Category: Statistics

Cancer Med. 2022 Oct 7. doi: 10.1002/cam4.5033. Online ahead of print.

ABSTRACT

This is the first large-scale cross-country analysis of patients with chronic lymphocytic leukemia (CLL) aimed to evaluate the incidence, types, and key prognostic factors of secondary malignancies, and to assess the impact on overall survival based on retrospective claims data from three Central European countries. We analyzed 25,814 newly diagnosed CLL patients from Czechia, Hungary, and Poland; 10,312 (39.9%) patients were treated for CLL in study periods between 2004 and 2016. Out of the treated patients, 1986 (19.3%) received the FCR therapy in the first line and 779 (7.6%) received FCR in subsequent lines. We observed that 33.7% of treated patients developed secondary malignancies during the study. Based on country estimates, the probability to develop a secondary malignancy within 4 years since starting the first-line FCR therapy ranged between 28.0% and 36.8%. We found the age at diagnosis, male gender, any malignancy prior to the CLL diagnosis, and the CLL treatment to be the key risk factors for developing secondary malignancies. Specifically, the FCR therapy was a statistically significant (p < 0.001) prognostic factor for risk increase with the hazard ratio between 1.46 and 1.60. Across the three Central European countries, we observed consistent results indicating FCR increased the risk of secondary malignancies in CLL patients. We conclude that secondary malignancies are clearly an undervalued burden for CLL patients, caregivers, and the healthcare system. When evaluating new therapies in regulatory and reimbursement decision making, the factor of secondary malignancies deserves deeper considerations.

PMID:36205198 | DOI:10.1002/cam4.5033

Circulation. 2022 Oct 7:101161CIRCULATIONAHA122060866. doi: 10.1161/CIRCULATIONAHA.122.060866. Online ahead of print.

ABSTRACT

BACKGROUND: A novel risk calculator based on clinical characteristics and noninvasive tests that predicts the onset of clinical sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been proposed and validated by recent studies. It remains unknown whether programmed ventricular stimulation (PVS) provides additional prognostic value.

METHODS: All patients with a definite ARVC diagnosis, no history of sustained VAs at diagnosis, and PVS performed at baseline were extracted from 6 international ARVC registries. The calculator-predicted risk for sustained VA (sustained or implantable cardioverter defibrillator treated ventricular tachycardia [VT] or fibrillation, [aborted] sudden cardiac arrest) was assessed in all patients. Independent and combined performance of the risk calculator and PVS on sustained VA were assessed during a 5-year follow-up period.

RESULTS: Two hundred eighty-eight patients (41.0±14.5 years, 55.9% male, right ventricular ejection fraction 42.5±11.1%) were enrolled. At PVS, 137 (47.6%) patients had inducible ventricular tachycardia. During a median of 5.31 [2.89-10.17] years of follow-up, 83 (60.6%) patients with a positive PVS and 37 (24.5%) with a negative PVS experienced sustained VA (P<0.001). Inducible ventricular tachycardia predicted clinical sustained VA during the 5-year follow-up and remained an independent predictor after accounting for the calculator-predicted risk (HR, 2.52 [1.58-4.02]; P<0.001). Compared with ARVC risk calculator predictions in isolation (C-statistic 0.72), addition of PVS inducibility showed improved prediction of VA events (C-statistic 0.75) (log-likelihood ratio for nested models, P<0.001). PVS inducibility had a 76% [67-84] sensitivity and 68% [61-74] specificity, corresponding to log-likelihood ratios (LR) of 2.3 and 0.36 for inducible (LR+) and noninducible (LR-) patients, respectively. In patients with a ARVC risk calculator-predicted risk of clinical VA events <25% during 5 years (ie, low/intermediate subgroup), PVS had a 92.6% negative predictive value.

CONCLUSIONS: PVS significantly improved risk stratification above and beyond the calculator-predicted risk of VA in a primary prevention cohort of patients with ARVC, mainly for patients considered to be at low and intermediate risk by the clinical risk calculator.

PMID:36205131 | DOI:10.1161/CIRCULATIONAHA.122.060866

J Cutan Med Surg. 2022 Oct 7:12034754221128798. doi: 10.1177/12034754221128798. Online ahead of print.

ABSTRACT

PURPOSE: To answer the following clinical research question: “Among patients with multiple basal cell carcinomas (mBCCs), can panoramic radiograph (PaR) facilitate the diagnosis of Gorlin-Goltz syndrome (GGS)?”

