Enhancing Pragmatic Language skills for Young children with Social communication difficulties (E-PLAYS-2) trial: study protocol for a cluster-randomised controlled trial evaluating a computerised intervention to promote communicative development and collaborative skills in young children.

BACKGROUND: A number of children experience difficulties with social communication and this has long-term deleterious effects on their mental health, social development and education. The E-PLAYS-2 study will test an intervention ('E-PLAYS') aimed at supporting such children. E-PLAYS uses a dyadic computer game to develop collaborative and communication skills. Preliminary studies by the authors show that E-PLAYS can produce improvements in children with social communication difficulties on communication test scores and observed collaborative behaviours. The study described here is a definitive trial to test the effectiveness and cost-effectiveness of E-PLAYS delivered by teaching assistants in schools. METHODS: The aim of the E-PLAYS-2 trial is to establish the effectiveness and cost-effectiveness of care as usual plus the E-PLAYS programme, delivered in primary schools, compared to care as usual. Cluster-randomisation will take place at school level to avoid contamination. The E-PLAYS intervention will be delivered by schools' teaching assistants. Teachers will select suitable children (ages 5-7 years old) from their schools using guidelines provided by the research team. Assessments will include blinded language measures and observations (conducted by the research team), non-blinded teacher-reported measures of peer relations and classroom behaviour and parent-reported use of resources and quality of life. A process evaluation will also include interviews with parents, children and teaching assistants, observations of intervention delivery and a survey of care as usual. The primary analysis will compare pragmatic language scores for children who received the E-PLAYS intervention versus those who did not at 40 weeks post-randomisation. Secondary analyses will assess cost-effectiveness and a mixed methods process evaluation will provide richer data on the delivery of E-PLAYS. DISCUSSION: The aim of this study is to undertake a final, definitive test of the effectiveness of E-PLAYS when delivered by teaching assistants within schools. The use of technology in game form is a novel approach in an area where there are currently few available interventions. Should E-PLAYS prove to be effective at the end of this trial, we believe it is likely to be welcomed by schools, parents and children. TRIAL REGISTRATION: ISRCTN 17561417, registration date 19th December 2022. PROTOCOL VERSION: v1.1 19th June 2023.

Robot-Assisted Pelvic Dissection for Enlarged Lymph Nodes in Melanoma Improves Recovery with Equivalent Oncological Outcomes to Open Pelvic Dissection.

BACKGROUND: Robot-assisted pelvic lymph node dissection (rPLND) has been reported in heterogenous groups of patients with melanoma, including macroscopic or at-high-risk-for microscopic metastasis. With changing indications for surgery in melanoma, and availability of effective systemic therapies, pelvic dissection is now performed for clinically detected bulky lymph node metastasis followed by adjuvant drug therapy. rPLND has not been compared with open pelvic lymph node dissection (oPLND) for modern practice. METHODS: All patients undergoing pelvic node dissection for macroscopic melanoma at a single institution were reviewed as a cohort, observational study. RESULTS: Twenty-two pelvic lymph node dissections were identified (8 oPLND; 14 rPLND). The number of pelvic lymph nodes removed was similar (median oPLND 6.5 (interquartile range [IQR] 6.0-12.5] versus rPLND 6.0 [3.75-9.0]), with frequent matted nodes (11/22, 50.0%). Operative time (median oPLND 130 min [IQR 95.5-182] versus rPLND 126 min [IQR 97.8-160]) and complications (Clavien-Dindo scale) were similar. Length of hospital stay (median 5.34 days (IQR 3.77-6.94) versus 1.98 days (IQR 1.39-3.50) and time to postoperative adjuvant therapy (median 11.6 weeks [IQR 10.6-18.5] versus 7.71 weeks [IQR 6.29-10.4]) were shorter in the rPLND group. No differences in pelvic lymph node recurrence (p = 0.984), distant metastatic recurrence (p = 0.678), or melanoma-specific survival (p = 0.655) were seen (median follow-up 21.1 months [rPLND] and 25.7 months [oPLND]). CONCLUSIONS: rPLND is an effective way to remove bulky pelvic lymph nodes in melanoma, with a shorter recovery and reduced interval to initiating adjuvant therapy compared with oPLND. This group of patients may especially benefit from neoadjuvant systemic approaches to management.

