Preserving effect of Loboob (a traditional multi-herbal formulation) on sperm parameters of male rats with busulfan-induced subfertility.

OBJECTIVE: Male infertility secondary to exposure to gonadotoxic agents during reproductive age is a concerning issue. The aim of this experimental study was to determine the effect of Loboob on sperm parameters. METHODS: 55 healthy rats were selected, weighted and divided into five groups consisting of 11 rats each. The control group received no medication. Rats in Treatment Group 1 received 10mg/kg Busulfan and rats in Treatment Groups 2, 3, and 4 received 35,70 and 140 mg/kg Loboob respectively in addition to 10mg/kg Busulfan. Finally, the sperm parameters and weights of the rats were compared using the Kolmogorov-Smirnov, non-parametric Kruskal-Wallis, and Dunn-Bonferroni tests. RESULTS: All sperm parameters and weights were significantly decreased among rats receiving Busulfan. All dosages of Loboob were effective to enhance the motility of slow spermatozoa, while only in the rats given 70 and 140 mg/kg of Loboob saw improvements in progressively motile sperm percentages (0.024 and 0.01, respectively). Loboob at a dosage of 140mg/kg improved sperm viability. It did not improve normal morphology sperm or decrease immotile sperm counts. Loboob did not affect mean rat weight. CONCLUSIONS: Loboob offered a dose-dependent protective effect on several sperm parameters in rats with busulfan-induced subfertility.

A New Method for Imputing Censored Values in Crossover Designs with Time-to-Event Outcomes Using Median Residual Life.

Crossover designs are commonly applied in research due to efficiency and subject parsimony compared to parallel studies. Baseline measurements would improve the power of comparison. For time to event outcomes, the sample size is reduced due to censorship, if they are ignored; thus, applying traditional regression models will be limited. A logical solution is to impute the censored observation and apply common analytical models for analyzing the data. Nevertheless, techniques to impute censored data in time-to-event outcomes in crossover designs are not practiced as much. Accordingly, we propose a method to impute the censored observation using median residual life regression and then analyze the data using analyses of covariance (ANCOVA), considering the difference of period-specific baselines as covariate. We used simulation to show the favorable performance of our method relative to a recently proposed method, multiple imputation with model averaging and ANCOVA (MIMI). Specifically, the censored observations were multiply-imputed using prespecified parametric event time models, and then, the methods were applied to a real data example.

Prevalence of Cytomegalovirus in Semen of Male Partners of Infertile Couples and the Virus Impact on Sperm Parameters.

BACKGROUND: Genital tract infection is one of the causes of male infertility. Several studies have shown a role for human cytomegalovirus (CMV) in this context. In the present study, the prevalence of CMV in a population of male partners of infertile couples was estimated and the impact of CMV on sperm parameters was determined. METHODS: In this cross sectional study, CMV DNA and virus copy number were examined in the semen of 150 participants including 80 with normal semen analysis (SA) and 70 with abnormal SA, by quantitative Real-Time PCR. Sperm parameters were compared between CMV positive and negative groups. Comparisons with p- values under 0.05 were considered significant. Logistic regression was performed to control the effect of some variables with p<0.25 on sperm parameters. RESULTS: CMV DNA was detected in the semen of 28 (18.6%) individuals. 21 men (30%) with abnormal SA and 7 (8.8%) with normal SA were positive for CMV DNA (p=0.001). The mean virus copy number was 883.1±4662.01 for the men with abnormal SA and 2525.7±12680.9 for those with normal SA (p=0.001). Sperm count was (32.1±23.5) ×106 in CMV positive and (44.2±24.1) ×106 in CMV negative groups (p=0.022). Normal sperm morphology was 2.73±2.83% and 5.99±5.44% in CMV positive and negative groups, respectively (p<0.001). After controlling some variables, the sperm morphology remains the only statistically significant sperm parameter that was reduced by CMV. CONCLUSION: The higher CMV prevalence in the semen of males with abnormal SA compared to normal SA and significant reduction of sperm morphology in the presence of CMV, are in favor of the negative impact of CMV on male fertility.

