Tag: pubmed

Trials. 2021 Sep 15;22(1):623. doi: 10.1186/s13063-021-05583-0.

ABSTRACT

INTRODUCTION: Despite several ongoing efforts in biomedicine and traditional medicine, there are no drugs or vaccines for coronavirus disease 2019 (COVID-19) as of May 2020; Kabasura Kudineer (KSK), a polyherbal formulation from India’s Siddha system of medicine, has been traditionally used for clinical presentations similar to that of COVID-19. We explored the efficacy of KSK in reducing viral load and preventing the disease progression in asymptomatic, COVID-19 cases.

METHODS: A prospective, single-center, open-labeled, randomized, controlled trial was conducted in a COVID Care Centre in Chennai, India. We recruited reverse-transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 of 18 to 55 years of age, without clinical symptoms and co-morbidities. They were randomized (1:1 ratio) to KSK (60 mL twice daily for 7 days) or standard of care (7 days supplementation of vitamin C 60,000 IU morning daily and zinc 100 mg evening daily) groups. The primary outcomes were reduction in the SARS-CoV-2 load [as measured by cyclic threshold (CT) value of RT-PCR], prevention of progression of asymptomatic to symptomatic state, and changes in the immunity markers including interleukins (IL-6, IL-10, IL-2), interferon gamma (IFNγ), and tumor necrosis factor (TNF α). Siddha clinical assessment and the occurrence of adverse effects were documented as secondary outcomes. Paired t-test was used in statistical analysis.

RESULTS: Viral load in terms of the CT value (RdRp: 95% CI = 1.89 to 5.74) declined significantly on the seventh day in the KSK group and that of the control group, more pronounced in the study group. None progressed to the symptomatic state. There was no significant difference in the biochemical parameters. We did not observe any changes in the Siddha-based clinical examination and adverse events in both groups.

CONCLUSION: KSK significantly reduced SARS-CoV-2 viral load among asymptomatic COVID-19 cases and did not record any adverse effect, indicating the use of KSK in the strategy against COVID-19. Larger, multi-centric trials can strengthen the current findings.

TRIAL REGISTRATION: Clinical Trial Registry of India CTRI2020/05/025215 . Registered on 16 May 2020.

PMID:34526104 | DOI:10.1186/s13063-021-05583-0

Orphanet J Rare Dis. 2021 Sep 15;16(1):389. doi: 10.1186/s13023-021-02016-8.

ABSTRACT

AIMS: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening intravascular hematologic disorder with significant morbidity and premature mortality. Clinical trials (NCT02946463 and NCT03056040) comparing ravulizumab with eculizumab for PNH have supported the non-inferiority of the former and similar safety and tolerability. This secondary analysis compared PNH trial participants after 26 weeks on either treatment (n = 438) to a general-population sample (GenPop) (n = 15,386) and investigated response-shift effects.

METHODS: Multivariate analysis of covariance (MANCOVA) investigated function and symptom scores on the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 of people with PNH as compared to GenPop, after covariate adjustment. Risk-factor groups were created based on clinical indicators known to be associated with worse PNH outcomes, and separate MANCOVAs were computed for lower- and higher-risk-factor groups. Differential item functioning (DIF) analyses examined whether item response varied systematically (1) by treatment, (2) compared to GenPop, and (3) over time, the latter two suggesting and reflecting response-shift effects, respectively. DIF analyses examined 24 items from scales with at least two items. Recalibration response shift was operationalized as uniform DIF over time, reflecting the idea that, for a given group, the difficulty of endorsing an item changes over time, after adjusting for the total subscale score. Reprioritization response shift was operationalized as non-uniform DIF over time, i.e., the relative difficulty of endorsing an item over time changes across the total domain score.

RESULTS: Across PNH risk-factor levels, people who had been on either treatment for 26 weeks reported better-than-expected functioning and lower symptom burden compared to GenPop. Ravulizumab generally showed larger effect sizes. Results were similar for lower and higher PNH risk factors, with slightly stronger effects in the former. DIF analyses revealed no treatment DIF, but did uncover group DIF (9 items with uniform DIF, and 11 with non-uniform) and DIF over time (7 items with uniform DIF, and 3 with non-uniform).