What is the impact of a Hepatitis C 'test, trace and treat' pilot using peer workers?

Chronic Hepatitis C virus (HCV) infection is a major cause of morbidity and deaths worldwide. HCV treating teams are working toward the goal of eliminating HCV by 2030. People who inject drugs (PWIDs) are at high risk of HCV but contact tracing is not routine practice. Here, we present the outcomes of a HCV 'test, trace and treat' pilot using peer workers to test contacts of individuals with HCV. PWIDs with HCV were invited to participate when they presented for treatment. For those agreeing to participate, a peer approached them to invite potential contacts for HCV testing. Data were collected on uptake, HCV test results, treatment rates and reasons for declining. Overall, 295 individuals (162 recent HCV [<1 year], 69 reinfections, 64 known chronic HCV) were invited to participate, of whom 147 (50%) agreed and 30 (20% of those agreeing) brought forward 120 contacts for testing. Of these, 44 (37%) were HCV RNA positive, including 23 who were not known to services. 34 (77%) started antiviral treatment. HCV RNA positivity was highest in contacts of reinfections (45%) compared with recent HCV (33%) and known chronic HCV (25%). The most common reason for index individuals declining participation was that they reported no longer being in contact with individuals from their injecting network (65%). In conclusion, half of PWIDs with HCV agreed to participate in the pilot, but only 20% of these brought contacts forward. The frequency of active HCV was high in the contacts and the majority started antiviral treatment.

Women's experiences of Hyperemesis Gravidarum (HG) and of attending a dedicated multi-disciplinary hydration clinic.

PROBLEM: Hyperemesis Gravidarum (HG) is a severe form of nausea and vomiting in pregnancy that affects 1-3 % of women and has profound nutritional, physical and psychological consequences. Previous research identified that women with HG report inadequate infrastructure for day case management. INTRODUCTION: A multi-disciplinary HG day case service (IRIS Hydration Clinic) was launched and provides routine care for women with HG in a dedicated unit. The multi-disciplinary team involves midwives, dietitians, obstetricians and perinatal mental health. AIMS: To explore women's experiences of HG and of attending the dedicated clinic. METHODS: Ten interviews were conducted with women who attended the clinic. Data were transcribed and analysed using Reflexive Thematic Analysis. FINDINGS: The physical and psychological impact of HG was captured. The appreciation for the dedicated clinic was a common theme, regarding having somewhere specific for treatment rather than ad-hoc treatment. 'Relationships' was a significant theme - women described the benefits of continuity of care and the positive impact of peer support. Areas for improvement were explored, such as expansion and extra sensitivity around some women's issues around weight gain/loss. DISCUSSION: HG causes significant ill-health and its impact remains undervalued. Women had highly positive experiences of attending the dedicated HG clinic. The impact of continuity and individualized care in a day-case setting improved women's experiences of this condition. CONCLUSION: The dedicated HG clinic was highly valued by women experiencing the condition. The IRIS clinic provides much-needed validation for a medical condition with little understanding from the general public or many healthcare professionals.

Endoscopy training through the COVID-19 pandemic: maintaining procedural volumes and key performance standards.

Objective: Endoscopy departments have experienced considerable challenges in the provision of endoscopy services since the start of the COVID-19 pandemic. Several studies have reported a reduction of procedures performed by trainee endoscopists during the pandemic. The aim of this study was to assess the impact on colonoscopy training and quality in an academic centre throughout successive waves of the pandemic. Methods: This was a single-centre, retrospective, observational study comparing colonoscopies performed at a tertiary endoscopy centre in Ireland at different stages of the pandemic with those performed during a similar time frame prepandemic. Data were collected using electronic patient records. Primary outcomes were procedure volumes, adenoma detection rate and mean adenoma per procedure. Results: In the prepandemic period, 798 colonoscopies were performed. During the same period in 2020, 172 colonoscopies were performed. In 2021, during the third wave of the pandemic, 538 colonoscopies were performed. Percentages of colonoscopies performed by trainees were 46.0% (n=367) in 2019, 25.6% (n=44) in 2020 and 45.2% (n=243) in 2021. Adenoma detection rate was 21.3% in 2019, 38.6% in 2020 and 23.9% in 2021. Mean adenoma per procedure was 0.45 in 2019, 0.86 in 2020 and 0.49 in 2021. Caecal intubation rate was 90.74% in 2019, 90.9% in 2020 and 95.88% in 2021. Conclusion: The COVID-19 pandemic initially had a negative impact on overall colonoscopy volumes and training. Despite a reduction in procedural volume, key performance standards were maintained by trainees. Maintenance of hands-on training is essential to allow trainees achieve and retain competency in endoscopy.

