Malignant mixed mullerian tumors: a SEER database review of rurality and treatment modalities on disease outcome.

Introduction: Malignant Mixed Mullerian Tumors (MMMT) are rare and poorly understood sarcomas with limited research on risk factors, pathogenesis, and optimal treatments. This study aimed to address this knowledge gap and explore the impact of community size, patient characteristics, disease characteristics, and treatment modalities on MMMT outcomes. Methods: Using the Surveillance, Epidemiology, and End Results database (SEER), the largest SEER cohort to date of 3,352 MMMT patients was analyzed for demographic factors, treatment modalities, and histologic characteristics. Data was processed, including the removal of incomplete entries, and analyzed in Python 3.1 using packages scikit-learn, lifelines, and torch; log-rank analysis and Cox proportional hazards models were used to evaluate a number of demographic characteristics and disease characteristics for significance in regard to survival. Results: Our study found adjuvant radiotherapy and chemotherapy significantly improved survival, with modest benefits from neoadjuvant chemotherapy. Our findings also suggest age at diagnosis, disease grade, and suburban versus rural geographic locations may play key roles in patient prognosis. On multivariable analysis both disease Grade and surgical treatment were significant factors. Discussion: MMMTs remain challenging, but appropriate treatment appears to enhance survival. The present findings suggest opportunities for improved outcomes and treatment strategies for patients with MMMTs.

Five-Repetition Sit-to-Stand Test: Responsiveness and Minimal Important Difference in Idiopathic Pulmonary Fibrosis.

Rationale: Standing from a sitting position is an important activity of daily living. The five-repetition sit-to-stand test (5STS) is a simple physical performance test that measures the fastest time taken to stand five times from a chair with arms folded. It can be measured in most healthcare settings and at home, where traditional field walking tests may not be possible. The 5STS has been validated in community-dwelling older adults and people with chronic obstructive pulmonary disease, but data in idiopathic pulmonary fibrosis (IPF) are limited.Objectives: The aims of this cohort study were to establish the construct validity, responsiveness to pulmonary rehabilitation (PR), and minimal important difference (MID) of the 5STS in IPF.Methods: In 149 people with IPF, we compared the 5STS with measures of lung function, exercise capacity, quadriceps strength, breathlessness, and health-related quality of life. Responsiveness and effect sizes were determined by measuring the 5STS before and after PR. The MID was estimated using anchor- and distribution-based methods.Results: The 5STS correlated significantly with incremental shuttle walk test (ISW) (r = -0.55), isometric quadriceps maximum voluntary contraction (QMVC) (r = -0.45), Medical Research Council dyspnea scale score (r = 0.40), Chronic Respiratory Questionnaire-Total (r = -0.21), and King's Brief Interstitial Lung Disease Questionnaire-Total (r = -0.21) but not forced vital capacity percentage predicted or quadriceps one-repetition maximum (1RM). There was a significant but very weak correlation between change in 5STS and changes in Medical Research Council (r = 0.18), ISW (r = -0.21), and Chronic Respiratory Questionnaire-Total (r = -0.26) but no significant correlation with change in 1RM (r = -0.12) or QMVC (r = -0.18). 5STS time improved with PR (median [25th percentile, 75th percentile] change, -1.97 [-3.47, -0.62] s; P < 0.001). The effect size for the 5STS was 0.66 and higher than quadriceps 1RM, QMVC, and ISW. The mean (range) MID estimate was -1.93 (-1.85 to -2.10) seconds.Conclusions: In people with IPF, the 5STS is a valid physical performance measure that is responsive to exercise-based interventions and suitable for use in most healthcare settings.

Identifying infection in chronic wounds in a community setting: A systematic review of diagnostic test accuracy studies.