CONCLUSIONS: This study revealed that people with PNH on ravulizumab or eculizumab for 26 weeks reported QOL levels better than those of the general population. Significant effects of DIF by group and DIF over time support recalibration and reprioritization response-shift effects. These findings suggest that the treatments enabled adaptive changes.

PMID:34526067 | DOI:10.1186/s13023-021-02016-8

Trials. 2021 Sep 15;22(1):626. doi: 10.1186/s13063-021-05590-1.

ABSTRACT

BACKGROUND AND AIM: Some parallel-group cluster-randomized trials use covariate-constrained rather than simple randomization. This is done to increase the chance of balancing the groups on cluster- and patient-level baseline characteristics. This study assessed how well two covariate-constrained randomization methods balanced baseline characteristics compared with simple randomization.

METHODS: We conducted a mock 3-year cluster-randomized trial, with no active intervention, that started April 1, 2014, and ended March 31, 2017. We included a total of 11,832 patients from 72 hemodialysis centers (clusters) in Ontario, Canada. We randomly allocated the 72 clusters into two groups in a 1:1 ratio on a single date using individual- and cluster-level data available until April 1, 2013. Initially, we generated 1000 allocation schemes using simple randomization. Then, as an alternative, we performed covariate-constrained randomization based on historical data from these centers. In one analysis, we restricted on a set of 11 individual-level prognostic variables; in the other, we restricted on principal components generated using 29 baseline historical variables. We created 300,000 different allocations for the covariate-constrained randomizations, and we restricted our analysis to the 30,000 best allocations based on the smallest sum of the penalized standardized differences. We then randomly sampled 1000 schemes from the 30,000 best allocations. We summarized our results with each randomization approach as the median (25th and 75th percentile) number of balanced baseline characteristics. There were 156 baseline characteristics, and a variable was balanced when the between-group standardized difference was ≤ 10%.

RESULTS: The three randomization techniques had at least 125 of 156 balanced baseline characteristics in 90% of sampled allocations. The median number of balanced baseline characteristics using simple randomization was 147 (142, 150). The corresponding value for covariate-constrained randomization using 11 prognostic characteristics was 149 (146, 151), while for principal components, the value was 150 (147, 151).

CONCLUSION: In this setting with 72 clusters, constraining the randomization using historical information achieved better balance on baseline characteristics compared with simple randomization; however, the magnitude of benefit was modest.

PMID:34526092 | DOI:10.1186/s13063-021-05590-1

Reprod Health. 2021 Sep 15;18(1):183. doi: 10.1186/s12978-021-01228-2.

ABSTRACT

BACKGROUND: Obstetric fistula occurs in all developing countries but it is confined to the “fistula belt” across the northern half of Sub-Saharan Africa from Mauritania to Eritrea and in the developing countries of the Middle East and Asia. Ending obstetric fistula is critical to achieving Sustainable Development by 2030. So creating awareness on obstetrics fistula among women in the reproductive age group have a crucial role in reducing morbidity, mortality, and social stigma.

OBJECTIVE: To assess awareness on obstetric fistula and its associated factors among reproductive-age women attending governmental hospitals in southwest Ethiopia, 2021.

METHODS: An Institutional based cross-sectional study design was conducted among 413 women. The sample size was estimated by using a single population proportion formula. The collected data were coded and entered into EPI-data version 3.1 then exported to SPSS version 24 for descriptive and inferential analysis. Adjusted odds ratio (AOR) along with 95% confidence level was estimated to assess the strength of the association and variables with a p-value < 0.05 were considered to declare the statistical significance in the multivariable analysis in this study.

