A systematic review and meta-analysis of randomized controlled trials comparing arthrocentesis with conservative management for painful temporomandibular joint disorder.

The aim of this study was to determine whether arthrocentesis is superior to conservative treatment in the management of painful temporomandibular joint disorders with restricted opening. A systematic review was undertaken of prospective randomized controlled trials (RCT) comparing arthrocentesis to conservative management, identified in the MEDLINE and PubMed databases. Inclusion criteria included a 6-month follow-up, with clinical assessment of the patients and painful restricted mouth opening. Data extracted included pain measured on a visual analogue scale and maximum mouth opening measured in millimetres. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2 for RCTs, and a meta-analysis with the random-effects model was undertaken. Of 879 records retrieved, seven met the inclusion criteria; these RCTs reported the results at 6 months for 448 patients. One study had a low risk of bias, four studies had an uncertain risk, and two had a high risk of bias. In the meta-analysis, arthrocentesis was statistically superior to conservative management at 6 months for an increase in maximum mouth opening (1.12 mm, 95% confidence interval 0.45-1.78 mm; P = 0.001; I2 = 87%) and borderline superior for pain reduction (-1.09 cm, 95% confidence interval -2.19 to 0.01 cm; P = 0.05; I2 = 100%). However, these differences are unlikely to be clinically relevant.

Self-reported health behaviors and risk perceptions following the COVID-19 vaccination rollout in the USA: an online survey study.

OBJECTIVES: Concerns have been raised that mass vaccination campaigns might lead to reduced engagement with other recommended health behaviors. We assessed self-reported behaviors and risk perceptions following the COVID-19 vaccine rollout in the USA. STUDY DESIGN: Between December 2, 2020, and March 23, 2021, we conducted three online survey studies with US adult respondents. METHODS: Respondents self-reported their COVID-19 vaccination status, their frequency of engaging in risk-increasing behaviors and wearing a mask when in public places, and their COVID-19 risk perceptions (i.e., perceived likelihood of getting COVID-19 and of being hospitalized if they got COVID-19). RESULTS: Our analytical sample included 832 respondents who had completed the first and final surveys and had received either 0 or 2 doses of a COVID-19 vaccine. Most respondents were non-Hispanic White (75%), male (77%), and US Veterans (64%), with the median age between 55 and 74 years. Overall, respondents reported frequently wearing masks when in public and rarely engaging in risk-increasing behaviors. Regardless of vaccination status, respondents reported more frequently engaging in risk-increasing behaviors and lower risk perceptions in March 2021 than in December 2020. Mask wearing did not change over the study period, with vaccinated respondents consistently reporting more frequent mask wearing than unvaccinated respondents. CONCLUSIONS: Taken together, our findings indicate that the COVID-19 vaccine rollout in the USA did not result in the rapid abandonment of protective behaviors or dramatic uptake of risk-increasing behaviors. Additional studies are needed to monitor how mass vaccination might impact public behaviors and risk perceptions as coverage widens.

