Forced and Coerced Sterilization of Indigenous Peoples: Considerations for Health Care Providers.

Forced and coerced sterilization refers to the provision of permanent contraception without true informed consent. In Canada, this topic is particularly relevant to Indigenous Peoples because of this country's history of racialized eugenics programs. In this commentary, we briefly review the history of forced and coerced sterilization in Canada, describe the clinical considerations for health care providers who work with Indigenous patients in this context, and outline calls to action for health care providers and organizations to support the provision of culturally appropriate reproductive health care to Indigenous people.

Retained Shotgun Pellets in the Vulva: Case Report.

BACKGROUND: Vulvar trauma is relatively uncommon and typically occurs in accidental or sports-related injuries. There is limited literature for management of penetrating trauma to the vulva. CASE: A 38-year-old G9, P9 woman presented to the gynaecology service for assessment of vulvar injury after a gunshot wound to the right lateral thigh. She underwent initial stabilization and operative management by the Trauma and Plastic Surgery services for predominantly soft-tissue injuries. Multiple gunshot pellets were found embedded in the right labia majora and medial thigh. On assessment, surgical removal was deemed necessary on the basis of symptoms and potential for functional impairment. CONCLUSION: We present the first reported case on the management of vulvar injury secondary to penetrating trauma. The principles of non-obstetrical vulvar trauma management are discussed.

Selecting contextually appropriate performance indicators in a circumpolar context: a modified Delphi approach.

BACKGROUND: Meaningful performance measurement requires indicators to be scientifically robust and strategically focused. For many circumpolar states, indicators aligned with national strategies may ignore the priorities of northern, remote, or Indigenous populations. The aim of this project was to identify contextually appropriate performance indicators for maternity care in circumpolar regions. METHODS: Fourteen maternity care and health systems experts participated in a modified Delphi consensus process. The list of proposed indicators was derived from a previously published scoping review. Fourteen participants rated each proposed indicator according to importance, circumpolar relevance, validity, and reliability and suggested additional indicators for consideration. RESULTS: Consensus was achieved after two rounds, as measured by a Cronbach's alpha of 0.87. Eleven indicators, many of which represented physical health outcomes, were ranked highly on all four criteria. Twenty-nine additional indicators, largely focused on social determinants of health, health care responsiveness, and accessibility, were identified for further research. Travel for care, cultural safety and upstream structural determinants of health were identified as important themes. CONCLUSIONS: This study identified the important gaps between current performance measurement strategies and the context and values that permeate maternal-child health in circumpolar regions. The indicators identified in this study provide an important foundation for ongoing work. We recommend that future work encompass an appreciation for the intersectoral nature of social, structural, and colonial determinants of maternal-child health in circumpolar regions.

Development of a Night Float Call Model for Obstetrics and Gynaecology Residency: The Process and Residents' Perceptions.

The 2013 pan-Canadian consensus Report on Resident Duty Hours identified that traditional 24-hour duty periods pose risks to the well-being of residents and should be avoided. In anticipation of duty-hour restrictions, the Obstetrics and Gynaecology Residency Program at the University of Toronto developed and implemented a night float (NF) call model over a three-year span. Quarterly resident surveys have consistently shown that the NF system is preferred to traditional 24-hour call and has resulted in reduced fatigue and improved continuity of patient care. Through many iterations, the NF model achieved levels of resident morale, surgical experience, and impact on family relationships that are comparable to the 24-hour call system. We review here our process for developing an NF call model and the perceptions and experiences of residents, with the goal of providing insight for other residency programs that are considering or instituting NF call systems.

Structural and functional analysis of betaine aldehyde dehydrogenase from Staphylococcus aureus.

When exposed to high osmolarity, methicillin-resistant Staphylococcus aureus (MRSA) restores its growth and establishes a new steady state by accumulating the osmoprotectant metabolite betaine. Effective osmoregulation has also been implicated in the acquirement of a profound antibiotic resistance by MRSA. Betaine can be obtained from the bacterial habitat or produced intracellularly from choline via the toxic betaine aldehyde (BA) employing the choline dehydrogenase and betaine aldehyde dehydrogenase (BADH) enzymes. Here, it is shown that the putative betaine aldehyde dehydrogenase SACOL2628 from the early MRSA isolate COL (SaBADH) utilizes betaine aldehyde as the primary substrate and nicotinamide adenine dinucleotide (NAD(+)) as the cofactor. Surface plasmon resonance experiments revealed that the affinity of NAD(+), NADH and BA for SaBADH is affected by temperature, pH and buffer composition. Five crystal structures of the wild type and three structures of the Gly234Ser mutant of SaBADH in the apo and holo forms provide details of the molecular mechanisms of activity and substrate specificity/inhibition of this enzyme.