RESULTS: In this study, a total of 400 clients have participated in the study. The mean ages of participants were 30.26 (SD ± 8.525) years old. Education of women who cannot read and write are 85% less likely to have good awareness than women who are above the secondary level of education [AOR = 0.162; 95% CI (0.081-0.364)]. While Women who have primary education level are 83% less likely to have good awareness than women who are above the secondary level of education [AOR = 0.170; 95% CI (0.085-0.446)]. In addition, This study shows women who have not heard about obstetric complications are 54% less likely to have awareness of obstetric fistula than those who heard about obstetric complications [AOR = 0.458; 95% CI (0.368-0.643)].

CONCLUSION: This study identifies that the educational level of women, history of pregnancy, distance to the nearby health institution, and awareness of obstetrics complications were the factors associated with awareness of reproductive age women on obstetrics fistula. Hence, increasing awareness on obstetric fistula plays a key role in averting this problem.

PMID:34526056 | DOI:10.1186/s12978-021-01228-2

J Neuroinflammation. 2021 Sep 15;18(1):200. doi: 10.1186/s12974-021-02245-5.

ABSTRACT

BACKGROUND: Treatment-resistant depression (TRD) and pain frequently coexist clinically. Ketamine has analgesic and antidepressant effects, but few studies have evaluated individual differences in antidepressant outcomes to repeated ketamine in TRD patients with comorbid pain. Our aims were to determine the difference in ketamine’s antidepressant effects in TRD patients with or without pain and then to examine whether inflammatory cytokines might contribute to ketamine’s effect.

METHODS: Sixty-six patients with TRD received six infusions of ketamine. Plasma levels of 19 inflammatory cytokines were assessed at baseline and post-infusion (day 13 and day 26) using the Luminex assay. Plasma inflammatory cytokines of sixty healthy controls (HCs) were also examined.

RESULTS: TRD patients with pain had a higher antidepressant response rate (χ² = 4.062, P = 0.044) and remission rate (χ² = 4.062, P = 0.044) than patients without pain. Before ketamine treatment, GM-CSF and IL-6 levels were higher in the pain group than in the non-pain and HC groups. In the pain group, levels of TNF-α and IL-6 at day 13 and GM-CSF, fractalkine, IFN-γ, IL-10, MIP-3α, IL-12P70, IL-17α, IL-1β, IL-2, IL-4, IL-23, IL-5, IL-6, IL-7, MIP-1β, and TNF-α at day 26 were lower than those at baseline; in the non-pain group, TNF-α levels at day 13 and day 26 were lower than those at baseline. In the pain group, the changes of IL-6 were associated with improvement in pain intensity (β = 0.333, P = 0.001) and depressive symptoms (β = 0.478, P = 0.005) at day 13. Path analysis showed the direct (β = 2.995, P = 0.028) and indirect (β = 0.867, P = 0.042) effects of changes of IL-6 on improvement in depressive symptoms both were statistically significant.

CONCLUSION: This study suggested that an elevated inflammatory response plays a critical role in individual differences in TRD patients with or without pain. Ketamine showed great antidepressant and analgesic effects in TRD patients with pain, which may be related to its effects on modulating inflammation.

TRIAL REGISTRATION: ChiCTR , ChiCTR-OOC-17012239. Registered on 26 May 2017.

PMID:34526064 | DOI:10.1186/s12974-021-02245-5

J Orthop Surg Res. 2021 Sep 15;16(1):558. doi: 10.1186/s13018-021-02695-w.

ABSTRACT

PURPOSE: The aim of this study was to investigate the effect of clozapine use on bone tissue by applying computerized tomography, dual-energy X-ray absorptiometry, and histological and biomechanical analyses in an experimental rat model.

METHODS: Sixteen female Wistar Albino rats were included in this study. These animals were divided into two groups: the control group and the clozapine group. The animals in the clozapine group received 10 mg/kg clozapine, and the animals in the control group received tap water by oral gavage daily for 28 days. After sacrification, the femurs of the rats were used for radiologic, histologic, dual-energy X-ray absorptiometry, and biomechanical evaluations.

