Category: Statistics

Drug Saf. 2022 May 24. doi: 10.1007/s40264-022-01180-5. Online ahead of print.

ABSTRACT

INTRODUCTION: The inclusion of herbal medicinal products and herbal supplements in pharmacovigilance systems is important because a systematic approach of collecting and analyzing adverse drug reactions related to these products will help practitioners, patients, and regulators to gain more knowledge and prevent harm.

OBJECTIVE: We aimed to categorize the adverse drug reaction reports on herbal medicinal products and herbal supplements submitted to the Pharmacovigilance Centre Lareb between 1991 and February 2021 on the basis of their regulatory status, herbs included, and adverse drug reactions involved.

METHODS: We categorized products on the basis of their registration status and herbal ingredients. The products were then categorized according to the Herbal Anatomical Therapeutic Chemical Classification System. We used descriptive statistics in Microsoft Excel 2019. Pivot tables were used for the analysis and presentation of the data.

RESULTS: Until February 2021, a total of 789 reports of herbal medicinal products and herbal supplements were received by Lareb. In these reports, a total of 823 herbal products were labeled as suspect. These products caused a total of 1727 adverse drug reactions. Of the 823 products, 229 were registered as a medicine, and 594 were on the market as a herbal supplement. Of the 823 herbal products, 522 reports concerned single-herb products, 256 reports concerned combination products, 27 reports concerned vitamin products containing herbal ingredients, and 18 reports concerned product issues. Approximately 15% of reports concerned serious adverse drug reactions, and adulterated products harbored a high risk of causing serious adverse drug reactions.

CONCLUSIONS: Analysis of the herbal medicinal products and herbal supplements in the Dutch pharmacovigilance database revealed a variety of suspected herbal ingredients. The reports provide insight into the variety of herbal products used in the Netherlands and the adverse reactions associated with their use. Pharmacovigilance of herbal products is essential to ensure their safe use.

PMID:35608783 | DOI:10.1007/s40264-022-01180-5

Ann Surg Oncol. 2022 May 24. doi: 10.1245/s10434-022-11839-z. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with sentinel lymph node-positive (SLN+) melanoma are increasingly undergoing active nodal surveillance over completion lymph node dissection (CLND) since the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II). Adherence to nodal surveillance in real-world practice remains unknown.

METHODS: In a retrospective cohort of SLN+ melanoma patients who underwent nodal surveillance at a single institution from July 2017 through April 2021, this study evaluated adherence to nodal surveillance ultrasound (US). Adherence to nodal US was compared with adherence to other surveillance methods based on receipt of adjuvant therapy. Early recurrence data were reported using descriptive statistics.

RESULTS: Among 109 SLN+ patients, 37 (34%) received US surveillance at recommended intervals. Of the 72 (66%) non-adherent patients, 16 were lost to follow-up, and 33 had planned follow-up at an outside institution without available records. More patients had a minimum of bi-annual clinic visits (83%) and cross-sectional imaging (53%) compared to those who were adherent with nodal US. The patients who received adjuvant therapy (60%) had fewer ultrasounds (p < 0.01) but more exams (p < 0.01) and a trend toward more cross-sectional imaging (p = 0.06). Of the overall cohort, 26 patients (24%) experienced recurrence at a median follow-up period of 15 months. Of these recurrences, 10 were limited to the SLN basin, and all of these isolated nodal recurrences were resectable.

CONCLUSIONS: Pragmatic challenges to real-world delivery of nodal surveillance remain after MSLT-II, and adjuvant therapy appears to be associated with a decreased likelihood of US adherence. Understanding US utility alongside cross-sectional imaging will be critical as increasingly more patients undergo nodal surveillance and adjuvant therapy.

PMID:35608800 | DOI:10.1245/s10434-022-11839-z

Environ Sci Pollut Res Int. 2022 May 24. doi: 10.1007/s11356-022-20651-x. Online ahead of print.

ABSTRACT

Within the scope of the present study, the marble cutting waste, which is an industrial waste of different sizes (< 75 µm and < 150 µm), was incorporated into the clay structure at various rates and a total of 36 series bricks were produced. The brick mixtures were prepared by the semi-dry molding method and the brick specimens were sintered for three temperatures (850 °C, 950 °C, and 1050 °C). The fired bricks containing marble cutting waste with a lower particle size (75 µm) have higher compressive strength. However, all samples produced can meet the relevant standard requirements in terms of compressive strength. Thermal conductivity decreased from 1.008 to 0.775 W/mK with the incorporation of marble cutting waste, a decrease of approximately 23.11%. The effects of grain size, firing temperature, and marble cutting waste concentration on the quadratic model were statistically determined by variance analysis (ANOVA). According to statistical findings, the order of importance of design factors for brick properties (except for compressive strength) is marble cutting waste > firing temperature > particle size. For compressive strength, the most dominant factor is amount of marble cutting waste, followed by particle size and firing temperature, respectively. Consequently, the results suggest that marble cutting waste does not need to be reduced to smaller particle sizes to improve the fired clay brick properties.