AIM: To determine the diagnostic accuracy of different methods currently available to identify infection in chronic wounds applicable to adult patients in a community setting. DESIGN: Systematic review of diagnostic test accuracy studies. REVIEW METHODS: Two authors independently completed screening, data extraction and quality and bias assessments (QUADAS2). Eligible studies compared a method (index test) for detecting infection (diagnosis of interest) with microscopy and culture of either deep tissue biopsy or wound swab (reference test) in adult patients with wounds of >4 weeks duration (participants). The results were synthesized narratively. DATA SOURCES: We systematically searched CINAHL, Embase and Medline from 2011 to April 2022. RESULTS: Four studies were included, all recruiting from secondary care wound clinics. Two studies assessed the diagnostic accuracy of Moleculight i:X, a bacterial fluorescence imaging device against deep tissue biopsy culture. One study assessed the diagnostic accuracy of the elevation of various enzymes detected in wound fluid against wound swab microscopy of culture. One study assessed the diagnostic accuracy of bacterial protease activity against wound swab microscopy and culture. Sensitivities of these methods ranged from 50 to 75% and specificities from 47 to 100%. CONCLUSION: Only a small number of studies were included in this systematic review due to our strict inclusion criteria. We have not identified any methods for diagnosing infection in chronic wounds with either a sufficient quality of evidence to recommend their use in community settings at present. Further research is needed to develop and evaluate appropriate diagnostics for this purpose. IMPACT: This study highlights the paucity of research into wound diagnostics in a community setting and should prompt further research in this area. Accurate diagnostic tests have the potential to improve community-based wound care by optimizing antibiotic use and potentially improving healing time. REPORTING METHOD: PRISMA-DTA checklist. PATIENT OR PUBLIC CONTRIBUTION: The PPI group for the NIHR Community Healthcare MIC were supportive of this topic of work.

A SEER database retrospective cohort of 547 patients with penile non-squamous cell carcinoma: demographics, clinical characteristics, and outcomes.

Introduction: Little research has investigated the prevalence and distribution of the diverse pathologies of non-squamous cell carcinoma (non-SCC) of the penis. Although rare in clinical practice, these cancers have become a focus of greater importance among patients, clinicians, and researchers, particularly in developing countries. The principal objective of this study was to analyze the major types of penile non-SCC, elucidate common treatment pathways, and highlight outcomes including 5-year survival. Materials/methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried between 2000 and 2018 to identify a retrospective cohort of patients with penile non-SCC. Demographic information, cancer characteristics, diagnostic methods, treatments administered, and survival were investigated. Results: A total of 547 cases of penile non-SCC were included in the analysis. The most prevalent non-SCC cancers included epithelial neoplasms, not otherwise specified (NOS) (15.4%), unspecified neoplasms (15.2%), basal cell neoplasms (13.9%), blood vessel tumors (13.0%), nevi and melanomas (11.7%), and ductal and lobular neoplasms (9.9%). Over half (56.7%) of patients elected to undergo surgical intervention. Patients rarely received systemic therapy (3.8%) or radiation (4.0%). Five-year survival was 35.5%. Patients who underwent surgery had greater annual survival for 0-10 years compared to those who did not have surgery. Significant differences in survival were found between patients who had regional, localized, and distant metastases (p < 0.05). A significant difference in survival was found for patients married at diagnosis versus those who were unmarried at diagnosis (p < 0.05). Lower survival rates were observed for patients older than 70 years. Discussion: Although less prevalent than SCC, penile non-SCC encompasses a diverse set of neoplasms. Patients in this cohort had a high utilization of surgical management leading to superior outcomes compared to those not receiving surgery. Radiation is an uncommonly pursued treatment pathway. Patient demographics and socioeconomic variables such as marital status may be valuable when investigating cancer outcomes. This updated database analysis can help inform diagnosis, management, and clinical outcomes for this rare group of malignancies.

Accuracy of parents' subjective assessment of paediatric fever with thermometer measured fever in a primary care setting.

BACKGROUND: Fever is a common symptom of benign childhood illness but a high fever may be a sign of a serious infection. Temperature is often used by parents to check for illness in their children, and the presence of a high temperature can act as a prompt to consult a healthcare professional. It would be helpful for GPs to understand how well parental assessment of the presence of fever correlates with temperature measurement in the clinic in order to incorporate the history of the child's fever into their clinical assessment. METHODS: Secondary analysis of a cross-sectional diagnostic method comparison study. Parents were asked whether they thought their child had fever before their temperature was measured by a researcher. Fever was defined as a temperature of 38 °C and higher using either an axillary or tympanic thermometer. RESULTS: Of 399 children recruited, 119 (29.8%) were believed by their parents to be febrile at the time of questioning and 23 (6.3%) had a fever as measured by a researcher in the clinic. 23.5% of children with a parental assessment of fever were found to have a fever in the clinic. Less than 1% of children whose parents thought they did not have a fever were found to be febrile in the clinic. Having more than one child did not improve accuracy of parents assessing fever in their child. CONCLUSIONS: In the GP surgery setting, a child identified as afebrile by their parent is highly likely to be measured as such in the clinic. A child identified as febrile by their parent is less likely to be measured as febrile.

