Interprofessional Learning in Multidisciplinary Healthcare Teams Is Associated With Reduced Patient Mortality: A Quantitative Systematic Review and Meta-analysis.

OBJECTIVE: The aim of the study is to identify quantitative evidence for the efficacy of interprofessional learning (IPL) to improve patient outcomes. METHODS: We conducted a systematic review and meta-analysis of quantitative patient outcomes after IPL in multidisciplinary healthcare teams reported in the Medline, Scopus, PsycInfo, Embase, and CINAHL databases. RESULTS: In 2022, we screened 15,248 reports to include 20 and extracted rates of mortality and primary outcomes in conventional care groups and intervention groups (involving initiatives to promote IPL in multidisciplinary teams). The meta-analysis of the 13 studies reporting mortality outcomes demonstrated that the 7166 patients in the intervention group had a significant 28% (95% confidence interval [CI], 40%-14%; P < 0.0003) reduced risk of dying compared with the 6809 patients in the conventional care group. The meta-analysis of the 14 studies reporting other treatment-related adverse outcomes demonstrated that the 4789 patients in the intervention group had a significant 23% (95% CI, 33%-12%; P < 0.0001) reduced risk of experiencing an adverse outcome during care compared with the 4129 patients in the conventional care group. Sensitivity analysis, involving the exclusion of the 20% of individual studies with the widest 95% CIs, confirmed the precision and reliability of our findings. CONCLUSIONS: We believe that our results are the first to demonstrate significant quantitative evidence for the efficacy of IPL to translate into changes in clinical practice and improved patient outcomes. Our results reinforce earlier qualitative work of the value of IPL, but further prospective quantitative and mixed-methods research is needed to better define such benefits.

A cross-sectional study of pediatric dermatoses in a specialized pigment and skin-of-color center in Australia.

There is a paucity of literature on pediatric skin conditions in skin of color, of which old epidemiological data are likely to become outdated as the ethnic diversity in developed countries such as Australia continues to grow. We analyzed the prevalence of presenting conditions of pediatric patients with skin of color attending an urban dermatology clinic in Melbourne, Australia over an 18-month period. The major presenting issues were vitiligo, atopic dermatitis, and acne vulgaris, the majority of which did not significantly differ by ethnicity; however, there was a statistically significantly higher proportion of Chinese and Indian patients presenting with atopic dermatitis. Given the varying presentations of these conditions in skin of color, our findings highlight the importance of increasing education for dermatologists and health personnel in pigmentary disorders and the need for further focused studies comparing the prevalence of skin disease across ethnicities.

International differences and inaccuracies in the public advertising about calcaneal apophysitis: an audit of websites originating in Australia, UK and USA.

BACKGROUND: Calcaneal apophysitis is a common condition in childhood. Parents often seek online information for children's' health care concerns prior to seeking care. Therefore, we aimed to evaluate the credibility, readability, and accuracy of calcaneal apophysitis advertising on popular websites in three countries. METHODS: We used content analysis of publicly accessible data. This involved identifying the top 50 websites in each country from their hit rates. We used elements of validated tools to audit and determine frequencies relevant to credibility (e.g. publisher), readability (e.g. literacy score) and accuracy (e.g. alignment with evidence). Data were analysed quantitatively and reported against each element. RESULTS: Websites were predominantly hosted by private health services (n = 118, 79%). The mean (SD) SMOG (readability) score was 9.3 (4.5). The majority of websites (n = 140, 93%) provided at least one treatment recommendation, and less than 10% (n = 11) of websites advertised treatments fully aligned with evidence. Use of treatment modalities without evidence and with high risk to children were also found including surgery, extracorporeal shock wave therapy and laser. CONCLUSIONS: Calcaneal apophysitis online advertising is mostly curated by clinicians. Clinicians should consider revising online advertising to increase understandability and accuracy to reduce health care wastage, risk, and low value care.

Clinical documentation requirements for the accurate coding of hospital-acquired urinary tract infections in Australia.

