Nevin Manimala

CNS Neurosci Ther. 2024 Apr;30(4):e14712. doi: 10.1111/cns.14712.

ABSTRACT

BACKGROUND: The specific non-motor symptoms associated with α-synucleinopathies, including orthostatic hypotension (OH), cognitive impairment, and emotional abnormalities, have been a subject of ongoing controversy over the mechanisms underlying the development of a vicious cycle among them. The distinct structural alterations in white matter (WM) in patients with α-synucleinopathies experiencing OH, alongside their association with other non-motor symptoms, remain unexplored. This study employs axial diffusivity and density imaging (NODDI) to investigate WM damage specific to α-synucleinopathies with concurrent OH, delivering fresh evidence to supplement our understanding of the pathogenic mechanisms and pathological rationales behind the occurrence of a spectrum of non-motor functional impairments in α-synucleinopathies.

METHODS: This study recruited 49 individuals diagnosed with α-synucleinopathies, stratified into an α-OH group (n = 24) and an α-NOH group (without OH, n = 25). Additionally, 17 healthy controls were included for supine and standing blood pressure data collection, as well as neuropsychological assessments. Magnetic resonance imaging (MRI) was utilized for the calculation of NODDI parameters, and tract-based spatial statistics (TBSS) were employed to explore differential clusters. The fibers covered by these clusters were defined as regions of interest (ROI) for the extraction of NODDI parameter values and the analysis of their correlation with neuropsychological scores.

RESULTS: The TBSS analysis unveiled specific cerebral regions exhibiting disparities within the α-OH group as compared to both the α-NOH group and the healthy controls. These differences were evident in clusters that indicated a decrease in the acquisition of the neurite density index (NDI), a reduction in the orientation dispersion index (ODI), and an increase in the isotropic volume fraction (FISO) (p < 0.05). The extracted values from these ROIs demonstrated significant correlations with clinically assessed differences in supine and standing blood pressure, overall cognitive scores, and anxiety-depression ratings (p < 0.05).

CONCLUSION: Patients with α-synucleinopathies experiencing OH exhibit distinctive patterns of microstructural damage in the WM as revealed by the NODDI model, and there is a correlation with the onset and progression of non-motor functional impairments.

PMID:38615364 | DOI:10.1111/cns.14712

J Biopharm Stat. 2024 Apr 14:1-20. doi: 10.1080/10543406.2024.2341674. Online ahead of print.

ABSTRACT

Indirect mechanisms of cancer immunotherapies result in delayed treatment effects that vary among patients. Consequently, the use of the log-rank test in trial design and analysis can lead to significant power loss and pose additional challenges for interim decisions in adaptive designs. In this paper, we describe patients’ survival using a piecewise proportional hazard model with random lag time and propose an adaptive promising zone design for cancer immunotherapy with heterogeneous delayed effects. We provide solutions for calculating conditional power and adjusting the critical value for the log-rank test with interim data. We divide the sample space into three zones – unfavourable, promising, and favourable -based on re-estimations of the survival parameters, the log-rank test statistic at the interim analysis, and the initial and maximum sample sizes. If the interim results fall into the promising zone, the sample size is increased; otherwise, it remains unchanged. We show through simulations that our proposed approach has greater overall power than the fixed sample design and similar power to the matched group sequential trial. Furthermore, we confirm that critical value adjustment effectively controls the type I error rate inflation. Finally, we provide recommendations on the implementation of our proposed method in cancer immunotherapy trials.

PMID:38615361 | DOI:10.1080/10543406.2024.2341674

Undersea Hyperb Med. 2024 First Quarter;51(1):71-83.

ABSTRACT

PURPOSE: Ultrasound imaging is commonly used in decompression research to assess venous gas emboli (VGE) post-dive, with higher loads associated with increased decompression sickness risk. This work examines, for the first time in humans, the performance of a novel electrical impedance spectroscopy technology (I-VED), on possible detection of post-dive bubbles presence and arterial endothelial dysfunction that may be used as markers of decompression stress.

METHODS: I-VED signals were recorded in scuba divers who performed standardized pool dives before and at set time points after their dives at 35-minute intervals for about two hours. Two distinct frequency components of the obtained signals, Low-Pass Frequency-LPF: 0-0.5 Hz and Band-Pass Frequency-BPF: 0.5-10 Hz, are extracted and respectively compared to VGE presence and known flow-mediated dilation trends for the same dive profile for endothelial dysfunction.

