Acetabular Fractures in older patients Intervention Trial (AceFIT): a feasibility triple-arm randomized controlled study.

Aims: To assess the feasibility of a randomized controlled trial (RCT) that compares three treatments for acetabular fractures in older patients: surgical fixation, surgical fixation and hip arthroplasty (fix-and-replace), and non-surgical treatment. Methods: Patients were recruited from seven UK NHS centres and randomized to a three-arm pilot trial if aged older than 60 years and had a displaced acetabular fracture. Feasibility outcomes included patients' willingness to participate, clinicians' capability to recruit, and dropout rates. The primary clinical outcome measure was the EuroQol five-dimension questionnaire (EQ-5D) at six months. Secondary outcomes were Oxford Hip Score, Disability Rating Index, blood loss, and radiological and mobility assessments. Results: Between December 2017 and December 2019, 60 patients were recruited (median age 77.4 years, range 63.3 to 88.5) (39/21 M/F ratio). At final nine-month follow-up, 4/60 (7%) had withdrawn, 4/60 (7%) had died, and one had been lost to follow-up; a 98% response rate (50/51) was achieved for the EQ-5D questionnaire. Four deaths were recorded during the three-year trial period: three in the non-surgical treatment group and one in the fix-and-replace group. Conclusion: This study has shown a full-scale RCT to be feasible, but will need international recruitment. The Acetabular Fractures in older patients Intervention Trial (AceFIT) has informed the design of a multinational RCT sample size of 1,474 or 1,974 patients for a minimal clinically important difference of 0.06 on EQ-5D, with a power of 0.8 or 0.9, and loss to follow-up of 20%. This observed patient cohort comprises a medically complex group requiring multidisciplinary care; surgeon, anaesthetist, and ortho-geriatrician input is needed to optimize recovery and rehabilitation.

The floating hip injury: a descriptive study and case-control analysis.

PURPOSE: A "floating hip" (FH) injury is a rare injury describing the simultaneous ipsilateral fracture of the femur and pelvis or acetabulum (P/A). We describe our experience with patients presenting with FH injuries and compare them to controls with similar P/A fractures but without femoral involvement. METHODS: Medical records and radiographs of FH patients and controls presenting to our tertiary centre between 2015 and 2020 were reviewed. Follow-up data from outpatient clinical records were also extracted. The control group were extensively matched by age, sex, body mass index, fracture classification and energy of injury. RESULTS: From 1392 recorded P/A fractures, 42 FH cases were identified (average age 39 years, 78.6% males). The most common femoral fracture was the midshaft (35.7%), followed by the neck of femur (26.2%). 90.5% of FH injuries were due to high-energy mechanisms. 64.3% of P/A fractures, and 100% of femoral fractures were managed surgically. Compared to controls, FH cases were more likely to have additional orthopaedic injuries (73.8% vs. 40.5%, p = 0.002), more total theatre admissions (mean 2.5 vs. 1.19, p < 0.001), longer hospital stays (28.3 vs. 14.9 days, p = 0.02), and a higher rates of post-op complications (53.8% vs. 20%, p = 0.025). CONCLUSIONS: We report differences in the presentation, management, and outcomes of FH injuries versus controls, even after extensive matching for confounders. These differences may inform future treatment strategies for the FH injury.

Using Artificial Intelligence as a Melanoma Screening Tool in Self-Referred Patients.

