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High-dose alkylating chemotherapy in BRCA-altered triple-negative breast cancer: the randomized phase III NeoTN trial

NPJ Breast Cancer. 2023 Sep 9;9(1):75. doi: 10.1038/s41523-023-00580-9.

ABSTRACT

Exploratory analyses of high-dose alkylating chemotherapy trials have suggested that BRCA1 or BRCA2-pathway altered (BRCA-altered) breast cancer might be particularly sensitive to this type of treatment. In this study, patients with BRCA-altered tumors who had received three initial courses of dose-dense doxorubicin and cyclophosphamide (ddAC), were randomized between a fourth ddAC course followed by high-dose carboplatin-thiotepa-cyclophosphamide or conventional chemotherapy (initially ddAC only or ddAC-capecitabine/decetaxel [CD] depending on MRI response, after amendment ddAC-carboplatin/paclitaxel [CP] for everyone). The primary endpoint was the neoadjuvant response index (NRI). Secondary endpoints included recurrence-free survival (RFS) and overall survival (OS). In total, 122 patients were randomized. No difference in NRI-score distribution (p = 0.41) was found. A statistically non-significant RFS difference was found (HR 0.54; 95% CI 0.23-1.25; p = 0.15). Exploratory RFS analyses showed benefit in stage III (n = 35; HR 0.16; 95% CI 0.03-0.75), but not stage II (n = 86; HR 1.00; 95% CI 0.30-3.30) patients. For stage III, 4-year RFS was 46% (95% CI 24-87%), 71% (95% CI 48-100%) and 88% (95% CI 74-100%), for ddAC/ddAC-CD, ddAC-CP and high-dose chemotherapy, respectively. No significant differences were found between high-dose and conventional chemotherapy in stage II-III, triple-negative, BRCA-altered breast cancer patients. Further research is needed to establish if there are patients with stage III, triple negative BRCA-altered breast cancer for whom outcomes can be improved with high-dose alkylating chemotherapy or whether the current standard neoadjuvant therapy including carboplatin and an immune checkpoint inhibitor is sufficient. Trial Registration: NCT01057069.

PMID:37689749 | DOI:10.1038/s41523-023-00580-9

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Spatial distribution of COVID-19 patients in Sri Lanka

BMC Public Health. 2023 Sep 9;23(1):1755. doi: 10.1186/s12889-023-16481-2.

ABSTRACT

BACKGROUND: A new type of viral pneumonia, which has been named Coronavirus disease (COVID-19) began in Wuhan, China in late 2019 and has spread across the world since then. It has claimed more than 370 million confirmed cases and over 5.6 million deaths have been reported globally by the end of January 2022. This study aimed to analyze the trends, highly-nuanced patterns, and related key results relative to COVID-19 epidemiology in Sri Lanka.

METHODS: Data on COVID-19 from March 2020 to January 2022 were obtained from published databases maintained by the Epidemiology Unit of the Ministry of Health in Sri Lanka and information regarding populations in administrative districts was obtained from the Department of Census and Statistics, Sri Lanka. Descriptive spatiotemporal analysis and autocorrelations were analyzed using SPSS statistical software.

RESULTS: In Sri Lanka, the first case of COVID-19 was a Chinese national and the first local case was identified in the second week of March. As of 31st of January 2022, a total of 610,103 COVID-19 cases had been recorded in the country, and 15,420 patients had died. At the beginning, the disease was mainly concentrated in the Western province and with time, it spread to other provinces. However, very low numbers of patients were identified in the North, Eastern, North Central, and Uva provinces until April 2021. The peak of COVID-19 occurred in August and September 2021 in all provinces in Sri Lanka. Then a decreasing trend of COVID-19 cases showed after September 2021.

CONCLUSIONS: COVID-19 is an emerging public health problem in Western and Southern Sri Lanka where the population density is high. A decreasing trend of COVID-19 cases showed in all provinces after September 2021. Public awareness programs for the prevention and control of the disease in endemic regions are essential to reduce the incidence of this infection.

PMID:37689685 | DOI:10.1186/s12889-023-16481-2

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Treatment patterns and clinical outcomes in patients with rheumatoid arthritis initiating etanercept, adalimumab, or Janus kinase inhibitor as first-line therapy: results from the real-world CorEvitas RA Registry

Arthritis Res Ther. 2023 Sep 9;25(1):166. doi: 10.1186/s13075-023-03120-9.

