Tag: statistics

Med Phys. 2023 Feb 13. doi: 10.1002/mp.16308. Online ahead of print.

ABSTRACT

BACKGROUND: Hematologic toxicity (HT) is a common adverse tissue reaction during radiotherapy for rectal cancer patients, which may lead to various negative effects such as reduced therapeutic effect, prolonged treatment period and increased treatment cost. Therefore, predicting the occurrence of HT before radiotherapy is necessary but still challenging.

PURPOSE: This study proposes a hybrid machine learning model to predict the symptomatic radiation hematologic toxicity in rectal cancer patients using the combined demographic, clinical, dosimetric, and Radiomics features, and ascertains the most effective regions of interest (ROI) in CT images and predictive feature sets.

METHODS: A discovery dataset of 240 rectal cancer patients, including 145 patients with hematologic toxicity (HT) symptoms and a validation dataset of 96 patients (63 patients with HT) with different dose prescription were retrospectively enrolled. Eight ROIs were contoured on patient CT images to derive Radiomics features, which were then respectively combined with the demographic, clinical and dosimetric features to classify patients with HT symptoms. Moreover, the survival analysis was performed on risky patients with HT in order to understand the HT progression.

RESULTS: The classification models in ROIs of bone marrow and femoral head exhibited relatively high accuracies (accuracy = 0.765 and 0.725) in the discovery dataset as well as comparable performances in the validation dataset (accuracy = 0.758 and 0.714). When combining the two ROIs together, the model performance was the best in both discovery and validation datasets (accuracy = 0.843 and 0.802). In the survival analysis test, only the bone marrow ROI achieved statistically significant performance in accessing risky HT (C-index = 0.658, p = 0.03). Most of the discriminative features were Radiomics features, and only gender and the mean dose in Irradvolume was involved in HT.

CONCLUSIONS: The results reflect that the Radiomics features of bone marrow is significantly correlated with HT occurrence and progression in rectal cancer. The proposed Radiomics-based model may help the early detection of radiotherapy induced HT in rectal cancer patients and thus improve the clinical outcome in future. This article is protected by copyright. All rights reserved.

PMID:36780152 | DOI:10.1002/mp.16308

JAMA Intern Med. 2023 Feb 13. doi: 10.1001/jamainternmed.2022.6787. Online ahead of print.

ABSTRACT

IMPORTANCE: Drug expenditures in the US are higher than in any other country and are projected to continue increasing, so US health systems may benefit from evaluating international regulatory and reimbursement decision-making of new drugs.

OBJECTIVE: To evaluate regulatory decisions and health technology assessments (HTAs) in Australia, Canada, and the UK regarding new drugs approved by the US Food and Drug Administration (FDA) in 2017 through 2020, as well as to estimate the US cost per patient per year for drugs receiving negative recommendations.

DESIGN AND SETTING: In this cross-sectional study, recommendations issued by agencies in Australia, Canada, and the UK were collected for new drugs approved by the FDA in 2017 through 2020. All data were current as of May 31, 2022.

EXPOSURES: Authorizations and HTAs in selected countries.

MAIN OUTCOMES AND MEASURES: All FDA-approved drugs were matched by active ingredient to decision summary reports published by drug regulators and HTA agencies in Australia, Canada, and the UK. Regulatory approval concordance and reasons for negative recommendations were assessed using descriptive statistics. For drugs not recommended by an international agency, the annual US drug cost per patient was estimated from FDA labeling and wholesale acquisition costs.

RESULTS: The FDA approved 206 new drugs in 2017 through 2020, of which 162 (78.6%) were granted marketing authorization by at least 1 other regulatory agency at a median (IQR) delay of 12.1 (17.7) months following US approval. Conversely, 5 FDA-approved drugs were refused marketing authorization by an international regulatory agency due to unfavorable benefit-to-risk assessments. An additional 42 FDA-approved drugs received negative reimbursement recommendations from HTA agencies in Australia, Canada, or the UK due to uncertainty of clinical benefits or unacceptably high prices. The median (IQR) US cost of the 47 drugs refused authorization or not recommended for reimbursement by an international agency was $115 281 ($166 690) per patient per year. Twenty drugs were for oncology indications, and 36 were approved by the FDA through expedited regulatory pathways or the Orphan Drug Act.

