Intra- and post-pandemic impact of the COVID-19 outbreak on Stanford Health Care.

Stanford Health Care, which provides about 7% of overall healthcare to approximately 9 million people in the San Francisco Bay Area, has undergone significant changes due to the opening of a second hospital in late 2019 and, more importantly, the COVID-19 pandemic. We examine the impact of these events on anatomic pathology (AP) cases, aiming to enhance operational efficiency in response to evolving healthcare demands. We extracted historical census, admission, lab tests, operation, and AP data since 2015. An approximately 45% increase in the volume of laboratory tests (P < 0.0001) and a 17% increase in AP cases (P < 0.0001) occurred post-pandemic. These increases were associated with progressively increasing (P < 0.0001) hospital census. Census increase stemmed from higher admission through the emergency department (ED), and longer lengths of stay mostly for transfer patients, likely due to the greater capability of the new ED and changes in regional and local practice patterns post-pandemic. Higher census led to overcapacity, which has an inverted U relationship that peaked at 103% capacity for AP cases and 114% capacity for laboratory tests. Overcapacity led to a lower capability to perform clinical activities, particularly those related to surgical procedures. We conclude by suggesting parameters for optimal operations in the post-pandemic era.

Rehabilitation following extra-articular proximal phalangeal fractures of the fingers in adults: a scoping review.

Introduction: Proximal phalangeal fractures are common and can have a significant impact on hand function. Therefore, it is important to optimise post-operative rehabilitation. A scoping review was undertaken to map the existing evidence on rehabilitation of proximal phalangeal fractures of the fingers in adults. Methods: A comprehensive search was conducted which included database searching, reference searching, hand searching of journals, and searching for grey literature. Eight articles were included after screening for eligibility. Results: Three studies researched surgical interventions and five studies conservative management. The immobilisation period varied between 5 days to 3 weeks in the surgical studies, and between 3 to 7 weeks in the conservative studies. Active exercise therapy was started immediately with conservative management, while in the surgical studies time to commence exercises varied between 5 days and 3 weeks. All studies reported good results in mobility with a mean total active motion ranging from 240° to 258.9°. Patients reported little pain at final follow-up and grip strength recovered to 96% compared to the unaffected side. Studies reporting on function and patient satisfaction lacked transparency. Conclusions: All studies had a moderate to high risk of bias and the results of the included studies should therefore be interpreted with caution. More high-quality randomised controlled studies with an a priori research protocol and a standard set of outcome measures are necessary to research whether early motion, an intrinsic plus splint leaving the wrist free, and the inclusion of additional treatment modalities can result in a better and/or faster recovery.

A Systematic Review of the 2016 National Academy of Engineering Exemplary Ethics Programs: Revisions to a Coding Framework.

Engineering ethics is a required aspect of accredited ABET programs, but there is widespread variation in how ethics is taught, to what ends, and how those ends are assessed. This variation makes it challenging to identify practices for teaching ethics to engineers aligned with extant practices in the field. In this study, we revise a recent coding framework by reviewing exemplary engineering ethics programs recognized by the National Academy of Engineering in 2016, or what we refer to as "exemplars." We pursue two primary objectives: (1) To apply and revise a prior coding framework to codify ethics learning objectives, instructional strategies, and assessment strategies in engineering education; and (2) To use the revised coding framework to identify trends in learning objectives, instructional strategies, and assessment strategies of NAE exemplars. We employ systemic review procedures to update the coding framework using 24 of 25 exemplars as a data source. The updated framework includes four primary categories associated with learning objectives, instructional strategies, assessment data collection strategies, and assessment design characteristics. Results indicate that ethical sensitivity or awareness was present in every exemplar as a learning objective, often alongside ethical reasoning-based learning objectives and the formation of professional skills. Exemplars employed numerous instructional strategies in tandem, as we coded eight out of 18 instructional strategies among at least half of the exemplars. Assignments/homework and summative reflections were the most oft-used sources of assessment data. Due to our challenges in coding assessment approaches, we offer practical suggestions for assessing engineering ethics instruction which are based on many of our coding discussions. We hope that this coding framework, the results classifying exemplary features of the NAE programs, and our practical suggestions can guide future instructors as they design, classify, assess, and report their approaches to engineering ethics education.

Dengue Outbreak Response during COVID-19 Pandemic, Key Largo, Florida, USA, 2020.

We report a dengue outbreak in Key Largo, Florida, USA, from February through August 2020, during the COVID-19 pandemic. Successful community engagement resulted in 61% of case-patients self-reporting. We also describe COVID-19 pandemic effects on the dengue outbreak investigation and the need to increase clinician awareness of dengue testing recommendations.

