Comparative effectiveness research (CER) has been proposedin the United States as a way to compare new drugs and technologies with established alternatives and determine not just whether a therapyworks, but how well it works compared to other options.To define the current use of CER in the development of newdrugs and technologies and explore what is needed for this research approach to reduce or stabilize health care costs in the United States.In 2010, the Patient-Centered Outcomes Research Institute (PCORI) was established by the Patient Protection and Affordable CareAct (PPACA) to coordinate federally funded CER and recommend research priorities. Hochman and McCormick’s (2010) evaluation of 328 randomized trials, observational studies, and meta-analyses involving medications published between June 2008 and September 2009 in 6 key journals show that most published research did not fulfill the criteria of CER (defined ascomparison to active treatment) and that most study design is driven by FDA requirements rather than the need to develop evidence to facilitate selection of the most effective therapy. Since PPACA provides alternative funding for CER, it could encourage funding more studies to help determinewhich treatment delivers the best value per unit of investment from clinical, humanistic, and economic perspectives. Manufacturers may avoid CER because it increases product development costs, but a drug proven more effective is more likely to be accepted by formulary committees, increasing the drug’s market share, whereas payers may reject or limit use of a newdrug that performs less effectively in comparative studies.CER may not directly reduce expenditures for drugs andmedical technologies. The results may vary widely from case to case; however, despite often significantly higher prices for new drugs, it is important to look beyond product costs to the overall impact on health carecosts, including medical cost offsets that may occur through improved health or decreased morbidity. To truly decrease cost and improve quality,cost-effectiveness will have to be integrated into CER with the objective of prioritizing efficient therapies in the real-world health care system. If the methods and output of CER improve, the resulting cost-effectiveness ratios will also be more useful to the payer. CER should ultimately, therefore, be a useful tool to help patients, providers, and decision makers provide themost effective and most cost-effective interventions.


Male-specific cancers, such as prostate cancer, male breast cancer, testicular cancer, etc., have become one of the major health issues worldwide . Except Johnson et al. presented a comprehensive review regarding the genetic contributions to prostate cancer in Men with West African ancestry. As one of the least developed regions in the world, very little evidence could be obtained regarding the disease characteristics. In this review, the authors discussed the potential disparities between West African ancestry and other ancestries . In addition to the evidence provided by this review, it may also bring more attention from the readers to the healthcare issues in under-represented populations in the world.Cheng et al., 2021;Yu et al., 2022). One of the studies presented a subgroup of prostate cancer with significant enrichment of genetic variants in metabolism-related genes . Another study identified a subgroup of prostate cancer with a poorer prognosis which embraces significant expression variations in immune-related genes . The results provided different angles in understanding the biological mechanisms of prostate cancer.Two research articles provided new classifications of prostate cancer using different genetic signatures  penoscrotal extramammary Paget diseases in Chinese male patients and found several potential genes that might contribute to the disease progression. This research article provides important new evidence to prompt further in-depth research into this poorly understood disease.Penoscrotal extramammary Paget disease is a rare and poorly studied malignancy in men. Though most male Paget diseases are indolent (but commonly recurrent), some cases could have very invasive phenotypes. Valentini et al., 2022). As one of the two studies explored the genomic landscape of male breast cancer to date, this research article would no doubt provide important information for us to better understand the mechanism of carcinogenesis, as well as to provide better disease management with precision medicine approaches. The results from this study also revealed the potential differences between male breast cancer and well-studied female breast cancer, which might raise the research interest in this topic among the readers for further investigation.In sharp contrast to female breast cancer, for which thousands of research articles have been published, male breast cancer has been less studied. Last but not least, a group of physicians and scientists from Italy reported their most recent results on this topic draw researchers’ attention to these under-represented diseases, known as male-specific cancers.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Coordinated activity in neural populations is crucial for information processing. Shedding light on the multivariate dependencies that shape multineuronal responses is important to understand neural codes. However, existing approaches based on pairwise linear correlations are inadequate at capturing complicated interaction patterns and miss features that shape aspects of the population function. Copula-based approaches address these shortcomings by extracting the dependence structures in the joint probability distribution of population responses. In this study, we aimed to dissect neural dependencies with a C-Vine copula approach coupled with normalizing flows for estimating copula densities. While this approach allows for more flexibility compared to fitting parametric copulas, drawing insights on the significance of these dependencies from large sets of copula densities is challenging. To alleviate this challenge, we used a weighted non-negative matrix factorization procedure to leverage shared latent features in neural population dependencies. We validated the method on simulated data and applied it on copulas we extracted from recordings of neurons in the mouse visual cortex as well as in the macaque motor cortex. Our findings reveal that neural dependencies occupy low-dimensional subspaces, but distinct modules are synergistically combined to give rise to diverse interaction patterns that may serve the population function. Information processing in the brain relies on the coordinated activity of neuronal circuits on multiple spatial and temporal scales. The neural population function is dynamically shaped by a rich mixture of distributed and interdependent processes ranging from representations of sensory inputs to signals related to behavioral outputs or internal states. While past research focused mainly on characterizing neural codes by looking at properties of single neurons, recent years have seen a shift towards a population-level approach ,2,3. ThiExisting literature on neural dependencies has predominantly focused on pairwise shared response variability between neurons, measured as linear correlations where the noise is assumed to follow Gaussian statistics ,16,17,18A suitable alternative approach for studying multivariate dependencies is using copulas, a statistical tool that has been widely used in economics , but hasIn our previous work , we follC . In this framework, the input matrix was weighted in order to aid detection of overlapping dependence structures with considerable differences in scale. We constructed weight matrices V according to:U. In order for the weight values to transition smoothly between high importance (tails) and low importance areas, we convolved the weight matrices with a Gaussian window of standard deviation equal to 5 bins in density space. Moreover, we added rotated versions of the outer product matrices such that all 4 corners of the copula space would be weighted heavily. Our approach and aim were therefore different from other examples of weighted NMF procedures we encountered in the literature [V as follows:NMF  is an al copulas C left. M modules C right a modules C middle.te rules :(7)Wi+1←terature ,47. Instlidation . This crWe validated our WNMF framework for describing dependence structures on a set of synthetic data consisting of two-dimensional copula densities on a 100 by 100 points grid. The densities were estimated using NSF on empirical copulas from 20,000 pairs of dependent Poisson samples generated using the mixed vines package developed by Onken and Panzeri . The denWe evaluated our framework on two different datasets involving recordings of neural activity. The first one consisted of 2-photon calcium imaging recordings in the mouse primary visual cortex (V1), that were collected at the Rochefort lab  responses of head restrained macaque monkeys during a delayed reaching task . We focuWe propose WNMF to identify structures in C-vine models composed of non-parametric copulas and estimated with normalizing flows. Since dependencies in a vine tree are known to be sparse and display common features in studies using parametric methods, we aimed to discover shared structures in copula-based models by decomposing copula densities into lower dimensional copula modules and neuron pair coefficients. We assessed this approach on synthetic data generated with parametric copulas models, and on recordings from a mouse visual cortex and macaque motor cortex.The addition of a weighting matrix to NMF was motivated by preliminary findings we had on synthetic data. One of these “toy” datasets we generated was composed of copula density estimates, namely 20 examples of Frank copulas and another 20 examples of Clayton copulas. We estimated the copula densities with NSF as outlined in the methods section out of copula samples generated using the mixed vines package . Then, wWhile NMF can usually separate overlapping structures due to its non-negativity constraint, outstanding features can dominate and potentially contaminate other factors in a low-dimensional representation ,57. WhenWe sought to validate whether weighting improved NMF performance by comparing WNMF to standard NMF on synthetic data that were generated in the same way as described above. There were