CONCLUSIONS AND RELEVANCE: This cross-sectional study assessed reasons for which drugs recently approved by the FDA were refused marketing authorization or not recommended for public reimbursement in other countries. Drugs with limited international market presence may require close examination by US health care professionals and health systems.

PMID:36780147 | DOI:10.1001/jamainternmed.2022.6787

CNS Drugs. 2023 Feb 13. doi: 10.1007/s40263-022-00982-6. Online ahead of print.

ABSTRACT

BACKGROUND: STRIVE was a prospective, 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative patients with early relapsing-remitting multiple sclerosis (RRMS).

OBJECTIVE: Study objectives examined the effects of natalizumab on cognitive processing speed, confirmed disability improvement (CDI), and patient-reported outcomes (PROs).

METHODS: Clinical and PRO secondary endpoints were assessed annually over 4 years in STRIVE. The Symbol Digit Modalities Test (SDMT) was used as a measure of cognitive processing speed. PROs were assessed using the Multiple Sclerosis Impact Score (MSIS-29) and the Work Productivity and Activity Impairment Questionnaire (WPAI).

RESULTS: At all four annual assessments, the proportion of patients in the intent-to-treat (ITT) population (N = 222) who exhibited clinically meaningful improvement in their SDMT score from baseline (i.e., change ≥ 4 points) ranged from 41.9 to 54.0%. The cumulative probability of CDI at 4 years in patients in the ITT population with a baseline Expanded Disability Status Scale score ≥ 2 (N = 133) was 43.9%. Statistically significant reductions in the mean change from screening in the MSIS-29 physical and psychological scores, indicating improved quality of life, were observed over all 4 years (P ≤ 0.0012 for all). A statistically significant decrease from screening in the impact of MS on regular activities, signifying an improvement in this WPAI measure, was also observed over all 4 years of the study.

CONCLUSION: These results further extend our knowledge of the effectiveness, specifically regarding improvements in cognitive processing speed, disability and PROs, of long-term natalizumab treatment in early RRMS patients.

CLINICALTRIALS: GOV: NCT01485003 (5 December 2011).

PMID:36780107 | DOI:10.1007/s40263-022-00982-6

Oral Radiol. 2023 Feb 13. doi: 10.1007/s11282-023-00673-y. Online ahead of print.

ABSTRACT

OBJECTIVE: To analyze the challenges and impacts of COVID-19 on the routine of Brazilian oral radiologists regarding changes in biosafety protocols, number of patients and staff, the flow of acquisition, and availability of images.

METHODS: Structured digital questionnaires with questions related to the impacts of the COVID-19 pandemic on Oral Radiology were applied and analyzed. Descriptive statistical analysis was used to describe the items included in the survey, and means and standard deviations were calculated to describe continuous variables and frequency percentages to describe categorical data.

RESULTS: A high number of Brazilian oral radiologists continued to work in the pandemic period, with little or no change in their working hours. Digital flow and teleradiology are in most of their workplaces and the changes imposed by the pandemic will be incorporated and permanent, according to most of the participants in this study.

CONCLUSIONS: The COVID-19 pandemic brought important impacts on radiology clinics, with changes in the flow of patients, in the service and in the type of exam performed. In addition, adaptation to biosafety standards became necessary, with a significant increase in spending on personal protective equipment.

PMID:36780102 | DOI:10.1007/s11282-023-00673-y

Ir J Med Sci. 2023 Feb 13. doi: 10.1007/s11845-023-03308-7. Online ahead of print.

ABSTRACT

PURPOSE: This research was conducted to determine the effect of COVID-19 on fear, anxiety, and sleep in nursing students.

METHODS: The sample of the study consisted of 1222 students in the 2019-2020 academic year who were members of the student nurses association. The data were collected online via Google Form between June and August 2020 using the student information form containing socio-demographic characteristics, the Generalized Anxiety Disorder 7-Item (GAD-7) Scale, the fear of COVID-19 scale, and the Bergen Insomnia Scale.

RESULTS: In our study, the mean score of the fear of COVID-19 scale of nursing students was 18.23 ± 6.31, and it was determined that 51.8% had sleep problems and 70.9% had anxiety (39.9% mild, 20.8% moderate, and 10.2% severe). In simple linear regression analysis, the fear of COVID-19 was found to be statistically significant and positively correlated with anxiety (β: 0.383, p = 0.001), and the fear of COVID-19 (β: 0.120, p = 0.001) and anxiety (β: 0.346, p = 0.001) was found to be statistically significant and positively correlated with sleep.

