Spinal cord injury etiology, severity, and care in East Asia: a cross-sectional analysis of the International Spinal Cord Society Database Project.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To evaluate etiologic factors associated with spinal cord injury (SCI) severity and to identify predictive factors of reduction in SCI severity in six countries. SETTING: SCI centers in Bangladesh, India, Malaysia, Nepal, Sri Lanka, and Thailand. METHODS: Data from centers collected between October 2015 and February 2021 were analyzed using descriptive statistics and logistic regression. RESULTS: Among 2634 individuals, the leading cause of SCIs was falls (n = 1410, 54%); most occurred from ≥1 meter (n = 1078). Most single-level neurological injuries occurred in the thoracic region (n = 977, 39%). Greater than half of SCIs (n = 1423, 54%) were graded American Spinal Injury Association Impairment Scale (AIS) A. Thoracic SCIs accounted for 53% (n = 757) of all one-level AIS A SCIs. The percentage of thoracic SCIs graded AIS A (78%) was significantly higher than high cervical (52%), low cervical (48%), lumbar (24%), and sacral (31%) SCIs (p < 0.001). Regression analyses isolated predictive factors both of SCI severity and inpatient improvement. Four factors predicted severity: age, neurological level, etiology, and country of residence. Four factors predicted improvement: age, neurological level, AIS grade on intake, and country of residence. CONCLUSIONS: Findings can be used by healthcare providers and public health agencies in these countries to inform the public of the risk of SCI due to falls. Future studies should examine the social and occupational milieux of falls. Country-to-country comparisons of prehospital and inpatient care are also justified. Fall prevention policies can encourage the use of safety equipment when performing tasks at heights ≥1 meter.

The Synchronous Application of Yoga and Myofascial Release Therapy for Musculoskeletal Pain: A Case Report.

Introduction: Musculoskeletal (MSK) pain is common and costly, and conventional care is often inadequate for pain resolution. Although evidence supports movement and manual therapy treatments, the benefits of the synchronous application of these two therapies are sparsely documented and poorly understood. Case presentation: A 40-year-old female presented to a chiropractic practice within a large multispecialty clinic with chronic right-sided thoracolumbar and posterior ribcage, abdominal wall, and anterior hip pain, despite extensive medical workup and multifaceted treatment. Intervention description: Initial chiropractic treatment entailed manual therapy and yoga-based home exercise prescription. Outcome measures during the first two months of treatment fluctuated erratically. In an effort to facilitate at-home yoga practice and to bolster the patient's self-efficacy, myofascial release therapy was combined synchronously with in-clinic yoga practice ("yoga release therapy", YRT). Outcomes: The shift in treatment to YRT was associated with improvements measured on the Patient-Reported Outcomes Measurement Information System (PROMIS) instrument, including: pain rating (50 - 20), pain interference (60 - 47), sleep disturbance (54 - 37), anxiety (46 - 42), fatigue (57 - 43), physical function (32 - 51), and social function (44 - 65). Conclusion: These outcomes indicate a potential role for YRT in an integrative approach to managing MSK pain. They justify prospective research to validate YRT's efficacy and explore its mechanisms.

EsophAguS Deviation During RadiofrequencY Ablation of Atrial Fibrillation: The EASY AF Trial.

BACKGROUND: Injury to the esophagus has been reported in a high percentage of patients undergoing ablation of atrial fibrillation (AF). OBJECTIVES: This study assessed the incidence of esophageal injury in patients undergoing ablation of AF with and without an esophageal deviating device. METHODS: This prospective, randomized, multicenter, double-blinded, controlled Food and Drug Administration investigational device exemption trial compared the incidence of ablation-related esophageal lesions, as assessed by endoscopy, in patients undergoing AF ablation assigned to a control group (luminal esophageal temperature [LET] monitoring alone) compared with patients randomized to a deviation group (esophagus deviation device + LET). This novel deviating device uses vacuum suction and mechanical deflection to deviate a segment of the esophagus, including the trailing edge. RESULTS: The data safety and monitoring board recommended stopping the study early after randomizing 120 patients due to deviating device efficacy. The primary study endpoint, ablation injury to the esophageal mucosa, was significantly less in the deviation group (5.7%) in comparison to the control group (35.4%; P < 0.0001). Control patients had a significantly higher severity and greater number of ablation lesions per patient. There was no adverse event assigned to the device. By multivariable analysis, the only feature associated with reduced esophageal lesions was randomization to deviating device (OR: 0.13; 95% CI: 0.04-0.46; P = 0.001). Among control subjects, there was no difference in esophageal lesions with high power/short duration (31.8%) vs other radiofrequency techniques (37.2%; P = 0.79). CONCLUSIONS: The use of an esophageal deviating device resulted in a significant reduction in ablation-related esophageal lesions without any adverse events.