INTRODUCTION: Early detection of melanoma requires timely access to medical care. In this study, we examined the feasibility of using artificial intelligence (AI) to flag possible melanomas in self-referred patients concerned that a skin lesion might be cancerous. METHODS: Patients were recruited for the study through advertisements in 2 hospitals in Halifax, Nova Scotia, Canada. Lesions of concern were initially examined by a trained medical student and if the study criteria were met, the lesions were then scanned using the FotoFinder System®. The images were analyzed using their proprietary computer software. Macroscopic and dermoscopic images were evaluated by 3 experienced dermatologists and a senior dermatology resident, all blinded to the AI results. Suspicious lesions identified by the AI or any of the 3 dermatologists were then excised. RESULTS: Seventeen confirmed malignancies were found, including 10 melanomas. Six melanomas were not flagged by the AI. These lesions showed ambiguous atypical melanocytic proliferations, and all were diagnostically challenging to the dermatologists and to the dermatopathologists. Eight malignancies were seen in patients with a family history of melanoma. The AI's ability to diagnose malignancy is not inferior to the dermatologists examining dermoscopic images. CONCLUSION: AI, used in this study, may serve as a practical skin cancer screening aid. While it does have technical and diagnostic limitations, its inclusion in a melanoma screening program, directed at those with a concern about a particular lesion would be valuable in providing timely access to the diagnosis of skin cancer.

Instrumental variables methods reconcile intention-to-screen effects across pragmatic cancer screening trials.

Pragmatic cancer screening trials mimic real-world scenarios in which patients and doctors are the ultimate arbiters of treatment. Intention-to-screen (ITS) analyses of such trials maintain randomization-based apples-to-apples comparisons, but differential adherence (the failure of subjects assigned to screening to get screened) makes ITS effects hard to compare across trials and sites. We show how instrumental variables (IV) methods address the nonadherence challenge in a comparison of estimates from 17 sites in five randomized trials measuring screening effects on colorectal cancer incidence. While adherence rates and ITS estimates vary widely across and within trials, IV estimates of per-protocol screening effects are remarkably consistent. An application of simple IV tools, including graphical analysis and formal statistical tests, shows how differential adherence explains variation in ITS impact. Screening compliers are also shown to have demographic characteristics similar to those of the full trial study sample. These findings argue for the clinical relevance of IV estimates of cancer screening effects.

Lateral compression type 1 fracture fixation in the elderly (L1FE): study protocol for a randomised controlled trial (with internal pilot) comparing the effects of INFIX surgery and non-surgical management for treating patients with lateral compression type 1 (LC-1) fragility fractures.

BACKGROUND: Lateral compression type1 (LC-1) fragility fractures are a common, painful injury in older adults resulting in reduced mobility. The incidence of these fractures is increasing with the growing older adult population. The current standard of care is non-surgical management; however, patients with this injury are at risk of long-term immobility and related complications. INFIX is a pelvic fixation device used in younger patients with high-energy fractures. The device is fitted via a percutaneous technique with no external pin sites and has good purchase even in osteoporotic bone. It therefore has the potential to be well tolerated in patients with LC-1 fragility fractures. INFIX could improve patients' ability to mobilise and reduce the risk of immobility-related complications. However, there is a risk of complications related to surgery, and robust evidence is required on patient outcomes. This study will investigate the clinical and cost-effectiveness of surgical fixation with INFIX compared to non-surgical management of LC-1 fragility fractures in older adults. METHODS: A multi-centre randomised controlled trial of 600 patients allocated 1:1 to non-surgical management or INFIX surgery. The study will have a 12-month internal pilot to assess recruitment and trial feasibility. The primary outcome will be the patient quality of life over 6 months, measured by the patient-reported EQ-5D-5L. The secondary outcomes will include physical function, mental health, pain, delirium, imaging assessment, resource use, and complications. DISCUSSION: The L1FE study aims to compare the clinical and cost-effectiveness of surgical and non-surgical management of people aged 60 years and older with LC-1 fragility fractures. The trial is sufficiently powered and rigorously designed to inform future clinical and patient decision-making and allocation of NHS resources. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Registry ISRCTN16478561. Registered on 8 April 2019.

The clinical characteristics and management of paediatric pelvic fractures: a changing landscape based on skeletal maturity.

