Nevin Manimala

JAMA Pediatr. 2024 Mar 4. doi: 10.1001/jamapediatrics.2023.6790. Online ahead of print.

ABSTRACT

IMPORTANCE: Growing up in a language-rich home environment is important for children’s language development in the early years. The concept of “technoference” (technology-based interference) suggests that screen time may be interfering with opportunities for talk and interactions between parent and child; however, limited longitudinal evidence exists exploring this association.

OBJECTIVE: To investigate the longitudinal association between screen time and 3 measures of parent-child talk (adult words, child vocalizations, and conversational turns) when children are 12 to 36 months of age.

DESIGN, SETTING, AND PARTICIPANTS: This Australian prospective cohort study used advanced speech recognition technology to capture young children’s screen time and home language environment, on an average 16-hour day. Data were collected from 220 families once every 6 months in the family home when children were 12, 18, 24, 30, and 36 months of age, from January 1, 2018, to December 31, 2021. Statistical analysis took place from November 1, 2022, to July 31, 2023.

EXPOSURE: Language Environment Analysis (LENA) technology provided automated counts of children’s language environment and exposure to electronic noise. The exposure of interest was screen time, which was calculated based on manual coding of LENA electronic noise audio segments.

MAIN OUTCOMES AND MEASURES: Three measures of parent-child talk were outcomes of focus: adult words, child vocalizations, and conversational turns. Separate models were run for each of the 3 outcomes and included adjustment for child sex, child age, maternal educational level, number of children at home, number of home activities, and primary caregiver’s psychological distress.

RESULTS: The study included 220 families (120 girls [54.6%]; mean [SD] gestational age of children, 39.3 [1.5] weeks; mean [SD] age of mother at childbirth, 31.3 [4.8] years). Adjusted linear mixed-effect models demonstrated that increases in screen time were associated with decreases in measures of parent-child talk. The largest decreases were seen at 36 months, when an additional minute of screen time was associated with a reduction of 6.6 (95% CI, -11.7 to -1.5) adult words, 4.9 (95% CI, -6.1 to -3.7) child vocalizations, and 1.1 (95% CI, -1.4 to -0.8) conversational turns.

CONCLUSION AND RELEVANCE: Findings of this study support the notion of technoference for Australian families, whereby young children’s exposure to screen time is interfering with opportunities to talk and interact in their home environment. This finding has implications for interventions and supports aimed at promoting a language-rich home environment, with families needing support in understanding the potential association of screen time with opportunities for children and adults to talk and interact in their home environment.

PMID:38436942 | DOI:10.1001/jamapediatrics.2023.6790

Brain. 2024 Mar 4:awae068. doi: 10.1093/brain/awae068. Online ahead of print.

ABSTRACT

The subthalamic nucleus (STN) of the basal ganglia is key to the inhibitory control of movement. Consequently, it is a primary target for the neurosurgical treatment of movement disorders like Parkinson’s Disease, where modulating the STN via deep-brain stimulation (DBS) can release excess inhibition of thalamo-cortical motor circuits. However, the STN is also anatomically connected to other thalamo-cortical circuits, including those underlying cognitive processes like attention. Notably, STN-DBS can also affect these processes. This suggests that the STN may also contribute to the inhibition of non-motor activity, and that STN-DBS may cause changes to this inhibition. We here tested this hypothesis in humans. We used a novel, wireless outpatient method to record intracranial local field potentials (LFP) from STN DBS implants during a visual attention task (Experiment 1, N=12). These outpatient measurements allowed the simultaneous recording of high-density EEG, which we used to derive the steady-state visual evoked potential (SSVEP), a well-established neural index of visual attentional engagement. By relating STN activity to this neural marker of attention (instead of overt behavior), we avoided possible confounds resulting from STN’s motor role. We aimed to test whether the STN contributes to the momentary inhibition of the SSVEP caused by unexpected, distracting sounds. Furthermore, we causally tested this association in a second experiment, where we modulated STN via DBS across two sessions of the task, spaced at least one week apart (N=21, no sample overlap with Experiment 1). The LFP recordings in Experiment 1 showed that reductions of the SSVEP after distracting sounds were preceded by sound-related γ-frequency (>60Hz) activity in the STN. Trial-to-trial modeling further showed that this STN activity statistically mediated the sounds’ suppressive effect on the SSVEP. In Experiment 2, modulating STN activity via DBS significantly reduced these sound-related SSVEP reductions. This provides causal evidence for the role of the STN in the surprise-related inhibition of attention. These findings suggest that the human STN contributes to the inhibition of attention, a non-motor process. This supports a domain-general view of the inhibitory role of the STN. Furthermore, these findings also suggest a potential mechanism underlying some of the known cognitive side-effects of STN-DBS treatment, especially on attentional processes. Finally, our newly-established outpatient LFP recording technique facilitates the testing of the role of subcortical nuclei in complex cognitive tasks, alongside recordings from the rest of the brain, and in much shorter time than perisurgical recordings.

