Using digital technologies to diagnose in the home: recommendations from a Delphi panel.

Rapid advances in digital technology have expanded the availability of diagnostic tools beyond traditional medical settings. Previously confined to clinical environments, these many diagnostic capabilities are now accessible outside the clinic. This study utilized the Delphi method, a consensus-building approach, to develop recommendations for the development and deployment of these innovative technologies. The study findings present the 29 consensus-based recommendations generated through the Delphi process, providing valuable insights and guidance for stakeholders involved in the implementation and utilization of these novel diagnostic solutions. These recommendations serve as a roadmap for navigating the complexities of integrating digital diagnostics into healthcare practice outside traditional settings like hospitals and clinics.

Unsettled Liability Issues for "Prediagnostic" Wearables and Health-Related Products.

This Viewpoint examines the murky legal treatment of various health-related wearable or other general wellness products for patients, physicians, and manufacturers, and recommends solutions.

Should Alexa diagnose Alzheimer's?: Legal and ethical issues with at-home consumer devices.

Voice-based AI-powered digital assistants, such as Alexa, Siri, and Google Assistant, present an exciting opportunity to translate healthcare from the hospital to the home. But building a digital, medical panopticon can raise many legal and ethical challenges if not designed and implemented thoughtfully. This paper highlights the benefits and explores some of the challenges of using digital assistants to detect early signs of cognitive impairment, focusing on issues such as consent, bycatching, privacy, and regulatory oversight. By using a fictional but plausible near-future hypothetical, we demonstrate why an "ethics-by-design" approach is necessary for consumer-monitoring tools that may be used to identify health concerns for their users.

Skating the line between general wellness products and regulated devices: strategies and implications.

Health technology is advancing at a rapid clip, with many of these technologies appearing on consumer products like smartphones and tablets. Federal regulators have responded to these changes with a flexible approach that allows firms to manufacture a 'general wellness product' ('GWP') without being subject to regulation typically applied to 'devices' that diagnose or treat a disease or condition. Using currently available medical products and devices from across a spectrum of diseases, we describe how firms can use this existing regulatory framework to develop innovative products by 'skating the line' between mostly unregulated GWPs and regulated devices. On the one hand, we find that skating the line offers a variety of benefits, including potential improvements to product development, innovation, and patient access to medical technologies. On the other hand, we show that this technique has potential costs to patient safety, competition, and data sharing. Skating the regulatory line between GWP and devices, in other words, offers important benefits but is not without risks. Any further regulatory action to address such risks should be careful to leave significant unregulated space for product development.

Telehealth to Address Health Disparities: Potential, Pitfalls, and Paths Ahead.

Telehealth has the potential to address health disparities, but not without deliberate choices about how to implement it. To support vulnerable patients, health policy leaders must pursue creative solutions such as public-private partnerships, broadband infrastructure, and value-based payment. Without these initiatives or others like them, health disparities are likely to persist despite telehealth's tantalizing potential.

Patient data ownership: who owns your health?

This article answers two questions from the perspective of United Kingdom law and policy: (i) is health information property? and (ii) should it be? We argue that special features of health information make it unsuitable for conferral of property rights without an extensive system of data-specific rules, like those that govern intellectual property. Additionally, we argue that even if an extensive set of rules were developed, the advantages of a property framework to govern health information would be slight: propertization is unlikely to enhance patient self-determination, increase market efficiency, provide patients a foothold in the data economy, clarify legal uses of information, or encourage data-driven innovation. The better approach is to rely less, not more, on property. We recommend a regulatory model with four signature features: (i) substantial protection for personal health data similar to the GDPR with transparent limits on how, when, and by whom patient data can be accessed, used, and transmitted; (ii) input from relevant stakeholders; (iii) interoperability; and (iv) greater research into a health-data service, rather than goods, model.

Torsion of an Accessory Spleen in a Child With Biliary Atresia Splenic Malformation Syndrome.