The effectiveness of clinic versus home-based, artificial intelligence-guided therapy in patients with low back pain: Non-randomized clinical trial.

BACKGROUND: Low back pain is a common cause of disability in the US with increasing financial burden on healthcare. A variety of treatment options exist to combat LBP. Home-based therapy is a low-cost option, but there is a lack of data on how it compares to therapy in clinical settings. It was hypothesized that when using artificial intelligence-guided therapy, supervised in-clinic interventions would have a greater influence on patient-reported outcomes and strength than unsupervised, home interventions. METHODS: This is a non-randomized controlled trial of 51 patients (28 female, 23 male). The investigation compared an 8-week, core-focused exercise intervention in a Clinic (supervised) versus Home (unsupervised) setting. Outcome variables included measures of strength, performance, and patient-reported outcomes related to function. Generalized linear regression (p < 0.05) was used to evaluate outcomes were evaluated with respect to sex, intervention setting, and time. FINDINGS: Male subjects exhibited greater strength (p ≤ 0.02) but not greater patient-reported outcomes (p ≥ 0.30) than females. The Clinic group exhibited slightly greater lateral pull-down strength (p = 0.002), greater eccentric phase range of motion during overhead press (p < 0.01), and shorter concentric phase duration during bench press (p < 0.01) than the Home group. Significance between groups was not observed in any other strength, performance, or patient-reported outcome (p ≥ 0.11). INTERPRETATION: A lack of consistent significance indicated that the hypothesis was not supported. AI-guided, telehealth exercise produced comparable outcomes in both home and clinical settings. Telehealth options may offer a lower-cost alternative to clinic-based exercise therapy for patients with nonspecific lower back pain.

Group differences and associations between patient-reported outcomes and physical characteristics in chronic low back pain patients and healthy controls.

BACKGROUND: Patients with chronic low back pain can exhibit altered slower gait, poor balance, and lower strength/power, and psychological dysfunctions such as pain catastrophizing and fear of movement. Few studies have investigated the relationships between physical and psychological dysfunctions. This study examined associations between patient-reported outcomes (pain interference, physical function, central sensitization, and kinesiophobia) and physical characteristics (gait, balance, and trunk sensorimotor characteristics). METHODS: Laboratory testing included a 4-m walk, balance, and trunk sensorimotor testing with 18 patients and 15 controls. Gait and balance were collected with inertial measurement units. Isokinetic dynamometry measured trunk sensorimotor characteristics. Patient-reported outcomes included PROMIS Pain Interference / Physical Function, Central Sensitization Inventory, and Tampa Scale of Kinesiophobia. Independent t-tests or Mann-Whitney U tests were used to compare between groups. Additionally, Spearman's rank correlation coefficient (rs) established associations between physical and psychological domains, and Fisher z-tests compared correlation coefficient values between groups (significance P < 0.05). FINDINGS: The patient group had worse tandem balance and all patient-reported outcomes (P < 0.05) while no group differences were observed in gait and trunk sensorimotor characteristics. There were significant correlations between worse central sensitization and poor tandem balance (rs = 0.446-0.619, P < 0.05) and lower peak force and rate of force development (rs = -0.429-0.702, P < 0.05). INTERPRETATION: Observed group differences in tandem balance agree with previous studies, indicating impaired proprioception. The current findings provide preliminary evidence that balance and trunk sensorimotor characteristics were significantly associated with patient-reported outcomes in patients. Early and period screening could help clinicians further categorize patients and develop objective treatment plans.

Inferring Negative Molecular Biomarker Data at Scale.