three different cases with two, four and six copulas contained in the data matrices, each represented by 20 entries, which resulted in matrices with 40, 80 and 120 entries, respectively. Speckled cross validation for reconstruction error relative to the original matrices yielded similar curves for WNMF and NMF for two and four copulas and the validation error minimum landed at the correct number of factors B. In allIn our previous work , we studWe focused on the recording session on day 4 for mouse ST260 , where t therein B. The coOf additional interest was the fact that the WNMF copula modules exhibited a rather sharp divide between the first few trees and the deeper ones. The former were predominantly associated with the first copula module  followedSubsequently, we evaluated our framework on electrode array recordings from the macaque primary motor cortex during a delayed center-out reaching task . The exp factors C.In a somewhat similar fashion to what we observed in the case of the primary visual neurons, these copula modules also spanned the entirety of copula space and occupied all four corners (In this study, we conducted an analysis that focused on uncovering and summarizing complex dependence structures in neural population responses. We built up on our previous work  where weTo properly contextualize our findings, it is necessary to note that our framework has several components that are worth discussing separately to appreciate where our approach deviates from other ones in the literature. Non-parametric modeling of dependence structures allows for more flexibility compared to using parametric families of copulas, especially when faced with arbitrary interaction patterns. While one can fit parametric mixture models to increase their flexibility, these models can also inflate the number of components. Doing so can potentially overestimate the complexity of the dependence structure. It would most likely be a challenge for parametric models or mixtures of them to fit copulas like the ones in modules 3 and 4 in A downside of non-parametric modeling is the large number of copulas they yield that are not easy to make sense of, especially with larger ensembles of neurons. However, our findings demonstrated that there is only a low fraction of non-independent copulas in the recordings we analyzed and the rest do not need to be considered to study neural dependencies. In our C-vine fits, most conditional elements were independent, suggesting that the C-vine decomposition is appropriate for the data at hand. Besides the sparseness though, we also found that the number of factors required to describe the set of non-independent copulas was surprisingly low, albeit still allowing for a fair amount of variation in dependencies as linear combinations of simple modules C.These findings raise interesting questions regarding the function of neural dependencies in multineuronal responses. These questions have so far been discussed mostly in the context of linear correlations, which is rather limiting considering the complexity observed in these responses. Whether the synergistic combinations we found in copula modules in the mouse visual cortex C have a


The many stressors associated with teaching can take a toll, resulting in high levels of burnout among teachers and reduced motivation and academic performance among students. This is especially true in the context of science, technology, engineering, and mathematics (STEM) subjects. Despite the efficacy of emotion regulation interventions in pedagogical settings in general and in STEM teaching in particular, there is a lack of suitable interventions. We applied the process model of emotion regulation to STEM teaching and proposed a framework, STEM-Model of EmotioN regulation: Teachers’ Opportunities and Responsibilities (STEM-MENTOR), to elucidate how the high demands of STEM teaching and contextual factors  may lead to intensified negative emotions and deficits in executive functioning and emotion regulation implementation. Teacher emotions, in turn, shape students’ STEM-related achievements and epistemic emotions. Thus, teachers’ emotion regulation skills have pervasive effects on teaching outcomes for both teachers and students. We illustrate how at each level of our framework, steps could be taken to improve teachers’ emotional trajectory. Our proposed STEM-MENTOR framework has implications for theoretical understanding and may help to shape future interventions that focus on cognitive-emotional processes in STEM education. Imagine two classrooms in which the teachers are pressured by parents and school officials to help students achieve the highest levels of academic excellence, while dealing with anxious students facing environmental pressure to achieve high grades. In the first classroom, the teacher is highly stressed, and regularly fails to control her anxiety, and this adversely affects the classroom environment. In the second classroom, the teacher is able to flexibly control her cognitive and emotional state of mind, so that she can act as a calm mentor and create a pleasant and supportive atmosphere.It is easy to see how both the teachers and students in these two classrooms would have very different outcomes. What is harder to see is which factors determine whether a teacher is more likely to be like the one in the first classroom or the second classroom. Given the stakes, this is a critical question. To date, most research concerned with these sorts of questions has focused on teachers’ academic background , experieIn what follows, we consider the unique emotional demands of science, technology, engineering, and mathematics (STEM) teaching in the K-12 classroom. We then present the process model of emotion regulation and discuss the effectiveness of emotion regulation-based intervention in educational settings. Next, we propose an emotion regulation framework for STEM teachers: STEM-Model of EmotioN regulation: Teachers’ Opportunities and Responsibilities (STEM-MENTOR). Our model targets STEM teachers because they may be more sensitive to school environments than non-STEM teachers , but it Teaching is considered to be an occupation that involves ‘emotional labour’ , causingThree common sources of stress are teachers’ perceptions of unusual working time , students’ misbehavior, and high or unrealistic expectations of authorities and parents with respect to students’ achievement . These sYet the importance of STEM in Western societies , now andWe argue that teachers’ emotional state matters and emotion regulation skills should therefore be considered a crucial component of teaching opportunities and responsibilities , especiaThere is general consensus that affective and cognitive processes are deeply intertwined , includiEmotional states depend on how the individual evaluates the situation  may affect STEM teachers’ motivation to regulate emotions . The motIn the classroom, teachers use emotion regulation on a daily basis and even from lesson to lesson . They maAlthough suppression can be an effective form of emotion regulation for managing the classroom environment , studiesIn contrast, the use of reappraisal diminishes the negative influence of reencountered emotional information . For insAnswering calls to incorporate an interpersonal perspective on emotion regulation, which involves regulation processes by and with the help of others , researcTeachers’ emotions have been associated with self-efficacy  and selfSecondary school teachers who use reappraisal to reinterpret stressful classroom situations have been found to demonstrate more positive emotions , such asThe emotional state of teachers is arguably one of the key factors in creating a positive classroom environment . For exaBy implementing reappraisal, teachers may demonstrate more effective pedagogical behaviors , particularly reappraisal, is an important skill not only for STEM teachers , but alsTo avoid the negative outcomes of teaching-related stress, it is necessary to improve the emotional trajectory at each step in our framework. Actions must be taken to reduce STEM teachers’ job stress or at least to protect against escalating stress. A recent study  examininPrevious work on reducing teachers’ occupational stress has included organization-level  and persAlthough emotion regulation skills have far-reaching implications in the context of teaching and learning , and teaReappraisal-based interventions for STEM teachers may benefit from the existing studies on similar interventions among students. Such interventions have multiple advantages. First, managing emotions is an integral part of teachers’ work . Second,Note that such interventions may need to be adapted in different cultures because cultural norms shape individuals’ perceptions about the appropriate expression of emotions  and which emotion regulation strategies are adaptive or maladaptive . In addiConsiderable evidence in the literature confirms the validity of the units in our STEM-MENTOR model indicating the critical role of STEM teachers’ emotion regulation knowledge and abilities. Simply stated, effective emotion regulation yields benefits to teachers and students alike. However, the model should be tested in follow-up studies, especially meta-analyses examining the variables simultaneously in different cultures and at diverse educational levels. Our model may be fertile ground for research and interventions that will promote STEM teachers’ well-being, thus improving students’ epistemological experience and achievements.Because of the emotional demands of STEM teaching, STEM teachers face a wide range of stressors, including low student achievement and negative attitudes towards STEM subjects. Applying the process model of emotion regulation to the STEM teaching context, the STEM-MENTOR framework designates how contextual factors increase STEM teachers’ stress and how STEM teaching-related stress impairs emotion regulation resources, thereby promoting emotion dysregulation. Importantly, we emphasize the effects of STEM teachers’ intensified negative emotions and emotion dysregulation not only on themselves, but also on their students’ emotions, behaviors, and learning processes. Given the positive emotional and academic outcomes of stress reappraisal interventions in the STEM fields of study, we suggest that future research should focus on developing STEM teachers’ emotion regulation knowledge and abilities.