RESULTS: Subjects with VGE counts above the median for all subjects were found to have an elevated average LPF compared to subjects with lower VGE counts, although this was not statistically significant (p=0.06), as well as significantly decreased BPF standard deviation post-dive compared to pre-dive (p=0.008).

CONCLUSIONS: I-VED was used for the first time in humans and operated to provide qualitative in-vivo electrical impedance measurements that may contribute to the assessment of decompression stress. Compared to ultrasound imaging, the proposed method is less expensive, not operator-dependent and compatible with continuous monitoring and application of multiple probes. This study provided preliminary insights; further calibration and validation are necessary to determine I-VED sensitivity and specificity.

PMID:38615356

Undersea Hyperb Med. 2024 First Quarter;51(1):7-15.

ABSTRACT

BACKGROUND: Hyperbaric oxygen (HBO₂) therapy is an alternative method against the deleterious effects of ischemic/reperfusion (I/R) injury and its inflammatory response. This study assessed the effect of preoperative HBO₂ on patients undergoing pancreaticoduodenectomy.

STUDY DESIGN: Patients were randomized via a computer-generated algorithm. Patients in the HBO₂ cohort received two sessions of HBO₂ the evening before and the morning of surgery. Measurements of inflammatory mediators and self-assessed pain scales were determined pre-and postoperatively. In addition, perioperative variables and long-term survival were collected and analyzed. Data are presented as median (mean ± SD).

RESULTS: 33 patients were included; 17 received preoperative HBO₂, and 16 did not. There were no intraoperative or postoperative statistical differences between patients with or without preoperative HBO₂. Erythrocyte sedimentation rate (ESR), IL-6, and IL-10 increased slightly before returning to normal, while TGF-alpha decreased before increasing. However, there were no differences with or without HBO₂. At postoperative day 30, the pain level measured with VAS score (Visual Analog Score) was lower after HBO₂ (1 ± 1.3 vs. 3 ± 3.0, p=0.05). Eleven (76%) patients in the HBO₂ cohort and 12 (75%) patients in the non- HBO₂ had malignant pathology. The percentage of positive lymph nodes in the HBO₂ was 7% compared to 14% in the non-HBO₂ (p<0.001). Overall survival was inferior after HBO₂ compared to the non- HBO₂ (p=0.03).

CONCLUSIONS: Preoperative HBO₂ did not affect perioperative outcomes or significantly change the inflammatory mediators for patients undergoing robotic pancreaticoduodenectomy. Long-term survival was inferior after preoperative HBO₂. Further randomized controlled studies are required to assess the full impact of this treatment on patients’ prognosis.

PMID:38615348

Undersea Hyperb Med. 2024 First Quarter;51(1):1-5.

ABSTRACT

Chronic wounds have a significant impact on a patient’s quality of life. Different pathologies, such as poor blood supply and tissue breakdown, may lead to inadequate oxygenation of the wound. Hyperbaric oxygen (HBO₂) is a widely used treatment for an increasing number of medical practices. A new so-called “hyperbaric treatment” trend has emerged. The use of low-pressure, soft-sided, or inflatable chambers represents a growing trend in hyperbaric medicine. Used in professional settings as well as directly marketed to individuals for home use, they are promoted as equivalent to clinical hyperbaric treatments provided in medical centers. However, these chambers are pressurized to 1.3 atmospheres absolute (ATA) on either air or with an oxygen concentrator, both generate oxygen partial pressures well below those used in approved hyperbaric centers for UHMS-approved indications. A total of 130 consecutive patients with chronic ulcers where tested. TcPO₂ was measured near the ulcer area while the patient was breathing 100% O₂ at 1.4 ATA for five and 10 minutes. The average TcPO₂ at 1.4 ATA after 10 minutes of O₂ breathing was 161 mmHg (1-601 mmHg, standard deviation 137.91), compared to 333 mmHg in 2 ATA (1-914±232.56), p < 0.001. Each electrode tested was also statistically significant, both after five minutes of O₂ breathing and after 10 minutes. We have not found evidence supporting the claim that 1.4 ATA treatment can benefit a chronic ulcer patient. The field of HBO₂ is constantly evolving. We have discovered new ways to treat previously incurable ailments. Nevertheless, it is important to note that new horizons must be examined scientifically, supported by evidence-based data. The actual effect of 1.4 ATA on many ailments is yet to be determined.