PURPOSE: Patients who represent the negative biomarker population, those tested for a biomarker but found to be negative, are a critical component of the growing molecular data repository. Many next-generation sequencing (NGS)-based tumor sequencing panels test hundreds of genes, but most laboratories do not provide explicit negative results on test reports nor in their structured data. However, the need for a complete picture of the testing landscape is significant. Syapse has created an internal ingestion and data transformation pipeline that uses the power of natural language processing (NLP), terminology management, and internal rulesets to semantically align data and infer negative results not explicitly stated. PATIENTS AND METHODS: Patients within the learning health network with a cancer diagnosis and at least one NGS-based molecular report were included. To obtain this critical negative result data, laboratory gene panel information was extracted and transformed using NLP techniques into a semistructured format for analysis. A normalization ontology was created in tandem. With this approach, we were able to successfully leverage positive biomarker data to derive negative data and create a comprehensive data set for molecular testing paradigms. RESULTS: The application of this process resulted in a drastic improvement in data completeness and clarity, especially when compared with other similar data sets. CONCLUSION: The ability to accurately determine positivity and testing rates among patient populations is imperative. With only positive results, it is impossible to draw conclusions about the entire tested population or the characteristics of the subgroup who are negative for the biomarker in question. We leverage these values to perform quality checks on ingested data, and end users can easily monitor their adherence to testing recommendations.

Physical clinical care and artificial-intelligence-guided core resistance training improve endurance and patient-reported outcomes in subjects with lower back pain.

BACKGROUND: Low back pain is an extremely prevalent issue with an extensive impact, ranging from decreased quality of life to lost years of productivity. Many interventions have been developed to alleviate chronic lower back pain, yet it remains a widespread problem. The objective of this study was to examine the role of artificial intelligence guided resistance training relative to clinical variables in subjects experiencing lower back pain. METHODS: 69 out of 108 enrolled and 92 accrued subjects completed the 8-week intervention. Subjects were randomized into four groups (Control, Training, Clinical, or Combined). The Training cohort received supervised artificial-intelligence-guided core-focused resistance training while the Clinical group received clinical care. The Combined group received both clinical care and artificial-intelligence-guided training and the Control group received no treatment. Participants were evaluated using functional testing and patient-reported outcomes at baseline, 4 weeks, and 8 weeks. FINDINGS: In the clinical tests, the Clinical and Combined cohorts showed increased total time for isometric extensor endurance and the Clinical cohort increased total distance traveled in the 6-min walk test at 8 weeks. The Training, Clinical, and Combined groups showed improvements in Patient-reported outcomes after 8 weeks. Most of the significant improvements were only seen at the 8-week evaluation for both the clinical evaluations and Patient-reported outcomes. The Control group did not show significant improvements in any outcome measures. INTERPRETATION: The present data indicate that core-focused interventions, including artificial-intelligence-guided moderate-resistance exercise, can increase objective functional outcomes and patient satisfaction using Patient-reported outcomes in individuals with lower back pain.

Antiemetic use and chemotherapy induced nausea and vomiting related hospitalization costs after highly or moderately emetogenic chemotherapy.

Aim: Despite numerous available antiemetics, chemotherapy induced nausea and vomiting (CINV) still affects many patients, and CINV related hospitalizations and costs often result. Materials & methods: PrecisionQ analyzed its database to evaluate CINV related hospitalizations and costs following antiemetics use including netupitant/fosnetupitant with palonosetron (NEPA), aprepitant/fosaprepitant with ondansetron (APON) or aprepitant/fosaprepitant with palonosetron (APPA) in patients receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy. Results: Database analysis identified 15,583 patient records (807 NEPA, 2023 APON, 12,753 APPA) and mean CINV related hospitalization costs were lower across all patients receiving NEPA (US$301) compared with patients receiving APON ($1006, p < 0.0001) or APPA ($321, p < 0.0001). Conclusion: NEPA is associated with lower CINV related hospitalization costs compared with APON and APPA among patients receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy.

Chemotherapy patients often experience nausea and vomiting that not only has a negative impact on the patient's quality of life but can also result in unplanned hospitalizations with high associated costs. Numerous medications and specific guidelines are available to prevent nausea and vomiting in patients with cancer. Specifically, the combination of two classes of medications (serotonin inhibitors + neurokinin type 1 inhibitors) has been shown to provide the greatest benefit. However, hospitalizations due to nausea and vomiting still occur, and providers require further information to determine the best options for their patients. In this study, the combination of netupitant/fosnetupitant with palonosetron resulted in lower hospitalization costs compared with aprepitant/fosaprepitant with ondansetron or aprepitant/fosaprepitant with palonosetron in chemotherapy patients.

Low back pain does not predict unemployment in a U.S. refugee population: A retrospective cohort study.

