Routine Statistical Methods Research Articles

Breast cancer awareness among Afghan refugee women in Turkey.

SummaryBackground Refugees and asylum-seekers have lower levels of cancer awareness and this contributes to low rates of screening and more advanced cancers at diagnosis, compared to non-refugee populations, due largely to reduced access to medical information and care. The global Afghan refugee population is rapidly increasing with the ongoing Afghan political crisis. The present study investigates breast cancer (BC) awareness among Afghan refugee women.MethodsA cross-sectional survey of Afghan refugee women residing in Turkey was performed in September 2021. A validated BC patient awareness assessment, the Breast Cancer Awareness Measure (BCAM), was used to assess participants’ knowledge of seven domains of BC: symptoms, self-examination, ability to notice breast changes, age-related risk of BC, urgency of addressing changes in the breast, BC risk factors, and BC screening. BCAM was translated into patients’ native language and administered verbally by a physician with the assistance of an official interpreter. Routine statistical methods were employed for data analysis.FindingsA total of 430 patients were recruited to the study. The response rate was 97·7% (420 patients). The median participant age was 35 years (range: 18 to 68 years). The majority of participants (84%) had no formal education. Most participants (96%) were married, and most (95%) were not employed. Awareness of warning signs of BC was low: only seven to 18% of participants recognized 11 common warning signs of BC. Participant use of breast self-exam (BSE) was low, with 82% of participants stating they rarely or never complete BSE. Zero of 420 patients reported ever seeing a physician for a change in their breasts. Awareness of risk factors for BC was also low: only 15% of participants recognized increasing age as a risk factor for BC, and other risk factors were only recognized by four to 39% of participants.InterpretationBC awareness among Afghan refugee women is critically low. There is an urgent need to target this population for practical interventions to increase BC awareness, in addition to screening and earlier diagnosis. Evidence-based interventions include educational sessions in patients’ native language and use of BSE and clinical breast examination for screening.FundingAmerican Society for Radiation Oncology (ASTRO) – Association of Residents in Radiation Oncology (ARRO) Global Health Scholar Grant, Dana-Farber Cancer Institute Jay Harris Junior Faculty Research Grant.

Outcomes of Total Hip Arthroplasty Via the Direct Anterior vs Alternative Approaches for Acute Femoral Neck Fractures.

BackgroundTotal hip arthroplasty (THA) performed for displaced femoral neck fractures (FNF) is becoming a more frequent treatment in the active elderly population. The complication profiles associated with THA surgical approaches in the fracture setting are unclear. The purpose of this study was to compare a series of THA for FNF performed via the direct anterior (DA) approach vs alternative approaches (anterolateral and posterolateral).MethodsA retrospective review identified 52 patients who underwent primary THA for FNF between 2009 and 2018, including 20 via the DA approach and 32 by alternative approaches. All procedures were exclusively performed by high-volume arthroplasty surgeons. Perioperative results, complications, and clinical outcomes were compared with those of routine statistical methods. Mean follow-up duration was 3 years (range, 1-8).ResultsThe average age was 74 years (range, 57-92) with similar baseline characteristics between the 2 groups (P = .09). The DA cohort demonstrated significantly shorter length of stay (3 days vs 5 days, P < .01) and discharge to home vs skilled nursing facility (40.0% vs 9.4% P = .014). There was a trend toward decreased complications (0% vs 16%, P = .08). There were no dislocations or fractures in either cohort. Final Harris Hip Scores (94 vs 81, P = .07) and return to community ambulation (96%) were similar between DA and alternative approach groups.ConclusionThe DA approach to THA performed for FNF appears safe with improved outcomes compared with alternative approaches. Larger studies are needed to verify these results.