INTRODUCTION: Paediatric pelvic fractures (PPFs) are uncommon but signify serious trauma. A comprehensive multidisciplinary approach is needed due to a high number of associated injuries. This study aims to retrospectively analyse PPFs over a 5-year period and evaluate how advancing skeletal maturity changes fracture patterns and management plans. METHODS: The trauma database was retrospectively reviewed for pelvic fractures in patients aged ≤ 18 years. Radiographs and CT scans were used to classify pelvic injuries according to the modified Torode classification and determine the status of the triradiate cartilage (open: skeletally immature; closed: skeletally mature). Data collected also included the mechanism of injury, clinical and functional outcomes, and associated injuries. Logistic regression analysis was performed to identify risk factors for associated abdominal injuries. RESULTS: 65 PPFs (2.8% of paediatric trauma admissions during the study period) were classified as type I (3.1%), type II (7.7%), type IIIa (32.3%), type IIIb (38.5%), type IV (18.5%) according to the modified Torode classification. The mean age was 13.41 ± 3.82. Skeletally immature children were more likely to be hit by a motor vehicle as a pedestrian (p < 0.001), be intubated (p = 0.009), acquire Torode type II (p = 0.047) and rami fractures (p = 0.037), and receive chest (p = 0.005) and head injuries (p = 0.046). Skeletally immature children were also less likely to acquire Torode type IV fractures (p = 0.018), receive surgical treatment for their pelvic injuries (p = 0.036), and had a faster time to full weight bearing (p = 0.013). Pelvis AIS score ≥ 4 (OR 5.3; 95% CI 1.3-22.6; p = 0.023) and a pedestrian accident (OR 4.9; 95% CI 1.2-20.7; p = 0.030) were risk factors for associated abdominal injuries. There was a strong association between a higher pelvic fracture grade and the proportion of patients with closed triradiate cartilage (p = 0.036), hospital length of stay (p = 0.034), mean pelvic AIS score (p = 0.039), a pelvis AIS score of ≥ 4 (p = 0.022), mean ISS (p = 0.003), an ISS score between 25 and 75 (p = 0.004), average time to FWB (p = 0.001), requirement of blood products (p = 0.015), and a motor vehicle accident (p = 0.037). CONCLUSION: PPFs occurring in skeletally mature and immature patients are significantly different in terms of mechanism of injury, fracture severity, fracture pattern, and management strategy. There is a high rate of associated injuries, necessitating an integrated multidisciplinary approach in paediatric trauma centres.

Nonrandom Exposure to Exogenous Shocks.

We develop a new approach to estimating the causal effects of treatments or instruments that combine multiple sources of variation according to a known formula. Examples include treatments capturing spillovers in social or transportation networks and simulated instruments for policy eligibility. We show how exogenous shocks to some, but not all, determinants of such variables can be leveraged while avoiding omitted variables bias. Our solution involves specifying counterfactual shocks that may as well have been realized and adjusting for a summary measure of non-randomness in shock exposure: the average treatment (or instrument) across shock counterfactuals. We use this approach to address bias when estimating employment effects of market access growth from Chinese high-speed rail construction.

Fix and replace: Simultaneous fracture fixation and hip replacement for acetabular fractures in older patients.