Background: Unemployment can limit host-community integration for refugees. Poor health is a leading cause of unemployment among refugees in the U.S. This study assesses whether low back pain (LBP) is predictive of unemployment among a group of refugees in the U.S. Methods: Electronic medical record data were collected for a total of 3,183 refugee patients. General patient characteristics (sex, age, home country, need for English interpretation, tobacco use, and illicit drug use), employment status, and mental illness and LBP diagnoses were studied. Descriptive and logistic regression analyses were used to explore relationships between LBP and unemployment. Results: Of the 12 home countries considered, seven were represented by >40 patients: Somalia (n=1696), Sudan/South Sudan (n=460), Bosnia and Herzegovina (n=280), Iraq (n=266), Ethiopia (n=261), Ukraine (n=72), and Syria (n=60). Nearly a quarter of Iraqi patients suffered from LBP as did approximately 15% of Somali, Syrian, Ethiopian, and Sudanese patients. Nearly half of Iraqi patients were unemployed, as were greater than 30% of Somali, Sudanese, Ukrainian, and Ethiopian patients. A statistically significantly higher percentage of unemployed patients suffered from LBP (17.9%) than employed patients (13.6%) (p=0.003). However, on regression analysis, LBP was not predictive of unemployment (OR: 1.12, p=0.336). Instead, predictive variables included: a patient-reported need for an English interpreter (OR: 3.35, p<.001), female sex (OR: 1.49, p<.001), mental illness (OR: 1.82, p<.001), and illicit drug use (OR: 1.92, p=0.032). Conclusions: Contrary to findings from multiple studies implicating LBP as a leading cause of unemployment in high-income countries, a diagnosis of LBP does not predict unemployment for this group of refugees in the U.S. This finding illuminates a novel dimension of the healthy immigrant effect and indicates a divergent perception of the relationship between LBP and work in the refugee population as compared to non-refugee populations studied in North America and Europe. Further investigation of refugees' perceptions of LBP in relation to work is indicated.

Customizable Natural Language Processing Biomarker Extraction Tool.

PURPOSE: Natural language processing (NLP) in pathology reports to extract biomarker information is an ongoing area of research. MetaMap is a natural language processing tool developed and funded by the National Library of Medicine to map biomedical text to the Unified Medical Language System Metathesaurus by applying specific tags to clinically relevant terms. Although results are useful without additional postprocessing, these tags lack important contextual information. METHODS: Our novel method takes terminology-driven semantic tags and incorporates those into a semantic frame that is task-specific to add necessary context to MetaMap. We use important contextual information to capture biomarker results to support Community Health System's use of Precision Medicine treatments for patients with cancer. For each biomarker, the name, type, numeric quantifiers, non-numeric qualifiers, and the time frame are extracted. These fields then associate biomarkers with their context in the pathology report such as test type, probe intensity, copy-number changes, and even failed results. A selection of 6,713 relevant reports contained the following standard-of-care biomarkers for metastatic breast cancer: breast cancer gene 1 and 2, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and programmed death-ligand 1. RESULTS: The method was tested on pathology reports from the internal pathology laboratory at Henry Ford Health System. A certified tumor registrar reviewed 400 tests, which showed > 95% accuracy for all extracted biomarker types. CONCLUSION: Using this new method, it is possible to extract high-quality, contextual biomarker information, and this represents a significant advance in biomarker extraction.

Small molecule inhibition of ATM kinase increases CRISPR-Cas9 1-bp insertion frequency.

Mutational outcomes following CRISPR-Cas9-nuclease cutting in mammalian cells have recently been shown to be predictable and, in certain cases, skewed toward single genotypes. However, the ability to control these outcomes remains limited, especially for 1-bp insertions, a common and therapeutically relevant class of repair outcomes. Here, through a small molecule screen, we identify the ATM kinase inhibitor KU-60019 as a compound capable of reproducibly increasing the fraction of 1-bp insertions relative to other Cas9 repair outcomes. Small molecule or genetic ATM inhibition increases 1-bp insertion outcome fraction across three human and mouse cell lines, two Cas9 species, and dozens of target sites, although concomitantly reducing the fraction of edited alleles. Notably, KU-60019 increases the relative frequency of 1-bp insertions to over 80% of edited alleles at several native human genomic loci and improves the efficiency of correction for pathogenic 1-bp deletion variants. The ability to increase 1-bp insertion frequency adds another dimension to precise template-free Cas9-nuclease genome editing.

Validation of a Mortality Composite Score in the Real-World Setting: Overcoming Source-Specific Disparities and Biases.