Rapid Deployment of Whole Slide Imaging for Primary Diagnosis in Surgical Pathology at Stanford Medicine: Responding to Challenges of the COVID-19 Pandemic.

CONTEXT.­: Stanford Pathology began stepwise subspecialty implementation of whole slide imaging (WSI) in 2018 soon after the first US Food and Drug Administration approval. In 2020, during the COVID-19 pandemic, the Centers for Medicare & Medicaid Services waived the requirement for pathologists to perform diagnostic tests in Clinical Laboratory Improvement Amendments (CLIA)-licensed facilities. This encouraged rapid implementation of WSI across all surgical pathology subspecialties. OBJECTIVE.­: To present our experience with validation and implementation of WSI at a large academic medical center encompassing a caseload of more than 50 000 cases per year. DESIGN.­: Validation was performed independently for 3 subspecialty services with a diagnostic concordance threshold above 95%. Analysis of user experience, staffing, infrastructure, and information technology was performed after department-wide expansion. RESULTS.­: Diagnostic concordance was achieved in 96% of neuropathology cases, 100% of gynecologic pathology cases, and 98% of immunohistochemistry cases. After full implementation, 8 high-capacity scanners were operational, with whole slide images generated on greater than 2000 slides per weekday, accounting for approximately 80% of histologic slides at Stanford Medicine. Multiple modifications in workflow and information technology were needed to improve performance. Within months of full implementation, most attending pathologists and trainees had adopted WSI for primary diagnosis. CONCLUSIONS.­: WSI across all surgical subspecialities is achievable at scale at an academic medical center; however, adoption required flexibility to adjust workflows and develop tailored solutions. WSI at scale supported the health and safety of medical staff while facilitating high-quality patient care and education during COVID-19 restrictions.

Community Assessment for Mental and Physical Health Effects After Hurricane Irma - Florida Keys, May 2019.

Disasters can adversely affect population health, resulting in increased need for health services. Hurricane Irma made landfall in the Florida Keys (Monroe County) as a Category 4 hurricane on September 10, 2017. The hurricane caused substantial damage to 65% of homes and resulted in 40 persons injured and 17 deaths from hurricane-related causes.* During 2018, the county suicide rate increased to 34.9 per 100,000 population from the 5-year (2013-2017) average of 25.2 per 100,000 population (1). In May 2019, 20 months after the hurricane, the Florida Department of Health (FDOH) conducted a modified Community Assessment for Public Health Emergency Response (CASPER) to assess the community's mental, physical, and economic health and develop public health interventions to decrease the suicide rate. A consenting adult member from 231 households was interviewed, and a weighted cluster analysis was conducted to estimate the number and percentage of households throughout the Florida Keys with a particular response, as well as the number and percentage of persons at risk for suicide. During the 20 months since Hurricane Irma, 17% of households reported a need for a mental health care provider; 37.9% of these did not receive those services. A modified CASPER was used to calculate population estimates of suicide risk in an area of high landfall for hurricanes; estimated population suicide risk was 7.3%. Respondents reported worsening of respiratory conditions (17.7%), anxiety (17.0%), and depression (11.3%). Emergency preparedness plans should consider strengthening mental health service delivery after a hurricane, particularly during the long-term recovery phase.

Building an electronic health record integrated quality of life outcomes registry for spine surgery.

OBJECTIVE: Demonstrating the value of spine care requires adequate outcomes assessment. Long-term outcomes are best measured as overall improvement in quality of life (QOL) after surgical intervention. Present registries often require parallel data entry, introducing inefficiencies and limiting compliance. The authors detail the methodology of constructing an integrated electronic health record (EHR) system to collect QOL metrics and demonstrate the effect of data collection on routine clinical workflow. A streamlined approach to collecting QOL data can capture patient data without requiring dual data entry and without increasing clinic visit times. METHODS: Through extensive literature review, a combination of QOL assessments was selected, consisting of the Patient Health Questionnaire-2 and -9, Oswestry Disability Index, Neck Disability Index, and visual analog scale for pain. These metrics were used to provide assessment of QOL following spine surgery and were incorporated into standard clinic workflow by a multidisciplinary team of surgeons, advanced practice providers, and health care information technology specialists. A clinical dashboard tracking more than 25 patient variables was developed. Clinic flow was assessed and opportunities for improvement reviewed. Duration of clinic visits before and after initiation of QOL measure capture was recorded, with assessment of mean clinic visit times for the 12 months before and the 12 months after implementation. RESULTS: The integrated QOL capture was instituted for 3 spine surgeons in a tertiary care academic center. In the 12-month period prior to initiating collection of QOL data, 806 new patient visits were completed with an average visit time of 127.9 ± 51.5 minutes. In the 12 months after implementation, 1013 new patient visits were recorded, with 791 providing QOL measures with an average visit time of 117.0 ± 45.7 minutes. Initially the primary means of collecting patient outcome data was via paper form, with gradual transition to collection via entry into the electronic medical records system. To improve electronic data capture, paper forms were eliminated and an online portal used as part of the patient rooming process. This improved electronic capture to nearly 98% without decreasing the number of patients enrolled in the process. CONCLUSIONS: A systematic approach to collecting spine-related QOL data within an EHR system is feasible and offers distinct advantages over registries that require dual data entry. The process of data collection does not impact patients' clinical visit or providers' clinical workflow. This approach is scalable, and may form the foundation for a decentralized outcomes registry network.