Nomogram Predicting Bladder Cancer-specific Mortality After Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-invasive Bladder Cancer: Results of an International Consortium.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) is associated with improved overall and cancer-specific survival. The post-NAC pathological stage has previously been reported to be a major determinant of outcome. OBJECTIVE: To develop a postoperative nomogram for survival based on pathological and clinical parameters from an international consortium. DESIGN, SETTING, AND PARTICIPANTS: Between 2000 and 2015, 1866 patients with MIBC were treated at 19 institutions in the USA, Canada, and Europe. Analysis was limited to 640 patients with adequate follow-up who had received three or more cycles of NAC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A nomogram for bladder cancer-specific mortality (BCSM) was developed by multivariable Cox regression analysis. Decision curve analysis was used to assess the model's clinical utility. RESULTS AND LIMITATIONS: A total of 640 patients were identified. Downstaging to non-MIBC (ypT1, ypTa, and ypTis) occurred in 271 patients (42 %), and 113 (17 %) achieved a complete response (ypT0N0). The 5-yr BCSM was 47.2 % (95 % confidence interval [CI]: 41.2-52.6 %). On multivariable analysis, covariates with a statistically significant association with BCSM were lymph node metastasis (hazard ratio [HR] 1.90 [95% CI: 1.4-2.6]; p < 0.001), positive surgical margins (HR 2.01 [95 % CI: 1.3-2.9]; p < 0.001), and pathological stage (with ypT0/Tis/Ta/T1 as reference: ypT2 [HR 2.77 {95 % CI: 1.7-4.6}; p < 0.001] and ypT3-4 [HR 5.9 {95 % CI: 3.8-9.3}; p < 0.001]). The area under the curve of the model predicting 5-yr BCSM after cross validation with 300 bootstraps was 75.4 % (95 % CI: 68.1-82.6 %). Decision curve analyses showed a modest net benefit for the use of the BCSM nomogram in the current cohort compared with the use of American Joint Committee on Cancer staging alone. Limitations include the retrospective study design and the lack of central pathology. CONCLUSIONS: We have developed and internally validated a nomogram predicting BCSM after NAC and radical cystectomy for MIBC. The nomogram will be useful for patient counseling and in the identification of patients at high risk for BCSM suitable for enrollment in clinical trials of adjuvant therapy. PATIENT SUMMARY: In this report, we looked at the outcomes of patients with muscle-invasive bladder cancer in a large multi-institutional population. We found that we can accurately predict death after radical surgical treatment in patients treated with chemotherapy before surgery. We conclude that the pathological report provides key factors for determining survival probability.

Postoperative complications of pulmonary resection.

Thoracic surgery has seen a resurgence in recent years with increasing numbers of cases taken on since the mid-2000s. There has been a paradigm shift in how we manage lung cancer with more emphasis on surgical resection, and this has been aided by minimally invasive video-assisted thoracic surgery (VATS) techniques. As a result, the prevalence of postoperative findings and complications is also increasing, and it is increasingly important for the general radiologist to recognise and diagnose these conditions as thoracic surgical patients may present acutely to non-thoracic surgical institutions. This review will cover both the early and late complications following a variety of lung resection surgeries.

Modelling the catabolic environment of the moderately degenerated disc with a caprine ex vivo loaded disc culture system.

Low-back pain affects 80 % of the world population at some point in their lives and 40 % of the cases are attributed to intervertebral disc (IVD) degeneration. Over the years, many animal models have been developed for the evaluation of prevention and treatment strategies for IVD degeneration. Ex vivo organ culture systems have also been developed to better control mechanical loading and biochemical conditions, but a reproducible ex vivo model that mimics moderate human disc degeneration is lacking. The present study described an ex vivo caprine IVD degeneration model that simulated the changes seen in the nucleus pulposus during moderate human disc degeneration. Following pre-load under diurnal, simulated physiological loading (SPL) conditions, lumbar caprine IVDs were degenerated enzymatically by injecting collagenase and chondroitinase ABC (cABC). After digestion, IVDs were subjected to SPL for 7 d. No intervention and phosphate-buffered saline injection were used as controls. Disc deformation was continuously monitored to assess disc height recovery. Histology and immunohistochemistry were performed to determine the histological grade of degeneration, matrix expression, degrading enzyme and catabolic cytokine expression. Injection of collagenase and cABC irreversibly affected the disc mechanical properties. A decrease in extracellular matrix components was found, along with a consistent increase in degradative enzymes and catabolic proteins [interleukin (IL)-1ß, -8 and vascular endothelial growth factor (VEGF)]. The changes observed were commensurate with those seen in moderate human-IVD degeneration. This model should allow for controlled ex vivo testing of potential biological, cellular and biomaterial treatments of moderate human-IVD degeneration.

Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. PATIENTS AND METHODS: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. RESULTS: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the 'CIS' versus 'no-CIS' groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63-1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01-1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23-2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34-0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82-1.35; p = 0.70). CONCLUSION: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.

Thermally triggered hydrogel injection into bovine intervertebral disc tissue explants induces differentiation of mesenchymal stem cells and restores mechanical function.