Interim results of prospective pilot phase II trial of concurrent anti-PD-1 and stereotactic radiosurgery (SRS) for melanoma and NSCLC patients with brain metastases (NCT02858869).

e22002 Background: The safety and efficacy of concurrent radiotherapy (SRS) and single agent (anti-PD-1) checkpoint inhibitor have not been established. We report the first results of an interim analysis from a prospective pilot phase II trial of cocurrent anti-PD-1 (pembrolizumab) and SRS for brain metastases Methods: Food and Drug Administration (FDA) and Institutional Review Board (IRB) approval were obtained to conduct a prospective trial with three different radiation dose arms (Arm A: 6 Gray (Gy) in 5 fractions (fx), 9 Gy in 3 fractions, and 18-21 Gy in single fraction) in combination with Pembrolizumab. Patients with not more than 10 brain metastasis who have not received prior brain radiation were eligible. Routine statistical methods were used to estimate control of brain metastases within the irradiated volume (local control, LC), anywhere intra-cranial control (AICC), progression free survival (PFS), and overall survival (OS). RECSIST 1.1 criteria were used to assess. Safety was monitored using NCI CTCAE v 4.0 criteria for toxicity assessment while intracranial and extracranial treatment response was assessed according to RECIST 1.1 criteria. Patients were enrolled from 2017-2020. Results: We report interim analysis from the first 18 patients of planned 36 patients who have completed treatments on each of the three different radiation dose arms (12 patients per arm). All patients received PD1 on day 0, immediately followed by SRS within 2-3 days. At 6 months, the LC (94.0% [CI: 65-99.1]), AICC (70.6% [CI: 43.1-86.65]), PFS (50% [24.5-71]), and OS (77.4% [50.3-90.9]) were higher than expected with either SRS alone or PD1 alone, and appear to be comparable to dual checkpoint, but with much less toxicity. No grade 4 or grade 5 toxicity was noted. The primary endpoint of safety, based on the absence of grade 3 CNS toxicity at 3 months was met with all three radiation dose arms. Overall rate of grade 1-3 toxicity was also within acceptable range. Conclusions: Preliminary prospective results of concurrent SRS and single agent pembrolizumab for brain metastases in melanoma and NSCLC supports this strategy as a safe and promising option compared with dual agent therapy. Clinical trial information: NCT02858869.

Antiepileptic drugs used in different types of epilepsy in childhood epileptic patients in Children Hospital and Institute of Child Health Lahore and its comparison with international studies

Objective: This study was under taken for the evaluation of pediatric epileptic patients and to determine the antiepileptic drugs used in treatment of different epilepsy types and its comparison with other studies. Method: This prospective study was conducted in the Neurology Department of the Children Hospital Lahore. A questionnaire was developed for collection of data. Three hundred patient’s upto fifteen years of age with uncomplicated epileptic seizures were included in study. Data was analyzed by routine statistical methods. Results: Commonly encountered cases were of tonic clonic seizures 39%, myoclonic 12%, petitmal 11% and complex partial seizures 9%. Results shows that most commonly prescribed drug was valproic acid used in 67% cases. Valproate was also administered in combination with Topiramate, Lamotrigene, Clonazepam and Phenobarbitone.Carbamazepine was also found to be administered along with valproate, topiramate, Phenobarbitonea and Lamotrigene. Patients stable on monotherapy were 57 % and those stable on combination therapy are 43%. Conclusion: The tonic clonic seizure is most common in pediatric epileptic patients and for its treatment most recommended medicine is valproate. A study conducted in Iran reveals that phenobarbitone is the commonest antiepileptic drug (33.7%) because of its broad antiepileptic action and economical price. So it is concluded that proper selection of economical antiepileptic drug must be done for the proper treatment of epileptic patient and monotherapy should be encouraged as compare to combination therapy.

How to reverse first time donors to become regular donors? A questionnaire survey in Estonia

BackgroundDonating blood in Estonia is non-remunerated and voluntary. Estonian Blood Service system has four independent regional blood centres that are responsible for blood collection, processing, screening and distribution of blood components to hospitals for clinical use. Study designThis research was carried out as a questionnaire survey. A questionnaire was developed to study lapsing first time donors’ (FTD) blood donation experience, intention and willingness to donate again. MethodsA thousand five hundred and forty-six questionnaires were posted to donors who had one successful donation in 2010 and who had not returned to second donation till the year 2012. For data analysis routine statistical methods were used. To evaluate the most appropriate number of classes, based on previous experience and future expectations, latent class analysis was used. ResultsThere were 453 respondents (29.3%). For the majority of aspects of blood donation experience the emotions were positive. Results of the study suggested that blood collection agencies should intervene to bolster donors’ attitudes, perceived control, and identity as a donor during this crucial post-first donation period. ConclusionFirst blood donation seems to have been a positive experience. Reasons leading to stopping blood donation should be studied further. Establishing a donor registry for Estonia would be essential to keep track of donors.

