Closing the Loop: The Value of Outcome Letters for Prehospital Pediatric Care.

OBJECTIVES: Providing emergency care to acutely ill or injured children is stressful and requires a high level of training. Paramedics who provide prehospital care are typically not involved in the circle of care and do not receive patient outcome information. The aim of this quality improvement project was to assess paramedics' perceptions of standardized outcome letters pertaining to acute pediatric patients that they had treated and transported to an emergency department. METHODS: Between December 2019 and December 2020, 888 outcome letters were distributed to paramedics who provided care for 370 acute pediatric patients transported to the Children's Hospital of Eastern Ontario in Ottawa, Canada. All paramedics who received a letter (n = 470) were invited to participate in a survey that collected their perceptions and feedback about the letters, as well as their demographic information. RESULTS: The response rate was 37% (172/470). Approximately half of the respondents were Primary Care Paramedics and half Advanced Care Paramedics. The respondents' median age was 36 years, median years of service was 12 years, and 64% identified as male. Most agreed that the outcome letters contained information pertinent to their practice (91%), allowed them to reflect on care they had provided (87%), and confirmed clinical suspicions (93%). Respondents indicated that they found the letters useful for 3 reasons: 1) increases capacity to link differential diagnoses, prehospital care, or patient outcomes; 2) contributes to a culture of continuous learning and improvement; and 3) gives closure, reduces stress, or provides answers for difficult cases. Suggestions for improvement included providing more information, provision of letters on all patients transported, faster turnaround time between call and receipt of letter and inclusion of recommendations or interventions/assessments. CONCLUSIONS: Paramedics appreciated receiving hospital-based patient outcome information after their provision of care and reported that the letters offered opportunities for closure, reflection, and learning.

2023 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces.

The International Liaison Committee on Resuscitation engages in a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation and first aid science. Draft Consensus on Science With Treatment Recommendations are posted online throughout the year, and this annual summary provides more concise versions of the final Consensus on Science With Treatment Recommendations from all task forces for the year. Topics addressed by systematic reviews this year include resuscitation of cardiac arrest from drowning, extracorporeal cardiopulmonary resuscitation for adults and children, calcium during cardiac arrest, double sequential defibrillation, neuroprognostication after cardiac arrest for adults and children, maintaining normal temperature after preterm birth, heart rate monitoring methods for diagnostics in neonates, detection of exhaled carbon dioxide in neonates, family presence during resuscitation of adults, and a stepwise approach to resuscitation skills training. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research. Additional topics are addressed with scoping reviews and evidence updates.

Clinical Practice Guideline Recommendations in Pediatric Mild Traumatic Brain Injury: A Systematic Review.

STUDY OBJECTIVE: Our primary objectives were to identify clinical practice guideline recommendations for children with acute mild traumatic brain injury (mTBI) presenting to an emergency department (ED), appraise their overall quality, and synthesize the quality of evidence and the strength of included recommendations. METHODS: We searched MEDLINE, EMBASE, Cochrane Central, Web of Science, and medical association websites from January 2012 to May 2023 for clinical practice guidelines with at least 1 recommendation targeting pediatric mTBI populations presenting to the ED within 48 hours of injury for any diagnostic or therapeutic intervention in the acute phase of care (ED and inhospital). Pairs of reviewers independently assessed overall clinical practice guideline quality using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. The quality of evidence on recommendations was synthesized using a matrix based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Evidence-to-Decision framework. RESULTS: We included 11 clinical practice guidelines, of which 6 (55%) were rated high quality. These included 101 recommendations, of which 34 (34%) were based on moderate- to high-quality evidence, covering initial assessment, initial diagnostic imaging, monitoring/observation, therapeutic interventions, discharge advice, follow-up, and patient and family support. We did not identify any evidence-based recommendations in high-quality clinical practice guidelines for repeat imaging, neurosurgical consultation, or hospital admission. Lack of strategies and tools to aid implementation and editorial independence were the most common methodological weaknesses. CONCLUSIONS: We identified 34 recommendations based on moderate- to high-quality evidence that may be considered for implementation in clinical settings. Our review highlights important areas for future research. This review also underlines the importance of providing strategies to facilitate the implementation of clinical practice guideline recommendations for pediatric mTBI.