"We Are All There to Make Sure the Baby Comes Out Healthy":: A Qualitative Study of Doulas' and Licensed Providers' Views on Doula Care.

Policymakers are exploring ways to expand access to doula care to address persistent inequities in maternal and infant health across the United States. Doulas are non-medical professionals who provide physical, emotional, and informational support to birthing people before, during and after childbirth. Growing evidence supports the role of doulas in improved birth outcomes. Delaware is among several states moving towards Medicaid reimbursement for doula care to serve those most at risk. Objective: To gain an in-depth understanding of key stakeholders' knowledge, attitudes, beliefs and experiences regarding doula training and certification, relationships among providers, and other potential needs related to infrastructure to identify areas of agreement and inform policy change in the state of Delaware. Methods: We conducted focus groups with 11 doulas and key-informant interviews with 12 licensed providers practicing in Delaware, including six nurses, four physicians and two certified nurse midwives. Qualitative data was collected via Zoom (video conferencing) between September 2022 and April 2023. Results: Analysis revealed themes related to training, credentials and competencies of doulas, including cultural competence; logistical, administrative, and financial considerations for policy and practice change; and the whole care team-relationships between doulas and medical partners, and opportunities for growth. Conclusions: Doulas and licensed providers agree on key elements of doula training, the value of certification, the need for financial support, and the importance of relationship-building across the care team. Policy implications: Areas of agreement among stakeholders provide a foundation for state leaders to move forward to ensure the delivery of the most accessible, high quality, and culturally competent doula care for birthing people in Delaware.

Evaluation of an Intensive Care Unit Sepsis Alert in Critically Ill Medical Patients.

BACKGROUND: Sepsis alerts commonly used for intensive care unit (ICU) patients can lead to alert fatigue because these patients generally meet 1 or more of the criteria for systemic inflammatory response syndrome. To identify ICU patients at greatest risk for sepsis-related consequences, an ICU-specific sepsis alert was implemented. OBJECTIVE: To evaluate an ICU sepsis alert based on modified criteria for systemic inflammatory response syndrome among critically ill medical patients. METHODS: This retrospective evaluation was conducted at a comprehensive tertiary referral center. Patients included were at least 18 years old, were admitted to the critical care medicine service, and had at least 1 sepsis alert between January 1 and February 29, 2020. The sepsis alert identified patients meeting at least 2 modified systemic inflammatory response syndrome criteria (white blood cell count, <4000/µL or >12 000/µL; body temperature, <36 °C or >38.3 °C; heart rate, >110/min; and respiratory rate, >21/min), with at least 1 of the 2 criteria being white blood cell count or body temperature. RESULTS: For 128 alerts evaluated, the positive predictive value was 72%. Of 713 patients who were admitted to the critical care medicine service and did not have a sepsis alert, 7 received a sepsis diagnosis. The ICU sepsis alert had a negative predictive value of 99%, sensitivity of 92.9%, and specificity of 95.1%. CONCLUSIONS: An ICU sepsis alert using modified systemic inflammatory response syndrome criteria was effective for identifying sepsis in critically ill medical patients.

Indigenous identity identification in administrative health care data globally: A scoping review.

