Category: Nevin Manimala

NPJ Prim Care Respir Med. 2023 May 13;33(1):21. doi: 10.1038/s41533-023-00341-y.

ABSTRACT

Despite national and international guidelines, asthma is frequently misdiagnosed, control is poor and unnecessary deaths are far too common. Large scale asthma management programme such as that undertaken in Finland, can improve asthma outcomes. A primary care asthma management quality improvement programme was developed with the support of the British Lung Foundation (now Asthma + Lung UK) and Optimum Patient Care (OPC) Limited. It was delivered and cascaded to all relevant staff at participating practices in three Clinical Commissioning Groups. The programme focussed on improving diagnostic accuracy, management of risk and control, patient self-management and overall asthma control. Patient data were extracted by OPC for the 12 months before (baseline) and after (outcome) the intervention. In the three CCGs, 68 GP practices participated in the programme. Uptake from practices was higher in the CCG that included asthma in its incentivised quality improvement programme. Asthma outcome data were successfully extracted from 64 practices caring for 673,593 patients. Primary outcome (Royal College of Physicians Three Questions [RCP3Q]) data were available in both the baseline and outcome periods for 10,328 patients in whom good asthma control (RCP3Q = 0) increased from 36.0% to 39.2% (p < 0.001) after the intervention. The odds ratio of reporting good asthma control following the intervention was 1.15 (95% CI 1.09-1.22), p < 0.0001. This asthma management programme produced modest but highly statistically significant improvements in asthma outcomes. Key lessons learnt from this small-scale implementation will enable the methodology to be improved to maximise benefit in a larger scale role out.

PMID:37179388 | DOI:10.1038/s41533-023-00341-y

NPJ Breast Cancer. 2023 May 13;9(1):38. doi: 10.1038/s41523-023-00535-0.

ABSTRACT

We assessed the predictive value of an image analysis-based tumor-infiltrating lymphocytes (TILs) score for pathologic complete response (pCR) and event-free survival in breast cancer (BC). About 113 pretreatment samples were analyzed from patients with stage IIB-IIIC HER-2-negative BC randomized to neoadjuvant chemotherapy ± bevacizumab. TILs quantification was performed on full sections using QuPath open-source software with a convolutional neural network cell classifier (CNN11). We used easTILs% as a digital metric of TILs score defined as [sum of lymphocytes area (mm²)/stromal area(mm²)] × 100. Pathologist-read stromal TILs score (sTILs%) was determined following published guidelines. Mean pretreatment easTILs% was significantly higher in cases with pCR compared to residual disease (median 36.1 vs.14.8%, p < 0.001). We observed a strong positive correlation (r = 0.606, p < 0.0001) between easTILs% and sTILs%. The area under the prediction curve (AUC) was higher for easTILs% than sTILs%, 0.709 and 0.627, respectively. Image analysis-based TILs quantification is predictive of pCR in BC and had better response discrimination than pathologist-read sTILs%.

PMID:37179362 | DOI:10.1038/s41523-023-00535-0

BMC Pregnancy Childbirth. 2023 May 13;23(1):349. doi: 10.1186/s12884-023-05665-8.

ABSTRACT

BACKGROUND: Women undergoing induction of labour (IOL) more often have poor childbirth experience compared to women with spontaneous onset of labour (SOL). For understanding and optimizing childbirth experience in IOL, we investigated the subjective maternal reasons and perceptions leading to poor childbirth experience in IOL compared to SOL, as well as the background factors and delivery outcomes associated with the poor experience.

METHODS: Two-year retrospective cohort study included 836/19442 deliveries (4.3%) with poor childbirth experience in induced or spontaneous onset at term in Helsinki University Hospital. Poor childbirth experience occurred in 389/5290 (7.4%) cases of IOL and in 447/14152 (3.2%) of SOL. Childbirth experience was measured after delivery using Visual Analog Scale (VAS) score, with poor experience defined as VAS < 5. The primary outcome of the study were the maternal reasons for poor childbirth experience. The parameters were collected in the hospital database and statistical analyses were performed by using Mann-Whitney U-test and t-test.