Aims We evaluated the accuracy of medical coders in distinguishing the aetiology of urinary tract infection according to clinical documentation. Methods The clinical documentation of patients coded as having had a hospital-acquired urinary tract infection from January to June 2020 at two Melbourne hospitals were assessed for community or hospital acquisition. Results We found that 48.89% of cases were inaccurately categorised as hospital-acquired, due to insufficient detail in clinical documentation. Risk factors for hospital-acquired urinary tract infection were present in at least 30% of correctly categorised cases. Conclusions Clinical documentation is not filled out with sufficient detail or in a timely enough manner for clinical coders to distinguish between hospital or community origin.

Ideal Anatomical Landmark Points for Thoracic Esophagus Segmentation in the Chinese Population.

Introduction: The standards of esophagus segmentation remain different between the Japan Esophageal Society (JES) guideline and the Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) guideline. This study aimed to present variations in the location of intrathoracic esophageal adjacent anatomical landmarks (EAALs) and determine an appropriate method for segmenting the thoracic esophagus based on the relatively fixed EAALs. Patients and Methods: The distances from the upper incisors to the upper border of the esophageal hiatus, lower border of the inferior pulmonary vein (LPV), tracheal bifurcation, lower border of the azygous vein (LAV), and thoracic inlet were measured in the patients undergoing thoracic surgery. The median distances between the EAALs and the specified starting points, as well as reference value ranges and ratios, were obtained. The variation coefficients of distances and ratios from certain starting points to different EAALs were calculated and compared to determine the relatively fixed landmarks. Results: This study included 305 patients. The average distance from the upper incisors to the upper border of the cardia, the midpoint between the tracheal bifurcation and esophageal hiatus (MTBEH), LPV, LAV, tracheal bifurcation, and thoracic inlet were 41.6, 35.3, 34.8, 29.4, 29.5, and 20.3 cm, respectively. The distances from the upper incisors or thoracic inlet to any intrathoracic EAALs in men were higher than in women. In addition, the height, weight, and body mass index (BMI) were correlated with the distances. The ratio of the distance between the upper incisors and tracheal bifurcation to the distance between the upper incisors and upper border of the cardia and the ratio of the distance between the thoracic inlet and tracheal bifurcation to the distance between the thoracic inlet and upper border of the cardia possessed relatively smaller coefficients of variation. Conclusion: The distances from the EAALs to the upper incisors vary with height, weight, BMI, and gender. Compared with distance, the ratios are more suitable for esophagus segmentation. Tracheal bifurcation and MTBEH are ideal EAALs for thoracic esophagus segmentation, and this is consistent with the JES guideline recommendation.

Australian medical student expectations of work-life balance as a doctor.

This article was migrated. The article was marked as recommended. Objectives: To explore the perceptions of medical students on achieving good work-life balance after graduation, and their opinions on parenting having an impact on their future careers. Methods: Cross-sectional cohort study of an online survey was distributed to students from all medical schools in Australia through the General Practice Students Network. Main outcome measures: Medical student perceptions on the effects of their future careers on the ability to maintain work-life balance and whether future parenting would impact their careers. Both quantitative and qualitative responses were collected. Results:The majority of survey respondents believed their careers would have a moderate or significant impact on the ability to achieve work-life balance. Thematic analysis revealed medical students perceived medical careers as lacking flexibility, being time-consuming, and potentially detrimental to health. Surveyed students indicated both parenting goals and specialty choice needed to be considered when planning their career. Conclusions: Australian medical students expressed significant concerns about their ability to juggle parenting and achieve work-life balance within the realities of a medical career.

[Expressions of TAK1 and TAB1 in esophageal cancer and their correlation with prognosis].

OBJECTIVE: To detect the expressions of transforming growth factor-ß (TGF-ß)-activated kinase (TAK1) and TGF-ß- activated protein kinase 1 (TAB1) in esophageal cancer tissues and explore their correlations with the clinicopathological features and prognosis of the patients. METHODS: The expressions of TAK1 and TAB1 in 84 esophageal cancer tissues and paired adjacent tissues was detected using immunohistochemical staining. The correlations of different patterns of TAK1 and TAB1 expressions (TAK1 alone, TAB1 alone, and both) with the clinicopathological features of the patients were analyzed. The correlation between TAK1 and TAB1 was assessed based on GEPIA datasets. Kaplan-Meier survival analysis was used to analyze the recurrence-free survival of the patients in relation with TAK1 and TAB1 expressions. RESULTS: TAK1 and TAB1 were highly expressed in 65.5% (55/84) and 52.4% (44/84) of the esophageal cancer tissues, respectively. The expression of TAK1, TAB1 and their co-expression were all correlated with tumor invasion depth, lymph node metastasis, and TNM staging (P < 0.05). A strong correlation was found between TAK1 and TAB1 expressions. A high expression of TAK1 and TAK1/TAB1 co-expression both predicted a poor recurrence-freed survival of the patients (P < 0.05). CONCLUSIONS: TAK1 and TAB1 are associated with the progression and prognosis of esophageal cancer and can serve as new prognostic biomarkers for esophageal cancer and as potential molecular targets for therapies.