Torsion of an accessory spleen is an exceedingly rare cause of abdominal pain in pediatric patients. The diagnosis is frequently challenging as presentation is variable and diagnostic imaging can be aspecific. The current case describes an unusual presentation of a torted accessory spleen in a 5-year-old girl with biliary atresia splenic malformation syndrome who initially presented with non-specific abdominal symptoms and fever. The diagnosis was made following fine-needle aspiration of a suspected intraabdominal abscess. The case highlights the diagnostic challenge of accessory splenic torsion and stresses the importance of its inclusion on the differential diagnosis of pediatric patients, especially those with known splenic or laterality abnormalities, presenting with both acute and sub-acute abdominal symptoms.

Biliary Dyskinesia in Children and Adolescents: A Mini Review.

Introduction: While functional gallbladder disorder is a well-recognized and defined condition in adults, its pediatric analog, biliary dyskinesia, lacks uniformity in diagnosis. Yet, biliary dyskinesia is among the most common conditions resulting in cholecystectomy in youth and its frequency continues to rise. The primary aims of the current review were assess the efficacy of cholecystectomy in children diagnosed with biliary dyskinesia and the utility of cholescintigraphy in predicting outcomes. Results: All previous studies assessing outcomes in youth with biliary dyskinesia have been retrospective and therefore of low quality. There is a lack of uniformity in patient selection. Short term follow-up reveals partial response in 63.4-100% with complete resolution in 44.2-100%. Only 4 studies have reported long-term outcomes with complete symptom resolution in 44-60.7%. The published research generally indicates that the gallbladder ejection fraction (GBEF) as determined by cholescintigraphy lacks utility in predicting cholecystectomy outcome utilizing the commonly used cut-off values. There are data suggesting that more extreme cut-off values may improve the predictive value of GBEF. Conclusion: There is a lack of consensus on the symptom profile defining biliary dyskinesia in youth and current literature does not support the use of cholescintigraphy to select patients for cholecystectomy. There is a substantial portion of pediatric patients diagnosed with biliary dyskinesia who do not experience long-term benefit from cholecystectomy. Well-designed prospective studies of surgical outcomes are lacking. Increasing the uniformity in patient selection, including both symptom profiles and cholescintigraphy results, will be key in understanding the utility of cholecystectomy for this condition.

Image Updating for Brain Shift Compensation During Resection.

BACKGROUND: In open-cranial neurosurgery, preoperative magnetic resonance (pMR) images are typically coregistered for intraoperative guidance. Their accuracy can be significantly degraded by intraoperative brain deformation, especially when resection is involved. OBJECTIVE: To produce model updated MR (uMR) images to compensate for brain shift that occurred during resection, and evaluate the performance of the image-updating process in terms of accuracy and computational efficiency. METHODS: In 14 resection cases, intraoperative stereovision image pairs were acquired after dural opening and during resection to generate displacement maps of the surgical field. These data were assimilated by a biomechanical model to create uMR volumes of the evolving surgical field. A tracked stylus provided independent measurements of feature locations to quantify target registration errors (TREs) in the original coregistered pMR and uMR as surgery progressed. RESULTS: Updated MR TREs were 1.66 ± 0.27 and 1.92 ± 0.49 mm in the 14 cases after dural opening and after partial resection, respectively, compared to 8.48 ± 3.74 and 8.77 ± 4.61 mm for pMR, respectively. The overall computational time for generating uMRs after partial resection was less than 10 min. CONCLUSION: We have developed an image-updating system to compensate for brain deformation during resection using a computational model with data assimilation of displacements measured with intraoperative stereovision imaging that maintains TREs less than 2 mm on average.

Intraoperative image updating for brain shift following dural opening.