INTERLEUKIN 1 AND INTERLEUKIN 4 GENES POLYMORPHISM ASSOCIATED WITH EARLY AND PRESCHOOL AGE CHILDREN SENSITIZATION TO STREPTOCOCCUS PYOGENES

Background. Streptococcus pyogenes infection and sensitization to its antigens is considered to be an unfavorable factor for the induction of rheumatic pathology. The search for genetic predictors of rheumatic diseases in general, and sensitization to S. pyogenes, in particular, is of high relevance in modern medicine.Objective. To study the associations between interleukin 1 and interleukin 4 gene polymorphisms and the development of sensitization to antigens of S. pyogenes in toddlers and preschool children.Materials and methods. 771 children aged 2–6 years with recurrent acute respiratory tract infections treated by allergist-immunologist and otorhinolaryngologist were included in the study. Antibodies against S. pyogenes were determined by ELISA using commercial kits “Immunoteks” (Stavropol, Russia) in all children. Children with IgG immune response to S. pyogenes were assigned to the study group (n = 306), whereas children without this response were assigned to the control group (n = 465). Both groups underwent gene typing of IL1B (+3953, C→T, rs 114634), IL1Ra (VNTR, intron 2, 89 bp) and IL4 (VNTR intron 3, 70 bp) gene polymorphisms in the Laboratory for Pharmacogenomics, ICBFM SB RAS. The data were processed using routine statistical methods for genetic analysis and the statistical software package Statistica 6.0. There were no deviations from Hardy–Weinberg equilibrium across all loci, suggesting validity of association studies between individual and combined genotypes and sensitization to antigens of S. pyogenes.Results. Positive association between sensitization to antigens of S. pyogenes and individual genotypes have been found: IL1B (+3953, C→T)*C,T (52.6% in the study group vs. 39.8% in the control group, p = 0.001; OR = 2.02; CI(99%) 0.47–5.93), IL1Ra (VNTR, intron 2, 89 bp)*2r,5r (7.19% in the study group vs. 1.29% in the control group, p = 0.001; OR = 5.59; CI(99%) 1.58–19.77), IL4 (VNTR intron 3, 70 bp)*2r,2r (6.86% in the study group vs 3.01% in the control group, p = 0.05; OR = 2.34; CI(99%) 0.66–8.29); as well as for combined genotypes: IL1B (+3953, C→T)*C,C / IL1Ra (VNTR, intron 2, 89 bp)*2r,4r / IL4 (VNTR intron 3, 70 bp)*2r,2r (OR = 46.15); IL1B (+3953, C→T)*T,T / I-1Ra (VNTR, intron 2, 89 bp)*4r,4r / IL4 (VNTR intron 3, 70 bp)*2r,3r (OR = 8.82) and IL1B (+3953, C→T)*C,T / IL1Ra (VNTR, intron 2, 89 bp)*2r,2r / IL4 (VNTR intron 3, 70 bp)*3r,3r (OR = 7.23). Conclusion. High odds ratio (OR = 46.15) for IL1B (+3953, C→T)*C,C / IL1Ra (VNTR, intron 2, 89 bp)*2r,4r / IL4 (VNTR intron 3, 70 bp)*2r,2r suggests that combined genotype is a main marker of sensitivity and impaired immune tolerance to S. pyogenes in toddlers and preschool children. Thus, this study has confirmed the association between gene polymorphisms, and pro-inflammatory and proallergic cytokines, and autoimmune and allergic diseases.