PMID:38436939 | DOI:10.1093/brain/awae068

Ocul Immunol Inflamm. 2024 Mar 4:1-7. doi: 10.1080/09273948.2024.2323094. Online ahead of print.

ABSTRACT

PURPOSE: Uveitis-Glaucoma-Hyphema (UGH) syndrome results from contact between the intraocular lens (IOL) and the iris or ciliary body, leading to uveal structure erosion and blood-aqueous barrier breakdown. Treatment involves various drugs, with IOL removal often being necessary. Diagnosis relies on clinical signs, but imaging techniques like ultrasound biomicroscopy (UBM) or anterior segment optical coherence tomography (AS-OCT) are crucial. AS-OCT accurately depicts IOL position and potential contact, emerging as a primary alternative to UBM in the diagnosis. Our study aimed to correlate AS-OCT findings with clinically detectable iris atrophy in pseudophakic patients with IOL-iris chafing and UGH syndrome.

METHODS: The study retrospectively analyzed patients diagnosed with UGH syndrome presenting at the Ocular Immunology Unit of Reggio Emilia, Italy, from January 2019 to August 2023. Patients’ data were collected. Ophthalmological exams and imaging were performed. The peephole sign in AS-OCT images was evaluated. Statistical analyses were conducted, with a significance level of p ≤ 0.05.

RESULTS: The study reviewed 22 eyes of 22 patients with UGH syndrome. Four eyes were excluded, leaving 18 patients (8 females, 10 males). Common misdiagnoses included idiopathic anterior uveitis (55.5%) and herpetic anterior uveitis (16.7%). All patients had iris transillumination defects, mostly focal (77.8%). AS-OCT revealed IOL chafing in all the eyes, with peephole sign correlation. More peephole signs occurred with IOL in the sulcus (p-value = 0.08).

CONCLUSION: The study recommends AS-OCT for UGH syndrome confirmation and UBM when IOL-iris chafing is not observed on AS-OCT scans.

PMID:38436932 | DOI:10.1080/09273948.2024.2323094

Clin Pharmacokinet. 2024 Mar 4. doi: 10.1007/s40262-023-01340-5. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: The combination of niraparib and abiraterone acetate (AA) plus prednisone is under investigation for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC). Regular-strength (RS) and lower-strength (LS) dual-action tablets (DATs), comprising niraparib 100 mg/AA 500 mg and niraparib 50 mg/AA 500 mg, respectively, were developed to reduce pill burden and improve patient experience. A bioequivalence (BE)/bioavailability (BA) study was conducted under modified fasting conditions in patients with mCRPC to support approval of the DATs.

METHODS: This open-label randomized BA/BE study (NCT04577833) was conducted at 14 sites in the USA and Europe. The study had a sequential design, including a 21-day screening phase, a pharmacokinetic (PK) assessment phase comprising three periods [namely (1) single-dose with up to 1-week run-in, (2) daily dose on days 1-11, and (3) daily dose on days 12-22], an extension where both niraparib and AA as single-agent combination (SAC; reference) or AA alone was continued from day 23 until discontinuation, and a 30-day follow-up phase. Patients were randomly assigned in a parallel-group design (four-sequence randomization) to receive a single oral dose of niraparib 100 mg/AA 1000 mg as a LS-DAT or SAC in period 1, and patients continued as randomized into a two-way crossover design during periods 2 and 3 where they received niraparib 200 mg/AA 1000 mg once daily as a RS-DAT or SAC. The design was powered on the basis of crossover assessment of RS-DAT versus SAC. During repeated dosing (periods 2 and 3, and extension phase), all patients also received prednisone/prednisolone 5 mg twice daily. Plasma samples were collected for measurement of niraparib and abiraterone plasma concentrations. Statistical assessment of the RS-DAT and LS-DAT versus SAC was performed on log-transformed pharmacokinetic parameters data from periods 2 and 3 (crossover) and from period 1 (parallel), respectively. Additional paired analyses and model-based bioequivalence assessments were conducted to evaluate the similarity between the LS-DAT and SAC.

