Category: Nevin Manimala

Vaccine. 2021 Jul 31:S0264-410X(21)00868-9. doi: 10.1016/j.vaccine.2021.07.009. Online ahead of print.

ABSTRACT

BACKGROUND: British Columbia (BC) introduced a publicly funded, school-based human papillomavirus (HPV) immunization program in 2008 with the quadrivalent vaccine. In 2010/2011, a baseline evaluation of HPV prevalence was conducted among women undergoing cervical cancer screening. After 10 years of publicly funded HPV vaccination, HPV-type prevalence was re-evaluated.

METHODS: From August 2017 to March 2018, 1107 physicians were invited to return cytobrushes used during routine Pap screening to the Cervical Cancer Screening Laboratory for HPV testing. Only age or year of birth was collected. Specimens were screened for high-risk HPV (hrHPV) and positive samples were genotyped. HPV type prevalence was compared for females 15-22 yrs (those eligible for the school-based vaccination) and 23+ yrs (ineligible for school-based vaccination) for the 2010/2011 and the 2017/2018 data.

RESULTS: There were 3309 valid samples received for testing; of these, 3107 were included in the analysis. The overall hrHPV prevalence was 12.2% (95% CI 11.3-13.3) in 2010/11, and 12.0% (95% CI 10.9-13.2) in 2017/18. For the 15-22 age group, the prevalence for any hrHPV was 26.8% (95% CI 23.1-30.8) in 2010/11 and 25.4% (95% CI 15.3-37.9) in 2017/18. For those aged 15-22, HPV16 prevalence in 2010/11 was 8.8% (95% CI 6.5-11.5) and in 2017/18 was 6.3% (95% CI 1.8-15.5), with corresponding figures for HPV18 3.7% (95% CI 2.3-5.7) and 0% (95% CI 0.0-5.7), respectively. For all hrHPV types, there were no statistically significant differences between the 2010/11 and 2017/18 periods.

CONCLUSIONS: This study illustrates the prevalence of hrHPV in BC over time in women undergoing cervical cancer screening, where an indication of a decline in HPV16/18 is seen in vaccine eligible women.

PMID:34344555 | DOI:10.1016/j.vaccine.2021.07.009

Ultrasound Med Biol. 2021 Jul 31:S0301-5629(21)00296-9. doi: 10.1016/j.ultrasmedbio.2021.06.020. Online ahead of print.

ABSTRACT

Microbubble contrast agents are commonly used for therapeutic and diagnostic imaging applications. Under certain conditions, these contrast agents can coalesce on ultrasound application and form larger bubbles than the initial population. The formation of large microbubbles potentially influences therapeutic outcomes and imaging quality. We studied clinically relevant ultrasound parameters related to low-pressure therapy and contrast-enhanced ultrasound imaging to determine their effect on microbubble coalescence and subsequent changes in microbubble size distributions in vitro. Results indicate that therapeutic ultrasound at low frequencies, moderate pressures and high duty cycles are capable of forming bubbles greater than two times larger than the initial bubble distribution. Furthermore, acoustic parameters related to contrast-enhanced ultrasound imaging that are at higher frequency, low-pressure and low-duty cycle exhibit no statistically significant changes in bubble diameter, suggesting that standard contrast ultrasound imaging does not cause coalescence. Overall, this work suggests that the microbubble coalescence phenomenon can readily occur at acoustic parameters used in therapeutic ultrasound, generating bubbles much larger than those found in commercial contrast agents, although coalescence is unlikely to be significant in diagnostic contrast-enhanced ultrasound imaging. This observation warrants further expansion of parameter ranges and investigation of resulting effects.

PMID:34344561 | DOI:10.1016/j.ultrasmedbio.2021.06.020

J Prosthet Dent. 2021 Jul 31:S0022-3913(21)00361-9. doi: 10.1016/j.prosdent.2021.06.043. Online ahead of print.

ABSTRACT

STATEMENT OF PROBLEM: The choice of retention type of an implant-supported fixed dental prosthesis (FDP) becomes critical when the dental implant is not placed in a prosthetically ideal location. In recent years, computer-aided design and computer-aided manufacturing (CAD-CAM) technology has enabled the correction of the location of screw access hole depending on the clinical needs of the patient. However, how FPDs with angulated screw channels (ASCs) perform clinically is unclear.