Improved Landmark Dynamic Prediction Model to Assess Cardiovascular Disease Risk in On-Treatment Blood Pressure Patients: A Simulation Study and Post Hoc Analysis on SPRINT Data.

Landmark model (LM) is a dynamic prediction model that uses a longitudinal biomarker in time-to-event data to make prognosis prediction. This study was designed to improve this model and to apply it to assess the cardiovascular risk in on-treatment blood pressure patients. A frailty parameter was used in LM, landmark frailty model (LFM), to account the frailty of the patients and measure the correlation between different landmarks. The proposed model was compared with LM in different scenarios respecting data missing status, sample size (100, 200, and 400), landmarks (6, 12, 24, and 48), and failure percentage (30, 50, and 100%). Bias of parameter estimation and mean square error as well as deviance statistic between models were compared. Additionally, discrimination and calibration capability as the goodness of fit of the model were evaluated using dynamic concordance index (DCI), dynamic prediction error (DPE), and dynamic relative prediction error (DRPE). The proposed model was performed on blood pressure data, obtained from systolic blood pressure intervention trial (SPRINT), in order to calculate the cardiovascular risk. Dynpred, coxme, and coxphw packages in the R.3.4.3 software were used. It was proved that our proposed model, LFM, had a better performance than LM. Parameter estimation in LFM was closer to true values in comparison to that in LM. Deviance statistic showed that there was a statistically significant difference between the two models. In the landmark numbers 6, 12, and 24, the LFM had a higher DCI over time and the three landmarks showed better performance in discrimination. Both DPE and DRPE in LFM were lower in comparison to those in LM over time. It was indicated that LFM had better calibration in comparison to its peer. Moreover, real data showed that the structure of prognostic process was predicted better in LFM than in LM. Accordingly, it is recommended to use the LFM model for assessing cardiovascular risk due to its better performance.

The Effect of Lactofem Oral Probiotic Capsule on Lactobacilli Colonization and Some Vaginal Health Parameters.

BACKGROUND AND OBJECTIVE: Healthy vaginal ecosystem is conserved with the connection of vaginal epithelium and flora in which lactobacilli play a significant role. The present study aimed to examine the effect of lactofem oral probiotic capsule on Lactobacillus colonization and some other vaginal health indices in women aged 18-55 years. MATERIALS AND METHODS: This interventional, double-blind controlled clinical trial was conducted on 70 women with Nugent score = 4-6 and vaginal pH >4.5. The participants were divided into an oral probiotic group and a control group. The oral probiotic group was required to take one 500 mg lactofem capsule daily for 2 months, while placebo was prescribed for the control group. Samples from 6 visits were examined during the period of prescription. The data were analyzed using the SPSS statistical software, version 18. RESULTS: The results showed no significant difference in the average colonization of vaginal Lactobacillus in the 2 groups before and during the intervention (p = 0.26). Also, no significant difference was observed in the 2 groups' Nugent mean scores before and after the intervention up to the 60th day. However, a statistically significant difference was found in this regard on the 70th day (p = 0.032). Moreover, the results indicated no significant difference in the 2 groups' mean vaginal pH before and after the intervention (p = 0.101). CONCLUSION: Lactofem oral capsule could improve the participants' Nugent scores, but caused no change in Lactobacillus colonization or vaginal pH.

A Comparative Study of Different Joint Modeling Approaches for HIV/AIDS Patients in Southern Iran.