Pornography addiction is not currently recognized in the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-V), but it can be broadly classified under compulsive sexual behavior disorder (CSBD) in the International Classification for Diseases (ICD). An increased incidence of CSBD has been reported in patients with bipolar I disorder (BPI) as an independent compulsion, not secondary to mania. Due to the ambiguity of identifying pornography addiction in the DSM-V, approved treatment for patients with a concurrent diagnosis of CSBD in the context of BPI is limited. We report the case of a patient with CSBD with concurrent BPI and investigate the treatment strategy taken in an inpatient setting. Though there are no FDA-approved treatment strategies currently approved for patients with concurrent CSBD and BPI, selective serotonin reuptake inhibitors, mood stabilizers, naltrexone, and cognitive behavioral therapy can be used in combination for maximal benefit. The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-V) does not provide a formal definition for “pornography addiction” . PornogrIn this case, pornography addiction in the setting of bipolar I disorder (BPI) has precipitated severe impairment in the function and integration of the patient. Patients with BPI have an increased incidence of CSBD . The sexA 31-year-old male with a past psychiatric history of BPI, cannabis use disorder, and panic attacks with no previous psychiatry-related hospitalizations or significant medical history presented to the emergency department with worsening suicidal ideation for several days. The patient had been experiencing worsening depressive symptomatology including depressed mood, anhedonia, hopelessness, guilt, and decreased sleep. There was no current manic or psychotic symptomatology. The patient reported that he is currently under the care of a psychiatrist and is prescribed quetiapine 50 milligrams (mg) once daily per os (PO), which he is adherent to. On mental status examination, the patient appeared well groomed and was in adequate behavioral control. His mood was “depressed” with a mood-congruent affect. The patient had a linear thought process with no current homicidal ideations or suicidal ideations at the time of interview, visual or auditory hallucinations, or delusions. There was no overt evidence of perceptual disturbances. The patient’s insight and judgment were fair. Lab workup including complete blood count and a comprehensive metabolic panel was normal Table . The patDuring the initial evaluation by the inpatient psychiatry team, the patient stated that his recent stressors leading to his depressive episode included worsening self-reported “pornography addiction.” The patient revealed that in his early teenage years, he began watching internet pornography as a coping mechanism secondary to social anxiety and bullying in school. He stated that at 16 years of age, watching pornography and masturbating began interfering with his life at school, relationships with family members, and daily activities. The inability to masturbate caused him a great deal of distress. He stated that over the next few years, he began watching pornography and masturbating up to 18 times per day and reported that there were days he masturbated 40 times to the point of injuring his genitals. He reported his longest period sustained from watching pornography and masturbating was over a 34-day period, during which he sought support via an internet forum, which helped maintain his abstinence. However, he later began masturbating after having a “sudden urge.” He stated that when he is unable to engage in watching pornography or masturbation, he experiences a great deal of anxiety and other “withdrawal symptoms” such as penile hypersensitivity, gnawing of his teeth, and pain when his penis is not erect. Further history reported by the patient included a history of sexual trauma in childhood at seven years of age and spending hundreds of dollars in exchange for sexual acts upon himself and others.Further workup included computed tomography of the brain, which revealed no acute intracranial pathology, as well as testosterone and prolactin levels, which were within normal limits. The patient was prescribed clonazepam 0.5 mg twice daily (BID) for anxiety with a plan to taper, mirtazapine 15 mg daily for depression and insomnia, paroxetine 30 mg daily for current depression, anxiety, and sexual compulsions, and risperidone 2 mg BID for mood stabilization. During his inpatient admission, the patient reported less sexual compulsions and noticeable improvement in mood overall. He continued to deny suicidal and homicidal ideations or any psychotic and manic symptoms. The patient was experiencing urges of sexual compulsion while in the hospital and requested a private room to avoid sexually harming a roommate. The patient was offered rehabilitation for sexual compulsions, but he declined. The patient was counseled on the importance of outpatient psychiatric follow-up and medication management, which he complied with. Upon discharge, the patient was sent back home to live with family in stable condition, and a follow-up appointment was arranged with an outpatient psychiatric clinic.CBSD is defined by the following criteria in the ICD: engrossment in repetitive sexual activities to where the patient fails to meet obligations of life and is neglectful of responsibilities; failed reduction of sexual behavior on multiple occasions; continued sexual behavior despite negative consequences (i.e. loss of employment); or persistence of repetitive behavior even when little or no satisfaction is obtained . These pDespite increasing research on the psychological and neural mechanisms of CBSD, little is known about the efficacy of pharmacotherapy in people with this condition, though there is evidence that effective approaches exist in reducing sexual urges and distress in patients. Selective serotonin reuptake inhibitors (SSRIs) have been reported to control sexual obsessions and compulsions in CSBD by utilizing their sexual side effects such as difficulty with arousal . A doublNaltrexone, an opioid receptor antagonist, has been previously used and found effective by reducing the symptoms in patients with CSBD . NaltrexPsychotherapy techniques including cognitive behavioral therapy (CBT) in conjunction with pharmacotherapy were determined to be successful in managing patients with CSBD . AcceptaThough there is no FDA-approved treatment strategy currently for patients with concurrent CSBD and BPI, there are reports of medication trials that have been effective in treating these patients. SSRIs were reported to be effective against sexual compulsions, while mood stabilizers demonstrated the ability to depreciate the intensity of sexual impulsivity. On the other hand, some evidence has revealed that naltrexone monotherapy has shown reduction in sexual urges in males. In conjunction with any of these pharmacological treatment modalities, CBT should be utilized for optimal benefit to the patient.


The global impact of diet-sensitive disease demands innovative nutrition education for health professionals and widespread, reimbursable clinical models to apply nutrition to practice. Interprofessional collaboration across disciplines and the optimization of emerging telemedicine consultation strategies, including electronic consultation (eConsult), merge to deliver vital innovation in the delivery of nutrition-based clinical care. Aligning with an existing eConsult infrastructure in the institutional electronic health record (EHR), a physician–dietitian team developed a novel Culinary Medicine eConsult. During a pilot phase, the service was introduced to primary care clinicians, and a response algorithm for eConsults was created. During the 12-month pilot phase, the Culinary Medicine team completed 25 eConsults from 11 unique primary care clinicians with a 76% (19/25) insurance reimbursement rate. Topics varied from dietary strategies for preventing and managing common metabolic diseases to specific dietary influences on microbiome health and disease flares. Requesting clinicians reported time saved in their clinic encounters and high patient satisfaction with expert nutrition guidance. EConsults in Culinary Medicine promote the integration of interprofessional nutrition care into existing clinical structures and empower enhanced access to the vital domain of dietary health. EConsults deliver timely answers to clinical questions and create opportunities for further innovation in care delivery as communities, health systems, and payors seek solutions to the growing burden of diet-sensitive diseases. The global impact ,2 of dieHistorically, the literature focuses on Culinary Medicine in an educational context, but this term has seen an evolution and expansion of scope in recent years. Multi-disciplinary, evidence-based, and clinically relevant, the Culinary Medicine hands-on teaching kitchen model seeks to equip trainees to engage patients in personalized dietary behavior change ,12,13,14Many clinicians incorporate nutritional counseling and behavior change coaching into routine clinical encounters, but a core limitation is time, an oft-cited challenge to meaningful preventive healthcare . PerhapsOver the past several years, electronic consultations (eConsults) emerged as a strategy for improving access to subspecialty care. Defined as “asynchronous, consultative, provider-to-provider communications within a shared electronic health record (EHR) or web-based platform” and approved by the Centers for Medicare and Medicaid Services (CMS) as under the umbrella of telehealth benefits, eConsult implementation demonstrates increased access to medical specialists and has also been used to improve mental health access . BenefitWith the growth of additional training and certification in Culinary Medicine ,21 and tTo establish an eConsult process for Culinary Medicine, the physician–dietitian Culinary Medicine team initially engaged the institutional billing team as well as administrative and physician leaders to identify current systems, potential barriers, and opportunities. Due to an existing eConsult workflow across many specialties on our campus, a Culinary-Medicine-specific eConsult was built within the EHR system, creating a straightforward process for consultation that paired an open-ended consult question text box with optional EHR buttons to highlight topics where Culinary Medicine can add value. Next, the Culinary Medicine team identified a small pilot group of primary care clinicians and presented service details, including the process and case examples of consult topics for which the team could provide written, tailored patient care guidance in Culinary Medicine. Rooted in an informal needs assessment, the team designed a five-part response algorithm to guide each consult: (1) patient context, health background, and goals; (2) brief narrative summary, including key