Graphical modeling of causal factors associated with the postoperative survival of esophageal cancer subjects.

PURPOSE: To clarify the causal relationship between factors contributing to the postoperative survival of patients with esophageal cancer. METHODS: A cohort of 195 patients who underwent surgery for esophageal cancer between 2008 and 2021 was used in the study. All patients had preoperative chest computed tomography (CT) and positron emission tomography-CT (PET-CT) scans prior to receiving any treatment. From these images, high throughput and quantitative radiomic features, tumor features, and various body composition features were automatically extracted. Causal relationships among these image features, patient demographics, and other clinicopathological variables were analyzed and visualized using a novel score-based directed graph called "Grouped Greedy Equivalence Search" (GGES) while taking prior knowledge into consideration. After supplementing and screening the causal variables, the intervention do-calculus adjustment (IDA) scores were calculated to determine the degree of impact of each variable on survival. Based on this IDA score, a GGES prediction formula was generated. Ten-fold cross-validation was used to assess the performance of the models. The prediction results were evaluated using the R-Squared Score (R2 score). RESULTS: The final causal graphical model was formed by two PET-based image variables, ten body composition variables, four pathological variables, four demographic variables, two tumor variables, and one radiological variable (Percentile 10). Intramuscular fat mass was found to have the most impact on overall survival month. Percentile 10 and overall TNM (T: tumor, N: nodes, M: metastasis) stage were identified as direct causes of overall survival (month). The GGES casual model outperformed GES in regression prediction (R2  = 0.251) (p < 0.05) and was able to avoid unreasonable causality that may contradict common sense. CONCLUSION: The GGES causal model can provide a reliable and straightforward representation of the intricate causal relationships among the variables that impact the postoperative survival of patients with esophageal cancer.

Pharmacological Management of Orofacial Pain.

Orofacial pain is a category of complex disorders, including musculoskeletal, neuropathic and neurovascular disorders, that greatly affect the quality of life of the patient. These disorders are within the fields of dentistry and medicine and management can be challenging, requiring a referral to an orofacial pain specialist, essential for adequate evaluation, diagnosis, and care. Management is specific to the diagnosis and a treatment plan is developed with diverse pharmacological and non-pharmacological modalities. The pharmacological management of orofacial pain encompasses a vast array of medication classes and approaches. This includes anti-inflammatory drugs, muscle relaxants, anticonvulsants, antidepressants, and anesthetics. In addition, as adjunct therapy, different injections can be integrated into the management plan depending on the diagnosis and needs. These include trigger point injections, temporomandibular joint (TMJ) injections, and neurotoxin injections with botulinum toxin and nerve blocks. Multidisciplinary management is key for optimal care. New and safer therapeutic targets exclusively for the management of orofacial pain disorders are needed to offer better care for this patient population.

Implementation and prospective real-time evaluation of a generalized system for in-clinic deployment and validation of machine learning models in radiology.

The medical imaging community has embraced Machine Learning (ML) as evidenced by the rapid increase in the number of ML models being developed, but validating and deploying these models in the clinic remains a challenge. The engineering involved in integrating and assessing the efficacy of ML models within the clinical workflow is complex. This paper presents a general-purpose, end-to-end, clinically integrated ML model deployment and validation system implemented at UCSF. Engineering and usability challenges and results from 3 use cases are presented. A generalized validation system based on free, open-source software (OSS) was implemented, connecting clinical imaging modalities, the Picture Archiving and Communication System (PACS), and an ML inference server. ML pipelines were implemented in NVIDIA's Clara Deploy framework with results and clinician feedback stored in a customized XNAT instance, separate from the clinical record but linked from within PACS. Prospective clinical validation studies of 3 ML models were conducted, with data routed from multiple clinical imaging modalities and PACS. Completed validation studies provided expert clinical feedback on model performance and usability, plus system reliability and performance metrics. Clinical validation of ML models entails assessing model performance, impact on clinical infrastructure, robustness, and usability. Study results must be easily accessible to participating clinicians but remain outside the clinical record. Building a system that generalizes and scales across multiple ML models takes the concerted effort of software engineers, clinicians, data scientists, and system administrators, and benefits from the use of modular OSS. The present work provides a template for institutions looking to translate and clinically validate ML models in the clinic, together with required resources and expected challenges.