PMID:35608771 | DOI:10.1007/s11356-022-20651-x

Radiol Med. 2022 May 24. doi: 10.1007/s11547-022-01502-8. Online ahead of print.

ABSTRACT

OBJECTIVES: The present study aims to investigate the role of the first magnetic resonances (MRI) following radio-chemotherapy (RT-CT) in patients diagnosed with high-grade glioma.

METHODS: We retrospectively recorded radiological evaluations following RT-CT, symptoms related to disease progression (avoiding any sign due to radiotherapy or chemotherapy) and the change of therapeutic strategy.

RESULTS: In March 2021, at data analysis, the data of 149 patients diagnosed with high-grade glioma and treated between May 2013 and July 2020 were retrieved for the present analysis. Two out of 122 (1.6%), 5 out of 106 (4.7%) and 8 out of 92 (8.6%) asymptomatic patients received the diagnosis of disease recurrence at the time of the first, second and third MRI, respectively. Otherwise, 16 out of 27 (59.2%), 16 out of 24 (66.6%) and 13 out of 16 (82.2%) symptomatic patients changed their therapy after the first, second and third MRI, respectively. Among patients that experienced radiological signs of distant progression, 10 out of 14 were symptomatic and changed their therapy.

CONCLUSIONS: MRIs performed by 6 months after the end of RT-CT lead to change treatment strategy mostly in symptomatic patients.

PMID:35608757 | DOI:10.1007/s11547-022-01502-8

Neurol Sci. 2022 May 24. doi: 10.1007/s10072-022-06136-2. Online ahead of print.

ABSTRACT

INTRODUCTION: Evidence is emerging about an extra-pulmonary involvement of SARS-CoV-2, including the nervous system. Autonomic dysfunction in patients recovering from acute coronavirus disease 2019 (COVID-19) has been recently described. Dysautonomic symptoms have been reported in the acute phase of the disease, but clear evidence is lacking, especially in the non-critical forms of the infection.

OBJECTIVE: The aim of this study is to assess the prevalence of dysautonomia in acute, non-critically ill COVID-19 patients.

METHODS: In this observational, cross-sectional study, we compared 38 non-critically ill patients with acute COVID-19 (COVID + group) to 38 healthy volunteers (COVID – group) in order to assess the prevalence of signs and symptoms of dysautonomia through the administration of the composite autonomic symptom score 31 (COMPASS-31) and an active standing test. Comparisons between groups were performed by means of both univariate and multivariate analyses.

RESULTS: The prevalence of orthostatic hypotension was significantly higher in the COVID + group. Higher total scores of COMPASS-31 were observed in the COVID + group than controls. Significant differences between groups emerged in the secretomotor, orthostatic intolerance, and gastrointestinal COMPASS-31 domains. All these results maintained the statistical significance after the adjustment for concomitant drugs with a known effect on the autonomic nervous system assumed by the study participants, except for the differences in the gastrointestinal domain of COMPASS-31.

CONCLUSION: Our results suggest that an autonomic dysfunction could be an early manifestation of COVID-19, even in the contest of mild forms of the infection.

PMID:35608736 | DOI:10.1007/s10072-022-06136-2

Ther Innov Regul Sci. 2022 May 24. doi: 10.1007/s43441-022-00416-x. Online ahead of print.

ABSTRACT

BACKGROUND: Decentralized clinical trials offer the promise of reduced patient burden, faster and more diverse recruitment, and have received regulatory support during the COVID-19 pandemic. However, lack of data accuracy or data validation poses a challenge for fully decentralized trials. A mixed data collection modality where onsite measurements are collected at key time points and decentralized measurements are taken at intermediate time points is attractive operationally. To date, the impact of decentralized measurements (which could presumably be less accurate) taken at intermediate time points on statistical inference on the primary or other key time points has not been evaluated.

METHODS: In this article we evaluate the estimation and statistical inference for three scenarios: (1) all onsite measurements, (2) a mixture of onsite and decentralized measurements, and (3) all decentralized measurements, in the setting of a chronic weight management trial. We consider scenarios where decentralized measurements have additional within- and between-subject variabilities and/or bias.

RESULTS: In the mixed modality setting, simulation studies showed that the estimation and inference for the key time points with onsite measurements have good properties and are not impacted by the additional variability and bias from intermediate decentralized measurements. However, estimates for intermediate decentralized time points for the mixed modality and estimates for the all decentralized modality measurements have increased variability and bias.

CONCLUSION: Mixed modality trials can help achieve the benefits of decentralized clinical trials by reducing the number of onsite visits with little impact on statistical inferences for various estimands, compared to traditional (all onsite) clinical trials.

PMID:35608729 | DOI:10.1007/s43441-022-00416-x

J Endocrinol Invest. 2022 May 24. doi: 10.1007/s40618-022-01816-4. Online ahead of print.

ABSTRACT

BACKGROUND: Klinefelter syndrome (KS) is frustratingly under-diagnosed. KS have a broad spectrum of clinical features, making it difficult to identify. OBJECTIVE: We describe KS clinical presentation in a large Italian cohort.