Prevalence and trends of pelvic floor disorders in late pregnancy and after delivery in a cohort of Israeli women using the PFDI-20

ObjectiveTo investigate the prevalence of pelvic floor disorders (PFD) in a cohort of Israeli women at late pregnancy and three months postpartum, to define changes in PFD rates and to evaluate various obstetrical factors that may correlate with these changes. MethodsA prospective longitudinal cohort study was conducted between March and July 2014. The PFDI-20 questionnaire (validated in the Hebrew language) was used to evaluate pelvic floor distress symptoms 24h and 3 months after delivery (representing the third trimester and post-partum period, respectively). Patients with a preterm delivery (<36 completed weeks of gestation), delivery of a stillbirth, non-fluency in Hebrew and patients with inability to complete the questionnaire due to a communication problem were excluded from the study. In addition to the PFDI results demographic and clinical data were collected from the patients’ medical records. Routine statistical methods were used to interpret the results. ResultsDuring the study period 117 women answered the first questionnaire and only 37 had filled the second questionnaire. The most prevalent item group reported in the third trimester was the urinary distress symptoms. Urinary frequency was the most common with 65% of patients reporting this symptom. At the post-partum period the most prevalent item group reported was the colorectal and anal distress with 31.5% of patients reporting increased straining efforts. There was a mixed trend in the changes noted between the two questionnaires. While some items improved in the puerperium as compared with late pregnancy others have worsened. In a multivariable analysis the only statistically significant finding was that at the post-partum follow-up, stress urinary incontinence was significantly associated with spontaneous perineal tears at delivery. Other obstetrical parameters including episiotomy and birth weight were not found to be significantly associated with any of the PFD items. ConclusionWe have demonstrated that PFD is prevalent both in late pregnancy and in the puerperium. There are mixed trends of spontaneous recovery following childbirth. A significant association between perineal tears and SUI 3 months after delivery was noted.

Implicit inequality constraints in a binary tree model

In this paper we investigate the geometry of a discrete Bayesian network whose graph is a tree all of whose variables are binary and the only observed variables are those labeling its leaves. We provide the full geometric description of these models which is given by a set of polynomial equations together with a set of complementary implied inequalities induced by the positivity of probabilities on hidden variables. The phylogenetic invariants given by the equations can be useful in the construction of simple diagnostic tests. However, in this paper we point out the importance of also incorporating the associated inequalities into any statistical analysis. The full characterization of these inequality constraints derived in this paper helps us determine how and why routine statistical methods can break down for this model class.

Criteria of the technogenic nature of heavy metals and metalloids in soils: A review of publications

Both routine statistical methods (the compliance of the heavy metal content with the exponent or ruling out abnormally high values of heavy metal concentrations in the Gaussian distribution) and new geostatistics based approaches are used as the criteria of the technogenic nature of heavy metals. Methods are being developed that take into consideration the marker element content (Al) in soil profiles. The geochemical criteria of the technogenic character are based on the statistical relationship between the content of the particular heavy metal (or metalloid) and its principal mineral phase carrier in the background soils, as well as on the disturbance of this relationship upon soil pollution. The chemical criteria are based on the different solubility of natural and technogenic heavy metals by reagents. A procedure of the quantitative assessment of the origin of technogenic lead depending on its isotopic composition is developed. The magnetic criteria of the technogenic nature of heavy metals are based on their association with technogenic magnetite.

Has time come for a re-assessment of spa therapy? The NAIADE survey in Italy

Goal of this study was to investigate whether appropriately applied spa therapy in several indications could be associated with a subsequent fall in the need for costly health services and missed working days due to sick-leave. The Naiade project was a multicenter observational, longitudinal, questionnaire-based study comparing an "entry" inquiry addressed to patients before an entry thermal cycle, and a "return" inquiry after 1 year. Routine statistical methods were used for comparisons. The study was carried out in 297 of the 340 certified Italian spa centers. Inquiries were managed by the spa doctor(s), with the collaboration of family doctors, and when necessary, hospitals, other health services, labour offices and employers. After exclusion of regular customers and of patients with acute disease phases or severe health conditions, 39,943 patients divided into eight diseases subgroups (rheumatic, respiratory, dermatologic, gynaecologic, otorhynologic, urinary, vascular and gastroenteric) underwent entry inquiry and appropriate spa treatment. Patients who returned for treatment after 1 year ("index year") were 23,680 (59.2%) and received return inquiry. Outcomes considered were: frequency and duration of hospitalisation periods; missed working days; regular use of disease-specific drugs; and resort to "non-spa" rehabilitation therapies. The data collected at return inquiry were compared with those of entry inquiry. All the considered outcomes appeared to be significantly reduced in the index year in seven of the eight disease subgroups in comparison with the previous year. In conclusion, disease-appropriate spa treatments were followed by a reduction in the need of subsequent health interventions in most disease subgroups. The health promoting value of spa treatments should therefore undergo more rigorous assessment with randomised controlled studies.