PURPOSE: The purpose of this prospective clinical study was to evaluate the mechanical complications and crestal bone loss (CBL) when posterior monolithic zirconia implant-supported FDPs with an ASC are used.

MATERIAL AND METHODS: Participants (N=37) with a missing single posterior tooth or multiple teeth, sufficient bone height, and an implant site without infection were included. Each participant received parallel-walled implants (Nobel Parallel CC) of 7-, 8.5-, or 10-mm length by using a 1-stage approach. After 4 months of healing, a conventional impression was made, and a digital workflow was followed. Monolithic zirconia restorations (Katana ML) were milled, stained, and mechanically attached to a titanium base (NobelProcera ASC abutment). CBL was measured from radiographs at 6, 12, 24, and 36 months after the placement of the prosthesis. Implant and prosthetic characteristics including implant diameter, implant length, screw channel angle (angle≤15 degrees versus angle>16 degrees), prosthetic type (single crown versus multiple-unit FDP), and antagonist dentition (natural versus prosthesis) were also recorded. A generalized linear mixed model with a log link was estimated to assess the independent predictors of CBL among the angles of ASC-retained definitive restorations and the clinically relevant variables (α=.05).

RESULTS: Thirty-seven participants received 51 implants, and the median follow-up period was 30 months (interquartile range: 22-36). Two single-crown implants failed within the first 12 months of delivery. The implant and restoration survival rate was 96% at 36 months. Screw loosening was recorded in 2 study participants. After a follow-up of 36 months, the mean ±standard deviation CBL value was 0.15 ±0.14 mm with an increase over time (P<.001). The effect of the angle of ASC, implant diameter, implant length, prosthetic type, and antagonist on the CBL was not statistically significant (P>.05).

CONCLUSIONS: CBL was not associated with the angle of ASC, implant diameter, implant length, prosthetic type, or antagonist when posterior monolithic zirconia implant-supported FDPs with ASCs were used. Screw loosening in 2 situations was the only mechanical complication during the first 3 years of service.

PMID:34344529 | DOI:10.1016/j.prosdent.2021.06.043

Eur J Cancer. 2021 Jul 31:S0959-8049(21)00369-5. doi: 10.1016/j.ejca.2021.06.005. Online ahead of print.

ABSTRACT

INTRODUCTION: Bone metastases occur frequently in castration-resistant prostate cancer (CRPC) and may lead to skeletal-related events (SREs), including symptomatic skeletal events (SSEs). Bone-modifying agents (BMAs) delay SREs and SSEs. However, the real-world use of BMAs is debated given the absence of demonstrated survival advantage and potential adverse events (AEs). Our retrospective study examined BMA use and SSE rates in Australian patients with CRPC.

METHODS: Patients with CRPC and bone metastases were identified from the electronic CRPC Australian Database. Patient characteristics, treatment patterns and AEs were analysed. Descriptive statistics reported baseline characteristics, SSE rates and BMA use. Comparisons between groups used t-tests and Chi-square analyses. Overall survival was calculated by the Kaplan-Meier method.

RESULTS: A total of 532 eligible patients were identified with a median age of 73 years (range: 44-97 years). BMAs were prescribed in 232 men (46%), 183 of whom received denosumab. Patients receiving first-line docetaxel for CRPC were more likely to commence BMAs than those receiving abiraterone or enzalutamide (51% vs 31% vs 38%; p = 0.004). SSEs occurred in 148 men (28%), most commonly symptomatic lesions requiring intervention (75%). At the time of initial SSEs, only 28% were receiving BMAs. Patients treated at sites with lower BMA use (<median) had higher SSE rates (32% vs 22%, p = 0.019).

CONCLUSION: In our real-world cohort, SSEs occurred in almost one-third of patients with CRPC and bone metastases, whereas less than half of patients received BMAs. The lower rate of SSEs in treatment sites with increased BMA use supports their benefit in this setting.

PMID:34344533 | DOI:10.1016/j.ejca.2021.06.005

Porcine Health Manag. 2021 Aug 3;7(1):45. doi: 10.1186/s40813-021-00225-y.

ABSTRACT

BACKGROUND: The use of processed secondary data for health monitoring of fattening pigs has been established in various areas, such as the use of antibiotics or in the context of meat inspection. Standardized scores were calculated based on several sources of production data and can be used to describe animal health in a large collective of pig units. In the present study, the extent to which these scores are related to different farm characteristics and management decisions were investigated. In addition, slaughter scores were compared with the results of a veterinary examination on the farms.