Lessons Learned about Developing Faith and Public Health Partnerships to Address Health Disparities.

Partnerships between public health and faith-based organizations draw on the strengths of both sectors to achieve a shared interest in promoting health and reducing disparities. However, information about implementation of faith and public health partnerships-particularly those involving diverse racial-ethnic groups-is limited. This paper reports on findings from qualitative interviews conducted with 16 public health and congregational leaders around the country as part of the early phase of the development of a faith and public health partnership to address health disparities in Los Angeles, CA. We identified eight themes regarding the barriers and facilitators to building faith and public health partnerships and distilled these into 10 lessons for developing such approaches. These interviews identified that engaging religious organizations often requires building congregational capacity of the congregation to participate in health programs; and that trust is a critically important element of these relationships. Further, trust is closely related to how well each organization involved in the partnership understands their partners' belief structures, approaches to addressing health and well-being and capacities to contribute to the partnership. Tailoring congregational health programs to match the interests, needs and capacity of partners was identified as an important approach to ensuring that the partnership is successful. But, this is complicated by working across multiple faith traditions and the racial-ethnic backgrounds, thus requiring increased and diverse communication strategies on the part of the partnership leadership. These lessons provide important information for faith and public health leaders interested in developing partnered approaches to address health in diverse urban communities.

2023 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces.

The International Liaison Committee on Resuscitation engages in a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation and first aid science. Draft Consensus on Science With Treatment Recommendations are posted online throughout the year, and this annual summary provides more concise versions of the final Consensus on Science With Treatment Recommendations from all task forces for the year. Topics addressed by systematic reviews this year include resuscitation of cardiac arrest from drowning, extracorporeal cardiopulmonary resuscitation for adults and children, calcium during cardiac arrest, double sequential defibrillation, neuroprognostication after cardiac arrest for adults and children, maintaining normal temperature after preterm birth, heart rate monitoring methods for diagnostics in neonates, detection of exhaled carbon dioxide in neonates, family presence during resuscitation of adults, and a stepwise approach to resuscitation skills training. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research. Additional topics are addressed with scoping reviews and evidence updates.

Intratracheal budesonide mixed with surfactant to increase survival free of bronchopulmonary dysplasia in extremely preterm infants: statistical analysis plan for the international, multicenter, randomized PLUSS trial.

BACKGROUND: Bronchopulmonary dysplasia (BPD), an inflammatory-mediated chronic lung disease, is common in extremely preterm infants born before 28 weeks' gestation and is associated with an increased risk of adverse neurodevelopmental and respiratory outcomes in childhood. Effective and safe prophylactic therapies for BPD are urgently required. Systemic corticosteroids reduce rates of BPD in the short term but are associated with poorer neurodevelopmental outcomes if given to ventilated infants in the first week after birth. Intratracheal administration of corticosteroid admixed with exogenous surfactant could overcome these concerns by minimizing systemic sequelae. Several small, randomized trials have found intratracheal budesonide in a surfactant vehicle to be a promising therapy to increase survival free of BPD. The primary objective of the PLUSS trial is to determine whether intratracheal budesonide mixed with surfactant increases survival free of bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age (PMA) in extremely preterm infants born before 28 weeks' gestation. METHODS: An international, multicenter, double-blinded, randomized trial of intratracheal budesonide (a corticosteroid) mixed with surfactant for extremely preterm infants to increase survival free of BPD at 36 weeks' postmenstrual age (PMA; primary outcome). Extremely preterm infants aged < 48 h after birth are eligible if (1) they are mechanically ventilated, or (2) they are receiving non-invasive respiratory support and there is a clinical decision to treat with surfactant. The intervention is budesonide (0.25 mg/kg) mixed with poractant alfa (200 mg/kg first intervention, 100 mg/kg if second intervention), administered intratracheally via an endotracheal tube or thin catheter. The comparator is poractant alfa alone (at the same doses). Secondary outcomes include the components of the primary outcome (death, BPD prior to or at 36 weeks' PMA), and potential systemic side effects of corticosteroids. Longer-term outcomes will be published separately, and include cost-effectiveness, early childhood health until 2 years of age, and neurodevelopmental outcomes at 2 years of age (corrected for prematurity). STATISTICAL ANALYSIS PLAN: A sample size of 1038 infants (519 in each group) is required to provide 90% power to detect a relative increase in survival free of BPD of 20% (an absolute increase of 10%), from the anticipated event rate of 50% in the control arm to 60% in the intervention (budesonide) arm, alpha error 0.05. To allow for up to 2% of study withdrawals or losses to follow-up, PLUSS aimed to enroll a total of 1060 infants (530 in each arm). The binary primary outcome will be reported as the number and percentage of infants who were alive without BPD at 36 weeks' PMA for each randomization group. To estimate the difference in risk (with 95% CI), between the treatment and control arms, binary regression (a generalized linear multivariable model with an identity link function and binomial distribution) will be used. Along with the primary outcome, the individual components of the primary outcome (death, and physiological BPD at 36 weeks' PMA), will be reported by randomization group and, again, binary regression will be used to estimate the risk difference between the two treatment groups for survival and physiological BPD at 36 weeks' PMA.