Can saliva be used for therapeutic drug monitoring of protease inhibitors in HIV-infected children?

Purpose HIV-infected children may become a target category for therapeutic drug monitoring (TDM) of antiretroviral therapy (ART) due to the unpredictability of plasma concentrations. Studies suggest that saliva could be used instead of blood for TDM. This has distinct advantages in pediatrics as saliva sampling is painless and prevents blood loss. The purpose of this study was to determine the total concentrations of lopinavir and ritonavir in plasma of children with HIV infection and compare them with the total saliva concentration. Methods 15 pediatric patients (median age 8.9 years) receiving combination ART were enrolled. Unbound lopinavir and ritonavir were separated by ultrafiltration. The drug serum and saliva concentrations were determined by a tandem-mass spectrometric method using Sciex APT-2000. Routine statistical methods were used to examine the relation between total drug plasma and saliva concentrations. Results The relation between total saliva and serum concentrations of lopinavir and ritonavir were highly significant with r values of 0.991 for ritonavir (RittotalSal = 0.043×RittotalPl+108.7, p<0.001) and 0.993 for lopinavir (LoptotalSal = 0.019×LoptotalPl-59.26, p<0.0001). Conclusion This pilot study demonstrated a significant linear correlation between total saliva and serum concentrations of lopinavir and ritonavir. The measurement of concentrations of these drugs in saliva may be useful for application of TDM of PIs in pediatric patients. Clinical Pharmacology & Therapeutics (2004) 75, P73–P73; doi: 10.1016/j.clpt.2003.11.275

The relation between total and free plasma concentrations of nucleoside reverse transcriptase inhibitors in HIV-infected children

Purpose A significant relationship between the intracellular concentrations (ICC) of nucleoside reverse transcriptase inhibitors (NRTIs) metabolites and outcome parameters in HIV infection exists. Variability in free plasma concentrations of NRTIs may contribute to the variability in ICC of their triphosphate metabolites. To date no studies have investigated the relation between total and free plasma concentration of NRTIs. Our purpose was to determine the total and free concentrations of lamivudine (3TC), stavudine (d4T) and zidovudine (AZT) in plasma in HIV-infected children. Methods 22 pediatric patients (median age 8.9 years) were enrolled in the study. Unbound 3Tc, d4T, and AZT were separated by ultrafiltration. The drug plasma concentrations were determined by tandem-MS using Sciex APT-2000. Routine statistical methods were used. Results There was a highly significant relation between total and free plasma concentrations for all three NRTIs with a r-value of 0.995 for 3TC (3TCfreepl=0.95×3TCtotalpl-36.51, p<0.0001), a r-value of 0.924 for d4T (d4Tfreepl= 0.65×d4Ttotalpl-3.61, p<0.0001), and a r- value of 0.907 for AZT (AZTfreepl= 0.14×AZTtotalpl+27.3, p<0.002). Conclusion This pilot study showed a significant linear correlation between total and free plasma concentration of 3TC, d4T and AZT in pediatric HIV-infected children. Future studies need to investigate the relation between free plasma concentrations of NRTIs and ICC of their active metabolites. Clinical Pharmacology & Therapeutics (2004) 75, P72–P72; doi: 10.1016/j.clpt.2003.11.273