RESULTS: For the RS-DAT versus SAC, the 90% confidence intervals (CI) of geometric mean ratios (GMR) for maximum concentration at a steady state (C_max,ss) and area under the plasma concentration-time curve from 0-24 h at a steady state (AUC _0-24h,ss) were respectively 99.18-106.12% and 97.91-104.31% for niraparib and 87.59-106.69 and 86.91-100.23% for abiraterone. For the LS-DAT vs SAC, the 90% CI of GMR for AUC_0-72h of niraparib was 80.31-101.12% in primary analysis, the 90% CI of GMR for C_max,ss and AUC _0-24h,ss of abiraterone was 85.41-118.34% and 86.51-121.64% respectively, and 96.4% of simulated LS-DAT versus SAC BE trials met the BE criteria for both niraparib and abiraterone.

CONCLUSIONS: The RS-DAT met BE criteria (range 80%-125%) versus SAC based on 90% CI of GMR for C_max,ss and AUC _0-24h,ss. The LS-DAT was considered BE to SAC on the basis of the niraparib component meeting the BE criteria in the primary analysis for AUC _0-72h; abiraterone meeting the BE criteria in additional paired analyses based on C_max,ss and AUC _0-24h,ss; and the percentage of simulated LS-DAT versus SAC BE trials meeting the BE criteria for both.

GOV IDENTIFIER: NCT04577833.

PMID:38436924 | DOI:10.1007/s40262-023-01340-5

J Gastrointest Cancer. 2024 Mar 4. doi: 10.1007/s12029-024-01035-5. Online ahead of print.

ABSTRACT

PURPOSE: Available data on hepatocellular carcinoma (HCC) recurrence after direct-acting antivirals (DAAs) treatment for hepatitis C virus (HCV) are conflicting. No randomized trials were done. This study aims to compare the 1-year HCC recurrence rates in patients who received DAAs after tumor ablation versus those who postponed HCV treatment for 1 year.

METHODS: Included patients were randomized after complete HCC ablation into two groups: a postponed DAAs group for whom DAAs initiation was postponed for 12 months and a DAAs group who were given sofosbuvir/velpatasvir. Patients were followed for 1 year.

RESULTS: Eighty-four HCV patients with a mean age of 56.35 ± 8.12 years were included; 78.57% of them were males. The number of lesions per patient ranged from 1 to 3 lesions, and the size of the largest lesion ranged from 1.5 to 5 cm. There were no statistically significant differences between both groups regarding baseline characteristics. In the DAAs group (43 patients), 11 patients had HCC recurrence, while 25 patients in the postponed DAAs group (41 patients) had HCC recurrence. Using Kaplan-Meier analysis, the 1-year recurrence-free survival (RFS) was significantly higher in the DAAs group (72.2% vs. 38%, P = 0.001). On multivariate analysis, both higher albumin levels (HR 0.147, 95% CI 0.066-0.329) and receiving DAAs (HR 0.358, 95% CI 0.176-0.730) 1 year after ablation were associated with significantly lower recurrence.

CONCLUSION: Direct-acting antiviral usage after complete hepatocellular carcinoma ablation significantly decreases the 1-year HCC recurrence rates, but the risk of recurrence is still not eliminated. The study registration number on clinicaltrials.gov : NCT04653818 (initial release on 28/11/2020).

PMID:38436921 | DOI:10.1007/s12029-024-01035-5

Obes Surg. 2023 Dec 19. doi: 10.1007/s11695-023-06979-4. Online ahead of print.

ABSTRACT

PURPOSE: Obesity and its related severe comorbidities are increasing rapidly. The duodenal-jejunal bypass is an endoscopically implanted device (mimicking the Roux-en-Y gastric bypass) developed to support weight reduction and improve type 2 diabetes control.

MATERIALS AND METHODS: Retrospective data analysis of consecutive patients undergoing duodenal-jejunal bypass (EndoBarrier®, DJB) implantation between 2013 and 2017 was performed to evaluate safety as well as short- and long-term efficacy.

RESULTS: One hundred and twenty-one patients (mean BMI of 43.1 ± 7.2 kg/m² and weight of 138.2 ± 28.6 kg) underwent DJB implantation. The mean dwelling time was 15.5 months, the mean total body weight loss (%TBWL) after explantation was 10.3% ± 7.9% (14.2 kg, p < 0.0001), and the mean BMI was 39.5 ± 7.3 kg/m² (p < 0.0001). There was no significant weight gain 24 months after the explantation. Seventy-seven patients had type 2 diabetes mellitus (T2DM) with a mean HbA1c before implantation of 5.6% (n = 52). The mean HbA1c after explantation was 5.1% (p = 0.0001). Significant reductions in transaminase and lipid levels before and after explantation were observed. One complication occurred during implantation and another during explantation. In 16 patients, the device had to be extracted earlier than expected (7 for severe adverse events and 9 for adverse events; 13.2%).