BACKGROUND: The prevalence of HIV/AIDS has been increasing in Iran, especially amongst the young population, recently. The joint model (JM) is a statistical method that represents an effective strategy to incorporate all information of repeated measurements and survival outcomes simultaneously. In many theoretical studies, the population under the study were heterogeneous. This study aimed at comparing three approaches by considering heterogeneity in the patients. METHODS: This study was conducted on 750 archived files of patients infected with HIV in Fars Province, southern Iran, from 1994 to 2017. Proposed Approach (PA), Joint Latent Class Models (JLCM), and Separated Approach (SA) were compared to evaluate the influence covariates on the longitudinal and time-to-event outcomes in the heterogeneous HIV/AIDS patients. RESULTS: Gender (P<0.001) and HCV (P<0.01) were two significant covariates in the classification of HIV/AIDS patients. Time had a significant effect on CD4 (P<0.001) in both classes in the three approaches. In PA and SA, females had higher CD4 than males (P<0.001) in the first class. In JLCM, females had higher CD4 than males (P<0.01) in both classes. The patients with higher Hgb had also higher CD4 (P<0.001) in both classes in the three approaches. HCV reduced the CD4 significantly in both classes in PA (P<0.05) and SA (P<0.001). Within the survival sub-model, HCV reduced survival rate significantly in the second class in PA (P<0.05), JLCM (P<0.01) and SA (P<0.001). CONCLUSION: PA was an appropriate approach for joint modeling longitudinal and survival outcomes for this heterogeneous population.

Bayesian Spatial Joint Model for Disease Mapping of Zero-Inflated Data with R-INLA: A Simulation Study and an Application to Male Breast Cancer in Iran.

Hierarchical Bayesian log-linear models for Poisson-distributed response data, especially Besag, York and Mollié (BYM) model, are widely used for disease mapping. In some cases, due to the high proportion of zero, Bayesian zero-inflated Poisson models are applied for disease mapping. This study proposes a Bayesian spatial joint model of Bernoulli distribution and Poisson distribution to map disease count data with excessive zeros. Here, the spatial random effect is simultaneously considered into both logistic and log-linear models in a Bayesian hierarchical framework. In addition, we focus on the BYM2 model, a re-parameterization of the common BYM model, with penalized complexity priors for the latent level modeling in the joint model and zero-inflated Poisson models with different type of zeros. To avoid model fitting and convergence issues, Bayesian inferences are implemented using the integrated nested Laplace approximation (INLA) method. The models are compared according to the deviance information criterion and the logarithmic scoring. A simulation study with different proportions of zero exhibits INLA ability in running the models and also shows slight differences between the popular BYM and BYM2 models in terms of model choice criteria. In an application, we apply the fitting models on male breast cancer data in Iran at county level in 2014.

The effect of training and awareness of subtle control on the frequency of hand hygiene among intensive care unit nurses.

OBJECTIVE: This study aimed to determine the effect of awareness of subtle control after training on the hand hygiene compliance among nurses in intensive care units (ICUs). The study was conducted in two ICUs of a trauma center in Shiraz, Iran on 48 nurses. The nurses of one ICU were randomly allocated to the intervention and the nurses of the other ICU were allocated to the control group. All nurses were trained on hand hygiene. Then a fake closed camera television (CCTV) was visibly installed in the intervention group's ICU, while the nurses were aware of it. The degree of compliance with hand hygiene was observed in both groups before and after the intervention. Data were gathered using a checklist based on the World Health Organization hand hygiene protocol and analyzed using SPSS 16 and the Chi square, Wilcoxon, Mann-Whitney U, and Independent T-tests, were performed. RESULTS: The mean percentage of hand hygiene compliance in the intervention group after the intervention was significantly higher than before the intervention (p < 0.001). Additionally, the changes in the mean percentage of the intervention group was significantly higher than that for the control group (p = 0.001). The findings showed that a fake CCTV after training, installed in ICUs, can improve hand hygiene compliance.

Development of an instrument based on the theory of planned behavior variables to measure factors influencing Iranian adults' intention to quit waterpipe tobacco smoking.