CONCLUSION: In our study, there is a relationship between nursing students’ fear of COVID-19 and anxiety and sleep quality. Accordingly, it is recommended to train students in effective methods for coping with the fear of COVID-19, and to take initiatives to reduce related anxiety and sleep problems.

PMID:36780096 | DOI:10.1007/s11845-023-03308-7

Pediatr Surg Int. 2023 Feb 13;39(1):119. doi: 10.1007/s00383-023-05395-0.

ABSTRACT

PURPOSE: Despite constantly improving developments in ventriculo-peritoneal shunt systems, most patients with hydrocephalus require revision or replacement at some point of time. Therefore, this study aimed to analyse parameters that are associated with shunt dysfunction.

METHODS: In this retrospective study, we included 81 patients aged 0-17 who were treated at our institution. Demographic data, etiology of the hydrocephalus, type of valve implanted, reason for any revision procedures, any complications and survival time of the ventriculo-peritoneal shunts were detected. Statistical analysis was performed using SPSS. The significance level was set at p ≤ 0.05.

RESULTS: Over a mean study period of 18 years, we analyzed 226 valves subjected to 146 revision operations in 81 patients. The etiology of the hydrocephalus (p = 0.874) and the age of the child at the time of VP shunt implantation (p = 0.308) did not have any impact on the shunt survival time. However, the type of the valve significantly changed the survival time of the shunt (p = 0.030). Pressure differential valves presented a longer survival time than gravitational valves.

CONCLUSION: The majority of patients in this study needed at least one replacement of the initial shunt system. Pressure differential valves may be beneficial for the survival time of the shunt system.

PMID:36780089 | DOI:10.1007/s00383-023-05395-0

Environ Sci Pollut Res Int. 2023 Feb 13. doi: 10.1007/s11356-023-25637-x. Online ahead of print.

ABSTRACT

Even if Archaea deliver important ecosystem services and are major players in global biogeochemical cycles, they remain poorly understood in freshwater ecosystems. To our knowledge, no studies specifically address the direct impact of xenobiotics on the riverine archaeome. Using environmental DNA metabarcoding of the 16S ribosomal gene, we previously demonstrated bacterial communities significant shifts linked to pollutant mixtures during an extreme flood in a typical Mediterranean coastal watercourse. Here, using the same methodology, we sought to determine whether archaeal community shifts coincided with the delivery of environmental stressors during the same flood. Further, we wanted to determine how archaea taxa compared at different seasons. In contrast to the bacteriome, the archaeome showed a specific community in summer compared to winter and autumn. We also identified a significant relationship between in situ archaeome shifts and changes in physicochemical parameters along the flood, but a less marked link to those parameters correlated to river hydrodynamics than bacteria. New urban-specific archaeal taxa significantly related to multiple stressors were identified. Through statistical modeling of both domains, our results demonstrate that Archaea, seldom considered as bioindicators of water quality, have the potential to improve monitoring methods of watersheds.

PMID:36780079 | DOI:10.1007/s11356-023-25637-x

J Endocrinol Invest. 2023 Feb 13. doi: 10.1007/s40618-023-02032-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Primary hyperparathyroidism (PHPT) caused by parathyroid tumours is mostly sporadic, with a genetic cause identified in 5-10% of cases. Familial parathyroid tumours can be included in complex syndromes, such as multiple endocrine neoplasia (MEN) type 1, 2A and 4 or hyperparathyroidism-jaw tumour syndrome (HPT-JT).

OBJECTIVE: Characterisation of the familial parathyroid tumours followed-up at our centre and comparison of the different clinicopathological manifestations between the syndromes.

METHODS: Retrospective analysis of 48 patients with familial parathyroid tumours harbouring RET (n = 11), CDC73 (n = 20) and MEN1 (n = 17) germline mutations was performed.