Risk Behavioral Contexts in Adolescence of Obese Adults.

PURPOSE: Previous research suggests that poor nutrition, physical activity, sleep, and social/emotional climate are associated with weight gain. However, few empirical studies have examined how these factors relate to each other in adolescents who are later obese. Are these factors uniformly present, or do some co-occur or occur independently? This study seeks to identify subgroups of obese individuals at ages 24-32 years who exhibited unique, co-occurring behavioral and emotional contexts for obesity at ages 14-17 years. METHODS: To identify subgroups of behavioral and contextual profiles in adolescence, the study applies latent class analysis to a sample of individuals who were obese in the fourth wave of the National Longitudinal Study of Adolescent to Adult Health (Add Health, N = 1,889). The study then explored covariates (e.g., gender, race) of class membership. RESULTS: Considerable heterogeneity exists in risk profiles of adolescents obese as adults. For example, 21.1 percent of the sample is in a class with no differentiating risk factors, whereas two classes containing 22.1 percent of the sample exhibit high levels of depression, and nearly all the emotional factors are considered. Although some covariates are predictive of class membership, clear patterns are difficult to discern. However, poor physical health is clearly predictive of membership in the classes exhibiting a high risk of depression. DISCUSSION: Clinicians should be aware that at younger ages, people who are ultimately obese display a range of factors linked to obesity. Although some exhibit behaviors such as high screen time and processed food consumption, others exhibit mainly poor social/emotional climate.

Aged Cattle Brain Displays Alzheimer's Disease-Like Pathology and Promotes Brain Amyloidosis in a Transgenic Animal Model.

Alzheimer's disease (AD) is one of the leading causes of dementia in late life. Although the cause of AD neurodegenerative changes is not fully understood, extensive evidence suggests that the misfolding, aggregation and cerebral accumulation of amyloid beta (Aß) and tau proteins are hallmark events. Recent reports have shown that protein misfolding and aggregation can be induced by administration of small quantities of preformed aggregates, following a similar principle by which prion diseases can be transmitted by infection. In the past few years, many of the typical properties that characterize prions as infectious agents were also shown in Aß aggregates. Interestingly, prion diseases affect not only humans, but also various species of mammals, and it has been demonstrated that infectious prions present in animal tissues, particularly cattle affected by bovine spongiform encephalopathy (BSE), can infect humans. It has been reported that protein deposits resembling Aß amyloid plaques are present in the brain of several aged non-human mammals, including monkeys, bears, dogs, and cheetahs. In this study, we investigated the presence of Aß aggregates in the brain of aged cattle, their similarities with the protein deposits observed in AD patients, and their capability to promote AD pathological features when intracerebrally inoculated into transgenic animal models of AD. Our data show that aged cattle can develop AD-like neuropathological abnormalities, including amyloid plaques, as studied histologically. Importantly, cow-derived aggregates accelerate Aß amyloid deposition in the brain of AD transgenic animals. Surprisingly, the rate of induction produced by administration of the cattle material was substantially higher than induction produced by injection of similar amounts of human AD material. Our findings demonstrate that cows develop seeding-competent Aß aggregates, similarly as observed in AD patients.

Pre-analytical error for three point of care venous blood testing platforms in acute ambulatory settings: A mixed methods service evaluation.