Validation and Comparison of Nutrient Intakes from Two Dietary Questionnaires Developed for the Multiethnic Cohort Study.

BACKGROUND: Quantitative food frequency questionnaires (QFFQs) are often used to measure dietary intakes in large cohort studies but the impact of updating these questionnaires over time is not often examined. OBJECTIVE: This study compared nutrient intakes estimated from two different QFFQs to each other and to intakes calculated from three 24-hour dietary recalls (24HDRs). DESIGN: This study used a cross-sectional design. PARTICIPANTS/SETTING PARTICIPANTS: Participants (N = 352) were members of the Multiethnic Cohort Study from five racial and ethnic groups (African American, Japanese American, Latino American, Native Hawaiian, and White) who lived in Hawaii and Los Angeles. They were recruited in 2010 and asked to complete two QFFQs, two months apart, and three 24HDRs in the time between completion of the QFFQs. One questionnaire had been developed for a baseline survey (baseline QFFQ) at the start of the Multiethnic Cohort Study during 1993-1996, and the other was updated for a follow-up study 10 years later (10-year QFFQ). MAIN OUTCOME MEASURES: Daily intakes of energy and nine nutrients were estimated from both QFFQs, and from the average of three 24HDRs. STATISTICAL ANALYSES PERFORMED: Pearson's correlation coefficients were calculated between log-transformed nutrient intakes from each QFFQ and the 24HDRs and between the two QFFQs overall, by sex, and by race and ethnicity. RESULTS: Correlations for the 10-year QFFQ with the 24HDRs (average = 0.45) were higher than for the baseline QFFQ (average = 0.41), although the differences were not statistically significant. The increase in correlations was particularly pronounced for Native Hawaiian and African American participants. When absolute values were adjusted for energy intake, the average correlations were higher at 0.57 for the baseline QFFQ and 0.58 for the 10-year QFFQ overall and this pattern was seen in most racial and ethnic subgroups. The average correlations between the two QFFQs were 0.73 for both absolute intakes and nutrient densities overall. CONCLUSIONS: Correlations of nutrient intakes between the two QFFQs and 24HDRs were similar, and intakes from the two QFFQs were highly correlated. QFFQs updated for changes to the food supply may provide improved assessment for cohort studies that include diverse populations.

Bilateral patellar tendon rupture following low-energy trauma in a young patient without predisposing risk factors.

We describe the case of a 25 year old male who presented with a bilateral patellar tendon ruptures without any of the identified risk factors for tendon injuries. Our patient is the youngest adult reported to date with confirmed bilateral, unprovoked, patellar tendon ruptures. We accompany our case with an up-to-date literature review on this topic. A degree of clinical suspicion is required for emergency room physicians as well as orthopaedic surgeons assessing such patients to avoid missing bilateral injuries. Point of care ultrasound may be utilised when there is doubt regarding the diagnosis. Prompt surgical management and a specific rehabilitation programme are both required to ensure maximum recovery of these patients.

Phosphaturic Mesenchymal Tumor of the Ankle: A Case Report and Review of the Literature.

We report the case of a phosphaturic mesenchymal tumor of the ankle; an extremely rare lesion that causes osteomalacia via paraneoplastic renal phosphate wasting. A 41-year-old man was referred to plastic surgery with a swelling over the anterior ankle, which had been increasing in size for 1 year. Focused ultrasound assessment was inconclusive, but excision biopsy demonstrated features in keeping with a phosphaturic mesenchymal tumor. Evidence of tumor-induced osteomalacia was subsequently identified on review of historical biochemistry. The patient was followed-up for 1 year with normalization of serum phosphate. In this case report, we present a discussion of the differential diagnosis for foot and ankle soft tissue lesions, and a review of the literature regarding the diagnosis and management of these tumors. Accurate identification of any soft tissue lesion on clinical examination alone is extremely challenging and excision biopsy should be considered in cases of diagnostic uncertainty.

