Nevin Manimala

Neurosurg Focus. 2024 Jul;57(1):E12. doi: 10.3171/2024.4.FOCUS24140.

ABSTRACT

OBJECTIVE: This study aimed to determine the validity of quantitative pupillometry to predict the length of time for return to full activity/duty after a mild traumatic brain injury (mTBI) in a cohort of injured cadets at West Point.

METHODS: Each subject received baseline (T0) quantitative pupillometry, in addition to evaluation with the Balance Error Scoring System (BESS), Standardized Assessment of Concussion (SAC), and Sport Concussion Assessment Tool 5th Edition Symptom Survey (SCAT5). Repeat assessments using the same parameters were conducted within 48 hours of injury (T1), at the beginning of progressive return to activity (T2), and at the completion of progressive return to activity protocols (T3). Pupillary metrics were compared on the basis of length of time to return to full play/duty and the clinical scores.

RESULTS: The authors’ statistical analyses found correlations between pupillometry measures at T1, including end-initial diameter and maximum constriction velocity, with larger change and faster constriction predicting earlier return to play. There was also an association with maximum constriction velocity at baseline (T0), predicting faster return to play.

CONCLUSIONS: The authors conclude that that pupillometry may be a valuable tool for assessing time to return to duty from mTBI by providing a measure of baseline resiliency to mTBI and/or autonomic dysfunction in the acute phase after mTBI.

PMID:38950435 | DOI:10.3171/2024.4.FOCUS24140

J Nerv Ment Dis. 2024 Jul 1. doi: 10.1097/NMD.0000000000001787. Online ahead of print.

ABSTRACT

The aim is to identify the causes of physical and emotional health disorders in men in terms of intimate interaction with partners, as well as how they can be prevented. The research used comparison, analysis, statistical methods, and surveys. The need for people to discover and study sexual health issues in the modern world in order to support not only the physical, but also the psychological aspects of their body, as well as the impact of lifestyle on this process, is shown. The research was conducted to better understand all diseases that are based on the deterioration of the psycho-emotional state of men, which leads to sexual disorders. A more detailed study of this topic will allow to better select treatment for patients and find different approaches to the problem in the future.

PMID:38950428 | DOI:10.1097/NMD.0000000000001787

Ann Intern Med. 2024 Jul 2. doi: 10.7326/M23-3236. Online ahead of print.

ABSTRACT

BACKGROUND: In patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) on the risk for kidney failure with replacement therapy (KFRT) and death remain unclear.

PURPOSE: To examine the association of ACEi or ARB treatment initiation, relative to a non-ACEi or ARB comparator, with rates of KFRT and death.

DATA SOURCES: Ovid Medline and the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium from 1946 through 31 December 2023.

STUDY SELECTION: Completed randomized controlled trials testing either an ACEi or an ARB versus a comparator (placebo or antihypertensive drugs other than ACEi or ARB) that included patients with a baseline estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m².

DATA EXTRACTION: The primary outcome was KFRT, and the secondary outcome was death before KFRT. Analyses were done using Cox proportional hazards models according to the intention-to-treat principle. Prespecified subgroup analyses were done according to baseline age (<65 vs. ≥65 years), eGFR (<20 vs. ≥20 mL/min/1.73 m²), albuminuria (urine albumin-creatinine ratio <300 vs. ≥300 mg/g), and history of diabetes.

DATA SYNTHESIS: A total of 1739 participants from 18 trials were included, with a mean age of 54.9 years and mean eGFR of 22.2 mL/min/1.73 m², of whom 624 (35.9%) developed KFRT and 133 (7.6%) died during a median follow-up of 34 months (IQR, 19 to 40 months). Overall, ACEi or ARB treatment initiation led to lower risk for KFRT (adjusted hazard ratio, 0.66 [95% CI, 0.55 to 0.79]) but not death (hazard ratio, 0.86 [CI, 0.58 to 1.28]). There was no statistically significant interaction between ACEi or ARB treatment and age, eGFR, albuminuria, or diabetes (P for interaction > 0.05 for all).

LIMITATION: Individual participant-level data for hyperkalemia or acute kidney injury were not available.

CONCLUSION: Initiation of ACEi or ARB therapy protects against KFRT, but not death, in people with advanced CKD.

PRIMARY FUNDING SOURCE: National Institutes of Health. (PROSPERO: CRD42022307589).

PMID:38950402 | DOI:10.7326/M23-3236

Pediatr Emerg Care. 2024 Jul 1. doi: 10.1097/PEC.0000000000003233. Online ahead of print.

ABSTRACT

OBJECTIVE: Bicycle helmet use has repeatedly been shown to protect riders from serious injury. Despite this, a majority of children and adolescents do not regularly wear helmets. Our primary objective was to determine if an emergency department (ED)-based helmet distribution program could increase the amount of time children report wearing helmets.