references for educational benefit of requesting clinician; (3) key dietary recommendations tailored to patient context and goals; (4) culinary strategies and recipes suggestions (with web links); and (5) recommendations for local resources to promote nourishing food access. After orienting the pilot primary care clinicians to the newly established eConsult workflow and clinical focus of Culinary Medicine support, the eConsult went live.All requesting primary care clinicians completed the brief referral tailored to their patient’s area of concern, which was then electronically transmitted to the Culinary Medicine consult team. The response to the requesting clinician’s consult also occurs via the EHR, including a permanent record of the Culinary Medicine team’s consult response note in the patient’s chart and the associated billing. Consistent with the established eConsult approach defined by CMS, the requesting primary care clinician communicates the Culinary Medicine specialist’s consult advice back to the patient in either written or verbal form. During a 12-month pilot phase from 1 August 2021 through 31 July 2022 of the Culinary Medicine eConsult program, the Culinary Medicine physician–dietitian team completed 25 eConsults. The team received at least one consult per month and a maximum of four consults in a single month. Many consult topics overlapped between patients, enabling the consulting team to repurpose prior content while individualizing recommendations in the context of each patient’s overall health circumstances.The consult team developed a database of key information, resources, and recommendations and stored topic-specific consults on an institutionally approved cloud storage site without protected health information. Common consult themes led to efficient responses tailored to the individual needs of each patient while also delivering a return on prior investment of effort and time. Common recurring consultation topics included dietary strategies to support the treatment of metabolic and other chronic conditions, such as diabetes, fatty liver disease, and irritable bowel syndrome, as well as guidance for general health promotion, including reducing chronic inflammation and maintaining a healthy weight. Unique and more complex consultation topics comprised the influence of diet and microbiome health on specific conditions, such as eczema and rosacea, as well as specific dietary needs for patients with physical disabilities or severe dietary allergies.During the pilot year, a total of 11 unique primary care clinicians initiated the 25 eConsults, with 4 of those clinicians requesting consults for several different patients. The assessment of billing data showed that 76% (19 of 25) of consults were reimbursed by payors, including Medicare and various private insurance companies. Documentation of patient consent by the original requesting clinician is a requirement for the consult to be billable, and rejected claims lacked this necessary documentation of consent.Qualitative feedback from requesting primary care clinicians consistently demonstrated the importance of this unique clinical support resource. Requesting clinicians cited the benefit of an eConsult when running out of time during a clinic visit and the convenience of the straightforward process of copying and pasting the response content into a patient portal message. Other key feedback included the ability to highlight the unique training and expertise of the Certified Culinary Medicine Specialist team, noting that some patients take nutrition and culinary guidance more seriously than those with specific additional credentialing and expertise.EConsults in Culinary Medicine offer the opportunity to brand Culinary Medicine as clinical care, even in the absence of resources for broader integration, such as individual Culinary Medicine consult appointments or shared medical visits. Expert consultation for nutrition concerns—from the routine to the complex—validates the vital role that diet plays in health promotion and the expertise necessary to provide evidence-based guidance. Additionally, the Culinary Medicine eConsult is collaborative at its foundation, with a cornerstone partnership between a physician and a registered dietitian nutritionist (RDN) as a core feature. This multi-disciplinary approach promotes a well-rounded, interprofessional perspective, and opportunities abound for collaboration in educational, research, and clinical domains. Clinician billing in nutritional domains can demonstrate the successful augmentation of reimbursement for this vital work and open doors to advocate for consistent reimbursement across professions, particularly in the field of dietetics.As a result of successful eConsult implementation, which demonstrated both primary care clinician and patient demand for this clinical support, the Culinary Medicine physician-dietitian team at our institution was asked to expand and develop a full Culinary Medicine Clinical Service Line. The eConsult model thus served as a gateway to additional services, including in-person Culinary Medicine consultations and shared medical visit cooking classes. The establishment of Culinary Medicine as an interprofessional clinical service that is billable and reimbursable was a vital first step to gaining stakeholder support for growth. Further, although medical nutrition therapy (MNT) is an effective intervention, it is time-intensive, and many eligible patients do not utilize this service . PhysiciThe application of the eConsult model necessitates institutional awareness and the implementation of the process of electronic consultation as well as billing negotiation and structure. Each institution varies, but the authors recognize this as a limitation to scalability. In the context of an existing eConsult structure, the primary limitation for application to Culinary Medicine is the necessity of an appropriately trained team to serve as the consultants.It is important to note that the Culinary Medicine eConsult is in no way intended to be a replacement for nutrition assessment and medical nutrition therapy conducted by a registered dietitian. Although most e-Consults recommend additional one-on-one sessions with a dietitian, current barriers to access can make navigation to a dietitian beyond the e-Consult difficult, and most patients in our system do not receive any nutrition-related care. As such, the culinary focus of the eConsult program provides practical, accessible support strategies to patients and primary care clinicians while also advocating for additional nutrition support when indicated.An additional limitation worth mentioning is the small sample size of our pilot feasibility study. This brief report introduces a novel concept pairing the relatively new process of eConsults for improved access to specialist input with the emerging clinical practice of Culinary Medicine. As such, we acknowledge that 20 patient consults and 11 requesting primary care clinicians represent a small volume of initial participants, and further work on the application and scalability of eConsults is needed.EConsults in Culinary Medicine provide an accessible, broadly relevant strategy for clinical teams with Culinary Medicine expertise to provide evidence-based guidance to primary care clinicians and their patients struggling to get access to nutritional support. This guidance serves to educate and guide the requesting clinician and ideally delivers tailored and actionable culinary nutrition guidance for the patient in a format that can be easily communicated via the electronic health record . This approach utilizes an existing, insurance-covered clinical workflow strategy to build a foundation of Culinary Medicine therapy as an interprofessional clinical service line.For many patients, eConsults can serve as their first interaction with a registered dietitian and can operate as a gateway, highlighting the potential benefits of additional nutrition clinical services. As the current literature suggests, some eConsults definitively answer clinical questions requiring no further interactions. In other cases, they provide a bridge to additional intervention, ensuring that the appropriate team engages in a patient’s ongoing care. For patients with nuanced nutritional needs, such as guidance for a new food allergy diagnosis or celiac disease, an eConsult may lead to a recommendation for such dietitian-led, individualized nutritional guidance. Other patients may benefit from referral to specific community resources or programs to support consistent access to nourishing food, including local food pantry programs, food prescription programs, or federal nutrition programs. Complex consultations also reveal opportunities for further engagement, particularly personalized medical nutrition therapy by referral to a registered dietitian nutritionist, one-to-one consults with the Culinary Medicine team, or group cooking classes via billable shared medical appointments. This growing model of care can take place in a teaching kitchen where a patient learns culinary skills and builds self-efficacy for dietary change, a method with the potential to revolutionize the prevention and treatment of chronic disease.Applying the established approach of eConsults, this intervention sought to increase access to culinary and nutritional support for patients while building Culinary Medicine as an interprofessional and reimbursable clinical care strategy. During this pilot study, the development of a Culinary Medicine eConsult service led by a physician–dietitian team was feasible both in process and reimbursement. Positive feedback from the participating primary care clinicians who requested Culinary Medicine eConsults showed interest and engagement in offering culinary nutrition to support their patients.Further, the Culinary Medicine eConsult is a promising tool that highlights the beneficial synergy of physician–dietitian partnerships in the food as medicine area of practice. Although the eConsult is not designed to replace traditional one-on-one clinical visits with either a physician or a dietitian, it can make a powerful auxiliary tool. In a current climate of overly taxed clinicians as well as scheduling difficulties and staffing shortages, innovative tools that help connect patients with resources and care in an efficient, timely, and reimbursable manner are sorely needed.To achieve successful progress in mitigating the tsunami of diet-related disease, an all-hands-on-deck strategy that emphasizes interprofessional teamwork is vital. Physician education in nutrition and subsequent engagement in clinical integration enhances reimbursement potential, elevating the vast importance of this field. As the evidence of impact grows and becomes impossible to ignore by payor models, clinicians, and patients alike, teams should be ready to bring everyone to their collaborative table, sharing the potential of food as medicine.