CONCLUSION: Despite an evident rate of adverse events, the DJB shows promise as a weight-loss procedure. Our results show that some patients implanted with the device maintained reduced weight even 24 months after explantation, while many improved T2DM control.

PMID:38436919 | DOI:10.1007/s11695-023-06979-4

J Racial Ethn Health Disparities. 2024 Mar 4. doi: 10.1007/s40615-024-01954-w. Online ahead of print.

ABSTRACT

Pre-exposure prophylaxis (PrEP) is an effective tool in protecting persons from acquiring HIV infection through sex or injection drug use. However, awareness and willingness to use PrEP among Black gay, bisexual, and other men who have sex with men (BMSM) remain suboptimal compared to White MSM (WMSM) in the United States. Our aims were to (1) assess the factors associated with PrEP awareness and willingness to use PrEP among MSM and (2) compare the PrEP perceptions among BMSM versus non-Black MSM. Data were drawn from two cross-sectional behavioral surveys in Baltimore, MD: Behavioral Surveillance Research (BESURE) conducted in 2017, and Safe Spaces 4 Sexual Health (SS4SH), conducted in 2018 and 2019. Descriptive statistics were used to summarize the study population. We used Poisson regression models to identify variables associated with awareness of PrEP and willingness to use PrEP. PrEP perceptions were assessed via 13 items scored on a 5-point Likert scale. Finally, we conducted a post-hoc exploratory bivariate analysis of the relationship between PrEP perception and willingness to use PrEP, stratified by race/ethnicity. A total of 261 MSM participated in this study. Many of the participants were aware of PrEP (75.1%). Factors associated with greater PrEP awareness included having greater than a high school education (aRR 1.22, 95% CI 1.04, 1.43); and earning more than $25,000 annually (aRR 1.24, 95% CI 1.08, 1.42). Participants who had received money in exchange for sex one or more times were less likely to be aware of PrEP (aRR 0.59, 95% CI 0.36, 0.95). More than half of the participants were willing to use PrEP (55.3%). In bivariate and multivariable analyses, demographic or behavioral characteristics were not significantly associated with willingness to use PrEP. Higher agreement with the following statements was associated with lower willingness to use PrEP: “Having to take a pill every day is difficult” (RR 0.89, 95% CI 0.82-0.97) and, “I am concerned about the side effects of PrEP” (RR 0.89, 95% CI 0.82-0.96), and “PrEP is for people who have riskier sex lives than I do” (RR 0.86, 95% CI 0.78-0.95). Conversely, higher willingness to use PrEP was associated with comfortable having sex without a condom (RR 1.11, 95% CI 1.02-1.21), less anxious about sex (RR 1.12, 95% CI 1.02-1.24), and my friends think that I should take PrEP (RR 1.19, 95% CI 1.07-1.32). We found BMSM compared to non-Black MSM had higher mean scores related to taking a daily pill (p = 0.041), concerns about side effects (p = 0.012), concerns about people thinking they had HIV (p = 0.001), concerns about the financial costs of PrEP (p = 0.038) and caution when dealing with healthcare organizations/medical mistrust (p = 0.019). Perceptions with a statistically significant lower score among BMSM versus non-Black MSM included statements such as, comfortable having sex without a condom (p = 0.003) and less anxious about sex (p < 0.001). We conclude HIV prevention strategies, programs, and interventions should be cognizant of PrEP perceptions that facilitate or hinder PrEP uptake in Baltimore City, MD.

PMID:38436888 | DOI:10.1007/s40615-024-01954-w

Phys Eng Sci Med. 2024 Mar 4. doi: 10.1007/s13246-024-01396-y. Online ahead of print.