IL-21 restricts T follicular regulatory T cell proliferation through Bcl-6 mediated inhibition of responsiveness to IL-2.

T follicular regulatory (Tfr) cells control the magnitude and specificity of the germinal centre reaction, but how regulation is contained to ensure generation of high-affinity antibody is unknown. Here we show that this balance is maintained by the reciprocal influence of interleukin (IL)-2 and IL-21. The number of IL-2-dependent FoxP3+ regulatory T cells is increased in the peripheral blood of human patients with loss-of-function mutations in the IL-21 receptor (IL-21R). In mice, IL-21:IL-21R interactions influence the phenotype of T follicular cells, reducing the expression of CXCR4 and inhibiting the expansion of Tfr cells after T-cell-dependent immunization. The negative effect of IL-21 on Tfr cells in mice is cell intrinsic and associated with decreased expression of the high affinity IL-2 receptor (CD25). Bcl-6, expressed in abundance in Tfr cells, inhibits CD25 expression and IL-21-mediated inhibition of CD25 is Bcl-6 dependent. These findings identify a mechanism by which IL-21 reinforces humoral immunity by restricting Tfr cell proliferation.

The primary immune response to Vaccinia virus vaccination includes cells with a distinct cytotoxic effector CD4 T-cell phenotype.

BACKGROUND: Smallpox was eradicated by a global program of inoculation with Vaccinia virus (VV). Robust VV-specific CD4 T-cell responses during primary infection are likely essential to controlling VV replication. Although there is increasing interest in cytolytic CD4 T-cells across many viral infections, the importance of these cells during acute VV infection is unclear. METHODS: We undertook a detailed functional and genetic characterization of CD4 T-cells during acute VV-infection of humans. VV-specific T-cells were identified by up-regulation of activation markers directly ex vivo and through cytokine and co-stimulatory molecule expression. At day-13-post primary inoculation with VV, CD38highCD45RO+ CD4 T-cells were purified by cell sorting, RNA isolated and analysed by microarray. Differential expression of up-regulated genes in activated CD4 T-cells was confirmed at the mRNA and protein levels. We compared analyses of VV-specific CD4 T-cells to studies on 12 subjects with primary HIV infection (PHI). VV-specific T-cells lines were established from PBMCs collected post vaccination and checked for cytotoxicity potential. RESULTS: A median 11.9% CD4 T-cells were CD38highCD45RO+ at day-13 post-VV inoculation, compared to 3.0% prior and 10.4% during PHI. Activated CD4 T-cells had an up-regulation of genes related to cytolytic function, including granzymes K and A, perforin, granulysin, TIA-1, and Rab27a. No difference was seen between CD4 T-cell expression of perforin or TIA-1 to VV and PHI, however granzyme k was more dominant in the VV response. At 25:1 effector to target ratio, two VV-specific T-cell lines exhibited 62% and 30% cytotoxicity respectively and CD107a degranulation. CONCLUSIONS: We show for the first time that CD4 CTL are prominent in the early response to VV. Understanding the role of CD4 CTL in the generation of an effective anti-viral memory may help develop more effective vaccines for diseases such as HIV.

Unidirectionally progressive resection of lower left lung carcinoma under video-associated thoracoscopy.

General anesthesia is adopted through double-lumen endotracheal intubation, one-lung ventilation on the contralateral, and intravenous injection. The patient took a 90 degree decubitus on his contralateral side. The operative incisions: the observation port was made in the mid-axillary line of the 7(th) intercostal section, a second horizontal incision of 4 cm as the main operation port at the 4(th) intercostal space between the anterior axillary line and the midclavicular line, and a 3(rd) incision of 1.5 cm as the secondary operation hole at the 9(th) intercostal space between the axillary line and the bottom scapular line. The surgeons were on the ventral side of the patient, and operated with endoscope apparatus in front of the monitor screen.