DESIGN: This is the first observational cohort study within a national network, the Klinefelter ItaliaN Group (KING). Primary outcomes were to describe the basic clinical features and the actual phenotype of KS in Italy. Secondary outcomes were to determine age at diagnosis and geographical distribution.

METHODS: We performed a basic phenotyping and evaluation of the hormonal values of 609 adult KS patients.

RESULTS: Mean age at diagnosis was 37.4 ± 13.4 years. The overall mean testicular size was 3 ml, and 2.5 ml in both testes in untreated KS group. BMI was 26.6 ± 5.8 kg/m², and 25.5% of KS had metabolic syndrome (MetS). LH and FSH were increased, and mean total testosterone were 350 ± 9.1 ng/dl. A descriptive analysis showed that 329 KS patients were evaluated in Northern Italy, 76 in Central and 204 in Southern Italy. Analysis of variance demonstrated significant statistical differences (p < 0001) between the age at diagnosis of the three geographical groups. Compared with the expected number among male patients matched for age in Italy, only 16% of KS patients received a diagnosis.

CONCLUSIONS: These data are the results of the only national database available that collects the clinical and hormonal data of the KS patients, currently referred at the KING centers. In Italy the typical KS patient is overweight, with small testes, and elevated LH and FSH. Only 25.5% of them are diagnosed with MetS. Early detection and timely treatment are mandatory.

PMID:35608733 | DOI:10.1007/s40618-022-01816-4

World J Pediatr. 2022 May 24. doi: 10.1007/s12519-022-00566-w. Online ahead of print.

NO ABSTRACT

PMID:35608720 | DOI:10.1007/s12519-022-00566-w

Arch Gynecol Obstet. 2022 May 24. doi: 10.1007/s00404-022-06605-1. Online ahead of print.

ABSTRACT

OBJECTIVES: Sentinel lymph node (SLN) biopsy is widely accepted in the surgical staging of early vulvar cancer, although the most accurate method for its identification is not yet defined. This meta-analysis aimed to determine the technique with the highest pooled detection rate (DR) for the identification of SLN and compare the average number of SLNs detected by planar lymphoscintigraphy (PL), single-photon emission computed tomography/computed tomography (SPECT/CT), blue dye and indocyanine green (ICG) fluorescence.

METHODS: The meta-analysis was conducted according to the PRISMA guideline. The search string was: “sentinel” and “vulv*”, with date restriction from 1st January 2010 until Dec 31st, 2020. Three investigators selected studies based on: (1) a study cohort or a subset of a minimum of 10 patients with vulvar cancer undergoing either PL, SPECT/CT, blue-dye, or ICG fluorescence for the identification of SLN; (2) the possibility to extrapolate the DR or the average number of SLNs detected by a single technique (3) no evidence of other malignancies in the patient history.

RESULTS: A total of 30 studies were selected. In a per-patient and a per-groin analysis, the DR for SLN of PL was respectively 96.13% and 92.57%; for the blue dye was 90.44% and 66.21%; for the ICG, the DR was 91.90% and 94.80%. The pooled DR of SPECT/CT was not calculated, since only two studies were performed in this setting. At a patient-based analysis, no significant difference was documented among PL, blue dye, and ICG (p = 0.28). At a per-groin analysis, PL and ICG demonstrated a significantly higher DR compared to blue dye (p < 0.05). The average number of SLNs, on a per-patient analysis, was available only for PL and ICG with a median number of 2.61 and 1.78 lymph nodes detected, respectively, and no significant statistical difference.

CONCLUSIONS: This meta-analysis favors the use of ICG and PL alone and in combination over blue dye for the identification of the SLN in vulvar cancer. Future studies may investigate whether the combined approach allows the highest DR of SLN in patients with vulvar cancer.

PMID:35608701 | DOI:10.1007/s00404-022-06605-1

Sex Transm Dis. 2022 May 24. doi: 10.1097/OLQ.0000000000001650. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to examine variations in the incidence rates of STIs (i.e., chlamydia, gonorrhea, and syphilis) across the urban-rural and area-deprivation continua from January of 2013 through December of 2018 in Yakima County, Washington. The rates of STIs has been increasing in the United States in the past decade. Historically, Yakima County has higher rates of STIs than state and national rates. Additionally, Yakima County contains rural areas and areas with greater deprivation which face gaps in access to care.

METHODS: The Washington State Department of Health Database Surveillance System was utilized to conduct the study. The dataset included diagnosed cases of chlamydia, gonorrhea, and syphilis with positive laboratory test results for the duration of the study period. Incidence rates of STIs were calculated and statistically analyzed across the urban-rural and area-deprivation continua using Rural-Urban Commuting Area codes and the Area Deprivation Index.

RESULTS: The incidence rates of STIs increased from January of 2013 through December of 2018. STI rates did not differ in micropolitan, small town, and rural block groups compared to the metropolitan block groups. Most-deprived block groups had significantly higher STI rates compared to less-deprived block groups.

CONCLUSIONS: There is a need for increased STI intervention in higher deprivation areas including STI education. Public health officials and health care providers should be aware of these risk factors and tailor interventions to the neighborhood they serve.

PMID:35608077 | DOI:10.1097/OLQ.0000000000001650