ABSTRACT

Functional gastric disorders entail chronic or recurrent symptoms, high prevalence and a significant financial burden. These disorders do not always involve structural abnormalities and since they cannot be diagnosed by routine procedures, electrogastrography (EGG) has been proposed as a diagnostic alternative. However, the method still has not been transferred to clinical practice due to the difficulty of identifying gastric activity because of the low-frequency interference caused by skin-electrode contact potential in obtaining spatiotemporal information by simple procedures. This work attempted to robustly identify the gastric slow wave (SW) main components by applying multivariate variational mode decomposition (MVMD) to the multichannel EGG. Another aim was to obtain the 2D SW vectorgastrogram VGG_SW from 4 electrodes perpendicularly arranged in a T-shape and analyse its dynamic trajectory and recurrence quantification (RQA) to assess slow wave vector movement in healthy subjects. The results revealed that MVMD can reliably identify the gastric SW, with detection rates over 91% in fasting postprandial subjects and a frequency instability of less than 5.3%, statistically increasing its amplitude and frequency after ingestion. The VGG_SW dynamic trajectory showed a statistically higher predominance of vertical displacement after ingestion. RQA metrics (recurrence ratio, average length, entropy, and trapping time) showed a postprandial statistical increase, suggesting that gastric SW became more intense and coordinated with a less complex VGG_SW and higher periodicity. The results support the VGG_SW as a simple technique that can provide relevant information on the “global” spatial pattern of gastric slow wave propagation that could help diagnose gastric pathologies.

PMID:38436885 | DOI:10.1007/s13246-024-01396-y

Dig Dis Sci. 2024 Mar 4. doi: 10.1007/s10620-024-08341-9. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Screening colonoscopy has significantly contributed to the reduction of the incidence of colorectal cancer (CRC) and its associated mortality, with adenoma detection rate (ADR) as the quality marker. To increase the ADR, various solutions have been proposed including the utilization of Artificial Intelligence (AI) and employing second observers during colonoscopies. In the interest of AI improving ADR independently, without a second observer, and the operational similarity between AI and second observer, this network meta-analysis aims at evaluating the effectiveness of AI, second observer, and a single observer in improving ADR.

METHODS: We searched the Medline, Embase, Cochrane, Web of Science Core Collection, Korean Citation Index, SciELO, Global Index Medicus, and Cochrane. A direct head-to-head comparator analysis and network meta-analysis were performed using the random-effects model. The odds ratio (OR) was calculated with a 95% confidence interval (CI) and p-value < 0.05 was considered statistically significant.

RESULTS: We analyzed 26 studies, involving 22,560 subjects. In the direct comparative analysis, AI demonstrated higher ADR (OR: 0.668, 95% CI 0.595-0.749, p < 0.001) than single observer. Dual observer demonstrated a higher ADR (OR: 0.771, 95% CI 0.688-0.865, p < 0.001) than single operator. In network meta-analysis, results were consistent on the network meta-analysis, maintaining consistency. No statistical difference was noted when comparing AI to second observer. (RR 1.1 (0.9-1.2, p = 0.3). Results were consistent when evaluating only RCTs. Net ranking provided higher score to AI followed by second observer followed by single observer.

CONCLUSION: Artificial Intelligence and second-observer colonoscopy showed superior success in Adenoma Detection Rate when compared to single-observer colonoscopy. Although not statistically significant, net ranking model favors the superiority of AI to the second observer.

PMID:38436866 | DOI:10.1007/s10620-024-08341-9

World J Urol. 2024 Mar 4;42(1):117. doi: 10.1007/s00345-024-04801-z.

ABSTRACT

PURPOSE: The objective of this study was to perform a retrospective cohort analysis, in which we measured the association of an acute pain service (APS)-driven multimodal analgesia protocol that included preoperative intrathecal morphine (ITM) compared to historic controls (i.e., surgeon-driven analgesia protocol without ITM) with postoperative opioid use.

METHODS: This was a retrospective cohort study in which the primary objective was to determine whether there was a decrease in median 24-h opioid consumption (intravenous morphine equivalents [MEQ]) among robotic nephrectomy patients whose pain was managed by the surgical team prior to the APS, versus pain managed by APS. Secondary outcomes included opioid consumption during the 24-48 h and 48-72 h period and hospital length of stay. To create matched cohorts, we performed 1:1 (APS:non-APS) propensity score matching. Due to the cohorts occurring at the different time periods, we performed a segmented regression analysis of an interrupted time series.

RESULTS: There were 76 patients in the propensity-matched cohorts, in which 38 (50.0%) were in the APS cohort. The median difference in 24-h opioid consumption in the pre-APS versus APS cohort was 23.0 mg [95% CI 15.0, 31.0] (p < 0.0001), in favor of APS. There were no differences in the secondary outcomes. On segmented regression, there was a statistically significant drop in 24-h opioid consumption in the APS cohort versus pre-APS cohort (p = 0.005).

CONCLUSIONS: The implementation of an APS-driven multimodal analgesia protocol with ITM demonstrated a beneficial association with postoperative 24-h opioid consumption following robot-assisted nephrectomy.

PMID:38436828 | DOI:10.1007/s00345-024-04801-z