ABSTRACT

BACKGROUND: Real-world studies assessing the comparative effectiveness of biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) as first-line targeted therapy are scarce. We analyzed the real-world persistence and effectiveness of etanercept (ETN), adalimumab (ADA), and Janus kinase inhibitors (JAKis) as first-line therapy in b/tsDMARD-naïve patients with rheumatoid arthritis (RA).

METHODS: Adults (≥ 18 years) enrolled in the CorEvitas RA Registry and initiating ETN, ADA, or a JAKi (alone or in combination with csDMARDs) between November 2012 and June 2021 were included if they had 6 and/or 12 months’ follow-up. Treatment persistence and effectiveness outcomes including the change in Clinical Disease Activity Index (CDAI) and patient-reported outcomes (PROs) were evaluated at follow-up, adjusting for covariates using linear and logistic regression models. An exploratory analysis for patients on monotherapy was also conducted.

RESULTS: Of 1059 ETN, 1327 ADA, and 581 JAKi initiators; 803 ETN, 984 ADA, and 361 JAKi initiators had 6 months’ follow-up. JAKi initiators were older and had a relatively longer disease duration than ETN or ADA initiators (mean age: 61.3 vs 54.5 and 55.5 years; mean duration of RA: 8.1 vs 5.7 and 5.6 years). Unadjusted mean improvements in CDAI and PROs were similar between the groups at 6 months, except the proportion achieving LDA, remission, and MCID in CDAI, which were numerically higher in the ETN and ADA groups vs JAKi group (LDA: 43.4% and 41.9% vs 32.5%; remission: 18.2% and 15.1% vs 11.5%; MCID: 46.5% and 47.8% vs 38.0%). Adjusted effectiveness results did not reveal statistically significant differences between treatment groups at 6 months, with an exception in MCID (odds ratio [95% CI] for JAKi vs ETN: 0.65 [0.43-0.98]). At 6 months, 68.2% of ETN, 68.5% of ADA, and 66.5% of JAKi initiators remained on therapy. The findings at 12 months’ follow-up and sensitivity analysis among monotherapy initiators also showed no differences in effectiveness outcomes between the groups.

CONCLUSIONS: This analysis of real-world data from the CorEvitas RA Registry did not show differences in clinical effectiveness and treatment persistence rates in b/tsDMARD-naïve patients initiating ETN, ADA, or JAKi as first-line targeted therapy either alone or in combination with csDMARDs.

PMID:37689684 | DOI:10.1186/s13075-023-03120-9

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One-hole split endoscopy technique versus unilateral biportal endoscopy technique for L5-S1 lumbar disk herniation: analysis of clinical and radiologic outcomes

J Orthop Surg Res. 2023 Sep 9;18(1):668. doi: 10.1186/s13018-023-04159-9.

ABSTRACT

BACKGROUND: Lumbar disk herniation (LDH) is one of the most common diseases of the spine, especially occurring in L4-5 and L5-S1 intervertebral disks, and surgery is a choice when conservative treatment is ineffective. The purpose of this study is to investigate the clinical efficacy and radiologic outcomes of one-hole split endoscopy (OSE) technique versus unilateral biportal endoscopy (UBE) technique in the treatment of L5-S1 lumbar disk herniation (LDH).

METHODS: A total of 133 patients of a single center surgically treated for L5-S1 LDH between 2019 and 2021 were retrospectively included in this study, of which 70 were treated by UBE technique and the rest were treated by OSE technique. Hospitalization time, operative time, intraoperative blood loss, fluoroscopy times, incision length and related complications were recorded. Bone resection area (BRA), articular process resection rate, range of motion (ROM), sagittal translation (ST), disk height (DH), Visual Analog Score (VAS), Oswestry Disability Index (ODI) and Macnab criteria were used to evaluated the clinical efficacy.

RESULTS: There was no statistically significant difference in hospitalization time or fluoroscopy times between the two groups. The operation time was shorter in the UBE group than that in the OSE group; however, the incision length was longer. Intraoperative blood loss and BRA were larger in the UBE group than in the OSE group. There was no significant difference in ROM, ST, DH, or postoperative facet resection rate between the two groups. There was no significant difference in ROM, ST, or postoperative facet resection rate compared with preoperative indicators in each group, but there was a significant difference in DH among distinct groups. At any time point, the lower back and leg VAS and ODI in each group were significantly improved compared to those before the operation, with no significant difference between the two groups. There was one case of dural tear in the UBE group. One case of transient hypoesthesia occurred in each of the two groups. The excellent-good rates of the UBE group and the OSE group were 88.6% and 90.5%, respectively.