Reply: Stents in Non Q Wave Myocardial Infraction

To investigate the prevalence of pelvic floor disorders (PFD) in a cohort of Israeli women at late pregnancy and three months postpartum, to define changes in PFD rates and to evaluate various obstetrical factors that may correlate with these changes.A prospective longitudinal cohort study was conducted between March and July 2014. The PFDI-20 questionnaire (validated in the Hebrew language) was used to evaluate pelvic floor distress symptoms 24 h and 3 months after delivery (representing the third trimester and post-partum period, respectively). Patients with a preterm delivery (<36 completed weeks of gestation), delivery of a stillbirth, non-fluency in Hebrew and patients with inability to complete the questionnaire due to a communication problem were excluded from the study. In addition to the PFDI results demographic and clinical data were collected from the patients’ medical records. Routine statistical methods were used to interpret the results.During the study period 117 women answered the first questionnaire and only 37 had filled the second questionnaire. The most prevalent item group reported in the third trimester was the urinary distress symptoms. Urinary frequency was the most common with 65% of patients reporting this symptom. At the post-partum period the most prevalent item group reported was the colorectal and anal distress with 31.5% of patients reporting increased straining efforts. There was a mixed trend in the changes noted between the two questionnaires. While some items improved in the puerperium as compared with late pregnancy others have worsened. In a multivariable analysis the only statistically significant finding was that at the post-partum follow-up, stress urinary incontinence was significantly associated with spontaneous perineal tears at delivery. Other obstetrical parameters including episiotomy and birth weight were not found to be significantly associated with any of the PFD items.We have demonstrated that PFD is prevalent both in late pregnancy and in the puerperium. There are mixed trends of spontaneous recovery following childbirth. A significant association between perineal tears and SUI 3 months after delivery was noted.

Methodological Issues in Assessing the Incidence of Peritoneal Dialysis-Associated Peritonitis in Children

To evaluate the distribution of peritonitis incidence and assess the usefulness of patient-specific peritonitis rates in children. 49 children on automated peritoneal dialysis (PD) followed during a 2-year observation period. Single-center, academic children's hospital. 49 children aged 2 months to 18 years; 24 prevalent, 25 incident during the observation period. Cumulative observation time was 639 patient-months. Cohort-specific peritonitis incidence, median patient-specific peritonitis incidence, mean peritonitis incidence by gamma-Poisson (negative binomial) modeling, peritonitis-free survival by Kaplan-Meier life-table analysis. 68 new peritonitis episodes and 21 relapses occurred in 27 patients. The distribution of patient-specific peritonitis incidence was bimodal, with a large group experiencing no or very few episodes, and another cluster around 1 episode per 6-9 months. Overall cohort-specific peritonitis incidence was 1.28, median subject-specific incidence 0.99, and mean incidence according to negative binomial modeling 1.04 (95% confidence interval 1.02-1.06) episodes per patient-year. Median peritonitis-free survival time was 6.9 months. In those patients who developed peritonitis, subject-specific peritonitis incidence was inversely correlated with patient age (r = -0.42, p < 0.05) and duration of chronic PD at last observation (r = -0.42, p < 0.05). Since the distribution of peritonitis in children is non-Gaussian, the average risk of peritonitis is more accurately expressed by the median of the individual subject-specific peritonitis rates or by the mean incidence estimate obtained by the negative binomial distribution model. The assignment of a personal peritonitis risk to each patient permits risk factor analysis by routine statistical methods, even in smaller populations.

Reproducibility of intravenous linear pharmacokinetic parameters of ethanol in dogs

Linear elimination parameters were computed after intravenous administration of the same dose (11 mmol/kg) of intravenous ethanol in anesthetized dogs twice with a period of 7–8 days (group A, n=10) or 6 hours (group B, n=8) between the two studies. For rate of elimination, clearance and time of disappearance of half the dose, routine statistical methods (paired t-test, correlation) showed no difference between the first and the second study of either group; however, for each of these three elimination parameters, quantitative analysis showed significant disparities between the first and second studies of each group. For Widmark ratio r, which is a measurement of ethanol distribution rather than elimination, both the routine statistical methods and the quantitative analysis showed no difference between the first and second study of either group. In dogs, the assumption that blood alcohol curve is reproducible in individuals may not be valid.