RESULTS: The comparison of the results of the uni- and multifactorial analyses revealed that almost all of the examined factors play a role in at least one of the scores when considered individually. However, when various significant influencing factors were taken into account at any one time, most of the variables lost their statistical significance due to confounding effects. In particular, production data such as production costs or daily feed intake remained in the final models of the scores on mortality, average daily gain and external lesions. Regarding the second part of the investigation, a basic technical correlation between the slaughter scores and the on-farm indicators could be established via principal component analysis. The modelling of the slaughter scores by the on-farm indicators showed that the score on external lesions could be represented by equivalent variables recorded on the farm (e.g., lesions caused by tail or ear biting).

CONCLUSIONS: It has been demonstrated that the examined health scores are influenced by various farm and management characteristics. However, when several factors are taken into account, confounding occurs in some cases, which must be considered by consultants. Additionally, it was shown that on-farm examination content is related to the scores based on equivalent findings from slaughter pigs.

PMID:34344485 | DOI:10.1186/s40813-021-00225-y

Surgery. 2021 Jul 31:S0039-6060(21)00695-4. doi: 10.1016/j.surg.2021.07.012. Online ahead of print.

ABSTRACT

BACKGROUND: The purpose of this study was to determine if observational therapy is noninferior to antibiotics for acute uncomplicated diverticulitis according to clinically relevant margins.

METHODS: MEDLINE, EMBASE, and Cochrane were systematically searched by 2 independent reviewers to identify comparative studies of observational therapy versus antibiotics for acute uncomplicated diverticulitis. Non-inferiority margins (ΔNI) for each outcome were based on Delphi consensus including 50 patients and 55 physicians: persistent diverticulitis (ΔNI = 4.0%), progression to complicated diverticulitis (ΔNI = 3.0%), and time to recovery (ΔNI = 5 days). Risk differences and mean differences were pooled using random-effects meta-analysis. One-sided 90% confidence intervals and Z-tests were used to determine non-inferiority. A sensitivity analysis was performed, excluding patients post hoc determined to have complicated diverticulitis.

RESULTS: Nine studies (3 randomized controlled trials, 6 observational studies) met inclusion criteria: observational therapy (n = 2,011) versus antibiotics (n = 1,144). Observational therapy was noninferior to antibiotics regarding the risk of persistent diverticulitis (pooled risk differences: -0.39%, 90% CI -3.22 to 2.44%, ΔNI: 4.0%, P_NI < 0.001; I² = 66%) and progression to complicated diverticulitis (pooled risk differences: -0.030%, 90% CI -0.99 to 0.92%, ΔNI: 3.0%, P_NI < 0.001; I² = 0%). On sensitivity analysis, observational therapy remained noninferior for both outcomes. When stratified by study design, observational therapy also remained noninferior for both outcomes among randomized controlled trials only. Only 1 study reported on time to recovery as a continuous outcome, with no statistical difference between antibiotics and observational therapy.

CONCLUSION: According to clinically relevant ΔNIs, observational therapy was noninferior to antibiotics for the treatment of acute uncomplicated diverticulitis with regard to persistent diverticulitis and progression to complicated diverticulitis.

PMID:34344525 | DOI:10.1016/j.surg.2021.07.012

Infect Dis Poverty. 2021 Aug 3;10(1):104. doi: 10.1186/s40249-021-00890-9.

ABSTRACT

BACKGROUND: HIV/AIDS has transformed into a chronic controllable but not yet curable infectious disease as other chronic diseases to some extent. The additional of so called fourth 90% that included the improved health-related quality of life (HRQoL) for people living with HIV (PLWHIV) required solutions beyond antiretroviral therapy and viral load suppression. This study will explore the role of personality, social economic and prevention strategy effection on HRQoL among people living with HIV/AIDS.