Advances in the development of pharmacological treatment in oral cancer require tumor models capable of simulating the complex biology of the tumor microenvironment. The spread of three-dimensional models has changed the scenery of in vitro cell culture techniques, contributing to translational oncology. Still, the full extent of their application in preclinical drug trials is yet to be understood. Therefore, the present scoping review protocol was established to screen the literature on using three-dimensional cell culture models in drug-testing assays in the context of oral cancer. This scoping review will be conducted based on the guidelines established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review guidelines (PRISMA-ScR). We will search the PubMed/Medline, Web of Science, Scopus, and Embase databases, as well as the gray literature, including peer-reviewed research articles involving 3D models applied to drug-assessment assays in oral cancer published from 1 March 2013 until 1 March 2023. Data will be charted, and findings will be described according to the predetermined questions of interest. We will present these findings in a narrative manner. A persistent challenge in oncology research is managing the complex biology behind tumor behavior and progression. This is true for aggressive diseases such as oral cancer, which remains among the most frequent and debilitating types of cancers worldwide ,2. Its mThe focus of preclinical research in oral cancer has shifted from studying only the tumor cell to studying the tumor microenvironment (TME), whose heterogeneous cell population and transformable extracellular matrix (ECM) define the way tumors behave and respond to treatment . The nonCell culture systems have significantly impacted the field of biology by reducing the necessity for laboratory animal use while advancing research, pharmaceutical discoveries, and the evolution of medicine . InitialPreclinical drug trials in cancer are reliant on models that allow for the pharmacological testing of tumor cell lines, such as adherent cell culture models, which are still a common resource for researchers worldwide for their technical simplicity, financial feasibility, and reproducibility inside a laboratory . NeverthThe application of 3D culture models in vitro to reconstitute essential aspects of the TME, such as cell heterogeneity ,20, nutrThis current study aims to evaluate how 3D in vitro methods have been employed in drug-testing assays in oral cancer, highlighting how available 3D technologies translate the reality of oral cancer’s susceptibility to anticancer drugs. A scoping review will be performed to map the current state of evidence and identify the lacunae in the literature related to the role of 3D culture methods applied to oral cancer and preclinical trials of anti-cancer drugs.What protocols and techniques are recommended for applying three-dimensional culture methods in preclinical trials of anti-cancer drugs targeting oral cancer?Which 3D culture models have been predominantly utilized in preclinical drug trials for oral cancer treatment, and what are their primary applications?What are the documented advantages and challenges of using 3D culture models in preclinical drug trials for oral cancer as compared to traditional 2D models?Considering this review’s aim, we intend to answer the following research questions:This scoping review protocol was formulated based on the guidelines set by Arksey and O’Malley  and aligThe search strategy for PubMed/Medline was formulated  and thenThe methods of this study are summarized in Searches will be performed, and results will be exported in Comma-Separated Values (CSV) format to Microsoft Excel (version 2302). Deduplication will be performed manually by two independent reviewers, who will proceed with the application of the inclusion and exclusion criteria.Studies that have been published in the last ten years were initially included before proceeding with exclusion criteria. All articles found were included regardless of language or journal source.Reviews of any sort, book chapters, author’s opinion/comments, editorials, meeting abstracts, conference abstracts and study protocols, and articles without available full text;Studies not regarding oral cancer;Studies that did not employ in vitro three-dimensional methods of any sort;Studies that did not perform preclinical drug trials or evaluations.Studies were excluded if they met any of the following criteria:The screening of studies was conducted by two authors independently. Inter-rater agreement was assessed through Cohen’s κ at the abstract review stage. Discrepancies were resolved by discussion or a third reviewer if they remained. Reviewers screened the search results initially based on the studies’ titles, proceeding to assess their abstracts and full text when necessary.Data extraction was performed by two reviewers according to predetermined extraction items. Data from eligible studies was tabulated in a Microsoft Excel sheet under headings compatible with the items defined in this protocol. After extraction, data was discussed among the authors. Since no standard checklist exists for in vitro studies, we created our items of assessment based on the most essential components of in vitro studies and relevant information to the question of our study. The items were answered by yes or no, followed by explanatory answers when necessary. No studies were excluded based on the quality assessment.What subtype or subtypes of oral cancer were evaluated ?What were the cell culture conditions ?What was the three-dimensional model or models used  and their specifications ?What were the evaluated compounds and their relevant information ? Were they antineoplastic agents?What was the treatment protocol ?What were the control group(s)/conditions?What assays were performed to evaluate compound effects ? What were their results?What statistical analysis was performed? How many samples  were used? How many assay repetitions were made?What are the authors’ conclusions?Overall, does the study mention all data accurately?The following items were assessed during data extraction:Quality of evidence was evaluated by the GRADE method  adapted We applied qualitative analysis of the extracted data to understand how 3D culture methods have been employed in preclinical trials of anti-neoplastic agents in oral cancer.We intend to present our results in narrative form, including tables containing the relevant extracted information. Findings will be described according to the review questions objectively, and the results section may undergo further adjustments after the results are reviewed. As a guideline, the PRISMA-ScR checklist was used in this review.Any further changes to the study protocol were made as necessary and reported accordingly.Oral cancer, the sixth leading cause of cancer-related deaths globally , is ofteTo meet the increasing demand for a single technology that adequately caters to 3D cell culture needs, various methods have been developed. The utilization of 3D culture models allows for the examination of morphological and cellular arrangements influenced by ECM interactions, crucially altered in oncogenic transformation. Consequently, these 3D in vitro tumor models play a vital role in studying cancer growth mechanisms and metastasis . EmployiIn the 3D cell culture environment, a significant increase in the resistance of neoplastic cells to treatment with chemotherapy drugs is noted. Heightened resistance to cytotoxic drugs within 3D culture models can be attributed to various factors. These encompass an elevated expression of cancer stem cell-associated proteins ,41,42,43Oral cancer is distinguished by a heightened presence of immune cells infiltrating the tumor, defining it as a highly immunogenic tumor . Within Diverse 3D monoculture and double/triple co-culture systems exhibit distinct responses of cancer cells to anti-cancer drugs based on the composition of the ECM, cellular interactions, and soluble factors secreted by the cells . In a seTumor organoids possess the potential to serve as an in vitro representation of a patient’s tumor, replicating its molecular and phenotypic diversity. This characteristic makes tumor organoids valuable for predicting how individual patients might respond to specific treatments in the realm of personalized medicine. Pasch et al.  successfThe results from this scoping review will map the current utilization of these approaches in drug assessment in oral cancer. We aim to contribute to a better understanding of the suitability of three-dimensional models in preclinical drug trials and their potential to improve treatment development in oncology.