INTRODUCTION: Point of care blood testing to aid diagnosis is becoming increasingly common in acute ambulatory settings and enables timely investigation of a range of diagnostic markers. However, this testing allows scope for errors in the pre-analytical phase, which depends on the operator handling and transferring specimens correctly. The extent and nature of these pre-analytical errors in clinical settings has not been widely reported. METHODS: We carried out a convergent parallel mixed-methods service evaluation to investigate pre-analytical errors leading to a machine error reports in a large acute hospital trust in the UK. The quantitative component comprised a retrospective analysis of all recorded error codes from Abbott Point of Care i-STAT 1, i-STAT Alinity and Abbott Rapid Diagnostics Afinion devices to summarise the error frequencies and reasons for error, focusing on those attributable to the operator. The qualitative component included a prospective ethnographic study and a secondary analysis of an existing ethnographic dataset, based in hospital-based ambulatory care and community ambulatory care respectively. RESULTS: The i-STAT had the highest usage (113,266 tests, January 2016-December 2018). As a percentage of all tests attempted, its device-recorded overall error rate was 6.8% (95% confidence interval 6.6% to 6.9%), and in the period when reliable data could be obtained, the operator-attributable error rate was 2.3% (2.2% to 2.4%). Staff identified that the most difficult step was the filling of cartridges, but that this could be improved through practice, with a perception that cartridge wastage through errors was rare. CONCLUSIONS: In the observed settings, the rate of errors attributable to operators of the primary point of care device was less than 1 in 40. In some cases, errors may lead to a small increase in resource use or time required so adequate staff training is necessary to prevent adverse impact on patient care.

Deficits in hippocampal-dependent transfer generalization learning accompany synaptic dysfunction in a mouse model of amyloidosis.

Elevated ß-amyloid and impaired synaptic function in hippocampus are among the earliest manifestations of Alzheimer's disease (AD). Most cognitive assessments employed in both humans and animal models, however, are insensitive to this early disease pathology. One critical aspect of hippocampal function is its role in episodic memory, which involves the binding of temporally coincident sensory information (e.g., sights, smells, and sounds) to create a representation of a specific learning epoch. Flexible associations can be formed among these distinct sensory stimuli that enable the "transfer" of new learning across a wide variety of contexts. The current studies employed a mouse analog of an associative "transfer learning" task that has previously been used to identify risk for prodromal AD in humans. The rodent version of the task assesses the transfer of learning about stimulus features relevant to a food reward across a series of compound discrimination problems. The relevant feature that predicts the food reward is unchanged across problems, but an irrelevant feature (i.e., the context) is altered. Experiment 1 demonstrated that C57BL6/J mice with bilateral ibotenic acid lesions of hippocampus were able to discriminate between two stimuli on par with control mice; however, lesioned mice were unable to transfer or apply this learning to new problem configurations. Experiment 2 used the APPswe PS1 mouse model of amyloidosis to show that robust impairments in transfer learning are evident in mice with subtle ß-amyloid-induced synaptic deficits in the hippocampus. Finally, Experiment 3 confirmed that the same transfer learning impairments observed in APPswePS1 mice were also evident in the Tg-SwDI mouse, a second model of amyloidosis. Together, these data show that the ability to generalize learned associations to new contexts is disrupted even in the presence of subtle hippocampal dysfunction and suggest that, across species, this aspect of hippocampal-dependent learning may be useful for early identification of AD-like pathology.

Utility of a child abuse screening guideline in an urban pediatric emergency department.

BACKGROUND: Previous studies have found racial and socioeconomic status bias in the way clinicians screen for and detect child abuse in patients presenting to the emergency department. We hypothesized that implementing a guideline for screening would attenuate this bias. METHODS: An algorithm for child abuse screening in patients younger than 1 year presenting with fractures was developed for a pediatric trauma center emergency department. Data were collected 1.5 years before and after implementation of the algorithm to investigate implementation success. Data were compared before and after the implementation of the algorithm using χ and univariate logistic regression analysis. RESULTS: The characteristics of patients with fractures were similar before and after the algorithm implementation. Implementation of the algorithm was related to a significant increase in algorithm required screenings: skeletal survey (p < 0.001), urinalysis (p < 0.001), and transaminase levels (p < 0.001). The racial composition of those screened did not change after the implementation of the protocol. Children with government-subsidized or no insurance were more likely to be screened for child abuse via skeletal survey before the algorithm implementation compared with those with private insurance (odds ratio, 2.7; 95% confidence interval, 1.2-6.0; p = 0.017). This relationship did not exist after the algorithm implementation (odds ratio, 1.2; 95% confidence interval, 0.56-2.46; p = 0.66). Final determination of child abuse was related to insurance status both before and after the algorithm implementation. CONCLUSION: A child abuse screening algorithm was successfully implemented in an urban trauma center. After implementation, screening was no longer associated with socioeconomic status of the patient's family, although final determination of child abuse still was. Additional research is needed to determine utility of unbiased screening on patient outcomes. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Volunteer orthopedic surgical trips in Nicaragua: a cost-effectiveness evaluation.