Supplementation of diet with krill oil protects against experimental rheumatoid arthritis.

BACKGROUND: Although the efficacy of standard fish oil has been the subject of research in arthritis, the effect of krill oil in this disease has yet to be investigated. The objective of the present study was to evaluate a standardised preparation of krill oil and fish oil in an animal model for arthritis. METHODS: Collagen-induced arthritis susceptible DBA/1 mice were provided ad libitum access to a control diet or diets supplemented with either krill oil or fish oil throughout the study. There were 14 mice in each of the 3 treatment groups. The level of EPA + DHA was 0.44 g/100 g in the krill oil diet and 0.47 g/100 g in the fish oil diet. Severity of arthritis was determined using a clinical scoring system. Arthritis joints were analysed by histopathology and graded. Serum samples were obtained at the end of the study and the levels of IL-1alpha, IL-1beta, IL-7, IL-10, IL-12p70, IL-13, IL-15, IL-17 and TGF-beta were determined by a Luminex assay system. RESULTS: Consumption of krill oil and supplemented diet significantly reduced the arthritis scores and hind paw swelling when compared to a control diet not supplemented with EPA and DHA. However, the arthritis score during the late phase of the study was only significantly reduced after krill oil administration. Furthermore, mice fed the krill oil diet demonstrated lower infiltration of inflammatory cells into the joint and synovial layer hyperplasia, when compared to control. Inclusion of fish oil and krill oil in the diets led to a significant reduction in hyperplasia and total histology score. Krill oil did not modulate the levels of serum cytokines whereas consumption of fish oil increased the levels of IL-1alpha and IL-13. CONCLUSIONS: The study suggests that krill oil may be a useful intervention strategy against the clinical and histopathological signs of inflammatory arthritis.

Regulation of gene expression in Streptococcus pneumoniae by response regulator 09 is strain dependent.

Recent murine studies have demonstrated that the role of response regulator 09 (RR09) of Streptococcus pneumoniae in virulence is different in different strains. In the present study, we used a murine pneumonia model of infection to assess the virulence of a TIGR4 rr09 mutant, and we found that TIGR4Deltarr09 was attenuated after intranasal infection. Furthermore, we investigated the in vitro transcriptional changes in pneumococcal rr09 mutants of two strains, D39 and TIGR4, by microarray analysis. The transcriptional profiles of the rr09 mutants of both strains had clear differences compared to the profiles of the parental wild-type strains. In D39Deltarr09, but not in TIGR4Deltarr09, genes involved in competence (e.g., comAB) were upregulated. In TIGR4, genes located on the rlrA pathogenicity islet, which are not present in the D39 genome, appeared to be regulated by RR09. Furthermore, several phosphotransferase systems (PTSs) believed to be involved in sugar uptake (e.g., the PTS encoded by sp0060 to sp0066) were strongly downregulated in D39Deltarr09, while they were not regulated by RR09 in TIGR4. To examine the role of one of these PTSs in virulence, D39Deltasp0063 was constructed and tested in a murine infection model. No difference between the virulence of this strain and the virulence of the wild type was found, indicating that downregulation of the sp0063 gene alone is not the cause of the avirulent phenotype of D39Deltarr09. Finally, expression of rr09 and expression of three of our identified RR09 targets during infection in mice were assessed. This in vivo experiment confirmed that there were differences between expression in wild-type strain TIGR4 and expression in the rr09 mutant, as well as differences between expression in wild-type strain D39 and expression in wild-type strain TIGR4. In conclusion, our results indicate that there is strain-specific regulation of pneumococcal gene expression by RR09.