CONCLUSION: The OSE technique is an effective minimally invasive surgical option as well as the UBE technique in the treatment of L5-S1 LDH.

PMID:37689668 | DOI:10.1186/s13018-023-04159-9

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A prognostic model for systemic lupus erythematosus-associated pulmonary arterial hypertension: CSTAR-PAH cohort study

Respir Res. 2023 Sep 9;24(1):220. doi: 10.1186/s12931-023-02522-2.

ABSTRACT

BACKGROUND: Pulmonary arterial hypertension is a major cause of death in systemic lupus erythematosus, but there are no tools specialized for predicting survival in systemic lupus erythematosus-associated pulmonary arterial hypertension.

RESEARCH QUESTION: To develop a practical model for predicting long-term prognosis in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension.

METHODS: A prognostic model was developed from a multicenter, longitudinal national cohort of consecutively evaluated patients with systemic lupus erythematosus-associated pulmonary arterial hypertension. The study was conducted between November 2006 and February 2020. All-cause death was defined as the endpoint. Cox regression and least absolute shrinkage and selection operators were used to fit the model. Internal validation of the model was assessed by discrimination and calibration using bootstrapping.

RESULTS: Of 310 patients included in the study, 81 (26.1%) died within a median follow-up of 5.94 years (interquartile range 4.67-7.46). The final prognostic model included eight variables: modified World Health Organization functional class, 6-min walking distance, pulmonary vascular resistance, estimated glomerular filtration rate, thrombocytopenia, mild interstitial lung disease, N-terminal pro-brain natriuretic peptide/brain natriuretic peptide level, and direct bilirubin level. A 5-year death probability predictive algorithm was established and validated using the C-index (0.77) and a satisfactory calibration curve. Risk stratification was performed based on the predicted probability to improve clinical decision-making.

CONCLUSIONS: This new risk stratification model for systemic lupus erythematosus-associated pulmonary arterial hypertension may provide individualized prognostic probability using readily obtained clinical risk factors. External validation is required to demonstrate the accuracy of this model’s predictions in diverse patient populations.

PMID:37689662 | DOI:10.1186/s12931-023-02522-2

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Breastfeeding in primiparous women – expectations and reality: a prospective questionnaire survey

BMC Pregnancy Childbirth. 2023 Sep 9;23(1):654. doi: 10.1186/s12884-023-05971-1.

ABSTRACT

BACKGROUND: Breastfeeding provides the optimal nutrition for infants and offers numerous benefits for both mother and child. The World Health Organisation recommends exclusive breastfeeding during the first 6 months of life and the introduction of complementary feeding between the fifth and seventh months of life. There is a discrepancy between breastfeeding recommendations and the actual duration of breastfeeding. The aim of this study was to analyse breastfeeding behaviour in primiparous women in order to be able to provide support for mothers.

METHODS: In this prospective, questionnaire-based study conducted between 2020 and 2022, primiparous women were asked to complete three questionnaires at three defined survey time points (routine prepartum presentation, postpartum hospitalization, completed sixth month of life).

RESULTS: A total of 140 women were included and returned all three questionnaires. Fifty-eight percent performed breastfeeding exclusively at least until their baby had reached the age of 6 months, whereas 20% already stopped within the first 6 months. The main reasons given for early cessation were insufficient milk supply and inadequate infant weight gain. A comprehensive level of prepartum knowledge had a significant positive effect on participants’ sense of confidence with breastfeeding. Sociodemographic factors such as age and educational level were also associated with breastfeeding behaviour, but significant corresponding differences in the duration of breastfeeding were not observed. Women with postpartum midwifery care breastfed significantly longer (p < 0.05).

CONCLUSIONS: Breastfeeding behaviour and duration are influenced by multiple factors. Although certain sociodemographic factors are unalterable, comprehensive prepartum knowledge transfer and postpartum midwifery care have a positive impact on breastfeeding behaviour.

TRIAL REGISTRATION: The study was retrospectively registered at the German Clinical Trials Register (Deutsches Register Klinischer Studien, DRKS) on 6 December 2022 (DRKS00030763).