PURPOSE: This study tested whether a composite mortality score could overcome gaps and potential biases in individual real-world mortality data sources. Complete and accurate mortality data are necessary to calculate important outcomes in oncology, including overall survival. However, in the United States, there is not a single complete and broadly applicable mortality data source. It is further likely that available data sources are biased in their coverage of sex, race, age, and socioeconomic status (SES). METHODS: Six individual real-world data sources were combined to develop a high-quality composite mortality score. The composite score was benchmarked against the gold standard for mortality data, the National Death Index. Subgroup analyses were then conducted to evaluate the completeness and accuracy by sex, race, age, and SES. RESULTS: The composite mortality score achieved a sensitivity of 94.9% and specificity of 92.8% compared with the National Death Index, with concordance within 1 day of 98.6%. Although some individual data sources show significant coverage gaps related to sex, race, age, and SES, the composite score maintains high sensitivity (84.6%-96.1%) and specificity (77.9%-99.2%) across subgroups. CONCLUSION: A composite score leveraging multiple scalable sources for mortality in the real-world setting maintained strong sensitivity, specificity, and concordance, including across sex, race, age, and SES subgroups.

Risk Factors for Repeat Infection and Mortality After Extraction of Infected Cardiovascular Implantable Electronic Devices.

OBJECTIVES: This study sought to investigate the factors associated with repeat infection following lead extraction procedures. BACKGROUND: Although lead extraction is an essential therapy for patients with cardiovascular implantable electronic device (CIED) infection, repeat infection still occurs in some patients. METHODS: The authors reviewed data for consecutive patients who underwent extraction of infected CIEDs from August 2003 to May 2019. Repeat infection was defined as infective endocarditis, sepsis with no alternative focus, or pocket infection after extraction of infected CIEDs. RESULTS: Extraction of infected CIEDs was performed in 496 patients. The most commonly implicated pathogen was Staphylococcus aureus (n = 188). In 449 patients (90.5%), all leads were completely extracted using only transvenous techniques. Thirty-three patients (6.7%) underwent surgical lead extraction, and 14 (2.8%) had retained leads or lead components. After a median follow-up of 352 [40 to 1,255] days after CIED extraction, 144 patients (29.0%) died. Repeat infection occurred in 47 patients (9.5%) with the median time from the extraction to repeat infection of 103 [45 to 214] days. In multivariable analysis, presence of a left ventricular assist device, younger age at extraction, and S. aureus infection were independent predictors of repeat infection. Additionally, chronic kidney disease, congestive heart failure, presence of septic emboli, S. aureus infection, and occurrence of major complications were independent predictors of increased mortality. CONCLUSIONS: Patients with S. aureus infection have a high risk of repeat infection and poor prognosis after CIED extraction. Repeat infection is also predicted by younger age and the presence of a left ventricular assist device, whereas mortality was predicted by congestive heart failure, chronic kidney disease, and septic emboli.

Periaortic Ventricular Tachycardias in Nonischemic Cardiomyopathy: Substrate and Electrocardiographic Correlations.

BACKGROUND: Periaortic fibrotic ventricular tachycardia (VT) substrate is common in nonischemic cardiomyopathy (NICM), often intramural, and difficult to ablate. We sought to better characterize normal and abnormal periaortic voltage map parameters and NICM periaortic VTs. METHODS: In 15 patients without heart disease, the 5th percentile of endocardial voltage for increasing distance from the aortic valve ring was determined. In 53 consecutive patients with NICM (64±11 years; left ventricular ejection fraction 31±10%) undergoing ablation of recurrent VT, periaortic electrogram voltage and VT characteristics were analyzed. RESULTS: In healthy patients, the fifth percentile of the bipolar voltage increased proportional to the distance from the aortic valve ring, from 1.0 mV at 1 cm to 1.5 mV at 1.5 cm; the corresponding unipolar voltage cutoffs were 5.0 and 7.5 mV. A total of 160 VTs were induced in 53 patients with NICM, of which 28 VTs in 20 patients had periaortic origins. Periaortic VTs were associated with similar periaortic bipolar voltage, but lower UVs consistent with intramural fibrosis as an important substrate. Periaortic VTs could be divided into left and right bundle branch block forms with mapping showing right septal and lateral exits. Left bundle branch block VTs were more often acutely abolished with ablation (100% versus 69%; P=0.034), but with a 23% incidence of heart block. Greater extent of low voltage was associated with more induced VTs and worse acute outcome. CONCLUSIONS: Adjusting voltage parameters based on distance from the aortic valve may improve definition of left ventricular outflow tract arrhythmia substrate. Periaortic VTs are common in NICM, often associated with intramural substrate and can be divided into left bundle branch block and right bundle branch block types associated with different ablation outcomes and risks.