BACKGROUND: Theory of planned behavior (TPB) is one of the most widely used theoretical frameworks to explain addictive behaviors, such as tobacco smoking. The aim of this study is to develop and validate an instrument based on TPB variables to measure factors influencing Iranian rural adults' intention to quit waterpipe tobacco smoking. METHODS: This study was performed on a sample of rural adult waterpipe consumers living in two villages in Shiraz, Southern Iran. In the beginning, the initial items of instrument were extracted from the literature review and interviews with 20 waterpipe consumers. After that, face validity and qualitative content validity of the items were appraised. To measure quantitative content validity index (CVI) and the content validity ratio (CVR), a panel of experts reviewed the items. In addition, the exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were applied to characterize the construct validity of the instrument. Finally, Cronbach's alpha coefficient and intraclass correlation coefficient (ICC) were computed. RESULTS: CVI and CVR of items were within the ranges of 0.89-0.95 and 0.85-0.96, respectively. EFA indicated the Kaiser-Meyer-Olkin (=0.71) and Bartlett's test of sphericity was significant (=912.36, df=105, p<0.0001). Principal component analysis revealed that 15 items could be grouped into four subscales that accounted for 64.97% of the variance. Based on CFA, two items were deleted. CFA results showed that the remained data were fit to the model. The Cronbach's alpha and ICC of subscales were, respectively, in the ranges of 0.72-0.87 and 0.64-0.82. Finally, a 13-item instrument with four subscales was confirmed. CONCLUSIONS: The findings reveal that the developed TPB instrument is a reliable and valid scale to identify the determinants of the intention to quit waterpipe smoking among Iranian rural adults.

Hospitalized adolescents' perception of dignity: A qualitative study.

BACKGROUND: Adolescents can be vulnerable to diminished dignity in the hospital because young people have significantly different healthcare needs than children and adults. They like to cooperate with caregivers only when they get respectful and dignified care. Care without considering dignity can adversely influence the adolescents' recovery. However, many studies have been conducted on exploring the concept of the patients' dignity from the adult patients and fewer studies still have explored the dignity of young people. OBJECTIVE: This study explores the hospitalized adolescents' perception about dignity. RESEARCH DESIGN: A conventional qualitative content analysis method was used to explore the meaning of hospitalized adolescents' dignity. PARTICIPANTS AND RESEARCH CONTEXT: Hospitalized adolescents in general medical and surgical pediatric units were eligible to participate. Data were obtained through unstructured interviews. Purposive sampling was used and adolescents were recruited until data saturation was reached (n = 13). ETHICAL CONSIDERATIONS: Ethical approval for the study was granted by the Ethics Committee of Shiraz University of Medical Sciences. Participants were provided with information about the purpose, reasons for recording interviews, voluntary participation, and confidentiality of data and interviewees. FINDINGS: Dignity was reflected in four themes: (1) protection of personal privacy, (2) protection of autonomy, (3) respect for identity, and (4) intimate communication. DISCUSSION AND CONCLUSION: Hospitalized adolescents stated that healthcare services should protect their personal privacy and autonomy. Also, they should respect the adolescent's identity and communicate intimately with them to provide the dignity. Adolescence is a discrete developmental stage, with specific healthcare needs which must be addressed effectively by healthcare providers especially nurses.

How Do Hospitalized Adolescents Feel Safe? A Qualitative Study.

BACKGROUND: The feeling of safety makes an important contribution to the sense of well-being and quality of care for hospitalized adolescents, who are at a higher risk of feeling unsafe. Feeling unsafe during hospitalization may have a negative impact on recovery. Nurses must be sensitive to the possibility that patients feel unsafe, even in the absence of obvious direct physical threat. PURPOSE: This study explores the experiences of hospitalized adolescents to obtain an understanding of psychological safety. METHODS: A qualitative study using unstructured interviews was conducted to explore the sense of psychological safety of hospitalized adolescents aged 12-18 years and registered in a general medical or surgical pediatric unit. Purposive sampling was used to recruit new qualified participants until data saturation was reached (N = 16). RESULTS: Psychological safety is reflected by the four themes of receiving comprehensive support, protection of human dignity, relaxing environment, and attempts to adapt. CONCLUSIONS: Hospitalized adolescents stated that healthcare services should provide comprehensive support in a relaxing environment that allows them to retain their human dignity and that elicits feelings of psychological safety.