RESULTS: The subjective maternal reasons for poor childbirth experience were pain (n = 529, 63.3%), long labour (n = 209, 25.0%), lack of support by care givers (n = 108, 12.9%), and unplanned caesarean section (CS) (n = 104, 12.4%). The methods of labour analgesia were similar among the women who expressed pain as the main reason compared with those who didn’t. When comparing the reasons according to the onset of labour, IOL group more often reported unplanned CS (17.2% vs. 8.3%; p < 0.001) and lack of support by the care givers (15.4% vs. 10.7%; p = 0.04), while SOL group more often named pain (68.7% vs. 57.1%; p = 0.001) and rapid labour (6.9% vs. 2.8%; p = 0.007). In multivariable logistic regression model, IOL was associated with lower risk for pain compared to SOL (adjusted OR 0.6, 95%CI 0.5-0.8; p < 0.01). Primiparas more often reported long labour (29.3% vs. 14.3%; p < 0.001) and concern over own or baby’s wellbeing (5.7% vs. 2.1%; p = 0.03) compared to multiparas. Women who feared childbirth more often reported lack of support compared to women with no fear (22.6% vs. 10.7%; p < 0.001).

CONCLUSION: The main reasons for poor childbirth experience were pain, long labour, unplanned CS and the lack of support by care givers. The childbirth experience is complex and could be optimized by information, support and presence of care givers especially in induced labour.

PMID:37179323 | DOI:10.1186/s12884-023-05665-8

BMC Oral Health. 2023 May 13;23(1):286. doi: 10.1186/s12903-023-02971-7.

ABSTRACT

BACKGROUND: Periodontitis is a persistent inflammatory condition. Eliminating the infection and reducing its risk factors are the first steps in treating periodontitis. When the anti-infective therapy is complete, there may still be deep periodontal pockets and prolonged inflammation. Surgical pocket reduction or elimination is indicated under these circumstances. We aimed to evaluate the effect of bromelain on bleeding on probing (BOP), gingival index (GI), and plaque index (PI) after pocket elimination surgery.

METHODS: This double-blind randomized placebo-controlled trial included 28 candidates for pocket elimination surgery referred to the private office of a periodontist in Bandar Abbas, Iran, from April 18 to August 18, 2021. Patients’ general characteristics, such as age and sex, were recorded. Additionally, periodontal indices including BOP, PI, GI, and pocket probing depth (PPD) were evaluated in all subjects. All patients underwent pocket elimination surgery. Afterwards, they were randomized into two groups. The first group received 500 mg Anaheal (bromelain) capsules twice a day before meal for one week. The second group received placebo, prepared in similar shape and color by the same pharmaceutical company. BOP, PI, GI, and PPD were assessed four weeks after completion of the treatment course (five weeks after surgery).

RESULTS: Four weeks after intervention, BOP was significantly lower with Anaheal compared to placebo (0% vs. 35.7%, P = 0.014). However, there was no significant difference in GI between groups (P = 0.120). Mean PI was lower (17.71 ± 2.12 vs. 18.28 ± 2.49) and mean PPD higher (3.10 ± 0.71 vs. 2.64 ± 0.45) in the Anaheal group, but the differences did not reach statistically significant levels (P = 0.520 and P = 0.051, respectively).

CONCLUSIONS: One-week treatment with Anaheal at a dose of 1 g/d after pocket elimination surgery resulted in significantly lower BOP compared to placebo.

TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT), IRCT20201106049289N1. Registered 06/04/2021. Registered prospectively, https://www.irct.ir/trial/52181 .

PMID:37179311 | DOI:10.1186/s12903-023-02971-7

BMC Gastroenterol. 2023 May 13;23(1):151. doi: 10.1186/s12876-023-02710-w.

ABSTRACT

CONTEXT: Cholangiocarcinoma (CCA), a malignancy of the biliary tract epithelium is of increasing importance due to its rising incidence worldwide. There is a lack of data on cirrhosis in intrahepatic CCA (iCCA) and how it affects overall survival and prognosis.

