Nevin Manimala

CPT Pharmacometrics Syst Pharmacol. 2021 Apr;10(4):340-349. doi: 10.1002/psp4.12624.

ABSTRACT

Gene-treatment interactions, just like drug-drug interactions, can have dramatic effects on a patient response and therefore influence the clinician decision at the patient’s bedside. Crossover designs, although they are known to decrease the number of subjects in drug-interaction studies, are seldom used in pharmacogenetic studies. We propose to evaluate, via realistic clinical trial simulations, to what extent crossover designs can help quantifying the gene-treatment interaction effect. We explored different scenarios of crossover and parallel design studies comparing two symptom-modifying treatments in a chronic and stable disease accounting for the impact of a one gene and one gene-treatment interaction. We varied the number of subjects, the between and within subject variabilities, the gene polymorphism frequency and the effect sizes of the treatment, gene, and gene-treatment interaction. Each simulated dataset was analyzed using three models: (i) estimating only the treatment effect, (ii) estimating the treatment and the gene effects, and (iii) estimating the treatment, the gene, and the gene-treatment interaction effects. We showed how ignoring the gene-treatment interaction results in the wrong treatment effect estimates. We also highlighted how crossover studies are more powerful to detect a treatment effect in the presence of a gene-treatment interaction and more often lead to correct treatment attribution.

PMID:33951752 | DOI:10.1002/psp4.12624

Early Interv Psychiatry. 2021 May 5. doi: 10.1111/eip.13158. Online ahead of print.

ABSTRACT

BACKGROUND: The prescription of antipsychotics outside overt psychotic conditions remains controversial, especially in youth where it is relatively widespread. Furthermore, some studies seem to indicate that antipsychotic exposure in individuals at ultra-high-risk (UHR) for psychosis is associated with higher conversion rates. This study was set up to test whether the inter-current prescription of antipsychotics in UHR patients was related to the psychometric threshold for a diagnosis of psychosis.

METHODS: The 24-item Brief Psychiatric Rating Scale (BPRS) was used to quantify treatment response up to 2 years in 125 UHR participants. Standard psychometric criteria were used to quantify conversion to psychosis. Kaplan-Mayer and Cox proportional hazard survival analysis were applied to determine the impact of having or not received the prescription of an antipsychotic drug.

RESULTS: Over the study period 30 (24%) subjects received the prescription of an antipsychotic. In the sample, there were 31 participants (25%) who had reached the psychometric threshold for conversion to psychosis after 2 years of treatment. UHR people who received a prescription of antipsychotics during the first 2 years of treatment were statistically more likely to reach the psychometric threshold for conversion to psychosis on the BPRS: Hazard ratio = 3.03 (95%CI: 1.49-6.16); p = .003.

CONCLUSION: This finding supports the hypothesis that the prescription of antipsychotics within UHR cohorts is to be considered a red flag for higher incipient risk of conversion to psychosis.

PMID:33951751 | DOI:10.1111/eip.13158

Andrologia. 2021 May 5:e14091. doi: 10.1111/and.14091. Online ahead of print.

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is one of the risk factors for erectile dysfunction (ED). We aimed to predict the risk of ED in patients with NAFLD. The study included 146 male patients complaining impotence admitted to the urology outpatient clinic aged 24-80 years without a history of alcohol use who underwent abdominal ultrasonography between February 2018 and January 2019. 106 patients with NAFLD and 40 men without NAFLD were included in the study. Clinical and laboratory parameters, ED status according to International Index of Erectile Function-5 were compared between patients with and without NAFLD. The mean age of patients was 51.47 ± 10.34 years. NAFLD was detected in 72.6% of the patients. No statistically significant difference was found regarding mean age, BMI, IIEF-5 scores, DM status, serum glucose levels (p > .05). Fasting insulin levels, hypertension (HT), insulin resistance (IR) and ED status of the patients with NAFLD were significantly higher than patients without NAFLD (p < .05). NAFLD was found to be a significantly independent associated with ED. We also found that patients with NAFLD have risk of ED 2.92 times higher than without NAFLD (OR: 2.92). For the patients presenting with erectile dysfunction, hepatic steatosis should also be considered.