Rural pipeline approach has recently gain prominent recognition in improving the availability of health workers in hard-to-reach areas such as rural and poor regions. Understanding implications for its successful implementation is important to guide health policy and decision-makers in Sub-Saharan Africa. This review aims to synthesize the evidence on rural pipeline implementation and impacts in sub-Saharan Africa.We conducted a scoping review using Joanna Briggs Institute guidebook. We searched in PubMed and Google scholar databases and the grey literature. We conducted a thematic analysis to assess the studies. Data were reported following the PRISMA extension for Scoping reviews guidelines.Of the 443 references identified through database searching, 22 met the inclusion criteria. Rural pipeline pillars that generated impacts included ensuring that more rural students are selected into programmes; developing a curriculum oriented towards rural health and rural exposure during training; curriculum oriented to rural health delivery; and ensuring retention of health workers in rural areas through educational and professional support. These impacts varied from one pillar to another and included: increased in number of rural health practitioners; reduction in communication barriers between healthcare providers and community members; changes in household economic and social circumstances especially for students from poor family; improvement of health services quality; improved health education and promotion within rural communities; and motivation of community members to enrol their children in school. However, implementation of rural pipeline resulted in some unintended impacts such as perceived workload increased by trainee’s supervisors; increased job absenteeism among senior health providers; patients’ discomfort of being attended by students; perceived poor quality care provided by students which influenced health facilities attendance. Facilitating factors of rural pipeline implementation included: availability of learning infrastructures in rural areas; ensuring students’ accommodation and safety; setting no age restriction for students applying for rural medical schools; and appropriate academic capacity-building programmes for medical students. Implementation challenges included poor preparation of rural health training schools’ candidates; tuition fees payment; limited access to rural health facilities for students training; inadequate living and working conditions; and perceived discrimination of rural health workers.This review advocates for combined implementation of rural pipeline pillars, taking into account the specificity of country context. Policy and decision-makers in sub-Saharan Africa should extend rural training programmes to involve nurses, midwives and other allied health professionals. Decision-makers in sub-Saharan Africa should also commit more for improving rural living and working environments to facilitate the implementation of rural health workforce development programmes. The global shortfall of health workers (HWs) was estimated at 15 million in 2020 . The ineIn an effort to improve HWs development, attraction, recruitment, and retention in rural and remote areas, the World Health Organization (WHO) has recommended set of strategies including those pertaining to the development of HWs. Notably, targeted admission policies to enrol students with a rural background in HWs education programmes; locating health education facilities closer to rural areas; exposing students of a wide array of HWs disciplines to rural and remote communities and rural clinical practices; including rural health topics in HWs education. The WHO recommends a policy of having career development and advancement programmes, and career pathways for HWs in rural and remote areas . TogetheRural pipeline programmes have yielded positive results in many High-and-Middle Income countries like the USA, Canada, Australia, Sweden, and Norway –19. For Rural pipeline implementation is relatively new to SSA settings. However, there exists well known documented experiences from countries like South Africa , Uganda In a recent systematic review, the WHO has reported on strategies that increase the retention of HWs in rural areas in the global context, including in SSA . HoweverTo identify rural pipeline strategies/pillars implemented to improve the availability of qualified HWs in rural SSA and their impacts on health services and systems;To assess facilitators and challenges for the implementation of rural pipeline strategies to improve the availability of qualified HWs in rural SSA.We therefore undertook this scoping review of the literature relating to the status of rural pipeline programmes implementation and impacts in SSA. Specifically, we attempted to:This scoping review uses the guidance document developed by the Joanna Briggs Institute (JBI) . We opteWe followed the five stages for scoping review outlined by the JBI manual: (1) identification of research questions; (2) identification of relevant studies; (3) study selection; (4) data charting; and (5) results summarizing and reporting .For this scoping review, three key research questions were identified: (i) what is known on rural pipeline strategies or its pillars implemented to improve the availability of qualified HWs in rural Africa, (ii) what are the facilitators and challenges for the implementation of rural pipeline strategies to improve the availability of qualified HWs in rural SSA, and (iii) what have been the impacts of rural pipeline strategies on improving the availability of qualified HWs in rural SSA?Through these questions, we sought to map and summarize the range of rural pipeline interventions undertaken in SSA to improve the attraction and retention of qualified HWs in rural and remote areas.Population: This included the formal health workforce taking into account their varying profile ;Concept: search terms included “rural pipeline” or “rural pathways”, ‘rural training pathways’, ‘rural training programme’, ‘rural education’ ‘rural exposure’, ‘rural practice’, ‘rural experience’, ‘rural attraction programme’, ‘rural scholarship programme’; “return to service” programme, rural placement programme, rural retention programme, rural employment programme, rural development programme, or bundled interventions.Context: SSA countries according to WHO countries list.We used PubMed and Google scholar databases to search for empirical peer-reviewed literature that reported on rural pipeline interventions for increasing the availability of qualified HWs in rural SSA. These studies were published in English or French. The peer-reviewed literature search strategy was based on the “PCC approach”  of the JBI guide and included studies from 2000 onwards:We also used literature search through WONCA  websites and Google. Additionally, we used iterative snowball or citation tracking techniques—that is reviewing reference lists of primary included articles to identify additional relevant studies. These articles were assessed between November 2021 and February 2022.The principal investigator (DK) carried out the literature search. RvdP reviewed search strategies. All selected references were either saved using PubMed functions, or on Mendeley desktop software.Our search results were cleaned for duplicates by two members of our research team (DK and RvdP) using following eligibility criteria: (i) studies describing rural pipeline strategy or pillar; (ii) studies describing facilitators or challenges of rural pipeline implementation; (iii) studies describing the impacts of the rural pipeline intervention on local health services and communities . Discrepancies in study selection processes were resolved by a discussion between the two reviewers.Data, mainly qualitative, were extracted by the two reviewers (DK and RvdP) using an Excel spreadsheet. This Excel form was piloted on three articles before use. Data collected included: (i) study characteristics—authors name, year of publication, study country and study design; and (ii) information related to implemented interventions—implementation strategies, facilitators or barriers of rural pipeline programmes implementation, and programmes outcomes or effects. Given our research questions, both quantitative and qualitative data analyses were done.Characteristics of included studies were summarized using descriptive statistics. We then used thematic content analysis to sum up the main findings of the review. We reported the results following the PRISMA Extension for Scoping reviews guidelines .The present review includes 22 studies published between 2007 and 2021, with the majority (fifteen) published from 2015 , 36–47. One more rural pipeline pillar  was identified in addition to the four reported by Tesson et al.   to favour local medical training ; the secNone of the selected studies for this review directly reported impact of this pillar on health, and socio-economic situations.For this pillar, two strategies have been reported. In Mali, this consisted of organizing admission tests for medical studies in all regions . In MalaThis pillar has been documented to favour three impacts. First, it helps to increase the number of rural health practitioners; in Mali, enrolling in medical training programmes students who had secondary school in rural areas was reported to favour health practitioners’ intention and willingness to work in rural areas , 41. SecThird, this pillar is reported to contribute to socio-economic development of rural areas. McGregor et al. and Gumede et al. in South Africa reported major changes in household economic and social circumstances of students from poor family after their graduation , 41. ComThis pillar consists of two main strategies: emphasizing primary care throughout the curriculum  and placFor the placement of students in rural communities and health care settings, Amalba et al. reported that the Ghanaian context was marked by Community Based-Education services (COBES) that consisted of dispatching groups of 8–10 students to rural communities and health care settings for four weeks every year, during three consecutive years . In TanzSix impacts—of which four at the health facility level and two at the community level—are reportedly related to this pillar.At the facility level, this pillar contributes to increasing rural health practitioners. In Ghana, Amalba et al. found that making students follow a curriculum integrating exposure to rural training and practice increased their willingness to work in rural areas . This piHowever, increase in rural health workers’ workload and supervisors’ absenteeism rate have been reported as unexpected impacts of this pillar. First, Atuyambe et al. in Uganda reported the placement of students in rural facilities as an extra workload for the rural health workers, as the latter are assigned to supervise students’ practices . Indeed,At the community level, the deployment of medical students into rural communities for practical training has been reported in Ghana and Uganda to contribute to health education and promotion within these communities. Students’ activities in rural communities included communications on drinking water, hand hygiene, good sanitation practices including latrine construction, sexual health and other health issues , 46. StuNonetheless, patients’ discomfort of being attended by students has been reported as an impact of this pillar. A study in Uganda reported that some health managers had difficulties convincing community members to be attended by students as they perceived students as not qualified to provide care . This atThis pillar includes four aspects to account for. The first aspect is to ensure that rural health facilities are well equipped to allow smooth functioning of the facility, provision of quality care, thereby allow job-satisfaction of the staffs , 31. ThiThis pillar has been reported to increase the number of rural health workers; training health practitioners in primary health care was said to retain them in this location. Dormael et al. in Mali reported that 55 out of 65 trained young doctors (85%) deployed in rural areas remained at their location, two years after the training . In addiClithero et al. in South Africa reported about social accountability of health professionals as an important part of the rural pipeline . This coNone of the selected studies for this review directly reported impact for this pillar.Ten studies reported about drivers in implementing rural pipeline program in sub-Saharan Africa , 39, 41.Availability of medical school and health facility infrastructures has been mentioned in studies from Mali, Uganda and DRC as important facilitator in implementing rural pipeline in these countries. While the existence of 120 schools with medical programmes in Mali has been reported as an asset to promoting health professions in rural areas , engagemAnother reported facilitating factor of the rural pipeline is to ensure students’ accommodation and