OBJECTIVES: The primary objective of this study was to examine if there were differences in survival outcomes between iCCA patients with concomitant cirrhosis and those without cirrhosis.

METHODS: The National Cancer Database (NCDB) was used to identify and study patients with iCCA from 2004 to 2017. The presence of cirrhosis was defined using CS Site-Specific Factor 2 where 000 indicated no cirrhosis and 001 indicated the presence of cirrhosis. Descriptive statistics were utilized for patient demographics, disease staging, tumor, and treatment characteristics. Kaplan-Meier (KM) method with log-rank test and a multivariate logistic regression model was used to assess if the presence of cirrhosis in iCCA was associated with survival status and long-term survival (60 or more months after diagnosis).

RESULTS: There were 33,160 patients with CCA in NCDB (2004-2017), of which 3644 patients were diagnosed with iCCA. One thousand fifty-two patients (28.9%) had cirrhosis as defined by Ishak Fibrosis score 5-6 on biopsy and 2592 patients (71.1%) did not meet the definition for cirrhosis. Although in univariate analyses using KM/log-rank tests showed a survival advantage for non-cirrhotic patients, there was no statistically significant association found between cirrhosis and survival status (OR = 0.82, p = 0.405) or long-term survival (OR = 0.98, p = 0.933) when multivariate analysis was used. iCCA patients with cirrhosis and Stage 1 tumor had the highest median OS (132 months) vs 73.7 months in the non-cirrhotic arm, while patients with stage IV disease who had cirrhosis had half the survival time of those without. Our data thus indicates that the presence of cirrhosis is not an independent prognostic factor for survival.

PMID:37179301 | DOI:10.1186/s12876-023-02710-w

BMC Health Serv Res. 2023 May 13;23(1):485. doi: 10.1186/s12913-023-09479-4.

ABSTRACT

BACKGROUND: During the early stages of the COVID-19 pandemic, there was considerable uncertainty surrounding epidemiological and clinical aspects of SARS-CoV-2. Governments around the world, starting from varying levels of pandemic preparedness, needed to make decisions about how to respond to SARS-CoV-2 with only limited information about transmission rates, disease severity and the likely effectiveness of public health interventions. In the face of such uncertainties, formal approaches to quantifying the value of information can help decision makers to prioritise research efforts.

METHODS: In this study we use Value of Information (VoI) analysis to quantify the likely benefit associated with reducing three key uncertainties present in the early stages of the COVID-19 pandemic: the basic reproduction number ([Formula: see text]), case severity (CS), and the relative infectiousness of children compared to adults (CI). The specific decision problem we consider is the optimal level of investment in intensive care unit (ICU) beds. Our analysis incorporates mathematical models of disease transmission and clinical pathways in order to estimate ICU demand and disease outcomes across a range of scenarios.

RESULTS: We found that VoI analysis enabled us to estimate the relative benefit of resolving different uncertainties about epidemiological and clinical aspects of SARS-CoV-2. Given the initial beliefs of an expert, obtaining more information about case severity had the highest parameter value of information, followed by the basic reproduction number [Formula: see text]. Resolving uncertainty about the relative infectiousness of children did not affect the decision about the number of ICU beds to be purchased for any COVID-19 outbreak scenarios defined by these three parameters.

CONCLUSION: For the scenarios where the value of information was high enough to justify monitoring, if CS and [Formula: see text] are known, management actions will not change when we learn about child infectiousness. VoI is an important tool for understanding the importance of each disease factor during outbreak preparedness and can help to prioritise the allocation of resources for relevant information.

PMID:37179300 | DOI:10.1186/s12913-023-09479-4

J Transl Med. 2023 May 13;21(1):322. doi: 10.1186/s12967-023-04179-3.