IL-21 contributes to fatal inflammatory disease in the absence of Foxp3+ T regulatory cells.

The cytokine IL-21 has been shown to influence immune responses through both costimulatory effects on effector T cells and opposing inhibitory effects on T regulatory cells (Tregs). To distinguish the effect of IL-21 on the immune system from that of its effect on Tregs, we analyzed the role of IL-21/IL-21R signaling in mice made genetically deficient in IL-2, which exhibit a deficit in IL-2-dependent Foxp3 regulatory T cells and suffer from a fatal multiorgan inflammatory disease. Our findings demonstrate that in the absence of IL-21/IL-21R signaling, Il2(-/-) mice retained a deficiency in Tregs yet exhibited a reduced and delayed inflammatory disease. The improved health of Il2(-/-)Il21r(-/-) mice was reflected in reduced pancreatitis and hemolytic anemia and this was associated with distinct changes in lymphocyte effector populations, including the reduced expansion of both T follicular helper cells and Th17 cells and a compensatory increase in IL-22 in the absence of IL-21R. IL-21/IL-21R interactions were also important for the expansion of effector and memory CD8(+) T cells, which were critical for the development of pancreatitis in Il2(-/-) mice. These findings demonstrate that IL-21 is a major target of immune system regulation.

IL-21-producing Th cells in immunity and autoimmunity.

IL-21 is a member of the common γ-chain signaling family of cytokines. Analyses of the behavior of immune cells in response to IL-21 in vitro and studies of mice deficient in IL-21 or its receptor indicate that IL-21 has a role in lymphocyte activation, proliferation, differentiation, and survival. IL-21-producing CD4(+) Th cells constitute a broad array of helper subtypes including T follicular helper cells and Th17 cells. Both autocrine and paracrine utilization of IL-21 contributes to the overall signal transduction pathways of the Ag receptor to influence the growth and survival of lymphocytes. The redundancy that IL-21 exhibits in lymphoid organs during immune responses is in stark contrast to the evidence that pharmacological neutralization of this cytokine can halt inflammation in nonlymphoid organs where IL-21 becomes the dominant voice.

IL-21 promotes CD8+ CTL activity via the transcription factor T-bet.

CD8(+) T cells are fundamental for immune-mediated clearance of viral infections and contribute to immune pathology in autoimmune diseases such as type 1 diabetes. To execute these functions, CD8(+) T cells must differentiate into CTLs, a process that is precisely regulated by a variety of cytokines, costimulatory molecules, and transcription factors. IL-21 is an IL-2 family cytokine and a growth factor for multiple lymphocyte effector lineages, including cytotoxic CD8(+) T cells. Recent studies demonstrate that loss of IL-21 signaling results in reduced viral clearance in models of lymphocytic choriomeningitis virus infection, and also protection from type 1 diabetes in the NOD model. This is most likely the result of impaired CD8(+) CTL function in the absence of IL-21 signaling. Currently, the mechanisms by which IL-21 promotes CTL differentiation in CD8(+) T cells remain unclear, particularly the identity of the relevant transcription factor(s). We show that IL-21 promotes CTL function in vitro and killing of pancreatic islets in vivo via the use of transgenic mice expressing IL-21 in pancreatic ß cells. We demonstrate that IL-21 induces the expression of the transcription factor T-bet in CD8(+) T cells, predominantly via STAT1, and that T-bet is required for the induction of cytolytic molecules, including perforin and granzyme B in response to IL-21. Finally, we show that IL-21-induced CTL function is T-bet dependent, as T-bet deficiency results in defective IL-21-dependent cytotoxicity in CD8(+) T cells in vitro and in vivo. Thus, IL-21 drives CD8(+) CTL differentiation via the actions of the transcription factor T-bet.

Brain hemispheric differences in the neurochemical effects of lead, prenatal stress, and the combination and their amelioration by behavioral experience.