OBJECTIVE: Both Indigenous and non-Indigenous governments and organizations have increasingly called for improved Indigenous health data in order to improve health equity among Indigenous peoples. This scoping review identifies best practices, potential consequences and barriers for advancing Indigenous health data and Indigenous data sovereignty globally. METHODS: A scoping review was conducted to capture the breadth and nature of the academic and grey literature. We searched academic databases for academic records published between 2000 and 2021. We used Google to conduct a review of the grey literature. We applied Harfield's Aboriginal and Torres Strait Islander Quality Appraisal Tool (QAT) to all original research articles included in the review to assess the quality of health information from an Indigenous perspective. RESULTS: In total, 77 academic articles and 49 grey literature records were included. Much of the academic literature was published in the last 12 years, demonstrating a more recent interest in Indigenous health data. Overall, we identified two ways for Indigenous health data to be retrieved. The first approach is health care organizations asking clients to voluntarily self-identify as Indigenous. The other approach is through data linkage. Both approaches to improving Indigenous health data require awareness of the intergenerational consequences of settler colonialism along with a general mistrust in health care systems among Indigenous peoples. This context also presents special considerations for health care systems that wish to engage with Indigenous communities around the intention, purpose, and uses of the identification of Indigenous status in administrative databases and in health care settings. Partnerships with local Indigenous nations should be developed prior to the systematic collection of Indigenous identifiers in health administrative data. The QAT revealed that many research articles do not include adequate information to describe how Indigenous communities and stakeholders have been involved in this research. CONCLUSION: There is consensus within the academic literature that improving Indigenous health should be of high priority for health care systems globally. To address data disparities, governments and health organizations are encouraged to work in collaboration with local Indigenous nations and stakeholders at every step from conceptualization, data collection, analysis, to ownership. This finding highlights the need for future research to provide transparent explanation of how meaningful Indigenous collaboration is achieved in their research.

Perspectives of Indigenous medical students on a postgraduate Indigenous admissions pathway.

Objective: The objective of this study is to assess the perceptions of Indigenous medical students on postgraduate admissions through an Indigenous admissions pathway (IAP), and to determine what factors may influence Indigenous medical students' choice of residency training program. Methods: We distributed a survey to self-identified Indigenous students at settler Canadian medical schools. The survey questioned the students' acceptability of an IAP, and what factors would influence application through an IAP. Analysis included descriptive statistics and thematic analysis of open-ended questions. Results: Thirty-six participants responded to the survey. Location and proximity to family or support system were the most important factors in choosing a residency program. Participants identified mentorship from Indigenous physicians and community involvement as being important features of a residency program that has an IAP. Eighty-one percent of participants felt the availability of an IAP would influence their choice of residency program. Fear of judgement or stigma, concern about entrance requirements, and program logistics were identified as barriers to applying to residency through an IAP. All participants believed that an IAP would have a positive influence on the healthcare system more broadly. Conclusions: An IAP appears to be an acceptable residency application format to Indigenous students but cannot exist in isolation. It is important for programs to consider the needs and safety of Indigenous trainees within residency programs.

Objectif: L'objectif de cette étude était d'avoir le point de vue des étudiants en médecine autochtones sur une éventuelle voie d'admission aux études postdoctorales réservée aux candidats autochtones et de relever les facteurs qui influenceraient leur choix de programme de résidence. Méthodes: Nous avons fait parvenir un questionnaire aux étudiants inscrits dans les facultés de médecine canadiennes qui se définissent comme Autochtones. L'enquête portait sur l'acceptabilité par les étudiants d'un programme d'admission pour candidats autochtones (PACA) et sur les facteurs qui influenceraient leur choix de poser leur candidature dans le cadre d'un PACA. Les données ont été évaluées par des méthodes statistiques descriptives et par une analyse thématique des questions ouvertes. Résultats: Trente-six participants ont répondu à l'enquête. Le lieu et la proximité de la famille ou du réseau de soutien ressortent comme les facteurs les plus importants dans le choix d'un programme de résidence. Les répondants attachent également de l'importance à l'existence d'un mentorat de la part de médecins autochtones et à une participation de la communauté dans le cadre d'un programme de résidence doté d'un PACA. Quatre-vingt-un pour cent des participants ont estimé que l'existence d'un PACA influencerait leur choix de programme de résidence. La crainte d'être jugé ou stigmatisé, et une inquiétude par rapport aux conditions d'admission et la logistique du programme ont été identifiées comme des obstacles à la présentation d'une demande de résidence dans le cadre d'un PACA. Les participants sont unanimes quant à l'influence positive d'un tel programme sur le système de soins de santé en général. Conclusions: Les étudiants autochtones trouvent la formule d'une voie d'admission à la résidence réservée aux candidats autochtones acceptable, à condition qu'elle ne soit pas un élément isolé et qu'on tienne compte des besoins et de la sécurité des étudiants dans le cadre des programmes de résidence eux-mêmes.