PMID:33951744 | DOI:10.1111/and.14091

Z Geburtshilfe Neonatol. 2021 May 5. doi: 10.1055/a-1475-5413. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate whether placental protein-13 (PP-13) measured in the serum of pregnant women could predict abnormal invasive placentation (AIP) detected by color Doppler ultrasound (US) and magnetic resonance imaging scan in addition to the routine US scan during the third trimester.

MATERIALS AND METHODS: The prospective case-control study included patients subdivided in 2 groups: 42 pregnant women with a singleton pregnancy at 28-32 weeks of gestation with only suspected AIP, and 32 healthy pregnant women. The serum PP-13 levels were measured in both groups using an enzyme-linked immunosorbent assay (ELISA) method and statistically compared. The cases of AIP were confirmed by placental histopathological examination and/or the uterus removed by hysterectomy after elective caesarean section.

RESULTS: Serum PP-13 levels of pregnant women with AIP were significantly higher (p<0.001) than those of controls (650.32±387.33 vs. 231.43±94.33). Statistical analysis of maternal serum PP-13 levels above the threshold of 312 pg/ml (measured in the early third trimester) predicted AIP with 76.2% sensitivity and 75% specificity.

CONCLUSION: Maternal serum PP-13 may have a role in the pathophysiology of AIP owing to its high serum value in the AIP group. The maternal serum dosage of PP-13 levels could improve pregnancy management in those patients suspected of having AIP.

PMID:33951735 | DOI:10.1055/a-1475-5413

Urol Int. 2021 May 5:1-8. doi: 10.1159/000514041. Online ahead of print.

ABSTRACT

INTRODUCTION: Symptomatic lymphoceles (SLs) represent the most common complication after radical prostatectomy (RP) and pelvic lymph node dissection (PLND). To date, preoperative risk factors are missing.

METHODS: Clinical and pathological data of 592 patients who underwent RP and PLND were evaluated. Included parameters were age, BMI, prostate-specific antigen (PSA), PSA ratio, PSA density, number of resected and/or positive lymph nodes, previous abdominal surgery/pelvic radiotherapy, anticoagulation, and surgical approach.

RESULTS: Fifty-nine patients (10%) developed an SL, of which 57 underwent open retropubic radical prostatectomy (RRP) and 2 underwent robot-assisted radical prostatectomy (RARP). Multivariate logistic regression revealed the following parameters as statistically significant risk factors: PSA (odds ratio [OR] = 2.23; 95% CI [1.25; 5.04], p = 0.04), number of resected lymph nodes (OR = 1.47; 95% CI [1.10; 1.97], p < 0.01), previous abdominal surgery (OR = 2.58; 95% CI [1.38; 4.91], p < 0.01), and surgical approach (OR = 0.08; 95% CI [0.01; 0.27], p < 0.01). Previous oral anticoagulation showed almost statistically significant results (OR = 2.39 [0.92; 5.51], p = 0.05).

CONCLUSION: The risk for SL might be predictable considering preoperative risk factors such as PSA, previous abdominal surgery and anticoagulation. To avoid SL, RARP should be the procedure of choice. If RRP is considered, patients at risk for SL may benefit from peritoneal fenestration during RP.

PMID:33951669 | DOI:10.1159/000514041

Urol Int. 2021 May 5:1-7. doi: 10.1159/000515982. Online ahead of print.

ABSTRACT

BACKGROUND: There are limited data on the use and concern of telemedicine among German urologists, and thus, there are no established guidelines for telemedical diagnosis, treatment, and prevention of urological indications.

METHODS: An anonymized survey was conducted among German private practice urologists during the 2019 coronavirus disease (COVID-19) pandemic. The χ2 test, Mann-Whitney U-test, and Kruskal-Wallis test were used for statistical analysis.