A Proposed Approach for Joint Modeling of the Longitudinal and Time-To-Event Data in Heterogeneous Populations: An Application to HIV/AIDS's Disease.

In recent years, the joint models have been widely used for modeling the longitudinal and time-to-event data simultaneously. In this study, we proposed an approach (PA) to study the longitudinal and survival outcomes simultaneously in heterogeneous populations. PA relaxes the assumption of conditional independence (CI). We also compared PA with joint latent class model (JLCM) and separate approach (SA) for various sample sizes (150, 300, and 600) and different association parameters (0, 0.2, and 0.5). The average bias of parameters estimation (AB-PE), average SE of parameters estimation (ASE-PE), and coverage probability of the 95% confidence interval (CP) among the three approaches were compared. In most cases, when the sample sizes increased, AB-PE and ASE-PE decreased for the three approaches, and CP got closer to the nominal level of 0.95. When there was a considerable association, PA in comparison with SA and JLCM performed better in the sense that PA had the smallest AB-PE and ASE-PE for the longitudinal submodel among the three approaches for the small and moderate sample sizes. Moreover, JLCM was desirable for the none-association and the large sample size. Finally, the evaluated approaches were applied on a real HIV/AIDS dataset for validation, and the results were compared.

Investigation of breastfeeding training based on BASNEF model on the intensity of postpartum blues.

Postpartum blues is a major risk factor for the incidence of postpartum depression and disruption of breastfeeding. This semi-experimental study investigated the effect of breastfeeding training based on the BASNEF model on severity of postpartum blues in 2012. Four educational sessions based on the BASNEF model were held separately for pregnant women and their mothers, mothers-in-law and spouses. The control group received routine care at the clinic. After delivery, women's knowledge of and attitude towards postpartum blues were evaluated using the Zung Self- Rating Depression Scale. There were significant differences between the groups regarding mean scores of knowledge, mothers' evaluation of behaviour outcomes, attitude, and enabling factors. Also, the mean score for postpartum blues was significantly lower in the intervention group compared to the control group. In conclusion, training based on the BASNEF model had a positive effect on maternal knowledge and attitude and, consequently, the intensity of postpartum blues. Further studies are required to determine the reliability and effectiveness of this method.

Prognostic Factors of Breast Cancer Survival in the Islamic Republic of Iran: an Additive Empirical Bayesian Approach.

Breast cancer is a public health challenge in the Islamic Republic of Iran. Relatively few studies have dealt with large dataset and advanced statistical methods. Therefore, we aimed to investigate the role of prognostic factors on breast cancer survival using Additive Empirical Bayesian model with large data set. Breast cancer data set included 1574 women diagnosed with breast cancer from 2002 to 2012 that registered from Cancer Registry in Fars Province, Islamic Republic of Iran. Overall survival rates at 2, 3, 5 and 10 years were 0.98, 0.94, 0.87 and 0.76, respectively. Five years survival at stages 1, 2 and 3 were 0.94, 0.92 and 0.74, respectively. The younger patients with characteristics such as zero involved nodes, negative progesterone receptor, free skin and good prognostic level had a higher survival chance than others. The 5-year survival probability by stage in Fars Province was nearly the same as that reported by the American Cancer Society. The Nottingham prognostic index (NPI) related to nodal status, tumour size and nuclear grade was the main indicator of breast cancer mortality.

Psychometric Properties of the Iranian Brief Version of the Transtheoretical Model Instrument in Terms of Hookah Tobacco Smoking Cessation.