Improving Initial Sepsis Management Through a Nurse-Driven Rapid Response Team Protocol.

BACKGROUND: Rapid identification and timely management of sepsis improve survival. Therefore, a bundled approach to care is recommended. LOCAL PROBLEM: In an acute care area of the study institution, a 2016 internal evaluation of 27 patients with sepsis showed a median time to first-dose antibiotic administration of 269 minutes, with no patients receiving antibiotics within the 60-minute target time. Additionally, only one-third of patients received appropriate fluid resuscitation (30-mL/kg bolus of intravenous crystalloids). Given poor bundle compliance, a nurse-driven rapid response team protocol for suspected sepsis was implemented. The purpose of this project was to assess the protocol's impact on the timeliness of treatment for sepsis. METHODS: This retrospective quality improvement evaluation involved patients aged 18 years or older for whom the suspected sepsis protocol was initiated during their acute care area admission. The evaluation focused on improvements in time to intravenous antibiotic administration and volume of fluid resuscitation compared with before protocol implementation. The protocol empowers the rapid response team to initiate sepsis management and includes pertinent laboratory tests, blood cultures, intravenous broad-spectrum antibiotic administration, and a crystalloid bolus (30 mL/kg) if indicated. RESULTS: A total of 32 patients were evaluated. Time to first-dose antibiotic administration was reduced by half (from 269 to 135 minutes). Eighteen patients met criteria for fluid resuscitation, with twice as many receiving appropriate fluid volumes compared with before protocol implementation. CONCLUSION: Implementation of the suspected sepsis protocol demonstrates the substantial role nurses have in optimizing patient care, especially in the timely treatment of sepsis.

Establishing an alternative accommodation for stable hospitalised antepartum patients: barriers and challenges.

BACKGROUND: Patients in remote communities who risk premature delivery require transfer to a tertiary care centre for obstetric and neonatal care. Following stabilisation, many patients are candidates for outpatient management but cannot be discharged to their home communities due to lack of neonatal intensive care unit (ICU) support. PROBLEM: Without outpatient accommodation proximal to neonatal ICU, these patients face prolonged hospitalisation-an expensive option with medical, social and psychological consequences. Therefore, we sought to establish an alternative accommodation for out-of-town stable antepartum patients. METHODS: Quality Improvement approaches were used to identify process strengths and opportunities for improvement on the antepartum ward in a tertiary care centre. Physician and patient surveys informed outpatient accommodation programme development by a multidisciplinary team. The intervention was implemented using a plan-do-study-act cycle. Barriers to patient discharge and enrolment in the programme were analysed by completing thematic and strengths-weaknesses-opportunities-threats (SWOT) analysis. RESULTS: Physicians broadly supported safe outpatient management, whereas patients were hesitant to leave the hospital even when physicians assured safety. Our alternative accommodation was pre-existing and cost-effective, however, we encountered significant barriers. The physical space limited family visits and social interaction, lacked desired amenities,and the programme proved inconvenient to patients. The thematic and SWOT analysis identified aspects of the intervention which can be optimised to develop future actionable strategies. CONCLUSION: The utilisation of acute care beds is costly for the healthcare system and must be allocated judiciously. Patient needs, experience and health system barriers need to be considered when establishing alternative outpatient accommodations and strategies for stable antepartum patients.

Survey of the 2009 commercial optical biosensor literature.

We took a different approach to reviewing the commercial biosensor literature this year by inviting 22 biosensor users to serve as a review committee. They set the criteria for what to expect in a publication and ultimately decided to use a pass/fail system for selecting which papers to include in this year's reference list. Of the 1514 publications in 2009 that reported using commercially available optical biosensor technology, only 20% passed their cutoff. The most common criticism the reviewers had with the literature was that "the biosensor experiments could have been done better." They selected 10 papers to highlight good experimental technique, data presentation, and unique applications of the technology. This communal review process was educational for everyone involved and one we will not soon forget.

Biacore analysis with stabilized G-protein-coupled receptors.