OBJECTIVE Preoperative magnetic resonance images (pMR) are typically coregistered to provide intraoperative navigation, the accuracy of which can be significantly compromised by brain deformation. In this study, the authors generated updated MR images (uMR) in the operating room (OR) to compensate for brain shift due to dural opening, and evaluated the accuracy and computational efficiency of the process. METHODS In 20 open cranial neurosurgical cases, a pair of intraoperative stereovision (iSV) images was acquired after dural opening to reconstruct a 3D profile of the exposed cortical surface. The iSV surface was registered with pMR to detect cortical displacements that were assimilated by a biomechanical model to estimate whole-brain nonrigid deformation and produce uMR in the OR. The uMR views were displayed on a commercial navigation system and compared side by side with the corresponding coregistered pMR. A tracked stylus was used to acquire coordinate locations of features on the cortical surface that served as independent positions for calculating target registration errors (TREs) for the coregistered uMR and pMR image volumes. RESULTS The uMR views were visually more accurate and well aligned with the iSV surface in terms of both geometry and texture compared with pMR where misalignment was evident. The average misfit between model estimates and measured displacements was 1.80 ± 0.35 mm, compared with the average initial misfit of 7.10 ± 2.78 mm between iSV and pMR, and the average TRE was 1.60 ± 0.43 mm across the 20 patients in the uMR image volume, compared with 7.31 ± 2.82 mm on average in the pMR cases. The iSV also proved to be accurate with an average error of 1.20 ± 0.37 mm. The overall computational time required to generate the uMR views was 7-8 minutes. CONCLUSIONS This study compensated for brain deformation caused by intraoperative dural opening using computational model-based assimilation of iSV cortical surface displacements. The uMR proved to be more accurate in terms of model-data misfit and TRE in the 20 patient cases evaluated relative to pMR. The computational time was acceptable (7-8 minutes) and the process caused minimal interruption of surgical workflow.

Treatment With the SIGN Nail in Closed Diaphyseal Femur Fractures Results in Acceptable Radiographic Alignment.

BACKGROUND: The burden of orthopaedic trauma in the developing world is substantial and disproportionate. SIGN Fracture Care International is a nonprofit organization that has developed and made available to surgeons in resource-limited settings an intramedullary interlocking nail for use in the treatment of femoral and tibial fractures. Instrumentation also is donated with the nail. A prospectively populated database collects information on all procedures performed using this nail. Given the challenging settings and numerous surgeons with varied experience, it is important to document adequate alignment and union using the device. QUESTIONS/PURPOSES: The primary aim of this research was to assess the adequacy of operative reduction of closed diaphyseal femur fractures using the SIGN interlocking intramedullary nail based on radiographic images available in the SIGN database. The secondary aims were to assess correlations between postoperative alignment and several associated variables, including fracture location in the diaphysis, degree of fracture site comminution, and time to surgery. The tertiary aim was to assess the functionality of the SIGN database for radiographic analyses. METHODS: A review of the prospectively populated SIGN database was performed for patients with a diaphyseal femur fracture treated with the SIGN nail, which at the time of the study totaled 32,362 patients. After study size calculations, a random number generator was used to select 500 femur fractures for analysis. Exclusion criteria included open fractures and those without radiographs during the early postoperative period. The following information was recorded: location of the fracture in the diaphysis; fracture classification (AO/Orthopaedic Trauma Association [OTA] classification); degree of comminution (Winquist and Hansen classification); time from injury to surgery; and patient demographics. Measurements of alignment were obtained from the AP and lateral radiographs with malalignment defined as deformity in either the sagittal or coronal plane greater than 5°. Measurements were made manually by the four study authors using on-screen protractor software and interobserver reliability was assessed. RESULTS: The frequency of malalignment greater than 5° observed on postoperative radiographs was 51 of 501 (10%; 95% CI, 6.5-11.5), and malalignment greater than 10° occurred in eight of 501 (1.6%) of the femurs treated with this nail. Fracture location in the proximal or distal diaphysis was strongly correlated with risk of malalignment, with an odds ratio (OR) of 3.7 (95% CI, 1.5-9.3) for distal versus middle diaphyseal fractures and an OR of 4.7 (95% CI, 1.9-11.5) for proximal versus middle fractures (p < 0.001). Time from injury to surgery greater than 4 weeks also was strongly correlated with risk of malalignment (p < 0.001). Inherent fracture stability, based on fracture site comminution as per the Winquist and Hansen classification (Class 0-1 stable versus 2-4 unstable) showed an OR of 2.3 (95% CI, 1.2-4.3) for malalignment in unstable fractures. Interobserver reliability showed agreement of 88% (95% CI, 83-93) and mean kappa of 0.81 (95% CI, 0.65-0.87). The SIGN database of radiographic images was found to be an excellent source for research purposes with 92% of reviewed radiographs of acceptable quality. CONCLUSIONS: The frequency of malalignment in closed diaphyseal femoral fractures treated with the SIGN nail closely approximated the incidence reported in the literature for North American trauma centers. Increased time from injury to surgery was correlated with increased frequency of malalignment; as humanitarian distribution of the SIGN nail increases, local barriers to timely care should be assessed and improved as possible. Prospective clinical study with followup, despite its inherent challenges in the developing world, would be of great benefit in the future. LEVEL OF EVIDENCE: Level III, therapeutic study.