Women's Views on Factors that Influence Utilisation of Postnatal Follow-Up in Oman: A descriptive, qualitative study.

Objectives: Postnatal follow-up care (PNFC) is critical for promoting maternal and newborn health and well-being. In Oman, women's utilisation of postnatal follow-up services has declined, with rates as low as 0.29 (mean visits) in some governorates, and fails to meet the recommendation of postnatal follow-up visits at two and six weeks for assessment of the mother and her newborn. The reasons for this low utilisation are not well understood. This study aimed to explore women's views on and identify factors that influence their utilisation of postnatal follow-up services. Methods: Purposive sampling was employed and semi-structured telephone interviews were conducted with 15 women aged 20-39 years at six to eight weeks post-childbirth between May and August 2021. The data were analysed using Erlingsson and Brysiewicz's content analysis approach. Results: The following six categories were identified as influencing PNFC utilisation: 1) need for information; 2) experiences and expectations; 3) family support, expectations and customs; 4) sociocultural beliefs and practice; 5) impact of the COVID-19 pandemic; and 6) the healthcare environment. Influencing factors derived from each category include the need to empower women, provide individualised care, address family and community expectations, offer alternatives to face-to-face clinic visits and provide organised and scheduled appointments. Conclusion: Women in Oman identified the need for consistent information from healthcare providers and a more organised postnatal follow-up service that includes scheduled appointments and a woman-centred approach to PNFC.

Partnering With Patients, Caregivers, and Clinicians to Determine Research Priorities for Concussion.

Importance: Identifying research priorities of patients with concussion, their caregivers, and their clinicians is important to ensure future concussion research reflects the needs of those who will benefit from the research. Objective: To prioritize concussion research questions from the perspectives of patients, caregivers, and clinicians. Design, Setting, and Participants: This cross-sectional survey study used the standardized James Lind Alliance priority-setting partnership methods (2 online cross-sectional surveys and 1 virtual consensus workshop using modified Delphi and nominal group techniques). Data were collected between October 1, 2020, and May 26, 2022, from people with lived concussion experience (patients and caregivers) and clinicians who treat concussion throughout Canada. Exposures: The first survey collected unanswered questions about concussion that were compiled into summary questions and checked against research evidence to ensure they were unanswered. A second priority-setting survey generated a short list of questions, and 24 participants attended a final priority-setting workshop to decide on the top 10 research questions. Main Outcomes and Measures: Top 10 concussion research questions. Results: The first survey had 249 respondents (159 [64%] who identified as female; mean [SD] age, 45.1 [16.3] years), including 145 with lived experience and 104 clinicians. A total of 1761 concussion research questions and comments were collected and 1515 (86%) were considered in scope. These were combined into 88 summary questions, of which 5 were considered answered following evidence review, 14 were further combined to form new summary questions, and 10 were removed for being submitted by only 1 or 2 respondents. The 59 unanswered questions were circulated in a second survey, which had 989 respondents (764 [77%] who identified as female; mean [SD] age, 43.0 [4.2] years), including 654 people who identified as having lived experience and 327 who identified as clinicians (excluding 8 who did not record type of participant). This resulted in 17 questions short-listed for the final workshop. The top 10 concussion research questions were decided by consensus at the workshop. The main research question themes focused on early and accurate concussion diagnosis, effective symptom management, and prediction of poor outcomes. Conclusions and Relevance: This priority-setting partnership identified the top 10 patient-oriented research questions in concussion. These questions can be used to provide direction to the concussion research community and help prioritize funding for research that matters most to patients living with concussion and those who care for them.