METHODS: This retrospective study enrolled mBCCs subjects who presented to a German tertiary care center between 1 January 2015 and 31 December 2021. The primary predictor was presence of syndromic mBCCs, and the main outcomes were jaw cysts and odontogenic keratocysts (OKCs). Descriptive, bi- and multivariate statistics, diagnostic test evaluation, and number needed to screen (NNS) were computed at α = 95%.

RESULTS: The sample comprised 527 mBCCs patients (36.1% females; 6.8% GGS; 5.5% OKCs; mean age, 74.5 ± 15.8 years [range, 15-102]). There was a significant association between syndromic mBCCs and jaw cysts (P < .0001; NNS = 2 [95% CI, CI, 1.1 to 1.4]). In the adjusted logistic model, PaR identified GGS via radiographic diagnosis of jaw cysts in case of 1) age ≤ 35 years, 2) ≥ 5 BCCs, and 3) ≥ 1 high-risk BCCs. Nearly every jaw cyst identified by PaR was OKCs (P = .01; 95% CI, 3.1 to 3,101.4; NNS = 1.3 [95% CI, .9 to 2]). The post hoc power was 100%.

CONCLUSIONS: Dental screening with the use of PaR for mBCCs patients, especially those aged ≤35 years, or with ≥5 BCCs, or ≥1 high-risk BCCs, may be helpful in detection and identification of GGS through recognition of OKCs.

PMID:36205130 | DOI:10.1177/12034754221128798

Birth Defects Res. 2022 Oct 15;114(17):1092-1100. doi: 10.1002/bdr2.2073. Epub 2022 Aug 10.

ABSTRACT

BACKGROUND: Favipiravir is one of the essential antiviral drugs used for the treatment of coronavirus disease (COVID-19) in some countries. However, there is not enough information about used, especially in pregnancy. Therefore, in this study, it was aimed to determine the developmental toxicity of favipiravir on fetal bone development and embryonic development.

METHODS: In this study, 16 pregnant wistar albino rats were used. The rats were divided into four groups: Control (saline) and Group A (50 mg/kg × 5 days), Group B (50 mg/kg × 1 days + 20 mg/kg × 4 days), Group C (20 mg/kg × 5 days). Solutions were administered to the rats by oral gavage from the 10th to 14th days of pregnancy, twice a day. The skeletal system development of fetuses was examined with double skeletal staining and immunohistochemical staining methods.

RESULTS: A total of 72 fetuses from pregnant rats, 18 in each group, were included in the study. As a result, depending on favipiravir dose increase, in experimental groups, it was determined that the statistically significant decrease on the ossification rates of anterior and posterior extremity bones, and length and weight of fetuses.

CONCLUSION: Exposure to favipiravir during pregnancy impairs bone metabolism and bone formation-resorption stages and may cause developmental delay.

PMID:36205105 | DOI:10.1002/bdr2.2073

J Sports Med Phys Fitness. 2022 Oct 7. doi: 10.23736/S0022-4707.22.14177-0. Online ahead of print.

ABSTRACT

BACKGROUND: Central to the work of medical and pharmacy practitioners is the provision of pharmaceutical support for patients, who may also be competitive athletes. This study aimed to assess the knowledge gaps of medical and pharmacy students at the University of ** BLINDED ** regarding World Anti-Doping Code and the Prohibited List.

METHODS: All medical and pharmacy students studying at the University of **BLINDED** were invited to participate in an online questionnaire devised by the research team. This questionnaire assessed knowledge regarding the prohibited status of 19 substances, as well as knowledge regarding therapeutic use exemptions. The questionnaire was pre-piloted with local experts in the sports doping field to test face validity, and then tested for content clarity and easy of use by 20 medical and pharmacy students. Total scores were used to compare medical student vs pharmacy student and athlete vs non-athlete using the Mann-Whitney U Test.

RESULTS: A total of 242 students answered the questionnaire, 58% of which were female. 86% of respondents were medical students. From of the cohort of respondents, 22% identified themselves as athletes as per definition provided in the questionnaire. A number of substances, such as diuretics, morphine, cocaine and ecstasy, were incorrectly classified by the majority of participants. Paracetamol, caffeine, vitamins, NSAIDs, and antihistamines were mostly correctly classified. Pharmacy students had better knowledge when compared to medical students (U value = 2734.5, p-value = 0.034). Student athletes did not have more knowledge than non-athletes (U value = 4810.5, p-value = 0.659).

CONCLUSIONS: Medical and Pharmacy students have significant knowledge gaps when it comes to performance enhancing drugs in sport. Sports pharmacy should be included as part of the undergraduate curriculum for both medicine and pharmacy, but especially for medical students who will be future prescribers.