BACKGROUND: Transtheoretical model (TTM) has been recognized as a common theoretical model in researches in terms of addictive behaviors. The aim of this study was to examine the psychometric properties of the Persian brief version of the TTM for hookah tobacco smoking cessation in a sample of Iranian rural adults who were in the preparation stage for hookah cessation. METHODS: This was a validation study on Iranian rural adult hookah smokers by the TTM instrument. First, to translate the questionnaire items from English to Persian, backward-forward procedure was used. Face and content validity of the instrument items were assessed. Confirmatory factor analysis (CFA) was performed to determine the construct validity of the instrument. For this aim, 300 participants completed the instrument. Cronbach's alpha coefficient and intraclass correlation coefficient (ICC) were calculated to examine the internal consistency and reliability of the subscales of the instrument. FINDINGS: The content validity index (CVI) and content validity ratio (CVR) of the items were ≥ 0.80 and ≥ 0.60, respectively. Based on CFA, the data fitted the TTM model. root mean square error of approximation (RMSEA), the goodness of fit index (GFI), adjusted GFI, and comparative fit index (CFI) were 0.037, 0.960, 0.910, and 0.950, respectively. At this stage, 6 items were deleted. The ICC and Cronbach's alpha of the subscales ranged between 0.60-0.74 and 0.71-0.86, respectively. The final instrument with 29 items was confirmed. CONCLUSION: The findings suggest that translating Persian brief version of the TTM instrument was a reliable and valid tool to identify the determinants of hookah smoking cessation among Iranian rural adults.

Comparison of the Effects of Dry Cupping and Acupressure at Acupuncture Point (BL23) on the Women with Postpartum Low Back Pain (PLBP) Based on Short Form McGill Pain Questionnaires in Iran: A Randomized Controlled Trial.

Objective: To evaluate the effects of acupuncture branches on postpartum low back pain severity among the primiparous subjects visiting the selected educational centers affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. Materials and methods: This clinical trial was conducted on 150 (each group of 50 people) cases in 2012. Cupping therapy was done every other day in four 15-20 minute sessions a week. Besides, acupressure was applied according to the circular model for 20 minutes. The patients filled out the short form McGill Pain Questionnaires. Then, the data were analyzed using the SPSS statistical software (v. 16) and repeated measurements and Chi-square tests. Results: In the cupping group, the mean difference of postpartum Low Back Pain intensity reached from 31.8 ± 10.8 before the intervention to 9.0 ± 6.7, 7.5 ± 6.6, and 4.1 ± 3.6 immediately, 24 hours, and 2 weeks after the intervention, respectively and the results of repeated measures ANOVA showed a significant difference between the three follow-up periods (p < 0.05). On the other hand, this measure reached from 31.1 ± 11.0 before the intervention to 22.1 ± 7.3, 16.2±6.0, and 11.7 ± 5.3 immediately, 24 hours, and 2 weeks after the intervention, respectively in the acupressure group. Conclusion: The study results showed that these modalities could sedate the pain. Therefore, they can be applied as efficient treatments for reducing the low back pain.

A web-based anger management program for parent-female adolescents' conflicts: a cluster randomized controlled trial.

Objective This cluster randomized control trial was performed to evaluate the effectiveness of a web-based anger management program for mother-female adolescents' conflicts. Methods Eight out of 23 high-schools in District Two of Shiraz, Iran were chosen using random cluster sampling and randomly assigned to an intervention and a control group (each group consisted of four schools). The conflict tactics scale was filled out by all eligible third grade high school students in both groups and 140 students who had the scores higher than 30 were randomly selected; 70 adolescents in the intervention group participated in an 8 week intervention, while 70 adolescents in the control group did not undergo any intervention. Data collection was performed at the end of the intervention and 1 month later. Results The results of the t-test revealed no statistically significant differences between the study groups regarding the total conflict tactics scores (p = 0.935) or any of the three subscales before the intervention (p > 0.05). However, a significant difference was observed between the two groups in this regard immediately and 1 month after the intervention (p < 0.05). The results of repeated measure analysis of variance (ANOVA) demonstrated a significant difference between the intervention and control groups regarding the conflict scores and its subscales during the three study periods and groups (F = 79.43, p < 0.001). Conclusion This study highlighted the importance of applying a web-based anger management program in decreasing mother-female adolescents' conflicts. Similar studies are recommended to be conducted on the issue.

