Nevin Manimala

Int J Numer Method Biomed Eng. 2023 Dec 20:e3797. doi: 10.1002/cnm.3797. Online ahead of print.

ABSTRACT

In most variance-based sensitivity analysis (SA) approaches applied to biomechanical models, statistical independence of the model input is assumed. However, often the model inputs are correlated. This might alter the interpretation of the SA results, which may severely impact the guidance provided during model development and personalization. Potential reasons for the infrequent usage of SA techniques that account for input correlation are the associated high computational costs, especially for models with many parameters, and the fact that the input correlation structure is often unknown. The aim of this study was to propose an efficient correlated global sensitivity analysis method by applying a surrogate model-based approach. Furthermore, this article demonstrates how correlated SA should be interpreted and how the applied method can guide the modeler during model development and personalization, even when the correlation structure is not entirely known beforehand. The proposed methodology was applied to a typical example of a pulse wave propagation model and resulted in accurate SA results that could be obtained at a theoretically 27,000× lower computational cost compared to the correlated SA approach without employing a surrogate model. Furthermore, our results demonstrate that input correlations can significantly affect SA results, which emphasizes the need to thoroughly investigate the effect of input correlations during model development. We conclude that our proposed surrogate-based SA approach allows modelers to efficiently perform correlated SA to complex biomechanical models and allows modelers to focus on input prioritization, input fixing and model reduction, or assessing the dependency structure between parameters.

PMID:38116742 | DOI:10.1002/cnm.3797

Prostate. 2023 Dec 20. doi: 10.1002/pros.24659. Online ahead of print.

ABSTRACT

BACKGROUND: To test the efficacy of emotion-centered (EC) versus fact-centered (FC) written medical information for prostate biopsy to alleviate pain and anxiety in a randomized controlled trial.

METHODS: In a single-center, single-blinded study participants were randomized to receive FC or EC (DRKS00022361; 2020). In the EC, the focus was on possible stress reactions and stress-reducing strategies. Participants were asked to complete questionnaires on the day of MRI acquisition (T0) directly before (T1) and after the procedure (T2). The primary outcome measure was the assessment of worst pain in the last 2 h measured by the adapted brief pain inventory. Secondary outcome measures included state anxiety measured by the state-trait anxiety inventory and the subjective evaluation of the impact of the written medical information at T2. For statistical analysis, mixed models were calculated.

RESULTS: Of 137 eligible patients, 108 (79%) could be recruited and were randomized. There was a significant effect for time for the outcome variables pain and anxiety. Regarding the comparison for the primary outcome variable worst pain there was a significantly lower increase from T1 to T2 after FC compared to EC (p < 0.004). The course of anxiety displayed no overall group differences. The FC was evaluated as significantly more helpful regarding stress, pain, and anxiety with moderate effect sizes.

CONCLUSIONS: FC was favorable with regard to worst experienced pain, assuming that the brief introduction of emotional issues such as stress and coping in written information might be counterproductive particularly in men not used to these subjects.

PMID:38116739 | DOI:10.1002/pros.24659

J Clin Periodontol. 2023 Dec 20. doi: 10.1111/jcpe.13936. Online ahead of print.

ABSTRACT

AIM: To estimate association between the use of interdental cleaning aids (IDAs) and type on 7-year follow-up levels of interdental plaque, interdental gingival inflammation, interdental periodontitis severity, the number of interdental sound surfaces and the number of missing teeth in a population-based cohort study.

MATERIALS AND METHODS: We used 7-year follow-up data of 2224 participants from the Study of Health in Pomerania (SHIP-TREND). We applied generalized linear and ordinal logistic models, adjusting for confounding and selection bias using inverse probability treatment weighting and multiple imputation.