ABSTRACT

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, heterogenous disease characterized by unexplained persistent fatigue and other features including cognitive impairment, myalgias, post-exertional malaise, and immune system dysfunction. Cytokines are present in plasma and encapsulated in extracellular vesicles (EVs), but there have been only a few reports of EV characteristics and cargo in ME/CFS. Several small studies have previously described plasma proteins or protein pathways that are associated with ME/CFS.

METHODS: We prepared extracellular vesicles (EVs) from frozen plasma samples from a cohort of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) cases and controls with prior published plasma cytokine and plasma proteomics data. The cytokine content of the plasma-derived extracellular vesicles was determined by a multiplex assay and differences between patients and controls were assessed. We then performed multi-omic statistical analyses that considered not only this new data, but extensive clinical data describing the health of the subjects.

RESULTS: ME/CFS cases exhibited greater size and concentration of EVs in plasma. Assays of cytokine content in EVs revealed IL2 was significantly higher in cases. We observed numerous correlations among EV cytokines, among plasma cytokines, and among plasma proteins from mass spectrometry proteomics. Significant correlations between clinical data and protein levels suggest roles of particular proteins and pathways in the disease. For example, higher levels of the pro-inflammatory cytokines Granulocyte-Monocyte Colony-Stimulating Factor (CSF2) and Tumor Necrosis Factor (TNFα) were correlated with greater physical and fatigue symptoms in ME/CFS cases. Higher serine protease SERPINA5, which is involved in hemostasis, was correlated with higher SF-36 general health scores in ME/CFS. Machine learning classifiers were able to identify a list of 20 proteins that could discriminate between cases and controls, with XGBoost providing the best classification with 86.1% accuracy and a cross-validated AUROC value of 0.947. Random Forest distinguished cases from controls with 79.1% accuracy and an AUROC value of 0.891 using only 7 proteins.

CONCLUSIONS: These findings add to the substantial number of objective differences in biomolecules that have been identified in individuals with ME/CFS. The observed correlations of proteins important in immune responses and hemostasis with clinical data further implicates a disturbance of these functions in ME/CFS.

PMID:37179299 | DOI:10.1186/s12967-023-04179-3

BMC Oral Health. 2023 May 13;23(1):289. doi: 10.1186/s12903-023-02907-1.

ABSTRACT

BACKGROUND: This study aimed to evaluate periapical radiolucency of endodontically treated teeth before and after orthodontic treatment using cone-beam computed tomography (CBCT).

METHODS: Patients who underwent orthodontic treatment at Wonkwang University Daejeon Dental Hospital between January 2009 and June 2022 were included based on the following criteria: root canal treatment, and availability of CBCT images taken before and after orthodontic treatment with an interval of > 1 year between both scans. Patients with primary teeth or orthodontic tooth extractions were excluded. The size of the periapical radiolucency (SPR) of the endodontically treated tooth was evaluated using CBCT. Pre-orthodontic treatment CBCT images and the latest post-orthodontic treatment CBCT images were analyzed. The selected teeth were further categorized based on the orthodontic duration, CBCT interval, the patient sex and age, the tooth type and position (maxilla or mandible), and quality of root canal obturation. Statistical analyses were performed to evaluate changes in SPR using the paired t-test and multiple regression analysis.

RESULTS: In total, 115 teeth (37 anterior teeth, 22 premolars and 56 molars) from 61 patients (age, 14-54 years) were included, with 39 teeth from male patients and 76 teeth from female patients. The age was ranged between 14 and 54 years old, and mean age was 25.87 years old. The mean CBCT interval and orthodontic treatment period were 43.32 months and 36.84 months, respectively. Seventy-five teeth showed good obturation quality, 80 were not used as anchors during orthodontic treatment, and 71 were maxillary. The SPR size increased after orthodontic treatment for 56 teeth and decreased for 59 cases. The average change in SPR was -0.102 mm and the difference was not significant. Significant decrease of SPR were observed between female patients (p = 0.036) and maxillary teeth (p = 0.040).

CONCLUSION: Orthodontic treatment had no significant impact on the changes in the SPR in endodontically treated teeth in most categories. However, there was a significant difference among females and the maxillary teeth. In both categories, the size of radiolucency decreased significantly.