RESULTS: Although the mean values of the clozapine group were higher in terms of histological, bone mineral density, and biomechanical evaluations, the statistical analyses were not significantly different.

CONCLUSION: Clozapine use did not affect bone density in the rats. Clozapine can be the preferred treatment for patients with schizophrenia to avoid osteoporosis. It will be necessary to conduct further long-term follow-up and controlled studies in animals and humans to confirm these findings.

PMID:34526046 | DOI:10.1186/s13018-021-02695-w

Head Face Med. 2021 Sep 15;17(1):41. doi: 10.1186/s13005-021-00290-2.

ABSTRACT

BACKGROUND: Orbital decompression surgery is frequently the last therapeutic measure in the surgical treatment of endocrine orbitopathy (EO). Additional rehabilitative and corrective surgical treatments are often used to improve the resulting eyelid stigmata, such as an increased lid aperture and scleral show. The aim of the study was to evaluate the effect of adjunctive surgical procedures after orbital decompression surgery in patients with EO.

METHODS: A total of 120 orbitae from 65 patients with EO from 2010 to 2020 at a tertiary care center in Germany were retrospectively evaluated. Ocular surface area (OSA) and vertical palpebral fissures were three-dimensionally analyzed at the following stages: presurgical decompression, postsurgical decompression, and post-adjunctive surgical procedures. For the analysis of vertical palpebral fissures, predefined vertical line distances were measured on the upper and lower lids in the central, medial, and lateral pupillary regions.

RESULTS: The initial OSA was 2,98 ± 0.85 cm², and it decreased significantly after decompression surgery to 2.52 ± 0.62 cm². After adjunct surgical procedures, OSA further decreased to 2,31 ± 0,55 cm². Furthermore, a statistically significant reduction in all pupillary parameters was noted after each treatment step. More lid-lengthening procedures were performed on the lower lid than on the upper lid. Canthoplasty (n = 13) was the most frequently performed procedure during rehabilitation.

CONCLUSION: Surgical decompression surgery improves OSA and leads to a significant reduction in lid aperture. Adjunctive surgical procedures, addressing the upper and lower lid, have a significant influence on the ongoing clinical course and contribute to a reduction in OSA.

PMID:34526052 | DOI:10.1186/s13005-021-00290-2

Int Breastfeed J. 2021 Sep 15;16(1):69. doi: 10.1186/s13006-021-00413-0.

ABSTRACT

BACKGROUND: Prenatal medical risk describes physical health issues or biological factors that predate or arise during pregnancy which heighten the risk of adverse outcomes, and often warrant specialized obstetric care. The influence of the nature and magnitude of prenatal risk on breastfeeding outcomes remains poorly understood. The objective of this study was to determine the association between prenatal medical risk and breastfeeding initiation and duration up to 1 year postpartum.

METHODS: We analysed a subset of data from the All Our Families longitudinal cohort (n = 2706) of women in Calgary, Canada who delivered a liveborn infant between 2008 and 2010. Data were collected from self-report questionnaires and medical records. Women with complete data on prenatal medical risk factors and breastfeeding outcomes were included in this analysis. Prenatal medical risk was operationalized as one integer score of risk severity and four binary risk types capturing pre-pregnancy characteristics, past obstetric problems, current obstetric problems, and substance use. Outcomes were breastfeeding initiation defined as the infant ever receiving breast milk, and duration operationalized as still breastfeeding at 4 months, at 12 months, and time to breastfeeding cessation in weeks. We used logistic regression and Cox regression with right censoring at 52 weeks or attrition to calculate odds ratios (OR) and hazard ratios (HR), respectively, adjusting for sociodemographic vulnerability, parity, mode of delivery, and gestational age.

RESULTS: Prenatal medical risk severity and type were not significantly associated with breastfeeding initiation, with the exception of pre-pregnancy risk type (OR 0.45; 95% CI 0.26, 0.77). Risk severity was associated with lower odds of breastfeeding to 4 months (OR 0.94; 95% CI 0.90, 0.99), 12 months (OR 0.93; 95% CI 0.87, 0.98), and earlier breastfeeding cessation (HR 1.05; 95% CI 1.02, 1.08). Associations with shorter breastfeeding length across the first postpartum year were observed for pre-pregnancy, current obstetric, and substance use risk types, but not past obstetric problems.