Impact of botulinum toxin injection into the masticatory muscles on mandibular bone: A systematic review.

BACKGROUND: Botulinum toxin type A (BoNTA) injection into the masticatory muscles has been widely used to treat a number of painful and nonpainful conditions; however, no systematic reviews have been performed on the long-term effect to the mandibular bone. OBJECTIVE: Our systematic review aimed to evaluate the impact of botulinum toxin injection into the masticatory muscles on mandibular bone based. METHODS: PubMed, Embase, Ovid, CINAHL and Web of Science were searched for human studies assessing mandibular bone after injection of BoNTA using computed tomography (CT) and cone beam CT (CBCT). RESULTS: Seven studies were eligible for review; five reported significant bony changes to one or more areas of the mandible. Most frequently affected were the condylar head, coronoid process and ramus. The most frequent changes were decreased bone volume, cortical thickness and cortical and trabecular density. CONCLUSIONS: This is the first systematic review to examine an association between BoNTA injection into the masticatory muscles and mandibular bone quality. Data were analysed from a limited number of studies with a small sample size, and the quality of the included studies was very low. While the majority of available evidence suggests BoNTA injection results in bony change, further study is required to confirm a dose-dependence effect and the impact of gender and age. High-quality trials should utilise a combination of software analysis and radiologist review, with longer-term follow-up to monitor for persistence of bony effect and clinical significance.

High-yield dairy cattle breeds improve farmer incomes, curtail greenhouse gas emissions and reduce dairy import dependency in Tanzania.

Tanzania's dairy sector is poorly developed, creating reliance on imports for processed, value-added dairy products and threatening food security, particularly when supply chains are disrupted due to market volatility or armed conflicts. The Tanzanian Dairy Development Roadmap is a domestic development initiative that aims to achieve dairy self-sufficiency by 2030. Here, we model different outcomes of the roadmap, finding that adoption of high-yield cattle breeds is essential for reducing dairy import dependency. Avoided land use change resulting from fewer, higher yielding dairy cattle would lead to lower greenhouse gas emissions. Dairy producers' average incomes could increase despite capital expenditure and land allocation required for the adoption of high-yield breeds. Our findings demonstrate the importance of bottom-up development policies for sustainable food system transformations, which also support food sovereignty, increase incomes for smallholder farmers and contribute towards Tanzania's commitments to reduce greenhouse gas emissions.

First bite syndrome treated with onabotulinumtoxin A injections.

BACKGROUND AND OVERVIEW: First bite syndrome (FBS) is an orofacial pain condition characterized by moderate to severe unilateral facial pain associated with the first bite or taste of food. It is important that dentists and physicians be aware of patient history and examination findings commonly associated with FBS, as well as treatment options available for managing this condition. CASE DESCRIPTION: Described here is a case of FBS arising in a 43-year-old man after partial parotidectomy for the treatment of a mucoepidermoid carcinoma. His orofacial pain was being successfully treated by injection of onabotulinumtoxin A into the residual parotid tissue. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Onabotulinumtoxin A is a promising therapeutic option for FBS owing to its profound relief of pain and minimal reported adverse effects. Therefore, oral health care providers treating FBS should be aware of this option.

Paroxysmal hemifacial pain: A report of two cases.

Paroxysmal hemifacial pain (PHFP) is the orofacial counterpart to paroxysmal hemicrania headaches. This paper reports the cases of two patients suffering from episodic attacks of severe unilateral facial pain. In both cases, pain attacks were absolutely responsive to therapeutic doses of indomethacin. Both patients were diagnosed with PHFP, as per the International Classification of Orofacial Pain diagnostic guidelines. The diagnosis of PHFP, and a trial of indomethacin, must be considered in cases of severe unilateral facial pains not clearly explained by more common diagnoses.

Feeding efficiency gains can increase the greenhouse gas mitigation potential of the Tanzanian dairy sector.