We previously reported a synthetic Laponite® crosslinked pNIPAM-co-DMAc (L-pNIPAM-co-DMAc) hydrogel which promotes differentiation of mesenchymal stem cells (MSCs) to nucleus pulposus (NP) cells without additional growth factors. The clinical success of this hydrogel is dependent on: integration with surrounding tissue; the capacity to restore mechanical function; as well as supporting the viability and differentiation of delivered MSCs. Bovine NP tissue explants were injected with media (control), human MSCs (hMSCs) alone, acellular L-pNIPAM-co-DMAc hydrogel or hMSCs incorporated within the L-pNIPAM-co-DMAc hydrogel and maintained at 5% O2 for 6weeks. Viability of native NP cells and delivered MSCs was maintained. Furthermore hMSCs delivered via the L-pNIPAM-co-DMAc hydrogel differentiated and produced NP matrix components: aggrecan, collagen type II and chondroitin sulphate, with integration of the hydrogel with native NP tissue. In addition L-pNIPAM-co-DMAc hydrogel injected into collagenase digested bovine discs filled micro and macro fissures, were maintained within the disc during loading and restored IVD stiffness. The mechanical support of the L-pNIPAM-co-DMAc hydrogel, to restore disc height, could provide immediate symptomatic pain relief, whilst the delivery of MSCs over time regenerates the NP extracellular matrix; thus the L-pNIPAM-co-DMAc hydrogel could provide a combined cellular and mechanical repair approach. STATEMENT OF SIGNIFICANCE: Low back pain (LBP) is associated with degeneration of the intervertebral disc (IVD). We have previously described development of a jelly delivery system (hydrogel). This has the potential to deliver adult stem cells to the centre of the IVD, known as the nucleus pulposus (NP). Here, we have demonstrated that adult stem cells can be safely injected into the NP using small bore needles, reducing damage to the disc. Following injection the hydrogel integrates with surrounding NP tissue, promotes differentiation of stem cells towards disc cells and restores IVD mechanical function. The hydrogel could be used to restore mechanical function to the IVD and deliver cells to promote regeneration of the disc as a minimally invasive treatment for LBP.

Hydroxyapatite nanoparticle injectable hydrogel scaffold to support osteogenic differentiation of human mesenchymal stem cells.

Bone loss associated with degenerative disease and trauma is a clinical problem increasing with the aging population. Thus, effective bone augmentation strategies are required; however, many have the disadvantages that they require invasive surgery and often the addition of expensive growth factors to induce osteoblast differentiation. Here, we investigated a LaponiteÒ crosslinked, pNIPAM-DMAc copolymer (L-pNIPAM-co-DMAc) hydrogel with hydroxyapatite nanoparticles (HAPna), which can be maintained as a liquid ex vivo, injected via narrow-gauge needle into affected bone, followed by in situ gelation to deliver and induce osteogenic differentiation of human mesenchymal stem cells (hMSC). L-pNIPAM-co-DMAc hydrogels were synthesised and HAPna added post polymerisation. Commercial hMSCs from one donor (Lonza) were incorporated in liquid hydrogel, the mixture solidified and cultured for up to 6 weeks. Viability of hMSCs was maintained within hydrogel constructs containing 0.5 mg/mL HAPna. SEM analysis demonstrated matrix deposition in cellular hydrogels which were absent in acellular controls. A significant increase in storage modulus (G') was observed in cellular hydrogels with 0.5 mg/mL HAPna. Semi-quantitative immunohistochemistry and histological analysis demonstrated that bone differentiation markers and collagen deposition was induced within 48 h, with increased calcium deposition with time. The thermally triggered hydrogel system, described here, was sufficient without the need of additional growth factors or osteogenic media to induce osteogenic differentiation of commercial hMSCs. Preliminary data presented here will be expanded on multiple patient samples to ensure differentiation is seen in these samples. This system could potentially reduce treatment costs and simplify the treatment strategy for orthopaedic repair and regeneration.