Reflections on the constraints and opportunities in therapy in Rett syndrome.

More than 20 years of clinical and research experience with affected people in the British Isles has provided insight into particular challenges for therapists, educators, or parents wishing to facilitate learning and to support the development of skills in people with Rett syndrome. This paper considers the challenges in two groups: those due to constraints imposed by the disabilities associated with the disorder and those stemming from the opportunities, often masked by the disorder, allowing the development of skills that depend on less-affected areas of the brain. Because the disorder interferes with the synaptic links between neurones, the functions of the brain that are most dependent on complex neural networks are the most profoundly affected. These functions include speech, memory, learning, generation of ideas, and the planning of fine movements, especially those of the hands. In contrast, spontaneous emotional and hormonal responses appear relatively intact. Whereas failure to appreciate the physical limitations of the disease leads to frustration for therapist and client alike, a clear understanding of the better-preserved areas of competence offers avenues for real progress in learning, the building of satisfying relationships, and achievement of a quality of life.

The contribution of PspC to pneumococcal virulence varies between strains and is accomplished by both complement evasion and complement-independent mechanisms.

Pneumococcal surface protein C (PspC) is a virulence factor of Streptococcus pneumoniae previously shown to play a role in bacterial adherence, invasion, and evasion of complement. We investigated the role of this protein in our murine models of pneumococcal pneumonia with different pneumococcal strains. The deletion of pspC in strains of serotypes 2, 3, and 19F did not significantly alter host survival times in the pneumonia model. In contrast, pspC deletion significantly reduced the virulence of the serotype 4 strain, TIGR4, in both the pneumonia and bacteremia models. Therefore, pspC is a systemic and pulmonary virulence determinant for S. pneumoniae, but its effects are influenced by the pneumococcal strain. Finally, pneumonia infection of complement-deficient (C3(-/-)) mice enhanced pspC virulence, illustrating that PspC-mediated complement evasion contributes to virulence. However, other functions of PspC also contribute to virulence, as demonstrated by the finding that the pspC-deficient TIGR4 mutant was still attenuated relative to the wild-type parent, even in the absence of C3.

Increased skewing of X chromosome inactivation in Rett syndrome patients and their mothers.

Rett syndrome is a largely sporadic, X-linked neurological disorder with a characteristic phenotype, but which exhibits substantial phenotypic variability. This variability has been partly attributed to an effect of X chromosome inactivation (XCI). There have been conflicting reports regarding incidence of skewed X inactivation in Rett syndrome. In rare familial cases of Rett syndrome, favourably skewed X inactivation has been found in phenotypically normal carrier mothers. We have investigated the X inactivation pattern in DNA from blood and buccal cells of sporadic Rett patients (n=96) and their mothers (n=84). The mean degree of skewing in blood was higher in patients (70.7%) than controls (64.9%). Unexpectedly, the mothers of these patients also had a higher mean degree of skewing in blood (70.8%) than controls. In accordance with these findings, the frequency of skewed (XCI > or =80%) X inactivation in blood was also higher in both patients (25%) and mothers (30%) than in controls (11%). To test whether the Rett patients with skewed X inactivation were daughters of skewed mothers, 49 mother-daughter pairs were analysed. Of 14 patients with skewed X inactivation, only three had a mother with skewed X inactivation. Among patients, mildly affected cases were shown to be more skewed than more severely affected cases, and there was a trend towards preferential inactivation of the paternally inherited X chromosome in skewed cases. These findings, particularly the greater degree of X inactivation skewing in Rett syndrome patients, are of potential significance in the analysis of genotype-phenotype correlations in Rett syndrome.

NTNG1 mutations are a rare cause of Rett syndrome.

A translocation that disrupted the netrin G1 gene (NTNG1) was recently reported in a patient with the early seizure variant of Rett syndrome (RTT). The netrin G1 protein (NTNG1) has an important role in the developing central nervous system, particularly in axonal guidance, signalling and NMDA receptor function and was a good candidate gene for RTT. We recruited 115 patients with RTT (females: 25 classic and 84 atypical; 6 males) but no mutation in the MECP2 gene. For those 52 patients with epileptic seizure onset in the first 6 months of life, CDKL5 mutations were also excluded. We aimed to determine whether mutations in NTNG1 accounted for a significant subset of patients with RTT, particularly those with the early onset seizure variant and other atypical presentations. We sequenced the nine coding exons of NTNG1 and identified four sequence variants, none of which were likely to be pathogenic. Mutations in the NTNG1 gene appear to be a rare cause of RTT but NTNG1 function demands further investigation in relation to the central nervous system pathophysiology of the disorder.