INTRODUCTION: Displaced acetabular fractures in the elderly present significant treatment challenges. The 'fix and replace' concept involves open reduction and internal fixation of the acetabulum, providing bony stability to accept the press-fit of an acetabular cup, with a cemented femoral stem. This allows early mobilisation and the advantages this confers. This study of 57 patients treated with fix and replace describes our technique, outcomes, and survival analysis. METHODS: A retrospective review of 57 'fix and replace' procedures in patients aged over 60 was performed. Data was collected on mechanism, fracture type, demographics, time to surgery, comorbidity index, complications, EQ-5D and Oxford hip scores (OHS). Radiographs were reviewed for fracture healing, implant loosening, cup migration, and heterotopic ossification. RESULTS: 57 patients aged 60 to 95 had fix and replace surgery. The median ASA score was 3. The mean Charlson Index was 4.8. 45 patients had a low-energy fall, 6 had a road traffic accident, 3 fell off a bicycle, and 1 mechanism was unclear. The fracture patterns were anterior column posterior hemitransverse (67%), associated both columns (9%), posterior column (9%), posterior column and posterior wall (9%), and transverse (2%). The mean time to surgery was 8.4 days (0-14). 26 out of 57 (46%) received a blood transfusion. Mean length of stay was 17.6 days (7-86). The mean follow-up was 35.5 months. 4 dislocations were treated with closed reduction, whilst 1 required excision arthroplasty. 2 infections resolved with debridement, antibiotics, and implant retention (DAIR), whilst 1 required a two-stage revision. 1 acetabular component had migrated requiring revision. The median pre-injury OHS was 44 (26-48) compared to 37.3 (28-48) at 1 year. There were no deaths at 30-days, whilst at 1 year 7 patients had died. Kaplan Meier survival analysis showed mean survival was 1984.5 days. Implant survival was 90% at 1 year. CONCLUSION: While fix and replace is conceptually attractive, this medically complex patient group requires considerable support peri­ and post-operatively. Further studies are required to provide clinicians with more information to decide on how best to provide a holistic management strategy for such injuries in this frail patient cohort.

Cycling-related trauma admissions to the major trauma centre in the cycling capital of the United Kingdom.

PURPOSE: This study aims to characterise cycling related injuries presenting to a major trauma centre located within a region with the highest rates of cycling in the UK. METHODS: A retrospective analysis of cycling related trauma admissions occurring between January 2012 and June 2020 was performed. Our institution's electronic patient record system was used to collect relevant data for analysis including age, gender, mechanism of injury, Glasgow coma scale (GCS) on arrival, incident date and time, injured body regions, 30-day mortality, helmet use and intubation rate. Comparison was made between groups of patients based on mechanism of injury. RESULTS: A total of 605 cycling related trauma cases were identified, with 52 being excluded due to incomplete data. The most common mechanism was 'fall from cycle' (53.5%). The 'cyclist v vehicle' group was associated with a significantly higher Injury Severity score (ISS), lower GCS and higher intubation rate. Helmet wearers were significantly older than non-wearers and helmet use was associated with a significantly reduced risk of head injury, lower ISS and intubation rate and a higher GCS. DISCUSSION: With a likely increase in future cycling uptake, it is crucial that effective interventions are implemented to improve the safety of cyclists. The findings of this study may be used to guide any such intervention. A multi-faceted strategy involving driver and cyclist education, effective road infrastructure changes and helmet promotion campaigns specifically targeting the younger generation could be employed.

An Examination of Melanoma Detection and Characteristics at a Nova Scotia Tertiary Care Centre, From 2015-2019.

BACKGROUND: Melanoma is one of the most common cancers in Canada,1 with the highest incidence in Nova Scotia (NS). OBJECTIVES: To describe the demographics, lesion characteristics, and diagnostic accuracy of suspected melanomas excised at the largest center in NS. METHODS: The dermatopathology database was interrogated for cases of possible melanoma from 2015 through 2019. Age, gender, site of lesion, pathologic diagnosis, Breslow depth, and equivocal pathology were assessed. RESULTS: 984 lesions had a clinical diagnosis of possible melanoma, identifying 301 melanomas. Of these, 142 (47%) were melanoma in situ (MIS) which in females occurred mostly on the extremities, while in males the head predominated. For invasive melanoma (IM), the extremities remained predominant for women, while the back was most common in men. Lower extremity lesions were more likely to be invasive and female patients were more likely to present with them at a younger age compared to males. The pathology was challenging for 23.94% of MIS, and 16.18% of IM. A mean of 3.1 lesions were excised for every melanoma identified. CONCLUSIONS: Early diagnosis of melanoma is challenging clinically and pathologically. Our melanoma detection rate was 31%, with an increasing trend in the proportion of MIS, and decreasing trend in the proportion of IM over the years. Almost 50% of melanomas were detected in early stages, supporting positive outcomes. Melanomas were more common on extremities in females and the back in males. Melanomas on the lower limbs were more likely to be invasive regardless of gender.