Evaluating automated titre score as an alternative to continuous flow analysis for the prediction of passive anti-D in pregnancy.

OBJECTIVES: To evaluate the potential of the automated titre score (TS) as an alternative method to continuous flow analysis (CFA) for the prediction of the nature of anti-D in pregnancy. BACKGROUND: The 2016 revised British Society for Haematology (BSH) antenatal guidelines recommended a measurement of anti-D concentration by CFA to ensure the detection of potential immune anti-D. Due to high referral costs and resource pressures, uptake has been challenging for hospital laboratories. Serious Hazards of transfusion (SHOT) data have previously shown that this has contributed to missed antenatal follow ups for women with immune anti-D and neonates affected by haemolytic disease of the fetus/newborn. METHODS/MATERIALS: In this multicentre comparative study, samples referred for CFA quantification were also tested by an ORTHO VISION automated anti-D indirect antiglobulin test (IAT) serial dilution and then converted to TS. CFA results and history of anti-D prophylaxis were used to categorise samples as passive or immune, with the aim of determining a potential TS cut-off for CFA referral of at risk patients. RESULTS: Five UK National Health Service (NHS) trusts generated a total of 196 anti-D TS results, of which 128 were classified as passive and 68 as immune. Diagnostic testing of CFA and TS values indicated a TS cut-off of 35 to assist in distinguishing the nature of anti-D. Using this cut-off, 175 (89%) results were correctly assigned into the passive or immune range, giving a specificity of 92.19% and a negative predictive value of 91.47%. CONCLUSION: TS in conjunction with clinical and anti-D prophylaxis history can be used as a viable and cost-effective alternative to CFA in a hospital laboratory setting.

Candidemia in patients with cardiovascular implantable electronic devices.

PURPOSE: Current guidelines recommend complete extraction of cardiovascular implantable electronic devices (CIEDs) in the case of persistent or recurrent fungemia without other identifiable sources, though supporting evidence is lacking. We sought to evaluate the prognosis of patients with candidemia and CIEDs. METHODS: Twelve consecutive patients (54 ± 12 years, 8 male) with CIED and concurrent candidemia were reviewed. RESULTS: At the time of diagnosis with candidemia, seven patients were immunocompromised, six were on long-term antibacterial therapy, two were intravenous drug users, four were on chronic hemodialysis, and six had a central venous catheter. Four patients were confirmed as definite CIED infection as vegetation was visible on lead by echocardiogram. The other 8 patients were considered possible CIED infection with candidemia of unknown focus. All patients with visible vegetation underwent CIED removal without complications, and other patients were initially managed non-operatively. After 1 year of follow-up, 7 patients had died and at extended follow-up, all patients without lead removal died while 3 of 4 patients with lead extraction survived. Of note, 50% of deaths in the patients without lead removal were associated with fungal sepsis. CONCLUSIONS: Candida fungemia is associated with a high mortality. CIED removal should be an early consideration in these patients even if lead vegetations are not seen.

Chemogenetic System Demonstrates That Cas9 Longevity Impacts Genome Editing Outcomes.

Prolonged Cas9 activity can hinder genome engineering as it causes off-target effects, genotoxicity, heterogeneous genome-editing outcomes, immunogenicity, and mosaicism in embryonic editing-issues which could be addressed by controlling the longevity of Cas9. Though some temporal controls of Cas9 activity have been developed, only cumbersome systems exist for modifying the lifetime. Here, we have developed a chemogenetic system that brings Cas9 in proximity to a ubiquitin ligase, enabling rapid ubiquitination and degradation of Cas9 by the proteasome. Despite the large size of Cas9, we were able to demonstrate efficient degradation in cells from multiple species. Furthermore, by controlling the Cas9 lifetime, we were able to bias the DNA repair pathways and the genotypic outcome for both templated and nontemplated genome editing. Finally, we were able to dosably control the Cas9 activity and specificity to ameliorate the off-target effects. The ability of this system to change the Cas9 lifetime and, therefore, bias repair pathways and specificity in the desired direction allows precision control of the genome editing outcome.