We use an attributional life cycle assessment (LCA) and simulation modelling to assess the effect of improved feeding practices and increased yields of feed crops on milk productivity and GHG emissions from the dairy sector of Tanzania's southern highlands region. We calculated direct non-CO2 emissions from dairy production and the CO2 emissions resulting from the demand for croplands and grasslands using a land footprint indicator. Baseline GHG emissions intensities ranged between 19.8 and 27.8 and 5.8-5.9 kg CO2eq kg-1 fat and protein corrected milk for the Traditional (local cattle) and Modern (improved cattle) sectors. Land use change contributed 45.8-65.8% of the total carbon footprint of dairy. Better feeding increased milk yields by up to 60.1% and reduced emissions intensities by up to 52.4 and 38.0% for the Traditional and Modern sectors, respectively. Avoided land use change was the predominant cause of reductions in GHG emissions under all the scenarios. Reducing yield gaps of concentrate feed crops lowered emissions further by 11.4-34.9% despite increasing N2O and CO2 emissions from soils management and input use. This study demonstrates that feed intensification has potential to increase LUC emissions from dairy production, but that fertilizer-dependent yield gains can offset this increase in emissions through avoided emissions from land use change.

Entrustable Professional Activities in Postgraduate Orofacial Pain Programs.

Entrustable professional activities (EPAs) are a curriculum development and learner assessment tool that ensure a trainee is able to safely translate the skills they have learned during residency into unsupervised clinical practice. Although EPAs are used extensively across various health professions worldwide, dentistry is just beginning to call for their development at both the predoctoral and postgraduate levels. Given the complex, multifactorial nature of orofacial pain disorders and the need for an interdisciplinary approach to management, the specialty of orofacial pain is well suited to embracing EPAs to ensure program graduates are prepared for practice. Therefore, 10 EPAs have been developed in a combined effort from program directors from every CODA-accredited postgraduate orofacial pain residency program.

Trigeminal Neuralgia With Extraoral Trigger Zone Successfully Treated With Intraoral Injections of Botulinum Toxin: A Case Report.

Trigeminal neuralgia is a pain condition that is frequently misdiagnosed and challenging to manage. We present the case of a patient with trigeminal neuralgia with multiple misdiagnoses and poorly managed pain. Despite the presence of trigger zones both inside and outside her mouth, complete symptom resolution was ultimately achieved through onabotulinumtoxinA injections, delivered solely intraorally.

Access to and sustainability of abortion services: a systematic review and meta-analysis for the National Institute of Health and Care Excellence-new clinical guidelines for England.

BACKGROUND: Induced abortion is a common procedure. However, there is marked variation in accessibility of services across England. Accessing abortion services may be difficult, particularly for women who live in remote areas, are in the second trimester of pregnancy, have complex pre-existing conditions or have difficult social circumstances. OBJECTIVE AND RATIONALE: This article presents a two-part review undertaken for a new National Institute of Health and Care Excellence guideline on abortion care, and aiming to determine: the factors that help or hinder accessibility and sustainability of abortion services in England (qualitative review), and strategies that improve these factors, and/or other factors identified by stakeholders (quantitative review). Economic modelling was undertaken to estimate cost savings associated with reducing waiting times. SEARCH METHODS: Ovid Embase Classic and Embase, Ovid MEDLINE(R) Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R), PsycINFO, Cochrane Library via Wiley Online, Cinahl Plus and Web of Science Core Collection were searched for articles published up to November 2018. Studies were included if they were published in English after 2001, conducted in Organization for Economic Co-operation and Development (OECD) countries and were: qualitative studies reporting views of patients and/or staff on factors that help or hinder the accessibility and sustainability of a safe abortion service, or randomized or non-randomized studies that compared strategies to improve factors identified by the qualitative review and/or stakeholders. Studies were excluded if they were conducted in OECD countries where abortion is prohibited altogether or only performed to save the woman's life. One author assessed risk of bias of included studies using the following checklists: Critical Appraisal Skills Programme checklist for qualitative studies, Cochrane Collaboration quality checklist for randomized controlled trials, Newcastle-Ottawa scale for cohort studies, and Effective Practice and Organization of Care risk of bias tool for before-and-after studies.Qualitative evidence was combined using thematic analysis and overall quality of the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Confidence in the Evidence from Reviews of Qualitative Research (CERQual). Quantitative evidence was analysed in Review Manager 5.3 and overall quality of evidence was assessed using GRADE. OUTCOMES: Eight themes (service level barriers; financial barriers; logistical barriers; personal barriers; legal and policy barriers; privacy and confidentiality concerns; training and education; community prescribing and telemedicine introduce greater flexibility) and 18 subthemes were identified from 23 papers (n = 1016) included in the qualitative review. The quality of evidence ranged from very low to high, with evidence for one theme and seven subthemes rated as high quality. Nine studies (n = 7061) were included in the quantitative review which showed that satisfaction was better (low to high quality evidence) and women were seen sooner (very low quality evidence) when care was led by nurses or midwives compared with physician-led services, women were seen sooner when they could self-refer (very low quality evidence), and clinicians were more likely to provide abortions if training used an opt-out model (very low quality evidence). Economic modelling showed that even small reductions in waiting times could result in large cost savings for services. WIDER IMPLICATIONS: Self-referral, funding for travel and accommodation, reducing waiting times, remote assessment, community services, maximizing the role of nurses and midwives and including practical experience of performing abortion in core curriculums, unless the trainee opts out, should improve access to and sustainability of abortion services.