BACKGROUND: Injuries account for a substantial portion of the world's burden of disease and require effective surgical care. Volunteer surgical teams that form partnerships with hospitals help build local surgical capacity while providing immediate care. The purpose of the present study was to evaluate the cost-effectiveness of short orthopedic surgical volunteer trips as a method of reducing the global burden of surgical disease through both surgical and educational interventions. METHODS: Data were collected from a scheduled volunteer trip to Leon, Nicaragua, in January 2011 as part of the Cooperación Ortopédica Americano Nicaraguense (COAN), a 501c3 nonprofit organization established in 2002. Costs are from the COAN provider prospective with an additional analysis to include the Nicaraguan provider variable costs. The total burden of musculoskeletal disease averted from the patients receiving surgical intervention was derived using the disability-adjusted-life-years (DALYs) framework and disability weights from the disease control priority project. The cost-effectiveness ratio was calculated by dividing the total costs by the total DALYs averted. RESULTS: A total of 44.78 DALYs were averted in this study, amounting to an average of 1.49 DALYs averted per patient. The average cost per patient from the COAN provider perspective was $525.64, and from both the COAN and Nicaraguan provider perspective it was $710.97. In the base case, cost-effectiveness was $352.15 per DALY averted, which is below twice the Nicaraguan per capita gross national income ($652.40). CONCLUSIONS: Volunteer orthopedic surgical trips are cost-effective in Nicaragua. Further research should be conducted with multiple trips and with different patient populations to test the generalizability of the results.

Use of a TTA plate for correction of severe patella baja in a Chihuahua.

A 7 yr old spayed female Chihuahua presented for right hind limb lameness and reduced stifle range of motion. Radiographs showed a marked patella baja of the right stifle and evidence of a previous surgery to correct a medial patellar luxation. A tibial tuberosity osteotomy was performed to allow proximal translation of the tibial tuberosity, which was stabilized with a tibial tuberosity advancement plate. Four weeks postoperatively, lameness and articular range of motion were improved, and the use of anti-inflammatory and analgesic medications was discontinued. The dog was still ambulating well and had no lameness 12 mo postsurgically.

A validated disease-specific symptom index for adults with celiac disease.

BACKGROUND & AIMS: Although the incidence of celiac disease (CD) is increasing, studies have been hampered by the lack of validated outcome measures. We sought to create a disease-specific Celiac Symptom Index (CSI) to reliably assess relevant symptoms. METHODS: A 36-item questionnaire was created after design by an expert committee and review/revision by patient focus groups. The survey, covering domains of CD-related symptoms and general health, was initially administered to 154 individuals with biopsy-proven CD; immunoglobulin (Ig)A tissue transglutaminase titers were determined, and gluten-free diet adherence was evaluated by a dietitian. The questionnaire was then revised to exclude questions with poor test characteristics and administered to a second, independent group of 52 individuals, to ensure validity. RESULTS: The subscales of "specific symptoms" and "general health" had excellent psychometric qualities that consisted of 11 and 5 items, respectively. The additive score based on these items was correlated with current general health, as measured by a visual analog scale and short form 36 general health subscale (P < or = .001 for both), as well as degree of adherence to the gluten-free diet (P = .008), lending external validity to the CSI. The resulting 16 questions make up the first CD-specific symptom index. CONCLUSIONS: The CSI allows for disease-specific monitoring of symptoms as an independent outcome measure or as part of a surrogate for disease activity in individuals with CD. The CSI might be an important tool for future clinical CD research.

A simple validated gluten-free diet adherence survey for adults with celiac disease.