Identification of invasive serotype 1 pneumococcal isolates that express nonhemolytic pneumolysin.

Recently, there has been an increase in invasive pneumococcal disease (IPD) caused by serotype 1 Streptococcus pneumoniae throughout Europe. Serotype 1 IPD is associated with bacteremia and pneumonia in Europe and North America, especially in neonates, and is ranked among the top five most prevalent pneumococcal serotypes in at least 10 countries. The currently licensed pediatric pneumococcal vaccine does not afford protection to this serotype. Upon screening of 252 clinical isolates of S. pneumoniae, we discovered mutations in the pneumolysin gene of two out of the four serotype 1 strains present in the study group. Analysis of an additional 28 serotype 1 isolates from patients with IPD from various Scottish Health Boards, revealed that >50% had mutations in their pneumolysin genes. This resulted in the expression of nonhemolytic forms of pneumolysin. All of the strains producing nonhemolytic pneumolysin were sequence type 306 (ST306), whereas those producing "wild-type" pneumolysin were ST227. The mutations were in a region of pneumolysin involved in pore formation. These mutations can be made in vitro to give the nonhemolytic phenotype. Pneumolysin is generally conserved throughout all serotypes of S. pneumoniae and is essential for full invasive disease; however, it appears that serotype 1 ST306 does not require hemolytically active pneumolysin to cause IPD.

Construction and immunological characterization of a novel nontoxic protective pneumolysin mutant for use in future pneumococcal vaccines.

Pneumolysin, the pore-forming toxin produced by Streptococcus pneumoniae, may have an application as an immunogenic carrier protein in future pneumococcal conjugate vaccines. Most of the 90 S. pneumoniae serotypes identified produce pneumolysin; therefore, this protein may confer non-serotype-specific protection against pneumococcal infections such as pneumonia, meningitis, and otitis media. However, as pneumolysin is highly toxic, a nontoxic form of pneumolysin would be a more desirable starting point in terms of vaccine production. Previous pneumolysin mutants have reduced activity but retain residual toxicity. We have found a single amino acid deletion that blocks pore formation, resulting in a form of pneumolysin that is unable to form large oligomeric ring structures. This mutant is nontoxic at concentrations greater than 1,000 times that of the native toxin. We have demonstrated that this mutant is as immunogenic as native pneumolysin without the associated effects such as production of the inflammatory mediators interleukin-6 and cytokine-induced neutrophil chemoattractant KC, damage to lung integrity, and hypothermia in mice. Vaccination with this mutant protects mice from challenge with S. pneumoniae. Incorporation of this mutant pneumolysin into current pneumococcal vaccines may increase their efficacy.

Predictive value of the early clinical signs in Rett disorder.

The British Isles Survey for Rett has registered 1,159 cases over up to 20 years. Indicators of health and severity, recorded at intervals throughout life, are drawn from clinical examinations, reports and postal questionnaires. This study aimed to establish the stability and predictive value of an early severity score based on muscle tone, locomotor ability, feeding difficulty, scoliosis and epilepsy. Data from people with clinically documented classic or non-classic Rett and health records over 20-30 years indicate that severity scores tend to increase throughout the first 15 years and then to stabilise in mild and severe, classic and non-classic Rett. Severity scores before regression reflect later severity scores within relatively wide inter-quartile ranges. In general, the adult severity level is around 40 points above the pre-regression level for classic Rett and around 20 points for non-classic Rett. High early severity scores are associated with reduced cumulative survival. Used with caution, early signs are helpful in diagnosis and prognosis. The mutations T158M, R255X and R168X are generally associated with more severe and R306C and R133C with less severe disease but exceptions make these unreliable predictors of outcome.

Abnormal general movements in girls with Rett disorder: the first four months of life.

An apparently normal early development was one of the initial criteria for classical Rett syndrome. However, several investigators considered Rett syndrome to be a developmental disorder manifesting very soon after birth. Videos of 14 infants with Rett disorder were carefully assessed for their spontaneous movements, in particular general movements (GMs), during the first 4 months of life. A detailed analysis clearly demonstrated that none of the infants had normal GMs. However, a specific abnormal GM pattern could not be detected for Rett disorder. The abnormal GMs described here, and their individual developmental trajectories are different from the abnormal GMs described in infants with acquired brain lesion. Our study is the first to apply specific standardised measures of early spontaneous movements to infants with Rett syndrome, proving conclusively that the disorder is manifest within the first weeks of life.