Thermally triggered injectable hydrogel, which induces mesenchymal stem cell differentiation to nucleus pulposus cells: Potential for regeneration of the intervertebral disc.

There is an urgent need for new therapeutic options for low back pain, which target degeneration of the intervertebral disc (IVD). Here, we investigated a pNIPAM hydrogel system, which is liquid at 39°C ex vivo, where following injection into the IVD, body temperature triggers gelation. The combined effects of hypoxia (5% O2) and the structural environment of the hydrogel delivery system on the differentiation of human mesenchymal stem cells (hMSCs), towards an NP cell phenotype was investigated. hMSCs were incorporated into the liquid hydrogel, the mixture solidified and cultured for up to 6weeks under 21% O2 or 5% O2 where viability was maintained. Immunohistochemistry revealed significant increases in NP matrix components: aggrecan; collagen type II and chondroitin sulphate after culture for 1week in 5% O2, accompanied by increased matrix staining for proteoglycans and collagen, observed histologically. NP markers HIF1α, PAX1 and FOXF1 were also significantly increased where hMSC were incorporated into hydrogels with accelerated expression observed when cultured in 5% O2. hMSCs cultured under hypoxic conditions, which mimic the native disc microenvironment, accelerate differentiation of hMSCs within the hydrogel system, towards the NP phenotype without the need for chondrogenic inducing medium or additional growth factors, thus simplifying the treatment strategy for the repair of IVD degeneration.

Degeneration of the intervertebral disc with new approaches for treating low back pain.

This review paper discusses the process of disc degeneration and the current understanding of cellular degradation in patients who present with low back pain. The role of surgical treatment for low back pain is analysed with emphasis on the proven value of spinal fusion. The interesting and novel developments of stem cell research in the treatment of low back pain are presented with special emphasis on the importance of the cartilaginous end plate and the role of IL-1 in future treatment modalities.

Health and work: progress and priorities in 2011.

This article reflects on the progress that has been made in Britain since publication of the Black report on workplace health in 2008. It provides an overview of the key recommendations of the report, reflecting on the interventions that have been put in place in response to these recommendations by the end of September 2011.

Quantifying the effect of urodynamic catheters on urine flow rate measurement.

INTRODUCTION: The effect of urodynamic catheters on urine flow rate (Q(max) ) is well documented but under-researched. Several studies show reduced Q(max) but methodologies and patient demographics differ. The aims of this study were to further quantify the effect of urodynamic catheters on Q(max) and to explore if this was consistent across different urodynamic diagnoses. METHODS: Four groups of 50 consecutive men attending for urodynamic studies (UDS) were retrospectively analyzed: Group 1 comprised 50 men with normal UDS, Group 2 was 50 men with BOO, and Group 3 contained 50 men with detrusor underactivity. Groups 1-3 had UDS performed using both 10 Fr filling and 4 Fr measuring catheters in situ. Group 4 comprised 50 men who had UDS performed with a smaller catheter assembly (8 Fr dual-lumen). Values of Q(max) with and without catheters present were compared using paired Student's t-tests. Differences between groups were compared using ANOVA. RESULTS: Q(max) measured during UDS in men from Groups 1-3 showed a mean reduction of 38% compared to Q(max) from "free" uroflowmetry. ANOVA indicated this reduction was significantly greater among men with normal UDS. Interestingly the group who underwent UDS with a smaller catheter assembly showed no significant reduction in Q(max) measured with catheters in situ. CONCLUSION: Our findings are in line with previous work suggesting that smaller calibre urethral catheters do not cause a significant obstructive effect during voiding. In addition it would appear that the reduction in Q(max) with larger urethral catheters in situ is greatest in those with normal urodynamics.

The surgical treatment of female stress urinary incontinence.