Geographic access to federally qualified health centers before and after the affordable care act.

BACKGROUND: The Affordable Care Act (ACA) increased funding for Federally Qualified Health Centers (FQHCs). We defined FQHC service areas based on patient use and examined the characteristics of areas that gained FQHC access post-ACA. METHODS: We defined FQHC service areas using total patient counts by ZIP code from the Uniform Data System (UDS) and compared this approach with existing methods. We then compared the characteristics of ZIP codes included in Medically Underserved Areas/Populations (MUA/Ps) that gained access vs. MUA/P ZIP codes that did not gain access to FQHCs between 2011-15. RESULTS: FQHC service areas based on UDS data vs. Primary Care Service Areas or counties included a higher percentage of each FQHC's patients (86% vs. 49% and 71%) and ZIP codes with greater use of FQHCs among low-income residents (29% vs. 22% and 22%), on average. MUA/Ps that gained FQHC access 2011-2015 included more poor, uninsured, publicly insured, and foreign-born residents than underserved areas that did not gain access, but were less likely to be rural (p < .05). CONCLUSIONS: Measures of actual patient use provide a promising method of assessing FQHC service areas and access. Post-ACA funding, the FQHC program expanded access into areas that were more likely to have higher rates of poverty and uninsurance, which could help address disparities in access to care. Rural areas were less likely to gain access to FQHCs, underscoring the persistent challenges of providing care in these areas.

Measuring Racial Discrimination in Bail Decisions.

We develop new quasi-experimental tools to measure disparate impact, regardless of its source, in the context of bail decisions. We show that omitted variables bias in pretrial release rate comparisons can be purged by using the quasi-random assignment of judges to estimate average pretrial misconduct risk by race. We find that two-thirds of the release rate disparity between white and Black defendants in New York City is due to the disparate impact of release decisions. We then develop a hierarchical marginal treatment effect model to study the drivers of disparate impact, finding evidence of both racial bias and statistical discrimination.

Quasi-Experimental Shift-Share Research Designs.

Many studies use shift-share (or "Bartik") instruments, which average a set of shocks with exposure share weights. We provide a new econometric framework for shift-share instrumental variable (SSIV) regressions in which identification follows from the quasi-random assignment of shocks, while exposure shares are allowed to be endogenous. The framework is motivated by an equivalence result: the orthogonality between a shift-share instrument and an unobserved residual can be represented as the orthogonality between the underlying shocks and a shock-level unobservable. SSIV regression coefficients can similarly be obtained from an equivalent shock-level regression, motivating shock-level conditions for their consistency. We discuss and illustrate several practical insights of this framework in the setting of Autor et al. (2013), estimating the effect of Chinese import competition on manufacturing employment across U.S. commuting zones.

Factors associated with mortality in older patients sustaining pelvic or acetabular fractures.