Using stabilized forms of ß1 adrenergic and A2(A) adenosine G-protein-coupled receptors, we applied Biacore to monitor receptor activity and characterize binding constants of small-molecule antagonists spanning more than 20,000-fold in affinity. We also illustrate an improved method for tethering His-tagged receptors on NTA (carboxymethylated dextran preimmobilized with nitrilotriacetic acid) chips to yield stable, high-capacity, high-activity surfaces as well as a novel approach to regenerate receptor binding sites. Based on our success with this approach, we expect that the combination of stabilized receptors with biosensor technology will become a common method for characterizing members of this receptor family.

Safety of a Nurse-Driven Standardized Potassium Replacement Protocol in Critically Ill Patients With Renal Insufficiency.

BACKGROUND: In critically ill patients, maintaining appropriate serum potassium concentrations requires careful supplementation to correct hypokalemia but avoid hyperkalemia. At the study institution, an institution-based, nurse-driven standardized electrolyte replacement protocol is used in critically ill patients with a serum creatinine concentration of 2 mg/dL or less. If the serum creatinine concentration is greater than 2 mg/dL, electrolyte replacement requires a physician order. OBJECTIVE: To determine if standardized potassium supplementation is safe in critically ill patients with renal insufficiency not requiring renal replacement therapy. METHODS: This study was an institutional review board-approved, single-center, retrospective evaluation of critically ill patients receiving intravenous potassium replacement per protocol. Patients were grouped according to serum creatinine concentration (≤ 2 mg/dL or > 2 mg/dL) at the time of replacement. The primary outcome was the incidence of hyperkalemia (potassium concentration ≥ 5 mEq/L) following potassium replacement. Secondary outcomes were the incidence of hyperkalemia, change in serum potassium concentration, and need for hyperkalemia treatment. Outcomes were analyzed using χ2 and t tests. RESULTS: Of 814 patients screened, 145 were included (99 with serum creatinine ≤ 2 mg/dL and 46 with serum creatinine > 2 mg/dL). The incidence of hyperkalemia was not different between groups (P = .57). Five patients experienced hyperkalemia; none received hyperkalemia treatment. Change in serum potassium was similar for patients in the 2 groups (P = .33). CONCLUSIONS: A standardized, nurse-driven electrolyte replacement protocol can be used safely in critically ill patients with renal insufficiency not requiring renal replacement therapy.

Manual vs Automatic Prone Positioning and Patient Outcomes in Acute Respiratory Distress Syndrome.

BACKGROUND: Prone positioning is a standard treatment for moderate to severe acute respiratory distress syndrome (ARDS), but the outcomes associated with manual versus automatic prone positioning have not been evaluated. OBJECTIVE: To retrospectively evaluate outcomes associated with manual versus automatic prone positioning as part of a pronation quality improvement project implemented by a multidisciplinary team. METHODS: A retrospective, descriptive-comparative approach was used to analyze data from 24 months of a prone positioning protocol for ARDS. The study involved 37 patients, with 16 undergoing manual and 21 undergoing automatic prone positioning. Descriptive and nonparametric statistical analyses were used to evaluate outcomes associated with manual versus automatic prone positioning. RESULTS: Outcomes were similar between the 2 groups regarding time to initiation of prone positioning, discharge disposition, and length of stay. Manually pronated patients were less likely to experience interruptions in therapy (P = .005) and complications (P = .002). Pressure injuries were the most common type of complication, with the most frequent locations in automatically pronated patients being the head (P = .045), thorax (P = .003), and lower extremities (P = .047). Manual prone positioning resulted in a cost avoidance of $78 617 per patient. CONCLUSION: Manual prone positioning has outcomes similar to those of automatic prone positioning with less risk of interruptions in therapy, fewer complications, and lower expense. Further research is needed to determine whether manual prone positioning is superior to automatic prone positioning in patients with ARDS.

Multiple cellular proteins modulate the dynamics of K-ras association with the plasma membrane.