Nonodontogenic Odontalgia Referred from the Temporal Tendon: A Case Report.

INTRODUCTION: Temporal tendonitis (TT) is an orofacial pain disorder that can refer pain to the maxillary and mandibular molars, temporomandibular joint, masticatory muscles, eye, or ear. Patients often present to a dentist or physician with complaints reflecting these referral patterns, yet many healthcare providers are unfamiliar with TT because of the scarcity of literature published on this clinical entity. This may lead to diagnostic confusion, iatrogenic harm, and prolonged patient suffering. METHODS AND RESULTS: This case report describes TT that presented as maxillary and mandibular posterior tooth pain, preauricular pain, and decreased mandibular range of motion. Patient history and examination were suggestive of TT. Local anesthetic injection adjacent to the tendon eliminated all pain complaints and improved range of motion. The patient was given education on the condition and self-care instructions. At 1-week follow-up, the patient reported resolution of her pain complaint. CONCLUSIONS: As healthcare providers familiarize themselves with appropriate diagnostic and treatment options for TT, delayed or unnecessary care can be avoided, and proper management strategies can be implemented.

Long-acting reversible contraception immediately after medical abortion: systematic review with meta-analyses.

BACKGROUND: Long-acting reversible contraceptives (LARCs) are safe, effective and convenient post-abortal methods. However, there is concern that some LARCs may reduce the effectiveness of abortifacient drugs or result in other adverse outcomes. OBJECTIVE AND RATIONALE: We undertook two systematic reviews to examine the early administration of LARCs in women undergoing medical abortion with mifepristone and misoprostol. (i) For women who are having a medical abortion and who plan to use a progestogen-only contraceptive implant or injectable, does administration of the contraception at the same time as mifepristone influence the efficacy of the abortion? (Implant/injectable review). (ii) For women who have had a medical abortion, how soon after expulsion of the products of conception is it safe to insert an intrauterine contraceptive device/system? (LNG-IUS/Cu-IUD review). SEARCH METHODS: On 19 November 2018, we searched Embase Classic, Embase; Ovid MEDLINE(R) including Daily and Epub Ahead-of-Print, In-Process and Other Non-Indexed Citations; the Cochrane Library; Cinahl Plus; and Web of Science Core Collection. Eligible studies were randomised controlled trials (RCTs), in English from 1985 (Implant/injectable review) or 2007 (LNG-IUS/Cu-IUD review) onwards, conducted in women undergoing medical abortion with mifepristone and misoprostol and studying either (i) simultaneous administration of mifepristone and a progestogen-only contraceptive implant or injectable compared to administration >24 h after mifepristone, or (ii) immediate insertion of intrauterine contraception after expulsion of the products of conception compared to early insertion (≤7 days) or to delayed insertion (>7 days) or early compared to delayed insertion. One author assessed the risk of bias in the studies using the Cochrane Collaboration checklist for RCTs. All the outcomes were analysed as risk ratios and meta-analysed in Review Manager 5.3 using the Mantel-Haenszel statistical method and a fixed-effect model. The overall quality of the evidence was assessed using GRADE. OUTCOMES: Two RCTs (n = 1027) showed lower 'subsequent unintended pregnancy' rates and higher 'patient satisfaction' rates, and no other differences, after simultaneous administration of mifepristone and the implant compared to delayed administration. One RCT (n = 461) showed higher 'patient satisfaction' rates after simultaneous administration than after delayed administration of mifepristone and the injectable, but no other differences between these interventions. Three RCTs (n = 536) found no differences other than higher copper IUC uptake after early compared to delayed insertion at ≤9 weeks of gestation and higher rates of IUC expulsion, continuation and uptake after immediate compared to delayed insertion at 9+1-12+0 weeks of gestation and higher IUC continuation rates after immediate compared to delayed insertion at 12+1-20+0 weeks of gestation. The quality of this evidence ranged from very low to high and was mainly compromised by low event rates, high attrition and no blinding. WIDER IMPLICATIONS: The contraceptive implant or injectable should be offered on the day of taking mifepristone. Intrauterine methods of contraception should be offered as soon as possible after expulsion of the pregnancy.