INTRODUCTION: This study aimed to investigate potential factors, including delay to surgical stabilisation, affecting mortality in older patients sustaining pelvic or acetabular (PA) fractures. MATERIALS AND METHODS: A retrospective review of the Trauma Audit and Research Network (TARN) database was performed to identify older patients (aged 65 and over) sustaining PA fractures treated surgically in a UK Major Trauma Centre (MTC) between 2015 and 2019. Chi-squared and Fisher tests were used to compare 1-year mortality rates following operative intervention between patients treated within 72 h and after 72 h. Kaplan-Meier curves were used to visualise survival probability; significant predictors of survival were found using Cox proportional hazard models. RESULTS: Of 564 older patients with PA fractures, 70 met the inclusion criteria. The mean age was 76.1 years. The overall 1-year mortality rate was 20%. When patients were grouped by time to surgery (fracture fixation within or greater than 72 h), there was no statistically significant difference in 1-year mortality. Patients whose surgery was delayed more than 72 h were more likely to have longer hospital stays (p = 0.002) or to have suffered from polytrauma (p = 0.025). Age, Charlson Co-morbidities Index (CCI) and pre-op mobility status were associated with statistically significant differences in overall mortality. The same factors were associated with a significantly increased hazard of death in the multivariate Cox proportional hazards model. Patient gender, mechanism of injury, Injury Severity Score (ISS) > 15 and head injury were not significant predictors of mortality. CONCLUSION: Surgical intervention within 72 h of injury did not result in decreased mortality in older patients with PA fractures. The 1-year mortality rate between older PA fractures and hip fractures was comparable. Consideration should be given to a combined multidisciplinary approach between orthogeriatric and expert PA surgeons for these patients.

Trauma epidemiology after easing of lockdown restrictions: experience from a level-one major trauma centre in England.

PURPOSE: The COVID-19 pandemic transformed the delivery of trauma care. We examined the effect of lockdown easing on trauma presentation and management from one Major Trauma Centre (MTC). METHODS: Data was retrospectively analysed from Trauma Audit and Research Network (TARN) on patients presenting to our MTC with trauma. The first 47 days of lockdown (23rd March-9th May 2020, period 1) were compared with the next 47 (10th May-26th June 2020, period 2) and last (27th June-13th August 2020, period 3). Data collected included demographics, mechanism and severity of injury, management and length of stay. RESULTS: 1249 patients were included; 62.2% were male with a mean age of 57.73. Footfall declined in April 2020 compared with 2019 (56 vs. 143) but rebounded by May (123 vs. 120 patients). Road traffic collisions increased over periods one-three (18.8% vs. 23% vs. 30.1%, p = 0.038); deliberate self-harm (DSH) increased in period two compared with one and three (6.3% vs. 3.4% vs. 1.4%, p = 0.03), respectively. When compared with 2019, the 2020 patient age was lower, with less trauma relating to alcohol (7.3% vs. 13.2%, p = 0.009), but more from DSH (3.6% vs. 2.1%, p = 0.10). In 2020 less patients were assessed by a consultant and trauma team, with a shorter stay in hospital and critical care. CONCLUSION: This is the first study to document trauma trends through a lockdown and thereafter. After lockdown easing, trauma footfall rapidly rebounded to 2019 levels. This should be acknowledged in resource allocation decisions if future lockdowns are necessitated.

Sequential low molecular weight heparin and rivaroxaban for venous thromboprophylaxis in pelvic and acetabular trauma.

INTRODUCTION: Patients with pelvic trauma are at high risk of thromboembolic complications, but effective methods of prophylaxis are still to be accepted widely. The incidence of venous thromboembolism (VTE) has been reported to be as high as 61%, which represents the commonest cause of morbidity and mortality in this cohort. New oral anticoagulants are now available and may be used instead of LMWH injections for extended prophylaxis. Rivaroxaban has not been comprehensively considered in the previous pelvic and acetabular trauma literature, but its known benefits include increased patient compliance, especially in the minority of patients who are unable to self-administer injections, and that it does not require monitoring. MATERIALS AND METHODS: All patients referred to our pelvic trauma service between 2015 and 2020 were considered for this study, exclusion criteria involved those patients who had contraindications to rivaroxaban, those who were referred to our service but were never managed at our centre and those managed by other teams (e.g. neurosurgery). Operative patients were initially managed with LMWH until 24 h post-operatively when they started rivaroxaban. Conservatively managed patients started Rivaroxaban straight away. Data were collected on demographics, injury mechanism, fracture classification and clinically relevant VTE and bleeding events up until 3 months post discharge. RESULTS: The overall incidence of VTE was 2%. These represented 3 DVTs and 3 PEs, and occurred in patients who were managed operatively. No major bleeding events were observed. There were two minor bleeding events, both occurring in patients who were managed conservatively with rivaroxaban alone, and they did not require further intervention. 90% of patients surveyed expressed preference for oral prophylaxis. Reported compliance with rivaroxaban was 100%. CONCLUSION: Our data show that this VTE regimen protocol is safe and effective in this group of injured patients and is at least non-inferior to the standard prophylaxis of LMWH alone.