METHODS: This was a prospective cohort study of children aged 3 to 17 years presenting to the ED of an urban, tertiary care hospital. Participants were surveyed on their helmet use habits and perceptions regarding the efficacy and importance of helmets. Participants then received a bicycle helmet along with safety counseling in the ED and bicycle safety handouts provided by the American Academy of Pediatrics. Participants were contacted for follow-up 8 weeks after enrollment.

RESULTS: We enrolled a total of 94 patients. Post-intervention surveys were obtained from 47% of participants. Our helmet program resulted in a statistically significant increase in the amount of time children reported wearing bicycle helmets. Prior to ED intervention, 48% of participants reported wearing a helmet “most of the time” or “all of the time.” After participating, 86% of participants indicated that they wore a helmet “most of the time” or “all of the time.” Participants indicated a variety of reasons for not wearing helmets. Of all patients contacted for follow-up, 16% indicated that they were involved in an accident after participating where the helmet they were given prevented a head injury.

CONCLUSIONS: Helmet distribution programs based in the pediatric ED increase rates of bicycle helmet usage among pediatric patients. Additional study is needed to determine effect on head injury prevention.

PMID:38950378 | DOI:10.1097/PEC.0000000000003233

J Urol. 2024 Jul 1:101097JU0000000000004129. doi: 10.1097/JU.0000000000004129. Online ahead of print.

ABSTRACT

PURPOSE: Nocturnal urine volume and bladder reservoir function are key pathogenic factors behind monosymptomatic nocturnal enuresis (MNE). We investigated the predictive value of these together with other demographic and clinical variables for response to first-line treatments in children with MNE.

MATERIALS AND METHODS: A randomized, controlled, international multicenter study was conducted in 324 treatment-naïve children (6-14 years) with primary MNE. The children were randomized to treatment with or without prior consideration of voiding diaries. In the group where treatment choice was based on voiding diaries, children with nocturnal polyuria and normal maximum voided volume (MVV) received desmopressin (dDAVP) treatment and children with reduced MVV and no nocturnal polyuria received an enuresis alarm. In the other group, treatment with dDAVP or alarm was randomly allocated.

RESULTS: A total of 281 children (72% males) were qualified for statistical analysis. The change of responding to treatment was 21% higher in children where treatment was individualized compared to children where treatment was randomly selected (RR = 1.21 (1.02-1.45), P = .032). In children with reduced MVV and no nocturnal polyuria (35% of all children), individualized treatment was associated with a 46% improvement in response compared to random treatment selection (RR = 1.46 (1.14-1.87), P = .003). Furthermore, we developed a clinically relevant prediction model for response to dDAVP treatment (ROC 0.85).

CONCLUSIONS: The present study demonstrates that treatment selection based on voiding diaries improve response to first line treatment, particularly in specific subtypes. Information from voiding diaries together with clinical and demographic information provides the basis for predicting response.

PMID:38950376 | DOI:10.1097/JU.0000000000004129

Proc Natl Acad Sci U S A. 2024 Jul 9;121(28):e2401661121. doi: 10.1073/pnas.2401661121. Epub 2024 Jul 1.

ABSTRACT

In US cities, neighborhoods have long been racially segregated. However, people do not spend all their time in their neighborhoods, and the consequences of residential segregation may be tempered by the contact people have with other racial groups as they traverse the city daily. We examine the extent to which people’s regular travel throughout the city is to places “beyond their comfort zone” (BCZ), i.e., to neighborhoods of racial composition different from their own-and why. Based on travel patterns observed in more than 7.2 million devices in the 100 largest US cities, we find that the average trip is to a neighborhood less than half as racially different from the home neighborhood as it could have been given the city. Travel to grocery stores is least likely to be BCZ; travel to gyms and parks, most likely; however, differences are greatest across cities. For the first ~10 km people travel from home, neighborhoods become increasingly more BCZ for every km traveled; beyond that point, whether neighborhoods do so depends strongly on the city. Patterns are substantively similar before and after COVID-19. Our findings suggest that policies encouraging more 15-min travel-that is, to amenities closer to the home-may inadvertently discourage BCZ movement. In addition, promoting use of certain “third places” such as restaurants, bars, and gyms, may help temper the effects of residential segregation, though how much it might do so depends on city-specific conditions.

PMID:38950373 | DOI:10.1073/pnas.2401661121

Proc Natl Acad Sci U S A. 2024 Jul 9;121(28):e2317458121. doi: 10.1073/pnas.2317458121. Epub 2024 Jul 1.