Horseshoe abscess associated with acute carpal tunnel syndrome: somebody wake up the hand surgeon.

The horseshoe abscess is a rare variant of flexor tendon sheath infections. It involves the tendon sheaths of the first and fifth digits, which communicate through the deep potential space of the wrist. Neural compression is possible, leading to an acute carpal tunnel syndrome. The approach to such patients should include empirical antibiotic coverage and urgent consultation with a hand surgeon to facilitate operative management.

Initial evaluation of posterior cruciate ligament injuries: history, physical examination, imaging studies, surgical and nonsurgical indications.

Compared with anterior cruciate ligament injuries, posterior cruciate ligament injuries are a rare event. The mechanisms are predictable and a thorough physical examination is mandatory to rule out or define combined injury patterns. Stress radiography and magnetic resonance imaging studies are very helpful adjuncts. Acute and chronic injuries require slightly different approaches. As our understanding of normal and pathologic knee joint kinematics develops, nonoperative rehabilitation goals and operative techniques continue to evolve.

The use of platelet-rich plasma in arthroscopy and sports medicine: optimizing the healing environment.

Platelet-rich plasma (PRP) is a new technology focused on enhancing the healing response after injury of different tissue types. PRP is prepared by withdrawal of patients' peripheral blood and centrifugation to obtain a highly concentrated sample of platelets, which undergo degranulation to release growth factors with healing properties. It also contains plasma, cytokines, thrombin, and other growth factors that are implicated in wound healing and have inherent biological and adhesive properties. The prepared concentrate is then injected back into the patient at the site of morbidity. This may be intralesional, intra-articular, or surrounding the involved tissue bed. PRP preparations have been used therapeutically in various medical fields from implantology to vascular ulcers, with a more recent evolution and promising results in the field of sports medicine and arthroscopy. Sports medicine patients desire a rapid return to their preinjury level of function, and PRP may have certain applications that will speed recovery in cases of tendon, ligament, muscle, and cartilage disorders. In particular, anterior cruciate ligament reconstruction has shown better autograft maturation, improved donor site morbidity, and pain control, in addition to improved allograft incorporation. By acceleration of the biological integration of the graft by use of PRP, patients may undergo faster, more intensive rehabilitation programs and return to sports more rapidly. Because of its autogenous origin, easy preparation, and excellent safety profile, the advent of PRP has opened another therapeutic door for sports medicine physicians and orthopaedic surgeons. Future directions of PRP include improving the results of arthroscopic and related surgery, in addition to delineating correct dosage, timing, and quantification, as well as ideal techniques of PRP application.

Spatial and temporal expression of herpes simplex virus type 1 amplicon-encoded genes: implications for their use as immunization vectors.