Complications of Heart Rhythm Management Devices After Cardiac Rehabilitation Program.

OBJECTIVE: The aim of this study was to examine physical and heart rhythm management device malfunction complications after participating in a cardiac rehabilitation program intervention compared with usual care. METHOD: This study was a clinical trial of 100 patients. After randomization, intervention group patients received 8 cardiac rehabilitation program sessions for 8 weeks and follow-up phone calls. Each session consisted of exercise training, education, and psychological interventions. Data were collected at 3 points in both groups-baseline and 8 and 12 weeks after the first day of the intervention-using a researcher-designed case report form. Data were analyzed using descriptive and nonparametric tests. RESULTS: Of the participants, 59% were men, and the sample was aged 40 to 60 years. At the 8- to 12-week follow-up, there were less physical complications among the cardiac rehabilitation group (P < .001) and no between-group differences in complications related to device malfunction. By heart rhythm device type, cardiac rehabilitation had the greatest efficacy in reducing physical complications in patients with cardioverter/defibrillators. CONCLUSIONS: Cardiac rehabilitation reduced physical complications in patients with cardiac rhythm management devices, especially in patients with cardioverter/defibrillators. Cardiac clinical nurse specialists should recommend rehabilitation programs as part of postimplantation rhythm device treatment to decrease the risk of physical complications.

The study of waiting time to first pregnancy in the south of Iran: A parametric frailty model approach.

BACKGROUND: Time to first pregnancy (TTFP) has never been studied in an Iranian setting. Lifestyle, occupational and environmental factors have been suggested to affect the female reproduction. OBJECTIVE: This study was conducted to measure TTFP in the south of Iran and survey the effects of several similar factors on TTFP by frailty models. MATERIALS AND METHODS: The data on TTFP were available for 882 women who were randomly selected from the rural population (the south of Iran). Only the first and the planned pregnancies of every woman were included. The data were collected retrospectively by using self-administered questionnaires. Frailty and shared frailty models were used to determine which factors had the highest impact on TTFP. RESULTS: The median TTFP was 6.4 months and several factors were surveyed. However, only the age of marriage, height, maternal education and regularity of menstruation prior to conception were selected in the multivariable models. CONCLUSION: Among the several factors which were included in the study, the result of frailty model showed that the height, age of marriage and regular menstruation seemed more notable predictors of TTFP.

Adjusted adaptive Lasso for covariate model-building in nonlinear mixed-effect pharmacokinetic models.

One important aim in population pharmacokinetics (PK) and pharmacodynamics is identification and quantification of the relationships between the parameters and covariates. Lasso has been suggested as a technique for simultaneous estimation and covariate selection. In linear regression, it has been shown that Lasso possesses no oracle properties, which means it asymptotically performs as though the true underlying model was given in advance. Adaptive Lasso (ALasso) with appropriate initial weights is claimed to possess oracle properties; however, it can lead to poor predictive performance when there is multicollinearity between covariates. This simulation study implemented a new version of ALasso, called adjusted ALasso (AALasso), to take into account the ratio of the standard error of the maximum likelihood (ML) estimator to the ML coefficient as the initial weight in ALasso to deal with multicollinearity in non-linear mixed-effect models. The performance of AALasso was compared with that of ALasso and Lasso. PK data was simulated in four set-ups from a one-compartment bolus input model. Covariates were created by sampling from a multivariate standard normal distribution with no, low (0.2), moderate (0.5) or high (0.7) correlation. The true covariates influenced only clearance at different magnitudes. AALasso, ALasso and Lasso were compared in terms of mean absolute prediction error and error of the estimated covariate coefficient. The results show that AALasso performed better in small data sets, even in those in which a high correlation existed between covariates. This makes AALasso a promising method for covariate selection in nonlinear mixed-effect models.