Two SMARCAD1 Variants Causing Basan Syndrome in a Canadian and a Dutch Family.

Basan syndrome is an autosomal dominant genodermatosis characterized by congenital adermatoglyphia, transient congenital facial milia, neonatal acral bullae, and absent or reduced sweating. Basan syndrome is rare and has been reported in only 10 kindreds worldwide. It is caused by variants in the skin-specific isoform of SMARCAD1, which starts with an alternative exon 1. All reported variants, except for one large deletion, are point mutations within the donor splice site of the alternative exon 1. In this paper, we report two families with Basan syndrome and describe two SMARCAD1 variants. In one family, we have identified a complex structural variant (a deletion and a nontandem inverted duplication) using whole-genome optical mapping and whole-genome sequencing. Although this variant results in the removal of the first nine exons of SMARCAD1 and exon 1 of the skin-specific isoform, it manifested in the typical Basan phenotype. This suggests that unlike the skin-specific isoform, a single copy of full-length SMARCAD1 is sufficient for its respective function. In the second family, whole-exome sequencing revealed a deletion of 12 base pairs spanning the exon‒intron junction of the alternative exon 1 of the skin-specific SMARCAD1 isoform. In conclusion, we report two additional families with Basan syndrome and describe two SMARCAD1 pathogenic variants.

Primary Hyperoxaluria Type 1 (PH1) Presenting With End-Stage Kidney Disease and Cutaneous Manifestations in Adulthood: A Case Report.

RATIONALE: Primary hyperoxaluria (PH) is a rare autosomal recessive disorder more commonly diagnosed in children or adolescents. Owing to its rarity and heterogeneous phenotype, it is often underrecognized, resulting in delayed diagnosis, including diagnosis after end-stage kidney disease (ESKD) has occurred or recurrence after kidney-only transplantation. CASE PRESENTATION: A 40-year-old Caucasian Canadian woman with a history of recurrent nephrolithiasis since age 19 presented with ESKD and cutaneous symptoms. She had no known prior kidney disease and no family history of kidney disease or nephrolithiasis. DIAGNOSIS: A diagnosis of primary hyperoxaluria type 1 (PH1) due to homozygous splice donor mutation (AGXT c.680+1G>A) was made with kidney and cutaneous pathology demonstrating calcium oxalate deposition and ultrasound suggestive of nephrocalcinosis. INTERVENTIONS: She was initiated on frequent, high-efficiency, high-flux conventional hemodialysis and oral pyridoxine. Lumasiran was added 11 months later, after she developed bilateral swan-neck deformities. OUTCOMES: After 14 months of high-intensity dialysis and 3 months of lumasiran, there have been no signs of renal recovery, and extra-renal involvement has increased with progressive swan-neck deformities, reduced cardiac systolic function, and pulmonary hypertension. The patient has been waitlisted for kidney-liver transplantation. TEACHING POINTS: This case report describes an adult presentation of PH1. The case highlights the importance of timely workup of metabolic causes of recurrent nephrolithiasis or nephrocalcinosis in adults which can be a presenting sign of PH and genetic testing for PH to facilitate early diagnosis and treatment especially in the era of novel therapeutics that may alter disease course and outcomes. The case also demonstrates the value of testing for PH in adults presenting with unexplained ESKD and a history of recurrent nephrolithiasis or nephrocalcinosis due to implications for organ transplantation strategy and presymptomatic family screening.