METHODS: A cross-sectional study was conducted among PLWHIV aged more than 16 years old in the 10 municipalities in Yunnan Province, China from October 2019 to May 2020, enrolling total 1997 participants. Individual-level HRQoL data were measured by 12-item Short Form Health Survey (SF-12) and EuroQol Five Dimensions Questionnaire (EQ-5D-5L). We assembled municipal-level data about social economic from Yunnan Statistical Yearbook in 2020 and strategy practice information from the self-evaluation system. We used the principal component analysis to build the social economic and strategy effect on each area respectively and one-way ANOVA was used to perform univariate analysis to identify the predictors with significant differences. Finally we used multi-level model (MLM) to explore the personality, social economic and strategy effects in health-related quality of life among PLWHIV.

RESULTS: The global score for quality of life measured using EQ-5D-5L had an estimated mean score (standard deviation, SD) of 0.901 ± 0.146. The HRQoL score measured using PCS-12 had an estimated mean score (SD) of 46.62 ± 8.55. The mean MCS-12 score (SD) was estimated to be 47.80 ± 9.71. The area-level predictors explained a proportion of 13.6-17.2% for the between-area variation of the HRQoL scores, regardless of the total HRQoL, physical component and mental component. The impacts of stigma (P < 0.01), social support (P < 0.001), anxiety (P < 0.001), depression (P < 0.05) and social economic status (P < 0.05) on HRQoL at the individual-level were significantly different. The plots visualized the impact of individual-level factors on a respondent’s HRQoL was modified by the area-level characteristics.

CONCLUSIONS: The study identified the possible strategy determinant of individual HRQoL of PLWHIV and also the area effect on HRQoL. Stigma, social support, anxiety, depression and social economic status were the individual-level determinants on HRQoL. These could be a valuable resource for evaluating the overall health of the areas and help improve local decision making.

PMID:34344462 | DOI:10.1186/s40249-021-00890-9

Cancer Imaging. 2021 Aug 3;21(1):48. doi: 10.1186/s40644-021-00415-5.

ABSTRACT

OBJECTIVES: Tumor thickness and tumor volume measured by computed tomography (CT) were suggested as valuable prognosticator for patients’ survival diagnosed with malignant pleural mesothelioma (MPM). The purpose was to assess the accuracy of CT scan based preoperatively measured tumor volume and thickness compared to actual tumor weight of resected MPM specimen and pathologically assessed tumor thickness, as well as an analysis of their impact on overall survival (OS).

METHODS: Between 09/2013-08/2018, 74 patients were treated with induction chemotherapy followed by (extended) pleurectomy/decortication ((E)PD). In 53 patients, correlations were made between CT-measured volume and -tumor thickness (cTV and cTT) and actual tumor weight (pTW) based on the available values. Further cTV and pT/IMIG stage were correlated using Pearson correlation. Overall survival (OS) was calculated with Kaplan Meier analysis and tested with log rank test. For correlation with OS Kaplan-Meier curves were made and log rank test was performed for all measurements dichotomized at the median.

RESULTS: Median pathological tumor volume (pTV) and pTW were 530 ml [130 ml – 1000 ml] and 485 mg [95 g – 982 g] respectively. Median (IQR) cTV was 77.2 ml (35.0-238.0), median cTT was 9.0 mm (6.2-13.7). Significant association was found between cTV and pTV (R = 0.47, p < 0.001) and between cTT and IMIG stage (p = 0,001) at univariate analysis. Multivariate regression analysis revealed, that only cTV correlates with pTV. Median follow-up time was 36.3 months with 30 patients dead at the time of the analysis. Median OS was 23.7 months. 1-year and 3-year survival were 90 and 26% respectively and only the cTV remained statistically associated with OS.

CONCLUSION: Preoperatively assessed CT tumor volume and actual tumor volume showed a significant correlation. CT tumor volume may predict pathological tumor volume as a reflection of tumor burden, which supports the integration of CT tumor volume into future staging systems.

PMID:34344472 | DOI:10.1186/s40644-021-00415-5

Diagn Progn Res. 2021 Aug 4;5(1):14. doi: 10.1186/s41512-021-00103-9.

ABSTRACT

BACKGROUND: The United Kingdom Myeloma Research Alliance (UK-MRA) Myeloma Risk Profile is a prognostic model for overall survival. It was trained and tested on clinical trial data, aiming to improve the stratification of transplant ineligible (TNE) patients with newly diagnosed multiple myeloma. Missing data is a common problem which affects the development and validation of prognostic models, where decisions on how to address missingness have implications on the choice of methodology.