RESULTS: Flossers were 32% less likely to have higher interdental plaque (iPlaque) levels than non-users of IDAs (odds ratio [OR] = 0.68; 95% confidence interval [CI]: 0.50-0.94); flossing resulted in 5% lower means of iPlaque. Effects on interdental bleeding on probing (iBOP), mean interdental probing depths and mean interdental clinical attachment levels were direction-consistent but statistically non-significant. Interdental brushing was associated with lower follow-up levels for interdental plaque (OR = 0.73; 95% CI: 0.57-0.93) and iBOP (OR = 0.69; 95% CI: 0.53-0.89). IDAs were more effective in reducing iPlaque in participants with periodontitis, whereas iBOP reduction was more pronounced in participants with no or mild periodontitis. The analyses did not suggest that the use of IDAs affected caries. Finally, applying change score analyses, flossing reduced tooth loss incidence (incidence rate ratio [IRR] = 0.71) compared with non-users of IDAs.

CONCLUSIONS: Recommending flossing and interdental brushing in dental practices represents an approach to the prevention of gingivitis and consequently periodontitis.

PMID:38116705 | DOI:10.1111/jcpe.13936

Epilepsia. 2023 Dec 20. doi: 10.1111/epi.17871. Online ahead of print.

ABSTRACT

OBJECTIVE: Statistical learning, the fundamental cognitive ability of humans to extract regularities across experiences over time, engages the medial temporal lobe in the healthy brain. This leads to the hypothesis that statistical learning may be impaired in patients with epilepsy (PWE) involving the temporal lobe, and that this impairment could contribute to their varied memory deficits. In turn, studies done in collaboration with PWE, that evaluate the necessity of medial temporal lobe circuitry through disease and causal perturbations, provide an opportunity to advance basic understanding of statistical learning.

METHODS: We implemented behavioral testing, volumetric analysis of the medial temporal lobe substructures, and direct electrical brain stimulation to examine statistical learning across a cohort of 61 PWE and 28 healthy controls.

RESULTS: We found that behavioral performance in a statistical learning task was negatively associated with seizure frequency irrespective of seizure origin. The volume of hippocampal subfields CA1 and CA2/3 correlated with statistical learning performance, suggesting a more specific role of the hippocampus. Indeed, transient direct electrical stimulation of the hippocampus disrupted statistical learning. Furthermore, the relationship between statistical learning and seizure frequency was selective as behavioral performance in an episodic memory task was not impacted by seizure frequency.

SIGNIFICANCE: Overall, these results suggest that statistical learning may be hippocampally dependent and that the statistical learning task could serve as a clinically useful behavioral assay of seizure frequency that may complement existing approaches such as seizure diaries. Simple and short statistical learning tasks may thus provide patient-centered endpoints for evaluating the efficacy of novel treatments in epilepsy.

PMID:38116686 | DOI:10.1111/epi.17871

Scand J Urol. 2023 Dec 20;58:133-140. doi: 10.2340/sju.v58.14730.

ABSTRACT

In comparable men with non-metastatic prostate cancer, radical prostatectomy (RP), radiotherapy (RAD) and active surveillance (AS) are treatment options with similar survival rates, but different side-effects. Healthcare professionals consider pretreatment shared decision making (SDM) to be an essential part of medical care, though the patients’ view about SDM is less known. In this article, we explore prostate cancer (PCa) patients’ SDM wish (SDMwish), and experiences (SDMexp). Material and methods: This is a registry-based survey performed by the Cancer Registry of Norway (2017-2019). One year after diagnosis, 5,063 curatively treated PCa patients responded to questions about their pre-treatment wish and experience regarding SDM. Multivariable analyses identified factors associated with SDM. Statistical significance level: p < 0.05. Results: Overall, 78% of the patients wished to be involved in SDM and 83% of these had experienced SDM. SDMwish and SDMexp was significantly associated with decreasing age, increasing education, and living with a partner. Compared with the RP group, the probability of SDMwish and SDMexp was reduced by about 40% in the RAD and the AS groups. Conclusion: Three of four curatively treated PCa wanted to participate in SDM, and this wish was met in four of five men. Younger PCa patients with higher education in a relationship, and opting for RP, wanted an active role in SDM, and experienced being involved. Effective SDM requires the responsible physicians’ attention to the individual patients’ characteristics and needs.