PMID:36205087 | DOI:10.23736/S0022-4707.22.14177-0

Cleft Palate Craniofac J. 2022 Oct 7:10556656221131855. doi: 10.1177/10556656221131855. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the outcomes of orthognathic surgery (OGS) in patients with craniofacial microsomia (CFM) who had previously undergone mandibular distraction osteogenesis (MDO).

DESIGN: A retrospective cohort study was performed including all patients with CFM who were treated with OGS at a single institution between 1996 and 2019. The clinical records, operative reports, and cone beam computed tomography (CBCT) scans were reviewed. CBCT data before OGS (T1), immediately after OGS (T2), and at long-term follow-up (T3) were analyzed using Dolphin three-dimensional software to measure the occlusal cant and chin point deviation.

RESULTS: The study included 12 patients with CFM who underwent OGS (6 underwent OGS without MDO and 6 underwent OGS after MDO). There was a statistically significant improvement in occlusal cant and chin point deviation in both groups postoperatively. Occlusal cant relapsed by a mean of 0.6° (standard deviation [SD] 1.1°) in the patients who had OGS alone compared with 0.7° (SD 1.2°) in the patients who had OGS after MDO (P = .745) between T2 and T3. There was no statistically significant difference in chin point relapse between patients who had OGS alone compared with those who had OGS after MDO (0.1 mm [SD 2.5mm] vs 0.7mm [SD 2.2mm]; P = .808).

CONCLUSIONS: Within the limitations of this study, these findings suggest that OGS after MDO in patients with CFM can produce stable results.

PMID:36205083 | DOI:10.1177/10556656221131855

Nicotine Tob Res. 2022 Oct 7:ntac235. doi: 10.1093/ntr/ntac235. Online ahead of print.

ABSTRACT

BACKGROUND: We examined the differential impact of the 2012 Canadian GWL policy changes on key indicators of warning label impact and quit intentions using national cohorts of Canadian and US adults who smoke.

METHODS: We used data from all waves of the International Tobacco Control surveys (2002-2020) in Canada and the US. Our key measures were quit intentions and an index of warning label effectiveness (salience, cognitive and behavioral reactions). We estimated overall policy impact by comparing Canada (treatment group) with the US (control group) using controlled interrupted time series (CITS) regression models, with interactions to examine whether policy impact varied by sex, education, and income.

RESULTS: The CITS model showed a statistically significant increase in the warning label effectiveness in Canada post-policy, compared to the US (β= 0.84, 95% CI 0.35,1.33). Similarly, the odds of quit intentions were relatively higher among adults who smoked in Canada compared to the US (OR= 1.89, 95% CI 1.51,2.36) post-policy. The three-way interaction model showed that these associations were greater among adults from low socioeconomic status (SES) groups than in high SES groups.

DISCUSSION: The 2012 change in the Canadian GWL policy was associated with stronger cognitive and behavioral responses to GWLs and higher odds of quit intentions among adults who smoked in Canada when compared to the US, specifically among individuals from low SES groups, suggesting a positive equity impact. Our findings affirm the need for countries to implement or enhance GWLs, in line with the WHO Framework Convention on Tobacco Control.

IMPLICATIONS: The evidence on the potential health equity benefit of GWL policies is mixed. To further understand the influence of GWL policies on tobacco use disparities, more systematic research using pre/post policy designs with control groups is needed. Using a controlled interrupted time series model, we aimed to strengthen the available evidence on the causal influence of this tobacco control approach. Our findings show that the 2012 GWL policy change had a greater impact on adults who smoked from low SES groups than it did on adults who smoked from high SES groups, indicating a potentially positive equity impact and confirming the need for countries to implement or maximize the size of GWLs, as recommended by the WHO Framework Convention on Tobacco Control.

PMID:36205028 | DOI:10.1093/ntr/ntac235

J Hypertens. 2022 Oct 3. doi: 10.1097/HJH.0000000000003290. Online ahead of print.

ABSTRACT

OBJECTIVE: Errors in blood pressure (BP) measurement account for a large proportion of misclassified hypertension diagnoses. Ambulatory blood pressure monitoring (ABPM) is often considered to be the gold standard for measurement of BP, but uncertainty remains regarding the degree of measurement error. The aim of this study was to determine reproducibility of sequential ABPM in a population of normotensive and well controlled hypertensive individuals.

METHODS: Individual participant data from three randomized controlled trials, which had recorded ABPM and carotid-femoral pulse wave velocity (PWV) at least twice were combined (n = 501). We calculated within-individual variability of daytime and night-time BP and compared the variability between normotensive (n = 324) and hypertensive (n = 177) individuals. As a secondary analysis, variability of PWV measurements was also calculated, and multivariable linear regression was used to assess characteristics associated with blood pressure variability (BPV).