Paediatric neurosurgical implications of a ribosomopathy: illustrative case and literature review.

Ribosomopathies are rare, recently defined entities. One of these, Labrune syndrome, is recognisable radiologically by its distinctive triad of leukoencephalopathy, intracranial calcifications and cysts (LCC). These cysts may have neurosurgical implications at different ages because of their progressive expansion and local mass effect. The aetiology of LCC is related to a widespread cerebral microangiopathy and is due to a genetic mutation in SNORD118, responsible for stabilisation of the large ribosomal subunit during assembly.

Lumbar spinal intraosseous schwannoma: a non-operative approach.

Intraosseous schwannomas are benign tumours composed of nerve sheath cells, most commonly affecting the mandible and sacrum. Such intraosseous schwannomas in the vertebra can result in spinal instability causing deformity, pain and even neurological compression. Vertebral involvement in the lumbar spine is extremely rare. A case of a schwannoma of the lumbar spine at the level of L3/L4 is presented. It resulted in progressive lower back pain and right lower limb radiculopathy. The clinical findings, radiological reports and histological diagnosis of this case, along with a review of the literature, are presented. The rationale for non-surgical management of this rare benign tumour is also explored.

Evolving treatment landscape: 18 years of managing melanoma in a single patient.

A 57-year-old woman diagnosed with primary melanoma was managed with a wide variety of treatments over 18 years. Given her long history of disease, the array of therapies she has received range from those no longer recommended to those recently approved. This case highlights the extraordinary rate at which both the medical and surgical melanoma treatment landscape has evolved, alongside how professional consensus has changed over the past two decades. It also demonstrates the innovation and collaboration required between the patient and the multidisciplinary team, as well as how external factors such as national guidelines, eligibility for clinical trials and drug funding in the National Health Service (NHS) alter a management plan, presenting yet another set of challenges when managing cancer patients in the modern era.

Lymph node dissections in cutaneous malignancy: Where are we now? A review of 10 years' experience at a tertiary centre.

The surgical management of cutaneous malignancies has evolved over recent years with the introduction of novel medical therapies and an increasing emphasis upon early adjuvant systemic therapy. As such, completion lymph node dissection (cLND) is now no longer recommended following a positive sentinel lymph node biopsy (SLNB) in melanoma. We evaluated our ten-year practice at a regional tertiary centre, assessing the change in lymph node dissection (LND) caseload volume, anatomical distribution, and indication for the procedure. A retrospective search was carried out of all LNDs performed by the Plastic Surgery department at Cambridge University Hospitals NHS Trust, UK from 1 January 2010 to 31 December 2019. Case notes were retrospectively analysed for each procedure, with the site and pathology recorded. A total of 491 LNDs were performed over the 10-year period. Surgical volume peaked in 2015 with 67 cases, followed by a decline to 41 cases in 2019. The number of neck dissections increased over the decade, as well as the proportion of cases due to macroscopic nodal disease. We sub-analysed the number of LNDs in three contiguous 18-month intervals, corresponding to changes in practice due to evidence from the DeCOG and MSLT-II Trials. We found a 41.67% reduction in LNDs caseload between July 2018-Dec 2019, compared to a similar period prior to trial evidence (July 2015-Dec 2016) (p=0.0.14). In summary, the surgical volume of LNDs has decreased significantly since 2018, reflecting emerging evidence and changes to national guidelines. This will require ongoing monitoring for workforce planning and surgical training.

A Dietary Supplement Frequency Questionnaire Correctly Ranks Nutrient Intakes in US Older Adults When Compared to a Comprehensive Dietary Supplement Inventory.