Intratracheal budesonide mixed with surfactant to increase survival free of bronchopulmonary dysplasia in extremely preterm infants: study protocol for the international, multicenter, randomized PLUSS trial.

BACKGROUND: Bronchopulmonary dysplasia (BPD), an inflammatory-mediated chronic lung disease, is common in extremely preterm infants born before 28 weeks' gestation and is associated with an increased risk of adverse neurodevelopmental and respiratory outcomes in childhood. Effective and safe prophylactic therapies for BPD are urgently required. Systemic corticosteroids reduce rates of BPD in the short-term but are associated with poorer neurodevelopmental outcomes if given to ventilated infants in the first week after birth. Intratracheal administration of corticosteroid admixed with exogenous surfactant could overcome these concerns by minimizing systemic sequelae. Several small, randomized trials have found intratracheal budesonide in a surfactant vehicle to be a promising therapy to increase survival free of BPD. METHODS: An international, multicenter, double-blinded, randomized trial of intratracheal budesonide (a corticosteroid) mixed with surfactant for extremely preterm infants to increase survival free of BPD at 36 weeks' postmenstrual age (PMA; primary outcome). Extremely preterm infants aged < 48 h after birth are eligible if: (1) they are mechanically ventilated, or (2) they are receiving non-invasive respiratory support and there is a clinical decision to treat with surfactant. The intervention is budesonide (0.25 mg/kg) mixed with poractant alfa (200 mg/kg first intervention, 100 mg/kg if second intervention), administered intratracheally via an endotracheal tube or thin catheter. The comparator is poractant alfa alone (at the same doses). Secondary outcomes include the components of the primary outcome (death, BPD prior to or at 36 weeks' PMA), potential systemic side effects of corticosteroids, cost-effectiveness, early childhood health until 2 years of age, and neurodevelopmental outcomes at 2 years of age (corrected for prematurity). DISCUSSION: Combining budesonide with surfactant for intratracheal administration is a simple intervention that may reduce BPD in extremely preterm infants and translate into health benefits in later childhood. The PLUSS trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants regardless of their initial mode of respiratory support. Should intratracheal budesonide mixed with surfactant increase survival free of BPD, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( https://www.anzctr.org.au ), ACTRN12617000322336. First registered on 28th February 2017.

Community-Based Hospitals Benefit From Restrictive Transfusion Practices.

ABSTRACT: Blood availability was uncertain during the COVID-19 pandemic, yet transfusion remained a common and sometimes necessary procedure. Substantial work on optimizing transfusion practices is centered in tertiary hospitals as high utilizers of blood while the care delivered in smaller community hospitals comprises more than half the nation's transfusions. Improving transfusion practices in community hospitals represents a substantial opportunity to enhance patient safety and the availability of blood resources. Clinical specialists developed a dashboard to retrospectively examine transfusion events including an evidence-based analysis of the patient's clinical situation at the time of transfusion to more accurately identify how appropriately blood was used. The compiled data were discussed and shared with transfusing providers. It was hypothesized that the data provided and communication strategies used would educate providers to current evidence-based practice, leading to more appropriate transfusion with an overall reduction in packed red blood cell utilization. There was an 11% increase in transfusion appropriateness (p = <.001) and a 14% decrease in the units transfused (p = .004). Improvement in transfusion practices demonstrates a significant impact on patient safety and the availability of blood resources. Although absolute opportunity may be less in a community hospital, fewer resources are needed to achieve meaningful change.