Urinary incontinence is a common symptom experienced by significant numbers of adult women. Stress urinary incontinence (SUI) is the most frequently encountered type and affects around 50% of incontinent females. Many affected women do not consult their doctors about this troublesome symptom perhaps based on a belief that they cannot be helped. Recent years have seen the development of several new and popular techniques for the surgical treatment of this condition and many of the "gold standard" procedures for stress incontinence have been challenged. Currently, evidence in favor of the use of sub-urethral tapes especially tension-free vaginal tapes suggests that a new standard of low morbidity and high efficacy surgical treatment for SUI has been set. This review is intended to examine all of the surgical options for the treatment of SUI and provide health care professionals with an overview of the vast array of currently available procedures.

An ethnographic study of forensic nursing culture in an Australian prison hospital.

Forensic nurses are faced with unique challenges in their attempt to deliver nursing care in a custodial environment. * The impact of such challenges on the cultural dynamic of forensic nursing and consequently on healthcare delivery is largely unknown. * The aim of this ethnographic study was to explore the nursing culture within an Australian prison hospital and the migration of the culture over a 12-month period. * At the end of the study, the nursing culture was found to be one of hope, although with no clearly articulated vision of nurse-hood or patient-hood and model within which to practice nursing. * The ability to articulate practice is central to the development of mental health nursing in any context. Abstract Forensic nurses are faced with unique challenges in their attempt to deliver nursing care in a custodial environment. The impact of such challenges on the cultural dynamic of forensic nursing and consequently on healthcare delivery is largely unknown. The aim of this ethnographic study was to explore the nursing culture within an Australian prison hospital and the migration of the culture over a 12-month period. At the end of the study the nursing culture was found to be one of hope, although with no clearly articulated vision of nurse-hood or patient-hood and model within which to practice nursing.

Valproic acid reduces spatial working memory and cell proliferation in the hippocampus.

Valproic acid (VPA) is widely used clinically, as an anticonvulsant and mood stabilizer but is, however, also known to block cell proliferation through its ability to inhibit histone deacetylase enzymes. There have been a number of reports of cognitive impairments in patients taking VPA. In this investigation we examined the relationship between cognition and changes in cell proliferation within the hippocampus, a brain region where continued formation of new neurons is associated with learning and memory. Treatment of rats by i.p. injection of VPA, reduced cell proliferation in the sub granular zone of the dentate gyrus within the hippocampus. This was linked to a significant impairment in their ability to perform a hippocampus-dependent spatial memory test (novel object location). In addition, drug treatment caused a significant reduction in brain-derived neurotrophic factor (BDNF) and Notch 1 but not doublecortin levels within the hippocampus. These results support the idea that VPA may cause cognitive impairment and provide a possible mechanism for this by reducing neurogenesis within the hippocampus.

Is low bladder compliance predictive of detrusor overactivity?

AIMS: Bladder compliance (BC) expresses the relationship between bladder volume and bladder pressure and is generally regarded as a measure of bladder stiffness or distensibility. Many types of voiding dysfunction have been associated with low BC such as detrusor overactivity (DO). It has previously been reported that the presence of DO is an independent predictor of low BC. The aim of this study was to assess the predictive value of low BC for the diagnosis of idiopathic DO using ambulatory urodynamics as the gold standard investigation for comparison. METHODS: All patients with LUTS attending a single center for both conventional and ambulatory urodynamics over a 5-year period were reviewed. The predictive value of various set levels of BC was compared using a receiver-operator characteristics (ROC) curve in an attempt to find the optimal threshold of BC for the diagnosis of DO. RESULTS: 162 patients were identified and following exclusions 143 (88%) data sets were suitable for analysis. The mean (s.d.) BC in the 99 patients with DO was 92 (80) ml/cm H(2)O compared to 112 (91) ml/cm H(2)O in those who did not show DO on ambulatory urodynamics. This difference was not statistically significant according to a non-parametric Mann-Whitney test (P = 0.22). Furthermore no set threshold of BC was able to provide sufficient accuracy for the diagnosis of DO. The area under the curve was less than 0.5 (0.47) indicating a level of accuracy less than "chance". CONCLUSIONS: Low bladder compliance is not predictive of DO in our series. It is imperative to note that our results are obtained from a cohort comprising predominantly female patients without BOO and is therefore different to previous reports concentrating on male patients with BOO.