METHODS: Model building The training and test datasets were the TNE pathways from two large randomised multicentre, phase III clinical trials. Potential prognostic factors were identified by expert opinion. Missing data in the training dataset was imputed using multiple imputation by chained equations. Univariate analysis fitted Cox proportional hazards models in each imputed dataset with the estimates combined by Rubin’s rules. Multivariable analysis applied penalised Cox regression models, with a fixed penalty term across the imputed datasets. The estimates from each imputed dataset and bootstrap standard errors were combined by Rubin’s rules to define the prognostic model. Model assessment Calibration was assessed by visualising the observed and predicted probabilities across the imputed datasets. Discrimination was assessed by combining the prognostic separation D-statistic from each imputed dataset by Rubin’s rules. Model validation The D-statistic was applied in a bootstrap internal validation process in the training dataset and an external validation process in the test dataset, where acceptable performance was pre-specified. Development of risk groups Risk groups were defined using the tertiles of the combined prognostic index, obtained by combining the prognostic index from each imputed dataset by Rubin’s rules.

RESULTS: The training dataset included 1852 patients, 1268 (68.47%) with complete case data. Ten imputed datasets were generated. Five hundred twenty patients were included in the test dataset. The D-statistic for the prognostic model was 0.840 (95% CI 0.716-0.964) in the training dataset and 0.654 (95% CI 0.497-0.811) in the test dataset and the corrected D-Statistic was 0.801.

CONCLUSION: The decision to impute missing covariate data in the training dataset influenced the methods implemented to train and test the model. To extend current literature and aid future researchers, we have presented a detailed example of one approach. Whilst our example is not without limitations, a benefit is that all of the patient information available in the training dataset was utilised to develop the model.

TRIAL REGISTRATION: Both trials were registered; Myeloma IX- ISRCTN68454111 , registered 21 September 2000. Myeloma XI- ISRCTN49407852 , registered 24 June 2009.

PMID:34344484 | DOI:10.1186/s41512-021-00103-9

Arthritis Res Ther. 2021 Aug 3;23(1):205. doi: 10.1186/s13075-021-02555-2.

ABSTRACT

BACKGROUND: Circulating fibrocytes are an important source of fibroblasts and myofibroblasts, which are involved in fibrotic processes, including systemic sclerosis (SSc). The study aimed to investigate the effect of nintedanib (a tyrosine kinase inhibitor) in inhibiting the in vitro transition of circulating SSc fibrocytes into myofibroblasts and their pro-fibrotic activity.

METHODS: Circulating fibrocytes were obtained from 18 SSc patients and 5 healthy subjects (HSs). Cultured SSc fibrocytes were maintained in growth medium (untreated cells) or treated with nintedanib 0.1 and 1 μM for 3 and 24 h. Fibroblast-specific protein-1 (S100A4) and α-smooth muscle actin (αSMA), as markers of fibroblast/myofibroblast phenotype, together with type I collagen (COL1) and fibronectin (FN), were investigated by qRT-PCR and Western blotting. Non-parametric tests were used for statistical analysis.

RESULTS: Significantly elevated gene and protein expressions of αSMA, S100A4, COL1, and FN were observed in SSc fibrocytes compared to HS fibrocytes (gene: αSMA p < 0.001; others p < 0.0001; protein: all p < 0.05). Interestingly, an increased gene and protein expression of αSMA and S100A4 was found in fibrocytes from SSc patients positive for anti-Scl70 and with interstitial lung disease (ILD) (Scl70⁺ILD⁺) compared to Scl70^–ILD^– patients (S100A4: gene: p < 0.01; protein: p < 0.05), whereas no differences were observed for COL1 and FN. Nintedanib reduced gene and protein expression of αSMA, S100A4, COL1, and FN in SSc fibrocytes compared to untreated ones with different statistical significance. Noteworthy, nintedanib significantly downregulated gene and protein expression of αSMA, S100A4, COL1, and FN in Scl70⁺ILD⁺ fibrocytes (all p < 0.05), whereas only that of S100A4 and FN was significantly downregulated (p < 0.05) in Scl70^–ILD^– fibrocytes compared to the related untreated cells.

CONCLUSIONS: Nintedanib seems to downregulate in vitro the transition of fibrocytes into myofibroblasts and their pro-fibrotic activity, particularly in cells isolated from Scl70⁺ILD⁺ SSc patients.

PMID:34344444 | DOI:10.1186/s13075-021-02555-2