PMID:38116675 | DOI:10.2340/sju.v58.14730

Asia Pac J Public Health. 2023 Nov 21:10105395231211997. doi: 10.1177/10105395231211997. Online ahead of print.

ABSTRACT

The World Health Organization (WHO) recommends the use of color-coded cardiovascular disease (CVD) risk charts for CVD management. This study evaluated the agreement between the laboratory and non-laboratory 10-year CVD risks based on 2019 WHO CVD risk-prediction charts. The agreement of CVD risk scores among 40- to 69-year-old Bhutanese population stratified by gender and age groups (<60 and ≥60 years) was determined via weighted kappa statistics. In the general population, there was substantial agreement between the two CVD risk score charts for all ages and <60 years but a moderate agreement for participants aged ≥60 years. In males, substantial agreement was observed in all ages and in <60 years and moderate agreement in ≥60 years. In females, both the predictions showed substantial agreement in all ages and <60, but a moderate agreement for ≥60 years. The non-laboratory-based risk charts can be used interchangeably with laboratory-based charts for predicting 10-year CVD risk in resource-constrained countries like Bhutan.

PMID:38116599 | DOI:10.1177/10105395231211997

Iran J Pharm Res. 2023 Mar 23;22(1):e134772. doi: 10.5812/ijpr-134772. eCollection 2023 Jan-Dec.

ABSTRACT

BACKGROUND: Amphotericin B (AmB) is the first-line drug to treat invasive fungal infections. However, its delivery to the body and clinical use faces many challenges because of its poor solubility, poor pharmacokinetics, and severe nephrotoxicity.

OBJECTIVES: Due to the necessity for designing safer and more effective nanocarriers for AmB and the importance of preclinical pharmacokinetic studies in evaluating these novel drug delivery systems, the present study was framed to explore the influence of rat strain on the pharmacokinetic profile of this drug.

METHODS: Twenty-four Wistar and Sprague-Dawley (SD) rats were intravenously injected with 1 mg/kg AmB as Fungizone or AmBisome, which are the two most commonly marketed formulations of the drug. Blood samples were collected before and at regular intervals up to 24 h after administration. Drug concentration was analyzed by a validated HPLC method, and pharmacokinetic parameters were determined by the non-compartmental method.

RESULTS: Irrespective of the type of formulation, the AUC_0-t and AUC_0-∞ values were significantly higher (P < 0.001), and Cl as an important PK parameter was markedly lower (P < 0.001) in SD rats compared to the Wistar strain. For Fungizone, the mean Cl values in SD and Wistar rats were 206.90 and 462.95 mL/h/kg (P < 0.001), respectively. The apparent volume of distribution (V_ss) was also lower in SD rats compared to Wistar; however, for AmBisome, the difference in V_ss was not statistically significant. Our further investigation suggested that the higher amount of total protein in the SD strain may justify the higher plasma concentrations and lower Cl and V_ss of amphotericin B in this strain compared to the Wistar strain.

CONCLUSIONS: Overall, following intravenous administration of AmB, there were significant differences in the pharmacokinetic parameters of the drug between two rat strains for both formulations. The obtained data is important for correctly interpreting experimental data from different research groups.

PMID:38116555 | PMC:PMC10728861 | DOI:10.5812/ijpr-134772

Iran J Pharm Res. 2023 Apr 17;22(1):e132736. doi: 10.5812/ijpr-132736. eCollection 2023 Jan-Dec.

ABSTRACT

BACKGROUND: Community pharmacists play an important role in improving outcome by providing advice and counselling services to patients.

OBJECTIVES: The aim of this study was to measure the willingness to pay (WTP) for pharmacist counselling services in community pharmacies and identify determinant factors on consumers’ WTP.

METHODS: A self-administered questionnaire-based survey was conducted in community pharmacies in Tehran (capital of Iran) from January 1, 2020 to February 20, 2021. Contingent valuation method was applied to evaluate respondents’ maximum WTP using three hypothetical scenarios illustrating different levels of counselling services. Logistic regression was used to analyze the association between different variables and WTP for pharmacy services.