safety in rural areas. In the DRC, the Ministries of Health and Education proceeded in advance with the identification and preparation of specific rural sites that have the potential of accommodating an influx of students . In UganIn Mali, one strategy to promoting the implementation of the rural pipeline was to lift the age limit for candidates who were interested in attending training schools located in rural areas .In South Africa and the DRC, having an appropriate academic capacity-building program for medical students has also been reported as a rural pipeline facilitator. This consists of setting, in rural medical schools, training programmes and supervision strategies that help students to successfully complete the courses and build their capacities such as caring for patients and engaging in teamwork , 44.A set of motivational dynamics has been documented to be useful for implementing rural pipeline in Ghana and Mali. In Ghana, a partnership was built between a university located in the northern region  and community members to increase medical students’ awareness about the importance of working in rural areas . In MaliIn Uganda, HWs said they would only work in rural settings upon active improvement of their wages . As for Studies from South Africa, Uganda and Ghana mentioned that students’ personal competencies for and interests in rural practice are also key factor to implementing rural pipeline , 38, 44.In the particular context of Mali, marked by the overload of labour market in 1989, the government stopped recruiting HWs in urban areas . This leBarriers to the implementation of the rural pipeline were documented by seven studies in this review , 42, 46.Poor preparation of rural health training schools’ candidates has been found to decrease likelihood for rural candidates to be selected for medical studies, as these candidates studied in inappropriate secondary schools , 42. IndA study in Mali reported that tuition fees and complementary educational costs can represent a barrier to accessing medical school, especially for rural students . AccordiOne of the barriers to implementing rural pipeline in sub-Saharan Africa is the scarcity of medical schools in rural areas. Amalba et al. reported in 2019 that Ghana’s medical schools are mainly concentrated in the cities and that the country faces challenges to extend medical care to smaller towns and rural areas . KapandaLimited access to health facilities in rural areas has been said to harden rural medical practices in Mali and South Africa , 31. In Studies in Mali and Uganda have pointed out the inadequate living conditions of medical students and HWs in rural areas, as a key factor making the latter ones unwilling to work in rural areas , 31. ThePerceived inappropriate working conditions in rural health facilities have been documented as a barrier to achieving the rural pipeline in South Africa, Malawi, Uganda and Ghana. Medical students and health workers have reported across these countries that health professionals working in rural areas are commonly exposed to demotivating working conditions such as exceeding workload, lack of time for holydays, poor health equipment and infrastructures and poor support supervision from the hierarchy , 30, 46.Atuyambe et al. reported two aspects related to the discrimination of rural HWs, as reasons for low retention of medical graduates in rural areas . The firThis review contributes to complementing the existing literature regarding rural pipeline programmes implementation and their effects on rural health systems and communities in SSA. More specifically, it confirms the recommendations of updated WHO guideline on health workforce development, attraction, recruitment and retention in rural and remote areas from 2021 . This scRural pipeline strategies were reported to increase the number of rural health workers; to favour socio-economic well-being of health workers; to improve the quality of health services and access of rural community to healthcare; to reduce patient-provider communication barriers; to promote health education and promotion within rural communities; and to motivate communities to enrol their children in schools. Reviews on rural pipeline programmes have already been reported –53. HolsThis review pulls out the key implications for policy actions necessary to implementing rural pipeline programmes namely, ensuring that more rural students are selected into programs; developing curriculum for rural health training and delivery; and ensuring retention through educational and professional support. Strategies that prioritize rural students in selection processes were identified to increase health practitioner intention and willingness to work in rural areas and to reduce communication barriers between patients and healthcare providers. This strategy also contributes to socio-economic development of rural communities through the breaking of poverty cycle for rural students. Strategies that ensure curriculum development for rural health training and delivery were acknowledged to increase the availability of health workers in rural areas, improve quality of health services, favour health education and promotion within rural communities, and motivate communities for children’s schooling. Strategies that ensure rural retention through educational and professional support were reported to increase the number of health professional in rural areas and reinforces their social development—learn from community culture and lifestyle, and benefit for their hospitality. Nevertheless, it is worth noting that these findings might not be generalizable to all SSA region, as most of the papers included in this review were published from Southern and Eastern countries of Africa Fig. . This diOur finding adds to the understanding of implementation challenges of complex interventions such as rural pipeline. First, we assessed that only few studies reported the combination of two and more components of rural pipeline , 41, 49.Another finding that calls for policy considerations is the limited attention given to the allied health professions  in the implementation of the rural pipeline. Only five of the articles included in this study reported on rural pipeline programmes targeting nursing and midwifery learners , 29, 31.This review has identified an additional pillar to the already documented pillars . This reThe present review has some limitations. First, the methodological design of this study—scoping review—did not allow any quality assessment of included studies. Moreover, given that only two researchers checked and agreed on the database, there might be a risk of selection bias. This could limit the internal validity of the effectiveness of rural pipeline interventions reported in the present study. A meta-analysis study design could overcome this but given the criteria needed for inclusion in such a review, it is likely that very few articles would be included. Second, the geographical disparity of selected studies, with most studies published from Eastern and Southern regions could undermine the generalization of findings to the whole SSA. This could also hamper the external validity of the findings to other low-income countries. We argue for future studies to include an explorative case-study design for specific countries as this would provide for more contextual and robust evidence on the effectiveness, and eventual impact, of the rural pipeline implementation.This scoping review shows that rural pipeline programmes potentially impact rural health systems and services by increasing the number of rural health practitioners; reducing communication barriers between healthcare providers and community members; changing household economic and social circumstances especially for students from poor family; and improving the quality of health services. However, rural pipeline can result in some unintended impacts such as perceived workload increased by trainee’s supervisors; increased job absenteeism among senior health providers; discomfort of being attended by students; and perceived poor quality care provided by students. Additionally, poor preparation of rural health training schools’ candidates; tuition fees payment; limited access to rural health facilities for students training; inadequate living and working conditions; and perceived discrimination of rural health workers hamper the effective implementation of rural pipeline approach in sub-Saharan Africa. We recommend interconnecting interventions and tailoring them with country specific contexts to address rural health workforce development related challenges hereby improving rural pipeline programmes implementation and their impact in rural sub-Saharan Africa. Moreover, there is a need to undertake more health workforce development interventions targeting nursing and midwifery professions in Sub-Saharan Africa. Finally, we call for more governmental commitment for improving rural living, and working environments to facilitate the implementation of rural health workforce development programmes.


Pelvic exenteration is a radical procedure representing a salvage option in patients with recurrent or persistent gynaecological malignancies. It can be performed with an open or minimally invasive approach. Different studies have demonstrated optimal peri-operative outcomes of minimally invasive pelvic exenteration with no survival difference when compared with an open approach. In this article, we discuss the importance and the challenge of patient selection for pelvic exenteration and more specifically for minimally invasive pelvic exenteration. Pelvic exenteration is the salvage curative option for patients with recurrent or persistent gynaecological cancer after radiation therapy. It is a major radical procedure involving removal of two or more pelvic organs. .Different studies have assessed the feasibility  and the As pelvic exenteration is associated with major post-operative complications in 18-27%  and withMore recently, surgical boundaries for a potentially curative radical surgery have been pushed. Particularly, laterally extended disease which reaches the pelvic side wall  and evenIn this context, pre-operative, and intra- operative assessments before embarking on a pelvic exenteration, are of crucial importance to minimise harm to patients. In recent years, the advent of high-resolution MRI-scan and PET-CT scan can accurately define (if performed close to pelvic exenteration) the local infiltration and the potential presence of distant disease . ObviousWhen dealing with patients’ selection to minimally invasive pelvic exenteration, the triage process needs to be even more accurate. Despite the previously reported feasibility of a minimally invasive/ laparoscopic approach to laterally extended endopelvic resection (LEER)  and in lPalliative pelvic exenteration is performed in patients with no indications for curative exenteration. Curative pelvic exenteration is defined when clear margins can be pathologically ensured, and no distant metastases are found either intraabdominally or on the preoperative MRI/CT/ PET scan. An exenteration is defined as palliative in the presence of distant metastasis , positive peritoneal washing or tumour perforation into the pouch of Douglas, as well as in cases when complete tumour removal was not possible. The indication for palliative pelvic exenteration is usually related to fistula symptoms or major bleeding not amenable to palliative radiotherapy .We believe that a minimally invasive approach could be the procedure of choice for patients who are candidates for a palliative pelvic exenteration to provide symptom relief with the aim of achieving the least possible morbidity.Concerning the survival outcomes associated with pelvic exenteration in gynaecological cancers, this is fairly heterogeneous. Recently, we reported the survival analysis of propensity-matched series of open and minimally invasive pelvic exenteration performed for gynaecological cancers where no difference was found in disease-free or cancer-specific survival . PatientIt is important to mention that a minimally invasive approach to pelvic exenteration should be performed by teams with a high level of skills in laparoscopic and robotic surgery in high-volume referral centres, possibly in the setting of clinical trials and following the basic principles of oncological surgery, thus avoiding cancer cell spillage, with careful specimen manipulation and resection of tumour-free tissues.In conclusion, we believe that a minimally invasive approach to pelvic exenteration should be considered whenever possible, and gynaecological oncologists might want to consider it in selected cases like palliation and in the cases of small and central tumours. Such an approach should be avoided in large tumours (>5 cm) and in tumours with lateral sidewall involvement as achieving free surgical margins remains of crucial importance. Ideally, this approach should be used in the context of prospective clinical trials.