PMID:38615347

Biomol Biomed. 2024 Apr 13. doi: 10.17305/bb.2024.10449. Online ahead of print.

ABSTRACT

Vitamin D is commonly used to prevent and treat osteoporosis, with studies indicating its potential to reduce fractures, falls, and mortality. However, meta-analyses present inconsistent findings regarding its efficacy, particularly reflecting significant variability in data and outcomes related to various dosing regimens. In this meta-analysis, we assessed the impact of high-dose intermittent oral administration of vitamin D3 on serum 25(OH)D levels, fractures, falls, and mortality among elderly individuals. We included 14 randomized controlled trials (RCTs) and employed Review Manager 5.4 for statistical analysis. Our findings indicate that intermittent monthly administration of vitamin D3 (over 800 IU per day) significantly raised serum 25(OH)D levels at all timepoints after six months, maintaining levels above 75 nmol/L throughout the year. This regimen showed no increase in all-cause mortality, with a risk ratio (95% CI) of 0.95 (0.87-1.04). Likewise, it did not significantly reduce the risks of falls and fractures, with risk ratios of 1.02 (0.98-1.05) and 0.95 (0.87-1.04) respectively. Although one-year intermittent administration significantly increased the concentration of 25(OH)D in serum, further research is needed to determine if this method would increase the incidence of falls. Therefore, it is not recommended at this stage due to the lack of demonstrated safety in additional relevant RCTs. This study had been registered on PROSPERO (CRD42022363229).

PMID:38615341 | DOI:10.17305/bb.2024.10449

J Nurs Scholarsh. 2024 Apr 14. doi: 10.1111/jnu.12971. Online ahead of print.

ABSTRACT

BACKGROUND: Compared to other providers, nurses spend more time with patients, but the exact quantity and nature of those interactions remain largely unknown. The purpose of this study was to characterize the interactions of nurses at the bedside using continuous surveillance over a year long period.

METHODS: Nurses’ time and activity at the bedside were characterized using a device that integrates the use of obfuscated computer vision in combination with a Bluetooth beacon on the nurses’ identification badge to track nurses’ activities at the bedside. The surveillance device (AUGi) was installed over 37 patient beds in two medical/surgical units in a major urban hospital. Forty-nine nurse users were tracked using the beacon. Data were collected 4/15/19-3/15/20. Statistics were performed to describe nurses’ time and activity at the bedside.

RESULTS: A total of n = 408,588 interactions were analyzed over 670 shifts, with >1.5 times more interactions during day shifts (n = 247,273) compared to night shifts (n = 161,315); the mean interaction time was 3.34 s longer during nights than days (p < 0.0001). Each nurse had an average of 7.86 (standard deviation [SD] = 10.13) interactions per bed each shift and a mean total interaction time per bed of 9.39 min (SD = 14.16). On average, nurses covered 7.43 beds (SD = 4.03) per shift (day: mean = 7.80 beds/nurse/shift, SD = 3.87; night: mean = 7.07/nurse/shift, SD = 4.17). The mean time per hourly rounding (HR) was 69.5 s (SD = 98.07) and 50.1 s (SD = 56.58) for bedside shift report.

DISCUSSION: As far as we are aware, this is the first study to provide continuous surveillance of nurse activities at the bedside over a year long period, 24 h/day, 7 days/week. We detected that nurses spend less than 1 min giving report at the bedside, and this is only completed 20.7% of the time. Additionally, hourly rounding was completed only 52.9% of the time and nurses spent only 9 min total with each patient per shift. Further study is needed to detect whether there is an optimal timing or duration of interactions to improve patient outcomes.

CLINICAL RELEVANCE: Nursing time with the patient has been shown to improve patient outcomes but precise information about how much time nurses spend with patients has been heretofore unknown. By understanding minute-by-minute activities at the bedside over a full year, we provide a full picture of nursing activity; this can be used in the future to determine how these activities affect patient outcomes.

PMID:38615340 | DOI:10.1111/jnu.12971

Med Educ Online. 2024 Dec 31;29(1):2339569. doi: 10.1080/10872981.2024.2339569. Epub 2024 Apr 14.

ABSTRACT

BACKGROUND: eLearning can be an effective tool to achieve learning objectives. It facilitates asynchronous distance learning, increasing flexibility for learners and instructors. In this context, the high educational value of videos provides an invaluable primary component for longitudinal digital curricula, especially for maintaining knowledge on otherwise rarely taught subjects. Although literature concerning eLearning evaluation exists, research comprehensively describing how to design effective educational videos is lacking. In particular, studies on the requirements and design goals of educational videos need to be complemented by qualitative research using grounded theory methodology.