RESULTS: Total number of participants who completed the questionnaire were 332 and 60% of the participants were male. In the first scenario 70.2% of participants were willing to pay for oral counselling pharmacy services. In the second and third scenario, percentage of people willing to pay increased to 79.5%. and 86.1%, respectively. In the first scenario, monthly income (OR = 0.041, P value = 0.04), the duration of underlying illness (OR = 0.04, P value = 0.04) and the using internet (OR = 2.59, P value = 2.59) had a statistically significant relationship with willingness to pay. In the third scenario, the willingness to pay increased as the age decreased. The possibility of using the internet (OR = 3.32, P value = 0.00) and the need for a community pharmacist (OR = 2.19, P value = 0.03) increased the chance of willingness to pay.

CONCLUSIONS: More consumers are willing to pay for more pharmacist counselling services. Therefore, improving the quality of counselling services could have positive economic effects on community pharmacies.

PMID:38116550 | PMC:PMC10728831 | DOI:10.5812/ijpr-132736

Front Cardiovasc Med. 2023 Dec 5;10:1250404. doi: 10.3389/fcvm.2023.1250404. eCollection 2023.

ABSTRACT

BACKGROUND: To assess the relationship of genetically predicted sexual behavior (age at first sex (AFS) and the number of sexual partners (NSP)) on cardiovascular diseases (CVDs).

METHODS AND RESULTS: We performed two-sample Mendelian randomization (MR) with publicly available datasets from the UK Biobank and FinnGen Study, and analyzed genome-wide association results for sexual behaviors and twelve types of CVDs. The univariable MR method provided a total effect of AFS and NSP on CVDs, and showed evidence that early AFS rather than NSP was associated with CVDs, including angina pectoris (AP), atrial fibrillation and flutter (AFF), coronary atherosclerosis (CAS), deep vein thrombosis of the lower extremity (DVT-LE), heart failure (HF), hypertension (HTN), ischaemic stroke (IS), and myocardial infarction (MI). Given sex as a social determinant of CVD risk, we used gender-stratified SNPs to investigate gender differences in the development of CVDs. These results showed a stronger causal relationship of AFS on CVDs in females than in males. Further multivariable MR analyses indicated a direct effect after accounting for insomnia, number of days of vigorous physical activity 10 + minutes (VPA 10 + min), and time spent watching television (TV). Two-step MR demonstrated these three risk factors act as a mediator in AFS associated AP/HTN/HF.

CONCLUSIONS: We provide evidence that early AFS increased the risk of CVDs. These associations may be partly caused by VPA 10 + min, insomnia, and the time spent on TV. The causality of AFS on CVDs in females was stronger than in males. Conversely, genetically predicted NSP was not associated with CVDs.

PMID:38116537 | PMC:PMC10728475 | DOI:10.3389/fcvm.2023.1250404

Front Vet Sci. 2023 Dec 5;10:1274786. doi: 10.3389/fvets.2023.1274786. eCollection 2023.

ABSTRACT

Developing and evaluating novel diagnostic assays are crucial components of contemporary diagnostic research. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) are frequently used to evaluate diagnostic assays’ performance. The variation in AUC estimation can be quantified nonparametrically using resampling methods, such as bootstrapping, and then used to construct interval estimation for the AUC. When multiple observations are observed from the same subject, which is very common in veterinary diagnostic tests evaluation experiments, a traditional bootstrap-based method can fail to provide valid interval estimations of AUC. In particular, the traditional method does not account for the correlation among data observations and could result in interval estimation that fails to cover the true AUC adequately at the desired confidence level. In this paper, we proposed two novel methods to calculate the confidence interval of the AUC for correlated diagnostic test data based on cluster bootstrapping and hierarchical bootstrapping, respectively. Our simulation studies showed that both proposed methods had adequate coverage probabilities which were higher than the existing traditional method when there were intra-subject correlations. We also discussed applying the proposed methods to evaluate a novel whole-virus ELISA (wv-ELISA) diagnostic assay in detecting porcine parainfluenza virus type-1 antibodies in swine serum.

PMID:38116513 | PMC:PMC10728486 | DOI:10.3389/fvets.2023.1274786