ABSTRACT

Functional changes in the pediatric brain following neural injuries attest to remarkable feats of plasticity. Investigations of the neurobiological mechanisms that underlie this plasticity have largely focused on activation in the penumbra of the lesion or in contralesional, homotopic regions. Here, we adopt a whole-brain approach to evaluate the plasticity of the cortex in patients with large unilateral cortical resections due to drug-resistant childhood epilepsy. We compared the functional connectivity (FC) in patients’ preserved hemisphere with the corresponding hemisphere of matched controls as they viewed and listened to a movie excerpt in a functional magnetic resonance imaging (fMRI) scanner. The preserved hemisphere was segmented into 180 and 200 parcels using two different anatomical atlases. We calculated all pairwise multivariate statistical dependencies between parcels, or parcel edges, and between 22 and 7 larger-scale functional networks, or network edges, aggregated from the smaller parcel edges. Both the left and right hemisphere-preserved patient groups had widespread reductions in FC relative to matched controls, particularly for within-network edges. A case series analysis further uncovered subclusters of patients with distinctive edgewise changes relative to controls, illustrating individual postoperative connectivity profiles. The large-scale differences in networks of the preserved hemisphere potentially reflect plasticity in the service of maintained and/or retained cognitive function.

PMID:38950362 | DOI:10.1073/pnas.2317458121

J Clin Oncol. 2024 Jul 1:JCO2302261. doi: 10.1200/JCO.23.02261. Online ahead of print.

ABSTRACT

PURPOSE: To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC).

PATIENTS AND METHODS: We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT.

RESULTS: Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis (P < .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5% v 35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2% v 33.9%) during neoadjuvant treatment.

CONCLUSION: The iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.

PMID:38950321 | DOI:10.1200/JCO.23.02261

JCO Oncol Pract. 2024 Jul 1:OP2400164. doi: 10.1200/OP.24.00164. Online ahead of print.

ABSTRACT

PURPOSE: Cancer center clinical trial offices (CCTOs) support trial development, activation, conduct, regulatory adherence, data integrity, and compliance. In 2018, the Association of American Cancer Institutes (AACI) Clinical Research Innovation (CRI) Steering Committee conducted and published survey results to benchmark North American CCTOs, including trial volume, accrual, full time equivalents (FTEs), and budget. The survey was readministered in 2023 to assess contemporary CCTO performance and capacity with results presented here.

METHODS: The 28 question 2023 survey was sent to directors of AACI’s clinical member cancer centers. Survey participation was voluntary, no compensation was provided, and data requested covered operations during 2022. Definitions were consistent with National Cancer Institute (NCI) CCTO reporting requirements and AACI staff anonymously compiled results for descriptive statistical reporting.

RESULTS: The survey response rate was 61% (60/99). The median annual CCTO budget was $11.5 million (M) US dollars (USD) versus $8.2M USD in 2018. These budgets support a median of 150 FTEs versus 104 previously, and a median total of 384 versus 280 interventional treatment trials and a median of 479 versus 531 interventional treatment accruals. Sources of support for CCTO annual budgets were primarily from industry revenue (45.3%) or institutional support (31.7%). Nearly 60% of centers reported activating NCI-sponsored studies within 90 days but only 9% reported meeting a 90-day activation timeline for industry sponsored studies.

CONCLUSION: Contemporary benchmarks for CCTO operations through this survey demonstrate larger staff sizes, larger budgets, more trials supported, but fewer patients enrolled to interventional treatment trials in comparison with 2018. These data shine a critical light on the increasing complexity of cancer clinical trials, the importance of external funding sources, and necessary operational efficiency upgrades to provide cutting-edge cancer research and care.

PMID:38950320 | DOI:10.1200/OP.24.00164

JCO Clin Cancer Inform. 2024 Jun;8:e2400054. doi: 10.1200/CCI.24.00054.

ABSTRACT

There has been growing interest in the use of real-world data (RWD) to address clinically and policy-relevant (research) questions that cannot be answered with data from randomized controlled trials (RCTs) alone. This is, for example, the case in rare malignancies such as sarcomas as limited patient numbers pose challenges in conducting RCTs within feasible timeliness, a manageable number of collaborators, and statistical power. This narrative review explores the potential of RWD to generate real-world evidence (RWE) in sarcoma research, elucidating its application across different phases of the patient journey, from prediagnosis to the follow-up/survivorship phase. For instance, examining electronic health records (EHRs) from general practitioners (GPs) enables the exploration of consultation frequency and presenting symptoms in primary care before a sarcoma diagnosis. In addition, alternative study designs that integrate RWD with well-designed observational RCTs may offer relevant information on the effectiveness of clinical treatments. As, especially in cases of ultrarare sarcomas, it can be an extreme challenge to perform well-powered randomized prospective studies. Therefore, it is crucial to support the adaptation of novel study designs. Regarding the follow-up/survivorship phase, examining EHR from primary and secondary care can provide valuable insights into identifying the short- and long-term effects of treatment over an extended follow-up period. The utilization of RWD also comes with several challenges, including issues related to data quality and privacy, as described in this study. Notwithstanding these challenges, this study underscores the potential of RWD to bridge, at least partially, gaps between evidence and practice and holds promise in contributing to the improvement of sarcoma care.

PMID:38950319 | DOI:10.1200/CCI.24.00054