Brain lateralization, critical to mediation of cognitive functions and to "multitasking," is disrupted in conditions such as attention deficit disorder and schizophrenia. Both low-level lead (Pb) exposure and prenatal stress (PS) have been associated with mesocorticolimbic system-mediated executive-function cognitive and attention deficits. Mesocorticolimbic systems demonstrate significant laterality. Thus, altered brain lateralization could play a role in this behavioral toxicity. This study examined laterality of mesocorticolimbic monoamines (frontal cortex, nucleus accumbens, striatum, midbrain) and amino acids (frontal cortex) in male and female rats subjected to lifetime Pb exposure (0 or 50 ppm in drinking water), PS (restraint stress on gestational days 16-17), or the combination with and without repeated learning behavioral experience. Control males exhibited prominent laterality, particularly in midbrain and also in frontal cortex and striatum; females exhibited less laterality, and this was primarily striatal. Lateralized Pb ± PS induced neurotransmitter changes were assessed only in males because of limited sample sizes of Pb + PS females. In males, Pb ± PS changes occurred in left hemisphere of frontal cortex and right hemisphere of midbrain. Behavioral experience modified the laterality of Pb ± PS-induced neurotransmitter changes in a region-dependent manner. Notably, behavioral experience eliminated Pb ± PS neurotransmitter changes in males. These findings underscore the critical need to evaluate both sexes and brain hemispheres for the mechanistic understanding of sex-dependent differences in neuro- and behavioral toxicity. Furthermore, assessment of central nervous system mechanisms in the absence of behavioral experience, shown here for males, may constitute less relevant models of human health effects.

Variations in the nature of behavioral experience can differentially alter the consequences of developmental exposures to lead, prenatal stress, and the combination.

Behavioral experience (BE) can critically influence later behavior and brain function, but the central nervous system (CNS) consequences of most developmental neurotoxicants are examined in the absence of any such context. We previously demonstrated marked differences in neurotransmitter changes produced by developmental lead (Pb) exposure ± prenatal stress (PS) depending upon whether or not rats had been given BE (Cory-Slechta, D. A., Virgolini, M. B., Rossi-George, A., Weston, D., and Thiruchelvam, M. (2009). The current study examined the hypothesis that the nature of the BE itself would be a critical determinant of outcome in mice that had been continually exposed to 0 or 100 ppm Pb acetate in drinking water alone or in combination with prenatal restraint stress. Half of the offspring in each of the four resulting groups/gender were exposed to positively reinforced (food-rewarded Fixed Interval schedule-controlled behavior) or negatively reinforced (inescapable forced swim) BE. Brain monoamines and amino acids differed significantly in relation to BE, even in control animals, as did the trajectory of effects of Pb ± PS, particularly in frontal cortex, hippocampus (both genders), and midbrain (males). In males, Pb ± PS-related changes in neurotransmitters correlated with behavioral performance. These findings suggest that CNS consequences of developmental toxicants studied in the absence of a broader spectrum of BEs may not necessarily be predictive of human outcomes. Evaluating the role of specific BEs as a modulator of neurodevelopmental insults offers the opportunity to determine what specific BEs may ameliorate the associated impacts and can assist in establishing underlying neurobiological mechanisms.

Mice deficient in GEM GTPase show abnormal glucose homeostasis due to defects in beta-cell calcium handling.

AIMS AND HYPOTHESIS: Glucose-stimulated insulin secretion from beta-cells is a tightly regulated process that requires calcium flux to trigger exocytosis of insulin-containing vesicles. Regulation of calcium handling in beta-cells remains incompletely understood. Gem, a member of the RGK (Rad/Gem/Kir) family regulates calcium channel handling in other cell types, and Gem over-expression inhibits insulin release in insulin-secreting Min6 cells. The aim of this study was to explore the role of Gem in insulin secretion. We hypothesised that Gem may regulate insulin secretion and thus affect glucose tolerance in vivo. METHODS: Gem-deficient mice were generated and their metabolic phenotype characterised by in vivo testing of glucose tolerance, insulin tolerance and insulin secretion. Calcium flux was measured in isolated islets. RESULTS: Gem-deficient mice were glucose intolerant and had impaired glucose stimulated insulin secretion. Furthermore, the islets of Gem-deficient mice exhibited decreased free calcium responses to glucose and the calcium oscillations seen upon glucose stimulation were smaller in amplitude and had a reduced frequency. CONCLUSIONS: These results suggest that Gem plays an important role in normal beta-cell function by regulation of calcium signalling.