PMID:37179291 | DOI:10.1186/s12903-023-02907-1

BMC Oral Health. 2023 May 13;23(1):288. doi: 10.1186/s12903-023-02966-4.

ABSTRACT

BACKGROUND: The aim of this study was to investigate the effect of trehalose oral spray to relieve radiation-induced xerostomia on a randomized controlled trial (RCT).

METHODS: Prior to RCT, the effect of trehalose (5-20%) on the epithelial growth of fetal mouse salivary gland (SG) explants was evaluated to confirm if 10% trehalose exerted the best epithelial outcomes. Participants who completed radiotherapy for head and neck cancer (HNC) treatment were enrolled in a double-blind RCT, according to inclusion and exclusion criteria as per the CONSORT statement. The experimental group (n = 35) received 10% trehalose spray, while the control group (n = 35) received carboxymethylcellulose (CMC) spray to apply intra-orally 4 times/day for 14 days. Salivary pH and unstimulated salivary flow rate were recorded pre- and post-interventions. The Xerostomia-related Quality of Life scale (XeQoLs) was filled, and scores assessed post-interventions.

RESULTS: In the SG explant model, pro-acinar epithelial growth and mitosis was supported by 10% topical trehalose. As for RCT outcomes, salivary pH and unstimulated salivary flow rate were significantly improved after use of 10% trehalose spray when compared to CMC (p < 0.05). Participants reported an improvement of XeQoLs dimension scores after using trehalose or CMC oral sprays in terms of physical, pain/discomfort, and psychological dimensions (p < 0.05), but not social (p > 0.05). When comparing between CMC and trehalose sprays, XeQoLs total scores were not statistically different (p > 0.05).

CONCLUSIONS: The 10% trehalose spray improved salivary pH, unstimulated salivary flow rate, and the quality-of-life dimensions linked with physical, pain/discomfort, and psychological signs. The clinical efficacy of 10% trehalose spray was equivalent with CMC-based saliva substitutes for relieving radiation-induced xerostomia; therefore, trehalose may be suggested in alternative to CMC-based oral spray.(Thai Clinical Trials Registry; https://www.thaiclinicaltrials.org/ TCTR20190817004).

PMID:37179287 | DOI:10.1186/s12903-023-02966-4

J Cancer Res Clin Oncol. 2023 May 13. doi: 10.1007/s00432-023-04709-y. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the relationship between the microlymphangiogenesis, microangiogenesis, and combined detection of the programmed cell death-1 protein (PD-1)/ki67 in patients with gastric cancer as well as the disease prognosis.

METHODS: Immunohistochemistry was used to detect the microlymphatic density (MLD) and microvessel density (MVD) in the central and peripheral zones in 92 cases of gastric cancer, along with the number of PD-1- and ki67-positive tumor cells.

RESULTS: The central zone of the gastric cancer tissue contained fewer atretic cord-like lymphatic vessels than the peripheral zone, while the peripheral zone contained an increased number of lymphatic vessels compared with the central zone. In most cases, the lumen was also dilated. Compared with the MLD in the peripheral zone, the MLD in central zone was significantly decreased. Compared with the number of PD-1-positive cells in the peripheral zone, the number of PD-1-positive cells in the central zone was significantly decreased, and compared with the number of ki67-positive cells in the peripheral zone. The differences in the microlymphangiogenesis, microangiogenesis, and the number of PD-1- and ki67-positive cells among the different histological types were not statistically significant. The microlymphangiogenesis, microangiogenesis, and PD-1- and ki67-positive cells were significantly decreased in the gastric cancer tissues from the patients in stages T1 and T2 compared with the gastric cancer tissues from the patients in stages T3 and T4.

CONCLUSIONS: The detection of the MLD and MVD as well as the positive expression of PD-1 and ki67 in gastric cancer tissue are important reference indicators for judging the prognosis of gastric cancer.

PMID:37179266 | DOI:10.1007/s00432-023-04709-y