RESULTS: Within-individual coefficient of variation (CoV) for systolic BP was 5.4% (day) and 7.0% (night). Equivalent values for diastolic BP were 6.1% and 8.4%, respectively. No statistically significant difference in CoV was demonstrated between measurements for normotensive and hypertensive individuals. Within-individual CoV for PWV exceeded that of BP measurements (10.7%). BPV was associated with mean pressures, and BMI for night-time measurements. PWV was not independently associated with BPV.

CONCLUSION: The variability of single ABPM measurements will still yield considerable uncertainty regarding true average pressures, potentially resulting in misclassification of hypertensive status and incorrect treatment regimes. Repeated ABPM may be necessary to refine antihypertensive therapy.

PMID:36204998 | DOI:10.1097/HJH.0000000000003290

J Cosmet Dermatol. 2022 Oct 6. doi: 10.1111/jocd.15439. Online ahead of print.

ABSTRACT

BACKGROUND: Silymarin is the active component of milk thistle, which has antioxidant properties by scavenging free radicals and potential comedolytic properties.

AIMS: This study aimed to assess the efficacy and safety of 0.5% silymarin-loaded antioxidant serum (SAS) used to treat mild-to-moderate acne.

PATIENTS AND METHODS: A prospective, open-label pilot study was conducted. We enrolled 22 Korean acne patients who applied the 0.5% SAS on the whole face twice daily while continuing the current anti-acne medications. Grade of acne severity, individual lesion counts, sebum output levels, skin erythema, and melanin pigmentation were assessed.

RESULTS: After a 4-week application, the modified Global Acne Grading Score (mGAGS), Global Evaluation Acne (GEA) scale, and the acne lesion counts were significantly decreased. Sebum secretion, skin pigmentation, and erythema were also reduced during the study period, yet only the melanin pigmentation index reached statistical significance. Subgroup analysis revealed that the patients who took the low-dose oral isotretinoin during the study period showed more noticeable improvements in skin sebum output and melanin pigmentation. Additionally, no adverse event was associated with using the 0.5% SAS.

CONCLUSION: The 0.5% silymarin-containing antioxidant formulation improved acne’s clinical severity and related skin biophysical parameters.

PMID:36204969 | DOI:10.1111/jocd.15439

Shanghai Kou Qiang Yi Xue. 2022 Jun;31(3):322-326.

ABSTRACT

PURPOSE: To describe the MRI features of acinar cell carcinoma of parotid gland (AciCC) and to evaluate the diagnostic value of MR functional imaging.

METHODS: A total of 269 cases of maxillofacial AciCC confirmed by surgery and pathology were analyzed. Among them, nineteen subjects with AciCC in the parotid gland underwent preoperative MRI examination (non-enhanced scan for one case, enhanced scan for 18 cases), seventeen patients underwent diffusion-weighted imaging scan, and 15 patients underwent dynamic contrast-enhanced scan. MRI findings of 19 patients were retrospectively analyzed. The lesion size, location, morphology, margin, internal composition, enhancement pattern and functional imaging characteristics were analyzed. SPSS 25.0 software package was used for statistical analysis.

RESULTS: Among 269 cases of maxillofacial AciCC, there were 108 males and 161 females, male: female = 1:1.49, aged from 4 to 89 years, with a mean age of (45.95±17.33) years. 84.4% (227/269) were located in the parotid gland. On MRI images, 78.9% (15/19) had well-defined margin, 57.9% (11/19) were round or oval, and 36.8% (7/19) were lobed nodules. One case had irregular morphology and peripheral invasion. The range of maximum diameter was 6-56 mm, averaging (24.8±15.3) mm. Internal composition showed 57.9% (11/19) were cystic solid, 42.1% (8/19) were solid, 31.6% (6/19) had bleeding. T2-weighted MRI showed 52.6% (10/19) with envelope structure, 15.8% (3/19) with low signal separation inside, 38.9%(7/18) had uniform enhancement, and 61.1%(11/18) had uneven enhancement. Functional imaging showed the mean ADC value of tumor was (1.026±0.194)×10^-3 mm²/s(n=17). 86.7%(13/15) TIC was type Ⅱ.

CONCLUSIONS: Most maxillofacial AciCC are located in the parotid gland. It is difficult to distinguish AciCC from benign tumors with conventional MRI in morphology. The ADC value of AciCC is lower than that of benign tumors, and the type of TIC curve is mostly type Ⅱ. Combination of morphology and functional imaging can improve the diagnostic accuracy of this disease.

PMID:36204966