PMID:37689660 | DOI:10.1186/s12884-023-05971-1

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Healing effects of autologous platelet gel and growth factors on cutaneous leishmaniasis wounds in addition to antimony; a self-controlled clinical trial with randomized lesion assignment

BMC Res Notes. 2023 Sep 9;16(1):200. doi: 10.1186/s13104-023-06470-4.

ABSTRACT

OBJECTIVE: Autologous platelet gel (APG) is used in most surgeries to treat a variety of tissue defects because of its healing factors composition. This randomized parallel clinical trial was conducted to investigate the healing effects of APG on cutaneous leishmaniasis (CL) wounds. Eighteen male patients with CL wounds were recruited and followed for two months. The patients had more than one cutaneous wound, one of which was examined as the control and the other one as the intervention wound. APG was applied to the intervention wounds once a week, up to eight times. The primary endpoint was wound healing which defined as complete epithelialization and tissue granulation. Other clinical evaluation criteria were assessment of the wound size, and histopathology analyses.

RESULTS: Of 18 patients, 15 patients completed the trial (83.3%, mean age 28 years). The use of APG on the wounds was associated with complete and faster healing in 66% of the wounds and partial healing in 34% of the wounds. During the study, none of the control wounds were completely healed. The wound area in the intervention cases showed a statistically significant decrease throughout the study (P < 0.01) compared with controls. Following treatment of CL lesions with APG, the inflammatory process in the epidermis and dermis were decreased significantly (P < 0.01) compared with controls.

CONCLUSION: Our preliminary results confirm the clinical healing improvement described in the literature for APG-GF treatment of chronic non-leishmania wounds via immunomodulation.

TRIAL REGISTRATION: IRCT, IRCT20190212042694N1. Registered 20 February 2019, https://en.irct.ir/trial/37522.

PMID:37689656 | DOI:10.1186/s13104-023-06470-4

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Assessment of magnitude and associated factors of attitude towards time management among health professionals working in public hospitals of Dessie City, Northeast Ethiopia

BMC Health Serv Res. 2023 Sep 9;23(1):976. doi: 10.1186/s12913-023-10005-9.

ABSTRACT

BACKGROUND: Good attitude towards to time management is the backbone to bring a change at individual and organizational levels in different sectors across the globe. But it has been ignored by different institutions, particularly in low and middle-income countries including Ethiopia. However, this can be alleviated if there are punctual, committed, and accessible health professionals that could translate the national aspirations and the desire of the community into reality. This study aims to determine the magnitude and associated factors of attitude towards time management among health professionals working in public hospitals of Dessie City, Northeast Ethiopia, METHODS: Institution-based cross-sectional study was conducted from March 24 -April 24, 2021 among 409 health professionals using a stratified sampling technique, Frequency and percentage were used to describe the study population. Multivariable logistic regression analysis was used to identify independent predictors. A p-value of < 0.05 with 95% CI were used to declare statistically significant associations.

RESULTS: The overall good time management attitude among sample was 67%(95%CI:66.77-67.22%). Satisfaction with organizational policy and strategy (AOR: 2.69, 95%CI: 1.42-5.09), satisfaction with supervisor support (AOR: 2.12, 95% CI: 1.19-3.77), and managers’ good attitude towards time management (AOR: 2.00, 95%CI: 1.23-3.25) were significantly associated with good attitude towards time management among health professionals.

CONCLUSION: The attitude towards time management in public hospitals of Dessie City was low. Satisfaction with organizational policies and strategies, satisfaction with supervisor support, and managers’ good attitude towards time management were delineated factors. This low attitude towards time management could affect the practice and it compromise the health service coverage and quality unless timely and appropriate interventions should be taken. Strengthening strategies aimed at maximizing job satisfaction and emphasizing an attitude towards time might have a substantial contribution.

PMID:37689654 | DOI:10.1186/s12913-023-10005-9

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Discrepancy between two invasive blood pressure measurements in patients receiving intra-aortic balloon pump therapy

BMC Cardiovasc Disord. 2023 Sep 9;23(1):445. doi: 10.1186/s12872-023-03479-2.

ABSTRACT

BACKGROUND: Hemodynamic monitoring is imperative for patients with cardiogenic shock undergoing Intra-aortic Balloon Pump (IABP) therapy. Blood pressure monitoring encompasses non-invasive, invasive peripheral arterial pressure (IPAP), and invasive central aortic pressure (ICAP) methods. However, marked disparities exist between IPAP and ICAP. This study examined the discrepancies between IPAP and ICAP and their clinical significance.