JUSTIFICATION: L'hyperoxalurie primaire (HP) est un trouble récessif autosomique rare plus souvent rencontré chez les enfants ou les adolescents. En raison de sa rareté et de son phénotype hétérogène, cette affection est fréquemment sous-reconnue, ce qui entraîne un retard dans le diagnostic, et ce, même après l'apparition d'une insuffisance rénale terminale (IRT) ou une récidive suivant une greffe simple de rein. PRÉSENTATION DU CAS: Nous présentons le cas d'une Canadienne de race blanche âgée de 40 ans avec des antécédents de néphrolithiase récurrente depuis l'âge de 19 ans. La patiente était atteinte d'IRT et présentait des symptômes cutanés. Elle n'avait aucun antécédent connu de maladie rénale ou antécédent familial de maladie rénale ou de néphrolithiase. DIAGNOSTIC: Une pathologie rénale et cutanée montrant des dépôts d'oxalate de calcium et une échographie suggérant une néphrocalcinose ont permis de poser un diagnostic d'hyperoxalurie primaire de type 1 (HP1) due à une mutation de donneur d'épissage homozygote (AGXT c.680+1G>A). INTERVENTIONS: La patiente a amorcé des traitements d'hémodialyse conventionnelle à grande fréquence, à haut rendement et à flux élevé, et a reçu de la pyridoxine par voie orale. Un traitement par lumasiran a été ajouté 11 mois plus tard, après le développement de déformations bilatérales en col de cygne. RÉSULTATS: Après quatorze mois de dialyze à haute intensité et trois mois de lumasiran, aucun signe de récupération rénale n'a été observé. L'intervention d'épuration extra-rénale a été augmentée en raison de déformations progressives en col de cygne, d'une réduction de la fonction cardiaque systolique et d'une hypertension pulmonaire. La patiente a été placée sur la liste d'attente pour une transplantation rénale et hépatique. ENSEIGNEMENTS TIRÉS: Ce rapport de cas décrit une présentation adulte d'HP1. Ce cas souligne l'importance de traiter rapidement les causes métaboliques de la néphrolithiase ou de la néphrocalcinose récidivante chez les adultes, car celles-ci peuvent être des signes d'hyperoxalurie primaire (HP). Ce cas souligne en outre l'importance de procéder à des tests génétiques pour l'HP afin de permettre le diagnostic et le traitement précoces, en particulier à l'ère de nouveaux traitements susceptibles d'infléchir l'évolution et les résultats de la maladie. Enfin, il démontre la valeur du dépistage de l'HP chez les adultes présentant une IRT inexpliquée et des antécédents de néphrolithiase ou de néphrocalcinose récidivante, en raison de ses implications sur la stratégie de transplantation d'organes et sur le dépistage pré-symptomatique de la famille.

Mortality Effects and Choice Across Private Health Insurance Plans.

Competition in health insurance markets may fail to improve health outcomes if consumers are not able to identify high quality plans. We develop and apply a novel instrumental variables framework to quantify the variation in causal mortality effects across plans and how much consumers attend to this variation. We first document large differences in the observed mortality rates of Medicare Advantage plans within local markets. We then show that when plans with high (low) mortality rates exit these markets, enrollees tend to switch to more typical plans and subsequently experience lower (higher) mortality. We derive and validate a novel "fallback condition" governing the subsequent choices of those affected by plan exits. When the fallback condition is satisfied, plan terminations can be used to estimate the relationship between observed plan mortality rates and causal mortality effects. Applying the framework, we find that mortality rates unbiasedly predict causal mortality effects. We then extend our framework to study other predictors of plan mortality effects and estimate consumer willingness to pay. Higher spending plans tend to reduce enrollee mortality, but existing quality ratings are uncorrelated with plan mortality effects. Consumers place little weight on mortality effects when choosing plans. Good insurance plans dramatically reduce mortality, and redirecting consumers to such plans could improve beneficiary health.