Although specific proteins have been identified that regulate the membrane association and facilitate intracellular transport of prenylated Rho- and Rab-family proteins, it is not known whether cellular proteins fulfill similar roles for other prenylated species, such as Ras-family proteins. We used a previously described method to evaluate how several cellular proteins, previously identified as potential binding partners (but not effectors) of K-ras4B, influence the dynamics of K-ras association with the plasma membrane. Overexpression of either PDEδ or PRA1 enhances, whereas knockdown of either protein reduces, the rate of dissociation of K-ras from the plasma membrane. Inhibition of calmodulin likewise reduces the rate of K-ras dissociation from the plasma membrane, in this case in a manner specific for the activated form of K-ras. By contrast, galectin-3 specifically reduces the rate of plasma membrane dissociation of activated K-ras, an effect that is blocked by the K-ras antagonist farnesylthiosalicylic acid (salirasib). Multiple cellular proteins thus control the dynamics of membrane association and intercompartmental movement of K-ras to an important degree even under basal cellular conditions.

Grading the commercial optical biosensor literature-Class of 2008: 'The Mighty Binders'.

Optical biosensor technology continues to be the method of choice for label-free, real-time interaction analysis. But when it comes to improving the quality of the biosensor literature, education should be fundamental. Of the 1413 articles published in 2008, less than 30% would pass the requirements for high-school chemistry. To teach by example, we spotlight 10 papers that illustrate how to implement the technology properly. Then we grade every paper published in 2008 on a scale from A to F and outline what features make a biosensor article fabulous, middling or abysmal. To help improve the quality of published data, we focus on a few experimental, analysis and presentation mistakes that are alarmingly common. With the literature as a guide, we want to ensure that no user is left behind.

Kinetic analysis and fragment screening with Fujifilm AP-3000.

We evaluated the performance of Fujifilm's new AP-3000 surface plasmon resonance biosensor for kinetic analysis and fragment screening. Using carbonic anhydrase II as a model system, we characterized a set of 10 sulfonamide-based inhibitors that range in molecular mass from 98 to 341Da and approximately 10,000-fold in affinity (0.4mM to 20nM). Although the data collected from the AP-3000 were generally similar to those collected using a Biacore T100, the AP-3000's stop-flow analyte delivery system complicated the shapes of the association- and dissociation-phase binding responses. We illustrate how reasonable estimates of the kinetic rate constants can be extracted from AP-3000 data by limiting data analysis to only the regions of the responses collected during flow conditions. We also provide an example of the results obtained for a fragment-screening study with the AP-3000, which is the ideal application of this technology.

Biosensor-based fragment screening using FastStep injections.

We have developed a novel analyte injection method for the SensíQ Pioneer surface plasmon resonance-based biosensor referred to as "FastStep." By merging buffer and sample streams immediately prior to the reaction flow cells, the instrument is capable of automatically generating a two- or threefold dilution series (of seven or five concentrations, respectively) from a single analyte sample. Using sucrose injections, we demonstrate that the production of each concentration within the step gradient is highly reproducible. For kinetic studies, we developed analysis software that utilizes the sucrose responses to automatically define the concentration of analyte at any point during the association phase. To validate this new approach, we compared the results of standard and FastStep injections for ADP binding to a target kinase and a panel of compounds binding to carbonic anhydrase II. Finally, we illustrate how FastStep can be used in a primary screening mode to obtain a full concentration series of each compound in a fragment library.

Detergent screening of a G-protein-coupled receptor using serial and array biosensor technologies.

We describe the benefits and limitations of two biosensor approaches for screening solubilization conditions for G-protein-coupled receptors (GPCRs). Assays designed for a serial processing instrument (Biacore 2000/3000/T100) and an array platform (Biacore Flexchip) were used to examine how effectively 96 different detergents solubilized the chemokine receptor CCR5 while maintaining its binding activity for a conformationally sensitive Fab (2D7). Using the serial processing instrument, we were able to analyze three samples in each 30-min binding cycle, thereby requiring approximately 24h to screen an entire 96-well plate of conditions. In-line capturing allowed us to normalize the 2D7 binding responses for different receptor capture levels. In contrast, with the array system, we could characterize the effects of all 96 detergents simultaneously, completing the assay in less than 1h. But the current array technology requires that we capture the GPCR preparations off-line, making it more challenging to normalize for receptor capture levels. Also, the array platform is less sensitive than the serial platforms, thereby limiting the size of the analyte to larger molecules (>5000Da). Overall, the two approaches proved to be highly complementary; both assays identified identical detergents that produced active solubilized CCR5 as well as those detergents that either were ineffective solubilizers or inactivated the receptor.