METHODS: A retrospective analysis was conducted on cardiogenic shock patients who underwent IABP therapy and were admitted to the Coronary Care Unit (CCU) of a tertiary hospital in China from March 2017 to November 2022. The Bland-Altman plot illustrated the discrepancy between IPAP and ICAP. A clinically significant difference between ICAP and IPAP measurements was defined as ≥ 10 mmHg, which could necessitate alterations in blood pressure management according to current guidelines that recommend maintaining a mean arterial pressure (MAP) ≥ 70 mmHg.

RESULTS: In total, 162 patients were included in the final analysis. In patients without vasopressors, the difference between ICAP and IPAP was 5.73 mmHg (95% limits of agreement [LOA], -16.98 to 28.44), whereas, in patients with vasopressors, it was 4.36 mmHg (95% LOA, -17.31 to 26.03). ICAP measurements exceeded IPAP in patients undergoing IABP therapy. However, the difference was not statistically significant between the two groups. Multivariate logistic regression revealed that higher serum lactate levels (Odds ratio [OR], 1.14; 95% confidence interval [CI], 1.03-1.27; p = 0.013) and age ≥ 60 years (OR, 13.20; 95% CI, 1.50-115.51; p = 0.020) were associated with an increased likelihood of a clinically significant MAP discrepancy. Conversely, a history of coronary heart disease was associated with a decreased likelihood (OR, 0.34; 95% CI, 0.13-0.90; p = 0.031).

CONCLUSIONS: Notable discrepancies between ICAP and IPAP measurements exist in cardiogenic shock patients undergoing IABP therapy. ICAP exceeds IPAP, and factors such as age ≥ 60 years, elevated lactic acid levels, and absence of coronary heart disease contribute to this discrepancy. Enhanced vigilance is warranted for these patients, and the consideration of peripheral invasive monitoring in conjunction with IABP therapy is advised.

PMID:37689650 | DOI:10.1186/s12872-023-03479-2

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Classifying patients with non-specific chronic low back pain using the impact stratification score in an online convenience sample

BMC Musculoskelet Disord. 2023 Sep 9;24(1):719. doi: 10.1186/s12891-023-06848-2.

ABSTRACT

BACKGROUND: In 2014, the National Institute of Health Pain Consortium’s research task force (RTF) on research standards for chronic low back pain (CLBP) proposed the Impact Stratification Score (ISS) as a patient-reported outcome measure that could stratify patients by the impact CLBP has on their lives. This work compares three newly developed ISS-based classifications to the RTF’s original to provide an optimal recommendation.

METHODS: The online sample included 1226 individuals from Amazon’s Mechanical Turk who indicated having non-specific CLBP, average age of 40, 49% female, and 67% White. Participants completed the PROMIS-29 v2.1 profile survey that contains the 9 ISS items as well the Roland-Morris Disability Questionnaire (RMDQ) and Graded Chronic Pain Scale (GCPS). Other items included high-impact chronic pain; not working due to health problems; overall health; and number of healthcare visits for back pain in the past 6 months. Three new classifications were created using quartiles (Classification 2), latent profile analysis (Classification 3), and one modeled after the GCPS (Classification 4). Classifications were subsequently compared to the RTF-proposed classification (Classification 1) on several concurrent and prognostic criteria.

RESULTS: Classification 1 had three CLBP severity groups, four in Classification 2, three in Classification 3, and four in Classification 4. All novel classifications improved upon the original. Classification 2 performed best at minimizing the classification of those with negative outcomes into the lowest severity groups at baseline (e.g., 11% with RMDQ ≥ 7) and 6 months (e.g., 8.2% had fair/poor health). Classification 4 performed best at maximizing classification of those with negative outcomes into the most severe group concurrently (e.g., 100% had GCPS grade ≥ 2) and at 6 months (e.g., 100% with RMDQ ≥ 7).

CONCLUSIONS: We developed three ISS-based classification schemes and tested them against several outcomes. All three improved upon the original scheme. While appearing more optimal than other classifications in the lowest severity groups, Classification 2 presents some considerations and limitations. Given that Classification 4 was an improvement at the lowest end of severity and was the best at the highest end, it is our tentative recommendation that this approach be adopted to classify individuals with non-specific CLBP.

PMID:37689646 | DOI:10.1186/s12891-023-06848-2