BACKGROUND: Dietary supplements are commonly taken by adults in the United States and can contribute substantially to daily nutrient intakes. Short supplement-use questionnaires are often used in dietary surveys, but their accuracy has not been well studied. OBJECTIVES: The primary objective was to evaluate the accuracy of a short, self-administered supplement frequency questionnaire (SFQ) relative to a comprehensive 1-y inventory of supplement use. A secondary objective was to compare SFQ responses for participants in the intensive measurement study to those from a control group to investigate a possible research participation effect. METHODS: The Supplement Reporting study enrolled 1029 older adults in 2005-2006, with a mean age of 67.8 y, who participated in the Multiethnic Cohort and reported regular use of dietary supplements. Of these, 375 were interviewed quarterly to collect detailed information on types and amounts of dietary supplements used, while 654 served as the control group. All participants completed 2 SFQs, 1 y apart. RESULTS: Agreement between the 2 instruments in use at least weekly ranged from 88% to 97% for 15 of 16 supplement types, with a lower agreement of 74% for vitamin D. The correlations of nutrient intakes from supplements between the 2 instruments were high, ranging from 0.48 to 0.75, except for iron (r = 0.29). However, mean nutrient intakes as reported on the SFQ were higher than intakes from the inventory for most nutrients, sometimes twice as high. Nutrient intakes based on the SFQ were similar for the inventory and control groups, at both baseline and the end of the study. CONCLUSIONS: A self-administered short SFQ can be used in large surveys to identify participants who use 16 categories of dietary supplements at least once a week and can correctly rank participant intakes of nutrients. However, the SFQ does not accurately estimate absolute levels of nutrient intakes from supplements.

Overcoming hurdles to intervention studies with autistic children with profound communication difficulties and their families.

LAY ABSTRACT: Autistic children who speak few or no words or who have an intellectual disability are the most in need of new understandings and treatments, but the most often left out of the research that can bring these benefits. Researchers perceive difficulties around compliance with instructions, testing, challenging behaviours and family stress. Although research with these children can indeed be difficult, their continuing exclusion is unethical and unacceptable. Drawing on our experiences testing a possible treatment for children with profound autism, we provide 10 practical guidelines related to (1) interacting physically, (2) combining play and testing, (3) responding to challenging behaviour, (4) finding suitable tests, (5) relationships with parents, (6) relationships with siblings, (7) involving stakeholders, (8) planning the testing times, (9) the role of the clinical supervisor and (10) recruiting and retaining participants. We hope that these guidelines will prepare and embolden other research teams to work with profoundly autistic children, ending their historical exclusion from research. These guidelines also could be useful for conducting research with children with intellectual disabilities.

Regulation and validation of smartphone applications in plastic surgery: It's the Wild West out there.

BACKGROUND AND PURPOSE: The use of smartphone applications is ubiquitous within healthcare. Over recent years there have been multiple applications developed within the field of plastic surgery. In the UK, applications with a medical purpose should be registered with the Medicines and Healthcare products Regulatory Authority (MHRA) as a medical device. The aim of this study was to evaluate plastic surgery specific smartphone applications designed for healthcare professional usage, and determine what proportion meet the criteria of a medical device and are suitably certified. METHODS: A systematic review of the Apple and Google Play App stores was carried out using search terms relevant to plastic surgery. Data was extracted from the app store listing, developer website and the contents of each application. Each application was evaluated against the criteria given by the MHRA to determine whether it constituted a medical device. RESULTS: 215 applications for plastic surgery healthcare professionals were identified, of which 22 met the definition of a medical device. Only 14% (n = 3) of these applications were appropriately certified, 14% (n = 3) were validated in peer-reviewed literature and 45% (n = 10) had documented medical professional involvement. CONCLUSION: Most applications with a medical purpose were not certified as a medical device, had not been validated in any peer-reviewed research, and did not have any documented involvement of medical professionals. The potential consequences of such applications operating incorrectly are stark and represent a risk to patient safety. Usage of multiple applications in a single patient encounter may compound error and safety of clinical care.

Evaluating 'Enhancing Pragmatic Language skills for Young children with Social communication impairments' (E-PLAYS): a feasibility cluster-randomised controlled trial.