BACKGROUND & AIMS: Celiac disease is an increasingly prevalent disorder. To monitor response to treatment in clinical and research settings, it is essential to accurately measure gluten-free diet (GFD) adherence in a standardized manner. The aim of this study was to develop a valid and reliable Celiac Dietary Adherence Test (CDAT). METHODS: Items and domains believed to be essential for successful GFD adherence were used to develop an 85-item survey with input from patient focus groups. The survey was administered to 200 individuals with biopsy-proven celiac disease who underwent standardized dietician evaluation (SDE) and serologic testing. RESULTS: Of the initial 85 items, 41 were correlated highly with the SDE (P < .01). Responses for all 200 participants for the 41 items were entered into a single database. Computer-generated randomization produced a derivation cohort of 120 subjects and a validation cohort of 80. By using the derivation cohort, a 7-item questionnaire was developed using logistic regression. The additive score based on these items was correlated highly with the SDE in both the derivation and validation cohorts (P < .001) and performed significantly better than immunoglobulin A tissue transglutaminase titers in receiver operating characteristic curve analysis with areas under the curve of 0.830 and 0.652, respectively. CONCLUSIONS: The CDAT is a clinically relevant, easily administered, 7-item instrument that allows for standardized evaluation of GFD adherence and is superior to tissue transglutaminase serology. The CDAT may be useful in both research and clinical settings.

Psychological correlates of gluten-free diet adherence in adults with celiac disease.

GOALS: To determine whether personality traits and psychological characteristics are related to gluten-free diet (GFD) adherence in an adult population diagnosed with celiac disease (CD). BACKGROUND: Little research has examined psychological correlates of adherence to the GFD. STUDY: One hundred fifty-seven adults with biopsy-confirmed CD on the GFD for >3 months completed measures of personality and self-reported GFD adherence, provided a blood sample, and participated in an evaluation of GFD adherence conducted by an expert dietician at a clinical care center in a major teaching hospital in Boston, MA. RESULTS: An expert evaluation of GFD adherence remained the "gold standard" for measuring GFD adherence when compared with self-report and serology. Logistic regression results indicated that the following were independently associated with GFD adherence: conscientiousness (B=-0.04, SE=0.01, P<0.00), values (B=-0.10, SE=0.05, P<0.05), other food intolerances [odds ratio=0.28, 95% confidence interval=0.10-0.78], and CD symptoms (B=0.05, SE=0.02, P<0.03). A model accounting for these associations effectively predicted whether a participant was adherent or nonadherent on the basis of psychological and demographic/disease-specific factors. Successful prediction rates of GFD adherence for the final model were 75.8% for those rated to be adherent with the GFD and 54.5% for those rated to be nonadherent with the GFD. CONCLUSIONS: The model of psychological and demographic/disease-specific characteristics developed can be used to identify patients who may be at risk for poor dietary adherence to provide additional support, education, and encouragement to individuals with CD.

A prospective comparative study of five measures of gluten-free diet adherence in adults with coeliac disease.

BACKGROUND: Increasing numbers of individuals are now being diagnosed with coeliac disease. The only accepted treatment for coeliac disease is lifelong adherence to a strict gluten-free diet (GFD). Individuals' ability to adhere to the GFD varies, but systematic studies guiding the assessment of adherence are currently lacking. AIM: We sought to compare the predictive value of self-report and four serologic tests compared to expert nutritionist evaluation. METHODS: In all, 154 individual adults with biopsy-proven coeliac disease rated their adherence to the GFD on a Likert scale. Serum antibody titres of IgA anti-tissue transglutaminase, and IgA and IgG anti-deamidated gliadin peptides were determined. Using anova and ROC analyses, results were compared to a standardized evaluation by an expert nutritionist blinded to the participants' self-rated adherence and serology results. RESULTS: All serologic measures as well as participant reported adherence were significantly associated with GFD adherence as assessed by expert nutritionist evaluation. However, on ROC analysis no measure performed satisfactorily. The performance of serologic testing, but not self-report, improved with increased time on the GFD. CONCLUSION: Although current serologic tests have very high sensitivities and specificities for the diagnosis of coeliac disease, they cannot replace trained nutritionist evaluation in the assessment of GFD adherence.