RESULTS: Cases of PHPT in MEN2A syndrome presented with lower serum PTH (sPTH) and serum calcium (sCa) levels at diagnosis (sPTH = 108.0 (IQR 53.3) pg/mL, sCa = 10.6 ± 1.1 mg/dL) than MEN1 (sPTH = 196.9 (IQR 210.5) pg/mL, sCa = 11.7 ± 1.2 mg/dL) (p = 0.01, p = 0.03, respectively) or HPT-JT cases (sPTH = 383.5 (IQR 775.8) pg/mL, sCa = 12.9 ± 1.8 mg/dL) (p = 0.01; p < 0.001, respectively). There was a statistical difference in sCa levels between MEN1 and HPT-JT (p = 0.02), but not between sPTH (p = 0.07). The predominant first manifestation of the syndrome in MEN1 was gastroenteropancreatic neuroendocrine tumour (GEP-NET) in 47.1% of the cases, in MEN2A was medullary thyroid cancer (90.9%) and in HPT-JT was PHPT in 85% patients. In MEN1 syndrome, the number of affected parathyroid glands was significantly higher than in MEN2A (p < 0.001) and HPT-JT (p = 0.01).

CONCLUSION: The first manifestation of the syndrome in MEN1 cases was GEP-NET and not PHPT. Although presenting at similar ages, patients with MEN2A exhibit less severe biochemical and clinical PHPT at diagnosis than the other familial syndromes.

PMID:36780067 | DOI:10.1007/s40618-023-02032-4

Arch Gynecol Obstet. 2023 Feb 13. doi: 10.1007/s00404-023-06953-6. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the feasibility and diagnostic value of the combination of colposcopy, cytology and hrHPV (high-risk human papilloma virus) PCR (polymerase chain reaction) testing in patients with no or minor cytologic abnormalities and HPV high risk infection and to find the best predictors for the presence of CIN2 + in this patient collective.

METHODS: Three hundred and thirty-four hrHPV patients with normal cytology or minor cytologic abnormalities who had a colposcopic examination at the center of colposcopy at the university hospital Aachen in 2021 were enrolled in this retrospective cohort analysis. Multivariate logistic regression and a machine-learning technique (random forests, leave-one-out analysis) were used.

RESULTS: The overall risk for CIN2 + in hrHPV-positive patients with normal cytology was 7.7% (N = 18) (5% for CIN3 +), 18% (N = 16) (10.1% for CIN3 +) in patients with PAP IIp (ASC-US) and 62.5% (N = 5) (25% for CIN3 +) in patients with PAP IIg (AGC). Variables that show a statistically significant influence for the CIN-status are ‘major change’ as the result of colposcopy, transformation zone type T1, PAP IIg upon referral (AGC) and hrHPV category 1a (HPV 16/18) detection. Using machine learning (random forests) techniques, the main influencing variables were confirmed. A monotonously decreasing risk for CIN2 + from hrHPV category 1a to 3 (in accordance to the IACR guidelines) was found.

CONCLUSION: In the collective of hrHPV patients with no or minor cytologic abnormalities, the result of colposcopy and HPV PCR status are key predictors for the detection of CIN2 + with a monotonously decreasing risk for CIN2 + from hrHPV category 1a to 3.

PMID:36780042 | DOI:10.1007/s00404-023-06953-6

Int Microbiol. 2023 Feb 13. doi: 10.1007/s10123-023-00324-6. Online ahead of print.

ABSTRACT

BACKGROUND: Diabetes mellitus type 2 is a common disease that poses a challenge to the healthcare system. The disease is very often diagnosed late. A better understanding of the relationship between the gut microbiome and type 2 diabetes can support early detection and form an approach for therapies. Microbiome analysis offers a potential opportunity to find markers for this disease. Next-generation sequencing methods can be used to identify the bacteria present in the stool sample and to generate a microbiome profile through an analysis pipeline. Statistical analysis, e.g., using Student’s t-test, allows the identification of significant differences. The investigations are not only focused on single bacteria, but on the determination of a comprehensive profile. Also, the consideration of the functional microbiome is included in the analyses. The dataset is not from a clinical survey, but very extensive.

RESULTS: By examining 946 microbiome profiles of diabetes mellitus type 2 sufferers (272) and healthy control persons (674), a large number of significant genera (25) are revealed. It is possible to identify a large profile for type 2 diabetes disease. Furthermore, it is shown that the diversity of bacteria per taxonomic level in the group of persons with diabetes mellitus type 2 is significantly reduced compared to a healthy control group. In addition, six pathways are determined to be significant for type 2 diabetes describing the fermentation to butyrate. These parameters tend to have high potential for disease detection.

CONCLUSIONS: With this investigation of the gut microbiome of persons with diabetes type 2 disease, we present significant bacteria and pathways characteristic of this disease.

PMID:36780038 | DOI:10.1007/s10123-023-00324-6