METHODS: Due to the paucity of randomized controlled trials in this area, there is an urgent need to generate recommendations based on a broader fundament than a literature search alone. Thus, the authors have employed grounded theory as a guiding framework, augmented by Mayring’s qualitative content analysis and commonly used standards. An adaptive approach was conducted based on a literature search and qualitative semi-structured interviews. Drawing on these results, the authors elaborated a guide for creating effective educational videos.

RESULTS: The authors identified 40 effective or presumedly effective factors fostering the success of video-based eLearning in teaching evidence-based medicine, providing a ready-to-use checklist. The information collected via the interviews supported and enriched much of the advice found in the literature.

DISCUSSION: To the authors’ knowledge, this type of comprehensive guide for video-based eLearning needs has not previously been published. The interviews considerably contributed to the results. Due to the grounded theory-based approach, in particular, consensus was achieved without the presence of a formal expert panel. Although the guide was created with a focus on teaching evidence-based medicine, due to the general study selection process and research approach, the recommendations are applicable to a wide range of subjects in medical education where the teaching aim is to impart conceptual knowledge.

PMID:38615337 | DOI:10.1080/10872981.2024.2339569

J Math Biol. 2024 Apr 14;88(6):62. doi: 10.1007/s00285-024-02083-y.

ABSTRACT

The design of optimized non-pharmaceutical interventions (NPIs) is critical to the effective control of emergent outbreaks of infectious diseases such as SARS, A/H1N1 and COVID-19 and to ensure that numbers of hospitalized cases do not exceed the carrying capacity of medical resources. To address this issue, we formulated a classic SIR model to include a close contact tracing strategy and structured prevention and control interruptions (SPCIs). The impact of the timing of SPCIs on the maximum number of non-isolated infected individuals and on the duration of an infectious disease outside quarantined areas (i.e. implementing a dynamic zero-case policy) were analyzed numerically and theoretically. These analyses revealed that to minimize the maximum number of non-isolated infected individuals, the optimal time to initiate SPCIs is when they can control the peak value of a second rebound of the epidemic to be equal to the first peak value. More individuals may be infected at the peak of the second wave with a stronger intervention during SPCIs. The longer the duration of the intervention and the stronger the contact tracing intensity during SPCIs, the more effective they are in shortening the duration of an infectious disease outside quarantined areas. The dynamic evolution of the number of isolated and non-isolated individuals, including two peaks and long tail patterns, have been confirmed by various real data sets of multiple-wave COVID-19 epidemics in China. Our results provide important theoretical support for the adjustment of NPI strategies in relation to a given carrying capacity of medical resources.

PMID:38615293 | DOI:10.1007/s00285-024-02083-y

Cancer Causes Control. 2024 Apr 14. doi: 10.1007/s10552-024-01873-5. Online ahead of print.

ABSTRACT

PURPOSE: Breast cancer (BC) characteristics are known to influence patients survival. Social differences have been reported by previous studies for those characteristics but questions persist because of inconsistent conclusions. We aimed to investigate the impact of education on BC stage, grade, and hormone receptor (HR) status, while adjusting for potential confounders including a broad set of health behaviors, anthropometric measures, and reproductive factors.

METHODS: In the French E3N cohort, 5236 women developed a primary invasive BC for which there was available information on stage, grade, and HR status. No multivariate analyses was performed for BC stage based on the lack of association in bivariate analyses. Odds ratios and confidence intervals were estimated using multinomial logistic regression models for BC grade or binomial logistic regression models for HR status of BC.

RESULTS: Women with a lower education were diagnosed with higher grade BC compared to women with a higher education (1.32 [1.12; 1.57]). This association was slightly attenuated after adjustment for covariates independently and more strongly affected in the fully adjusted model (1.20 [0.99; 1.45]). A significant association was observed between lower education and HR- status of BC (1.20 [1.02; 1.42]) attenuated after adjustment for age at first childbirth (1.12 [0.95; 1.33]).

CONCLUSION: In this cohort, education was associated with BC grade and HR status but not stage at diagnosis. The link between education and BC grade was not entirely explained by the different adjustments. A specific mechanism could be at play and deserves further investigations.

PMID:38615276 | DOI:10.1007/s10552-024-01873-5