Anti-D prophylaxis for rhesus D (RhD)-negative women having an abortion of a pregnancy up to 13+6 weeks' gestation: a systematic review and new NICE consensus guidelines.

BACKGROUND: In order to develop the 2019 National Institute for Health and Care Excellence (NICE) national guideline on abortion care for the National Health Service1 we undertook a systematic review comparing anti-D prophylaxis to no prophylaxis in rhesus D (RhD)-negative women undergoing medical or surgical abortion of pregnancy at ≤13+6 weeks' gestation METHODS: We searched Embase, Medline and the Cochrane Library on 19 October 2018. We also consulted experts and checked reference lists for any missed trials. Eligible studies were randomised controlled trials and non-randomised comparative studies, published in English from 1985 onwards, comparing anti-D prophylaxis to no anti-D prophylaxis in RhD-negative women undergoing medical or surgical abortion at ≤13+6 weeks' gestation, and reporting subsequent anti-D isoimmunisation/sensitisation or subsequent affected pregnancy. These outcomes were to be analysed as risk ratios in Review Manager 5.3 using the Mantel-Haenszel statistical method and a fixed or random effect model. The overall quality of the evidence was planned to be assessed using GRADE. RESULTS: The search identified 426 potentially relevant studies of which none met the inclusion criteria. Recommendations for practice were therefore based on the clinical expertise of the guideline committee. CONCLUSIONS: (1) Offer anti-D prophylaxis to women who are Rhesus D negative who are having an abortion after 10+0 weeks' gestation. (2) Do not offer anti-D prophylaxis to women who are having a medical abortion up to and including 10+0 weeks' gestation. (3) Consider anti-D prophylaxis for women who are rhesus D negative and are having a surgical abortion up to and including 10+0 weeks' gestation.

Diagnosis and management of pancreatic cancer in adults: A summary of guidelines from the UK National Institute for Health and Care Excellence.

To enable standardisation of care of pancreatic cancer patients and facilitate improvement in outcome, the United Kingdom's National Institute for Health and Care Excellence (NICE) developed a clinical guideline for the diagnosis and management of pancreatic cancer in adults. Systematic literature searches, systematic review and meta-analyses were undertaken. Recommendations were drafted on the basis of the group's interpretation of the best available evidence of clinical and cost effectiveness. There was patient involvement and public consultation. Recommendations were made on: diagnosis; staging; monitoring of inherited high risk; psychological support; pain; nutrition management; and the specific management of people with resectable-, borderline-resectable- and unresectable-pancreatic cancer. The guideline committee also made recommendations for future research into neoadjuvant therapy, cachexia interventions, minimally invasive pancreatectomy, pain management and psychological support needs. These NICE guidelines aim to promote best current practice and support and stimulate research and innovation in pancreatic cancer.

Haematological cancers: improving outcomes. A summary of updated NICE service guidance in relation to Specialist Integrated Haematological Malignancy Diagnostic Services (SIHMDS).

Haematological malignancies are a diverse group of cancers that affect the blood, bone marrow and lymphatic systems. Laboratory diagnosis of haematological malignancies is dependent on combining several technologies, including morphology, immunophenotyping, cytogenetics and molecular genetics correlated clinical details and classification according to the current WHO guidelines. The concept of the Specialised Integrated Haematological Malignancy Diagnostic Services (SIHMDS) has evolved since the UK National Institute for Health and Care Excellence (NICE) Improving Outcomes Guidance (IOG) in 2003 and subsequently various models of delivery have been established. As part of the 2016 update to the NICE IOG, these models were systematically evaluated and recommendations produced to form the basis for quality standards for future development of SIHMDS. We provide a summary of the systematic review and recommendations. Although the recommendations pertain to the UK National Health Service (NHS), they have relevance to the modern delivery of diagnostic services internationally.