There is great interest in developing new immunization vectors. Helper virus-free herpes amplicons, plasmid-based vectors that encode no viral gene products and have an extremely large coding capacity, are attractive viral vaccine candidates for expressing recombinant proteins in vivo for immunization. Earlier studies in mice, using amplicons encoding the gp120 protein of human immunodeficiency virus (HIV), resulted in strikingly robust cellular immune responses as measured by cytotoxicity and interferon gamma enzyme-linked immunospot assays. To begin to understand how such vectors function in vivo to generate an immune response, we used amplicons encoding reporter constructs including green fluorescent protein (GFP) and luciferase to examine the duration of expression after administration to mice. Luciferase expression, measured with the IVIS system from Xenogen/Caliper Life Sciences (Hopkinton, MA) and by enzymatic assays of tissue extracts, revealed that expression after injection of the HSVluc amplicons peaked earlier than 24 hr after injection into mice. HSVegfp injection resulted in peak accumulation of GFP 24 hr after administration in vivo. Thus, both reporter genes revealed a rather rapid and robust expression pattern of short duration. The short period of expression appears in part to be due to gene silencing. Examination of the cells transduced by amplicons encoding GFP and human B7.1 suggested that the amplicons transduce a variety of cells, including professional antigen-presenting cells. From this and previous work, we conclude that amplicons may engender a potent immune response by directly transducing dendritic cells as well as by cross-priming of antigen produced by other transduced host cells.

Human papillomavirus-like particles mediate functional delivery of plasmid DNA to antigen presenting cells in vivo.

Because recombinant empty viral capsids are potentially attractive vectors for gene therapy, here we examined the ability of human papillomavirus (HPV) virus-like particles (VLPs) to mediate delivery and expression of DNA plasmids in vitro and in vivo. VLP-mediated delivery and expression of a GFP reporter construct in vitro was found to be highly dependent upon the presence of full-length L2 protein within the VLPs. Similarly, expression of GFP and luciferase reporter plasmids in vivo was strongly enhanced by co-administration of L1/L2 VLPs. Interestingly, in these experiments we routinely observed GFP expression in migrating antigen presenting cells (APC) recovered from mice inoculated with GFP plasmid in combination with VLPs, but not in APC recovered from mice inoculated with the plasmid alone. Additional evidence to support this concept was generated in experiments in which co-administration of VLPs with a plasmid designed to express HPV16 E6 oncoprotein was associated with significant enhancement of plasmid-encoded E6-specific cellular immune responses. These findings have implications for the design of vaccines for combined prophylaxis and therapy of HPV-associated diseases, and for other vaccines that rely on the administration of DNA-based immunogens, adjuvants, and/or other factors.

In vivo study of T-cell responses to skin alloantigens in Xenopus using a novel whole-mount immunohistology method.

BACKGROUND: The African clawed frog, Xenopus, is a widely used comparative model for studying the immune response to transplantation antigens. METHODS: To better define the effector cells involved in the immune response to skin alloantigens of the frog Xenopus laevis, we have adapted a whole-mount immunohistology procedure used in mice that enables us to visualize leukocyte infiltration into unfixed transplanted skin tissues using fluorescent antibodies. We characterized the leukocyte populations present in donor skin at different times after transplantation using anti-class II and CD8 monoclonal antibodies. RESULTS: In autografts, only class II Langerhans or dendritic-like cells and very few CD8 T cells were detected. In contrast, major histocompatibility complex (MHC) disparate skin grafts at the peak of acute rejection (seven days posttransplantation, 50% rejection of pigment cells) were infiltrated with a large number of bright class II leukocytes, the majority of which were CD8 T cells. Most of these cells were located outside blood vessels and often near areas lacking pigmentation. Compared to MHC-disparate skin grafts, skin differing from the host only by minor histocompatibility antigens undergoes slower (i.e., chronic) rejection; interestingly, however, it was infiltrated by similar numbers of class II and CD8 T cell effectors, but with delayed kinetics (i.e., peaked around 15 days posttransplantation). CONCLUSIONS: Our data provide direct in vivo evidence of marked infiltration of effector leukocytes, a majority of which are CD8 T cells that occurs at the onset of tissue destruction of skin allografts.