While the health of airline pilots is crucial to ensuring the safe travel of millions of people worldwide, they remain vulnerable to a variety of health challenges due to the nature of their job. The purpose of this narrative review is to provide a comprehensive summary of the most common health issues experienced by commercial airline pilots. By examining the published literature on this topic, we sought to identify areas where further research is needed to understand better the health risks associated with being a pilot and to develop effective interventions to address these risks. We also highlight how recent technological advances in digital health can be leveraged to conduct research into the potential usefulness of telehealth assessments for identifying occupational hazards in the aviation sector and providing targeted interventions. Overall, addressing the challenges of taking care of pilots’ health and ensuring public safety will require a collaborative effort among airlines, governments, and regulators. Prioritizing pilot health and safety can actually improve profitability in the aviation sector by reducing costs associated with absenteeism, turnover, and accidents. Commercial airline pilots are trained to fly various types of aircraft, including airplanes and helicopters, on short or long-haul flights ,2. They In recent decades, the aviation industry has faced increasing competition and pressure to reduce costs, which has raised concerns about the working conditions and job security of pilots . These cMethodologyIn order to review the available literature on the topic of airline pilots’ health, we searched electronic databases including PubMed, Web of Science, and Scopus for all studies published from January 1990 until July 2022 using a combination of the following terms: pilots, airlines, health, disease, prevention, and aircraft. A health information specialist (PM) performed the search with appropriate wildcards to take into account plurals and variations in spellings. The titles and abstracts of 605 articles were reviewed. The intent of reviewing the relevant literature on the subject of pilots’ health was not to conduct a systematic review. When a meta-analysis or a systematic review was already conducted on a specific topic , we mainly referred to the conclusions reported in these articles, without resorting to a narrative summary of the included studies. This ensured that the review covered substantial relevant literature on the subject and was not confined to one research methodology. The sections that follow are not meant to be comprehensive but rather to emphasize the aspects that are most important in investigating effective strategies for safeguarding pilots' health and ensuring the safety of the aviation sector. An in-depth examination of work-related disabilities and the impact of the coronavirus disease 2019 (COVID-19) pandemic on the aviation industry was beyond the scope of the review.ResultsCircadian Disruption and Sleep ProblemsCircadian desynchronization commonly experienced by pilots may interfere significantly with human well-being and homeostasis . During FatigueFatigue, a complex subjective phenomenon reflecting a high physical and mental load, is commonly reported by airline pilots, either alone or in combination with sleep-related issues . In recePsychological Distress and Psychiatric ConditionsFatigue and poor work-life balance are common sources of psychological distress in airline pilots. Persistent disruption of circadian rhythms and stressful working conditions may also lead to clinically significant mood disorders, including major depression . In receLower Back PainPhysical factors in the cockpit, including prolonged seating postures, lifting, and whole-body vibration, impose postural strains on lumbar spines and can result in lower back pain (LBP) . AlbermaVenous ThromboembolismProlonged seated immobility during long-haul flights is a well-known risk factor for venous thromboembolism (VTE) . While tMalignant MelanomaMalignant melanoma (MM) of the skin is thought to arise from different causal pathways and the potential causative role of cosmic and ultraviolet (UV) radiation has not been entirely elucidated . OccupatCardiovascular DiseasesAirline pilots experience occupational exposures that are widely recognized as having strong connections to cardiovascular disease (CVD). In a recent systematic review of 48 studies conducted in 20 different countries, Wilson et al.  analyzedTinnitusTinnitus, a symptom characterized by an auditory perception unrelated with any physical source, is commonly reported by subjects with prolonged exposure to occupational noise . AirlineGastrointestinal DisordersMeal times are important synchronizers of the human life and disruptions in circadian rhythms coupled with arduous working environment have been associated with gastrointestinal disorders (GIs) in airline pilots. In a USA study conducted from 2001 through 2013 in the population of active duty Air Force pilots, esophageal disease and dyspeptic conditions were the two most frequently encountered GIs . In an iOther Health IssuesOwing to their exposure to increased levels of cosmic radiation , it has Health-Related Quality of LifeHealth-related quality of life (HRQOL) is a multi-dimensional indicator of overall health that captures information on a person’s physical and mental health status, as well as on the impact of health status on quality of life . The maiDiscussionBased on the published literature, the occupational milieu experienced by commercial airline pilots appears to be linked with several potential health issues which are only partially addressed by current interventions . Another major issue is that preventive surveillance programs in the aviation industry may differ across countries and different civil aviation authorities. In light of this situation, it is imperative to conduct further research to examine the discrepancies and establish a unified understanding comprehensively. Enhanced collaboration among various authorities is also essential to ensure effective decision-making and alignment of policies. In general, effective prevention strategies against the full range of hazards encountered by pilots during their job should be aimed at reducing risk factors and strengthening protective measures. Apart from the specific paths for preventative interventions outlined below, the paramount contribution of guidelines released from civil aviation authorities for protecting pilots’ health should be adequately emphasized. Ideally, pragmatic action to improve pilots’ working conditions that cause common sleep- and fatigue-related health problems, including avoidance of irregular work schedules, optimization of work organization, and guarantee of adequate sleep. In light of recent technical advances, incorporating remote telehealth assessments and monitoring should also be explored in future studies as a meaningful strategy to address the gap in health care access that is still common for airline pilots , especiaReducing the Risk of Sleep and Mental Health-Related ProblemsOccupational physicians should inform airline pilots about proper sleep habits as well as on the relationships between sleep disorders, fatigue, and depression -11. CurrReducing the Risk of Radiation-Induced DamageThe issue of radiation-induced damage in pilots is mainly related to the risk of developing MM. Airlines should follow the International Commission on Radiological Protection (ICRP) guidance on radiological protection from cosmic radiations in aviation to reduce occupational exposure of the cockpit crew . UnfortuReducing the Burden of Cardiovascular and Metabolic DiseasesAviation medical examiners , who typically conduct medical evaluations for airline pilots, should consider not only lifestyle risk factors but also work-related conditions associated with CVD, such as OSA and depression. By doing so, they can identify pilots who would greatly benefit from targeted prevention strategies. Traditional modifiable risk factors may be targeted by encouraging physical activity during leisure time, promoting healthy dietary choices, favoring smoking cessation, and preventing excess alcohol drinking. Due to the impaired cardiometabolic risk profile of airline pilots , future Strenghts and limitationsThe current manuscript is an example of a narrative review with known limitations and caveats . While sEmphasizing pilot health and safety can enhance profitability within the aviation industry by minimizing expenses related to absenteeism, employee turnover, and accidents. Nevertheless, the examined evidence reveals that pilots continue to face numerous health-related obstacles. Consequently, it is essential for airline pilots to focus on their well-being and proactively address these potential concerns. Airlines can proactively enhance the health and safety of their pilots by offering access to mental health services, establishing fatigue risk management systems, and encouraging healthy lifestyle choices. Future high-quality intervention studies will play a crucial role in determining effective strategies for boosting pilot well-being, ultimately leading to improved flight safety and performance. Leveraging recent technological advancements in digital health can empower the aviation industry to identify and mitigate occupational hazards. For instance, telehealth assessments offer a valuable tool for screening pilots for sleep disorders, which may contribute to fatigue and compromised performance. In addition, remote monitoring devices, such as wearable sensors, can track pilots' radiation or noise exposure, allowing for timely interventions if required. This holistic approach to health and safety in the aviation sector will ensure that pilots remain in peak condition, resulting in safer skies for all.