BACKGROUND: This article reports the results from a feasibility study of an intervention ('E-PLAYS') aimed at supporting children who experience difficulties with social communication. E-PLAYS is based around a dyadic computer game, which aims to develop collaborative and communication skills. A pilot study found that when E-PLAYS was delivered by researchers, improvements on communication test scores and on collaborative behaviours were observed. The aim of this study was to ascertain the feasibility of running a full-scale trial to test the effectiveness of E-PLAYS in a National Health Service (NHS) setting with delivery by speech and language therapists and teaching assistants. METHODS: The study was a two-arm feasibility cluster-randomised controlled trial of the E-PLAYS intervention with a treatment as usual control arm. Data relating to recruitment and retention, treatment fidelity, acceptability to participants, suitability of outcomes and feasibility of collecting health economic measures and of determining cost-effectiveness were collected. Speech and language therapists selected suitable children (ages 4-7 years old) from their caseload. E-PLAYS intervention (experimental group) was then delivered by teaching assistants overseen by speech and language therapists. The control group received usual care. Assessments included blinded language measures and observations, non-blinded teacher-reported measures of peer relations and classroom behaviour and non-blinded parent-reported use of health and education resources and quality of life. RESULTS: Planned recruitment was for 70 children, in the event, 50 children were recruited which was sufficient for feasibility purposes. E-PLAYS was very highly rated by children, teaching assistants and speech and language therapists and treatment fidelity did not pose any issues. We were able to collect health economic data which suggests that E-PLAYS would be a low-cost intervention. CONCLUSION: Based on recruitment, retention and adherence rates and our outcome measures, a full-scale randomised controlled trial estimated appears feasible and warranted to assess the effectiveness of E-PLAYS for use by the NHS and schools. TRIAL REGISTRATION: ISRCTN 14818949 (retrospectively registered).

Planning Nutritionally Adequate Diets for Groups: Methods Used to Develop Recommendations for a Child and Adult Care Food Program.

Planning nutritionally adequate intakes for large groups of people presents many challenges. Because of between-person variations in both food choices and nutrient requirements, it is necessary to examine nutrient intake distributions and select a Target Median Intake (TMI) that will lead to a low prevalence of inadequate nutrient intakes. The TMI may then be used to guide a feeding or education program. A comprehensive report from the Institute of Medicine evaluated nutrient intakes from the NHANES and recommended new meal patterns for all age groups (other than infants) served by the Child and Adult Day Care Food Program, which provides meals and snacks to children and adults in a variety of care settings. The Estimated Average Requirement, a DRI value, for each nutrient of interest was used to estimate both the prevalence of inadequate intakes as well as the changes in the intake distribution that are needed to reduce unacceptably high levels of inadequacy. For nutrients with an Adequate Intake (AI), the prevalence of inadequacy could not be estimated, but the AI could be used as the TMI. Simultaneously, it was important to ensure that the new intake distributions did not result in intakes that exceeded the Tolerable Upper Intake Level for any nutrient. Data for 2- to 4-y-old children are presented in detail to illustrate this process. Of 18 nutrients examined, analyses showed that intakes of vitamin E, potassium, and fiber should be increased, while intakes of sodium should be decreased. If more recent nutrient standards are used, revised assessments show that calcium intake should also be increased, while potassium intake is adequate. These methods and results should be useful when designing feeding programs for other population groups within the United States, as well as in other countries.

Neurosurgery specialty training in the UK: What you need to know to be shortlisted for an interview.

Neurosurgery is one of the most competitive specialties in the UK. In 2019, securing an ST1 post in neurosurgery corresponds to competition ration of 6.54 whereas a CST1 post 2.93. Further, at ST3 level, neurosurgery is the most competitive. In addition, the number of neurosurgical training posts are likely to be reduced in the coming years. A number of very specific shortlisting criteria, aiming to filter and select the best candidates for interview exist. In the context of the high competition ratios and the specific shortlisting criteria, developing an interest in the neurosciences early on will allow individuals more time to meet the necessary standards for neurosurgery. Here, we aim to outline the shortlisting criteria and offer advice on how to achieve maximum scores, increasing the likelihood to be shortlisted for an interview.

ctDNA monitoring using patient-specific sequencing and integration of variant reads.

Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of >105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to parts per million. This resulted in median area under the curve (AUC) values of 0.98 in advanced cancers and 0.80 in early-stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that INVAR may be applied without requiring personalized sequencing panels so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.