RESULTS: 257 urologists were included in the final analysis. Thirty-five (14.0%) of urologists had used telemedicine as part of their consultation, and 221 (86.0%) had not used telemedicine. There was no difference between telemedicine adoption rates between rural and urban settings. Telemedicine users were significantly more satisfied with the information they had received regarding telemedicine issues. Users saw the greatest barrier to telemedicine that patients do not take up the offer of telemedicine. Nonusers were most concerned with unclear indications for telemedicine followed by lesser reimbursements during telemedicine than in-person visitations. Users were significantly more likely to use telemedicine beyond the COVID-19 pandemic. Urologists, who wanted to use the service in the future, wanted an active support by the German society of urology and guidelines for telemedicine. Last, users and nonusers preferred telemedicine for non-acute chronic diseases and follow-up visitations.

CONCLUSION: Despite the COVID-19 pandemic, telemedicine remains a rarely used service among German private practice urologists. Ultimately, to overcome the current challenges, urologists require an active support for the service through the German Society of Urology and telemedical guidelines.

PMID:33951666 | DOI:10.1159/000515982

Urol Int. 2021 May 5:1-7. doi: 10.1159/000514415. Online ahead of print.

ABSTRACT

INTRODUCTION: To avoid mesh-related complications, autologous transobturator-tape (a-TOT) technique is a viable option in stress urinary incontinence (SUI) surgery. The method differs from TOT and retropubic tape (RT) in the usage of autologous tissue. We hypothesized that a-TOT improves female sexual dysfunction (FSD) more than TOT and RT.

METHODS: This is a retrospective cohort study. Patients who underwent a-TOT, TOT, and RT surgeries were surveyed regarding the cure of SUI, complications, and FSD parameters. The groups were compared according to baseline and postoperative data.

RESULTS: A-TOT, TOT, and RT groups included 37, 69, and 36 patients, respectively. The median follow-up time was 19 months. The groups were similar in terms of preoperative characteristics. The objective cure, subjective cure, and overall complication rates were comparable among the groups (p > 0.05). A-TOT group had significant improvements in mean female sexual function index (FSFI) scores, TOT group deteriorated, and RT group remained stable (p = 0.001, p = 0.001, and p = 0.226, respectively). The postoperative mean total FSFI scores were 25.73 ± 2.46, 23.17 ± 3.35, and 21.53 ± 2.47 for the a-TOT, TOT, and RT groups, respectively. The a-TOT group had better results than the TOT and RT groups (p < 0.05 and p < 0.05), and besides, the difference between the TOT and RT groups was statistically significant (p < 0.05). According to percentage changes in domain scores following the operations, the a-TOT group had significantly better results in desire, arousal, lubrication, satisfaction, and pain domains than the TOT group (p < 0.05) as well as better desire, arousal, and pain domains (p < 0.05) than the RT group.

DISCUSSION/CONCLUSIONS: Besides comparable outcomes in SUI treatment, the a-TOT technique provides improvements in female sexual functions while TOT worsens and RT does not change. Favorable outcomes in sexual functions caused by improvements in desire, arousal, satisfaction, and pain domains are observed following the a-TOT technique.

PMID:33951661 | DOI:10.1159/000514415

Urol Int. 2021 May 5:1-7. doi: 10.1159/000513320. Online ahead of print.

ABSTRACT

INTRODUCTION: The aim of this study was to investigate the sexual intercourse frequency (SIF) of infertile couples without sexual dysfunction and analyze its related influencing factors.

MATERIALS AND METHODS: We retrospectively analyzed the data of a total number of 4,923 infertile couples without sexual dysfunction who received treatment in our assisted reproductive center from October 2016 to October 2018. Both partners of couples were inquired about their information of demographic statistics, occupations, lifestyles, education backgrounds, psychological characteristics, and testostrone levels of male patients. The multivariable linear regression analysis was applied to evaluate the influence of various variables on SIF.

