. 3T MRI tended to over-score the extent of disc degeneration with 28.6% of discs scored as grade 3 or higher compared with 2.7% at 9.4T MRI. CONCLUSION: 9.4T MRI study of IVD degeneration using the Pfirrmann grading system demonstrated excellent inter- and intraobserver reliability. Comparatively, 3T MRI demonstrated a tendency to over score the extent of disc degeneration. This improved reliability of 9.4T MRI holds great potential for its clinical applications. LEVEL OF EVIDENCE: 3.

A Comparison of Two Ovine Lumbar Intervertebral Disc Injury Models for the Evaluation and Development of Novel Regenerative Therapies.

STUDY DESIGN: Large animal research. OBJECTIVE: Lumbar discectomy is the most commonly performed spinal surgical procedure. We investigated 2 large animal models of lumbar discectomy in order to study the regenerative capacity of mesenchymal stem cells following disc injury. METHODS: Twelve adult ewes underwent baseline 3-T magnetic resonance imaging (MRI) followed by lumbar intervertebral disc injury by either drill bit (n = 6) or annulotomy and partial nucleotomy (APN) (n = 6). Necropsies were performed 6 months later. Lumbar spines underwent 3-T and 9.4-T MRI prior to histological, morphological and biochemical analysis. RESULTS: Drill bit-injured (DBI) and APN-injured discs demonstrated increased Pfirrmann grades relative to uninjured controls (P < .005), with no difference between the 2 models. Disc height index loss was greater in the APN group compared with the DBI group (P < .005). Gross morphology injury scores were higher in APN than DBI discs (P < .05) and both were higher than controls (P < .005). Proteoglycan was reduced in the discs of both injury models relative to controls (P < .005), but lower in the APN group (P < .05). Total collagen of the APN group disc regions was higher than DBI and control discs (P < .05). Histology revealed more matrix degeneration, vascular infiltration, and granulation in the APN model. CONCLUSION: Although both models produced disc degeneration, the APN model better replicated the pathobiology of human discs postdiscectomy. We therefore concluded that the APN model was a more appropriate model for the investigation of the regenerative capacity of mesenchymal stem cells administered postdiscectomy.

Mesenchymal progenitor cells primed with pentosan polysulfate promote lumbar intervertebral disc regeneration in an ovine model of microdiscectomy.

BACKGROUND CONTEXT: Neural compression associated with lumbar disc herniation is usually managed surgically by microdiscectomy. However, 10%-20% of patients re-present with debilitating back pain, and approximately 15% require further surgery. PURPOSE: Using an ovine model of microdiscectomy, the present study investigated the relative potential of pentosan polysulfate-primed mesenchymal progenitor cells (pMPCs) or MPC alone implanted into the lesion site to facilitate disc recovery. STUDY DESIGN: An ovine model of lumbar microdiscectomy was used to compare the relative outcomes of administering MPCs or pMPCs to the injury site postsurgery. METHODS: At baseline 3T magnetic resonance imaging (MRI) of 18 adult ewes was undertaken followed by annular microdiscectomy at two lumbar disc levels. Sheep were randomized into three groups (n=6). The injured controls received no further treatment. Defects of the treated groups were implanted with a collagen sponge and MPC (5×105 cells) or pMPC (5×105 cells). After 6 months, 3T MRI and standard radiography were performed. Spinal columns were dissected, individual lumbar discs were sectioned horizontally, and nucleus pulposus (NP) and annulus fibrosus (AF) regions were assessed morphologically and histologically. The NP and AF tissues were dissected into six regions and analyzed biochemically for their proteoglycans (PGs), collagen, and DNA content. RESULTS: Both the MPC- and pMPC-injected groups exhibited less reduction in disc height (p<.05) and lower Pfirrmann grades (p≤.001) compared with the untreated injury controls, but morphologic scores for the pMPC-injected discs were lower (p<.05). The PG content of the AF injury site region (AF1) of pMPC discs was higher than MPC and injury control AF1 (p<.05). At the AF1 and contralateral AF2 regions, the DNA content of pMPC discs was significantly lower than injured control discs and MPC-injected discs. Histologic and birefringent microscopy revealed increased structural organization and reduced degeneration in pMPC discs compared with MPC and the injured controls. CONCLUSIONS: In an ovine model 6 months after administration of pMPCs to the injury site disc PG content and matrix organization were improved relative to controls, suggesting pMPCs' potential as a postsurgical adjunct for limiting progression of disc degeneration after microdiscectomy.

A Review of Animal Models of Intervertebral Disc Degeneration: Pathophysiology, Regeneration, and Translation to the Clinic.

Lower back pain is the leading cause of disability worldwide. Discogenic pain secondary to intervertebral disc degeneration is a significant cause of low back pain. Disc degeneration is a complex multifactorial process. Animal models are essential to furthering understanding of the degenerative process and testing potential therapies. The adult human lumbar intervertebral disc is characterized by the loss of notochordal cells, relatively large size, essentially avascular nature, and exposure to biomechanical stresses influenced by bipedalism. Animal models are compared with regard to the above characteristics. Numerous methods of inducing disc degeneration are reported. Broadly these can be considered under the categories of spontaneous degeneration, mechanical and structural models. The purpose of such animal models is to further our understanding and, ultimately, improve treatment of disc degeneration. The role of animal models of disc degeneration in translational research leading to clinical trials of novel cellular therapies is explored.

In vivo engineering of blood vessels.

The inadequacy of conventional synthetic grafts has led to efforts to construct a superior vascular graft. In vivo tissue engineering is one approach to this problem that has been investigated for half a century and enables the construction of autogenous vascular prostheses. Three types of in vivo engineering are explored: remodelling of implanted scaffolds, fibrocollagenous tubes, and the artificial artery generated in the peritoneal cavity. Scaffolds designed to be remodelled may be synthetic or biological and have been remodelled in animal models to form vasoactive neoarteries with arterial morphology. The differences in vascular remodelling ability, particularly spontaneous endothelialisation, between animal models and humans may impair the effectiveness of this approach in the clinic. Fibrocollagenous tubes such as the Sparks Mandril have demonstrated poor performance in the clinic and are prone to aneurysm formation. The artificial artery generated in the peritoneal cavity is a novel addition to the ranks of in vivo engineered vascular prostheses and combines many of the best features of scaffolds designed to be remodelled and fibrocollagenous tubes. However, understanding and manipulating the vascular remodelling process will be the key to producing the ideal arterial prosthesis.

Treating alcohol dependence in a district general hospital.

A strategy for managing alcohol problems within the general hospital setting should involve improved recognition of acute physical complications of alcohol withdrawal and dependence. Research shows that opportunistic interventions at this stage can reduce alcohol consumption by 25% in excessive drinkers. Support should be available from a local community alcohol service.

Vascular engineering for bypass surgery.

Since the introduction of synthetic vascular grafts in the 1960s, only two-stage endothelial cell seeding has demonstrated any significant improvement over conventional vascular grafts, and its benefits have yet to be demonstrated on a large scale. Tissue engineering is a rapidly expanding field with great potential, but efforts to construct tissue-engineered arterial grafts have, to date, yielded little clinical success. This review explores the latest approaches to the construction of a superior vascular graft, along with its potential for use in the clinic in the future.