CONCLUSION: Prenatal medical risk is associated with shortened duration of breastfeeding. Women with prenatal medical risk may benefit from the proactive arrangement of lactation support before and following delivery to promote continued breastfeeding.

PMID:34526043 | DOI:10.1186/s13006-021-00413-0

Infect Agent Cancer. 2021 Sep 15;16(1):60. doi: 10.1186/s13027-021-00400-4.

ABSTRACT

INTRODUCTION: We evaluated several biological indicators based on inflammation and/or nutritional status, such as systemic immune-inflammation index (SII), early warning score (ANDC) and prognostic nutritional index (PNI) in hospitalized COVID-19 patients with and without malignancies for a prognostic significance.

METHODOLOGY: This is a retrospective and observational study on 186 patients with SARS-CoV-2, who were diagnosed with COVID-19 by real-time PCR testing and hospitalized due to COVID-19 pneumonia. 75 patients had various malignancies, and the rest (111), having a similar age and comorbidity profile based on propensity score matching, had no malignancy.

RESULTS: None of the measures as neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, monocyte to lymphocyte ratio, SII, PNI or ANDC was found to be significantly different between two groups. Odds ratio for the mortality, OR 2.39 (%95 CI 1.80-3.16) was found to be significantly higher for the malignancy group, even though the duration of hospitalization was statistically similar for both groups. PNI was found to be significantly lower for deceased patients compared with survivors in the malignancy group. Contrarily, ANDC was found to be significantly higher for deceased patients in the malignancy group.

CONCLUSIONS: PNI and ANDC have independent predictive power on determining the in-hospital death in COVID-19 malignancy cases. It is suggested that ANDC seems to be a more sensitive score than SII in COVID-19 cases with malignancies.

PMID:34526045 | DOI:10.1186/s13027-021-00400-4

BMC Med. 2021 Sep 16;19(1):214. doi: 10.1186/s12916-021-02069-3.

ABSTRACT

BACKGROUND: Studies on allergy-related diseases in relation to abdominal pain-related functional gastrointestinal disorders (AP-FGIDs) in children are few and results are contradictory. We examined the associations between childhood allergy-related diseases and adolescent AP-FGIDs in general and irritable bowel syndrome (IBS) in particular.

METHOD: Prospective population-based birth cohort study of 4089 children born in Sweden 1994-1996. We analysed data from 2949 children with complete follow-up at 16 years (y) and no diagnosis of inflammatory bowel disease or coeliac disease at 12y or 16y. Asthma, rhinitis, eczema, and food hypersensitivity (FH) were assessed through questionnaires at 1-2y, 4y, 8y, 12y, and 16y. AP-FGIDs and IBS were assessed through questionnaires at 16y and defined according to the Rome III criteria. Associations between childhood allergy-related diseases and any AP-FGID and IBS and 16y respectively were examined using binomial generalized linear models with a log link function and described as relative risk with 95% confidence intervals.

RESULTS: The prevalence of any AP-FGID and IBS at 16y were 12.0% and 6.0% respectively. Eczema at 1-2y, 4y, and 8y, and FH at 12y and 16y were associated with an increased risk for any AP-FGID at 16y. Asthma and FH at 12y and 16y were associated with an increased risk for IBS at 16y. The relative risk for IBS at 16y increased with increasing number of concurrent allergy-related diseases at 16y, but linear trend for relative risk was only borderline statistically significant (P for trend = 0.05).

CONCLUSIONS: This prospective population-based study demonstrated positive associations between childhood allergy-related diseases and adolescent AP-FGIDs, including IBS, implicating shared pathophysiology among these disorders.

PMID:34526042 | DOI:10.1186/s12916-021-02069-3