RESULTS: The median (interquartile range) SIF of infertile couples without sexual dysfunction was 7 (6.5-8) times per month. Lower academic qualification and younger age were predictive of increased SIF in both partners. The SIF of Chinese Han women and Chinese Zang women is higher than that of other ethnic groups. Men with lower testosterone (<10 nmol/L) were associated with lower SIF. The BMI, occupation, alcohol consumption, races of both partners of couples, and smoking status of males were not associated with SIF. Multivariable linear regression analysis indicated that only the age and the education level of men played an important role in SIF, and educational level of men had the greatest impact, followed by men’s age.

CONCLUSION: In our study, we analyzed demographics data, occupational characteristics, and lifestyle behaviors of both partners, as well as men’s testosterone levels; we also reported the related SIF. According to our research, men’s education level was the most important factor in predicting SIF, followed by men’s age. Testosterone levels of men do not appear to play a substantial role in predicting SIF in infertile couples.

PMID:33951657 | DOI:10.1159/000513320

J Radiol Prot. 2021 May 5. doi: 10.1088/1361-6498/abfe50. Online ahead of print.

ABSTRACT

Several national regulations and good international practices promote the existence of a central register with the results of individual radiological monitoring. In the majority of the countries (Latin American region), dosimetry data were neither harmonized, nor managed by a unique database, therefore the possibility of using such data, for proper characterization of the radiological conditions, integrally at national level, in a territory or a sector, and by practices or occupational categories, was very limited. All these considerations justified the need for developing a prototype of National Dose Register (NDR) for Latin America. The main objectives were the strengthening of safety supervision in nuclear applications and the surveillance system for occupational exposure as well as the centralization of personal dosimetry data, compiling all doses evaluated by the different dosimetric service providers. The experience of Cuba and Brazil in the implementation of their national registers was well known and accordingly used as bases to design this software. The first version of the NDR prototype, developed in the Spanish language has been designed, developed, and validated. So far, sixteen countries have started to implement the NDR. The present work describes aspects such as the technical bases of the NDR design, its characteristics, and functionalities. Experience gained during implementation in Latin America is also addressed. Having a common system of dosimetric information management in the region has opened an important space for scientific exchanges between the countries and their competent authorities. The NDR implementation has provided regulatory authorities with a tool that permits the verification of the level of compliance with dose limits and restrictions, as well as to carry out statistics assessments of the results of individual radiological surveillance that may permit evaluation of the appropriateness and effectiveness of radiation protection programs implemented in the practices and to contribute to their optimization.

PMID:33951614 | DOI:10.1088/1361-6498/abfe50

Comput Biol Chem. 2021 Mar 29;92:107479. doi: 10.1016/j.compbiolchem.2021.107479. Online ahead of print.

ABSTRACT

Development of protein 3-D structural comparison methods is essential for understanding protein functions. Some amino acids share structural similarities while others vary considerably. These structures determine the chemical and physical properties of amino acids. Grouping amino acids with similar structures potentially improves the ability to identify structurally conserved regions and increases the global structural similarity between proteins. We systematically studied the effects of amino acid grouping on the numbers of Specific/specific, Common/common, and statistically different keys to achieve a better understanding of protein structure relations. Common keys represent substructures found in all types of proteins and Specific keys represent substructures exclusively belonging to a certain type of proteins in a data set. Our results show that applying amino acid grouping to the Triangular Spatial Relationship (TSR)-based method, while computing structural similarity among proteins, improves the accuracy of protein clustering in certain cases. In addition, applying amino acid grouping facilitates the process of identification or discovery of conserved structural motifs. The results from the principal component analysis (PCA) demonstrate that applying amino acid grouping captures slightly more structural variation than when amino acid grouping is not used, indicating that amino acid grouping reduces structure diversity as predicted. The TSR-based method uniquely identifies and discovers binding sites for drugs or interacting proteins. The binding sites of nsp16 of SARS-CoV-2, SARS-CoV and MERS-CoV that we have defined will aid future antiviral drug design for improving therapeutic outcome. This approach for incorporating the amino acid grouping feature into our structural comparison method is promising and provides a deeper insight into understanding of structural relations of proteins.

PMID:33951604 | DOI:10.1016/j.compbiolchem.2021.107479