Impact of SERPINC1 mutation on thrombotic phenotype in children with congenital antithrombin deficiency-first analysis of the International Society on Thrombosis and Haemostasis pediatric antithrombin deficiency database and biorepository.

BACKGROUND: The natural history and genotype-phenotype correlation of congenital antithrombin (AT) deficiency in children are unknown. OBJECTIVES: To describe the clinical presentation of congenital AT deficiency in children and evaluate its correlation to specific mutations in SERPINC1. METHODS: In 2017, a prospective pediatric database and DNA biorepository for congenital AT deficiency was established. During the pilot phase, the database was opened at 4 tertiary care centers in Canada and US. Approval from research ethics board was obtained at each participating center. Written consent/assent was obtained from guardians/subjects who met eligibility. Demographic/clinical data were uploaded into a database. DNA extraction and SERPINC1 sequencing were centralized for US centers. Standard statistical methods were used to summarize parameters. Probability of VTE-free survival was assessed using the Kaplan-Meier method. RESULTS: Overall, 43 participants (25 females) from 31 unique kindreds were enrolled. Median age (range) at enrollment was 14.8 years (1-21 years). Median AT activity was 52% (24%-87%), and median AT antigen (n = 20) was 55% (38%-110%). Nineteen (44%) participants had a history of venous thromboembolism (VTE). Median age at VTE diagnosis was 12.8 years (0.1-19.2 years). SERPINC1 sequencing was completed for 31 participants and 21 unique mutations were identified, including 5 novel variants. Probability of 5-year VTE-free survival (95% CI) for carriers of missense mutations (92.0% [95% CI: 71.6%-97.9%]) was significantly higher compared with carriers of null mutations (66.7% [95% CI: 19.5%-90.4%]); p = .0012. CONCLUSION: To our knowledge, this is the first pediatric study to document a severe thrombotic phenotype in carriers of null mutations in SERPINC1, when compared with carriers of missense mutations; underscoring the importance of genetic testing.

Healthcare Providers' Views of Information, Support, and Services Offered to Women in the Postnatal Follow-up Care Period in Oman: A Qualitative Study.

Background: Postnatal care is a component of the maternity care continuum, which is often under-valued and under-offered. The aim of this study was to explore healthcare providers' (HCPs) views about postnatal follow-up care (PNFC) offered to women in Oman. Methods: This qualitative study was performed from May 2021 to January 2022; 29 individual participated in semi-structured telephone interviews with staff nurses (N=20), nurse/midwives (N=5), and doctors (N=4) from Khoula and Ibra hospitals and Al Amerat, Muttrah and Al Qabil health centers in Oman. Conventional content analysis was guided by Erlingsson and Brysiewicz. Results: Seventeen sub-categories and four categories emerged from the data; they included communication and timing of PNFC, provision of PNFC with various components, challenges and needs for providing PNFC, and the impact of COVID-19 on PNFC. Conclusion: Providing postnatal follow-up care in Oman is challenging for HCPs due to lack of clinics dedicated to postnatal care, no scheduled appointment times for women, very limited guidance within the National Maternity Care guideline, and some HCPs (i.e., nurses) with no formal education on the components of postnatal care. These hinder the ability to provide information, education, support, and services to women.

Comparative Protein Structural Network Analysis Reveals C-Terminal Tail Phosphorylation Structural Communication Fingerprint in PTEN-Associated Mutations in Autism and Cancer.

PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a tightly regulated dual-specificity phosphatase and key regulator of the PI3K/AKT/mTOR signaling pathway. PTEN phosphorylation at its carboxy-terminal tail (CTT) serine/threonine cluster negatively regulates its tumor suppressor function by inducing a stable, closed, and inactive conformation. Germline PTEN mutations predispose individuals to PTEN hamartoma tumor syndrome (PHTS), a rare inherited cancer syndrome and, intriguingly, one of the most common causes of autism spectrum disorder (ASD). However, the mechanistic details that govern phosphorylated CTT catalytic conformational dynamics in the context of PHTS-associated mutations are unknown. Here, we utilized a comparative protein structure network (PSN)-based approach to investigate PTEN CTT phosphorylation-induced conformational dynamics specific to PTEN-ASD compared to PTEN-cancer phenotypes. Results from our study show differences in structural flexibility, inter-residue contacts, and allosteric communication patterns mediated by CTT phosphorylation, differentiating PTEN-ASD and PTEN-cancer phenotypes. Further, we identified perturbations among global metapaths and community network connections within the active site and inter-domain regions, indicating the significance of these regions in transmitting information across the PSN. Together, our studies provide a mechanistic underpinning of allosteric regulation through the coupled interplay of CTT phosphorylation conformational dynamics in PTEN-ASD and PTEN-cancer mutations. Importantly, the detailed atomistic interactions and structural consequences of PTEN variants reveal potential allosteric druggable target sites as a viable and currently unexplored treatment approach for individuals with different PHTS-associated mutations.

Analyzing Patient-Provided Responses to Improve Collection of Health Equity Data Elements.

Self-report is purported to be the gold standard for collecting demographic information. Many entry forms include a free-text "write-in" option in addition to structured responses. Balancing the flexibility of free-text with the value of collecting data in a structured format is a challenge if the data are to be useful for measuring and mitigating health disparities. While much work has been done to improve collection of race and ethnicity information, how to best collect data related to sexual and gender minority status and military veteran status has been less commonly studied. We analyzed 3,381 patient-provided free-text responses collected via a patient portal for gender identity, sexual orientation, pronouns, and veteran experiences. We identified common responses to better understand our patient population and help improve future iterations of data collection tools.

Women's Utilisation, Experiences and Satisfaction with Postnatal Follow-up Care: Systematic literature review.

Postnatal follow-up care is reported to be the 'underutilised' aspect of the maternity care continuum. This review explores women's utilisation of early and late postnatal follow-up and their experiences and satisfaction with it. Five online databases were searched for English or Arabic articles published between 2011 and 2021. Methodological quality of included studies was assessed using the Mixed Methods Appraisal Tool; the Andersen healthcare utilisation model was the framework for data analysis. A total of 19 articles met all inclusion criteria. Utilisation facilitators included complications, travel distance, knowledge of the importance for attending and being offered a telephone call and home visit or clinic visit as options for follow-up. Impediments included lack of perceived need and not being provided with information about postnatal care. Comprehensive discussions with and examination by health providers were reported as positive experiences and influenced repeat utilisation. Dissatisfaction was associated with inconsistent information provided by health providers.

Structural and Dynamic Effects of PTEN C-Terminal Tail Phosphorylation.

The phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor gene encodes a tightly regulated dual-specificity phosphatase that serves as the master regulator of PI3K/AKT/mTOR signaling. The carboxy-terminal tail (CTT) is key to regulation and harbors multiple phosphorylation sites (Ser/Thr residues 380-385). CTT phosphorylation suppresses the phosphatase activity by inducing a stable, closed conformation. However, little is known about the mechanisms of phosphorylation-induced CTT-deactivation dynamics. Using explicit solvent microsecond molecular dynamics simulations, we show that CTT phosphorylation leads to a partially collapsed conformation, which alters the secondary structure of PTEN and induces long-range conformational rearrangements that encompass the active site. The active site rearrangements prevent localization of PTEN to the membrane, precluding lipid phosphatase activity. Notably, we have identified phosphorylation-induced allosteric coupling between the interdomain region and a hydrophobic site neighboring the active site in the phosphatase domain. Collectively, the results provide a mechanistic understanding of CTT phosphorylation dynamics and reveal potential druggable allosteric sites in a previously believed clinically undruggable protein.