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Does clozapine really affect bone mineral density? An experimental study

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

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Eyes wide shut: necessity and effect of adjunctive procedures after decompression surgery in patients with endocrine orbitopathy

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

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Comparison of systemic immune-inflammation index (SII), early warning score (ANDC) and prognostic nutritional index (PNI) in hospitalized patients with malignancy, and their influence on mortality from COVID-19

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

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Association of prenatal medical risk with breastfeeding outcomes up to 12 months in the All Our Families community-based birth cohort

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

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Allergy-related diseases in childhood and risk for abdominal pain-related functional gastrointestinal disorders at 16 years-a birth cohort study

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

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A comparison of meta-analysis results with and without adjustment for healthy worker effect: cancer mortality among workers in the semiconductor industry

Epidemiol Health. 2021 Sep 8:e2021057. doi: 10.4178/epih.e2021057. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare meta-analysis results with and without adjustment for healthy worker effect on the association between working in the semiconductor industry and cancer mortality.

METHODS: A total of six studies that reported standardized mortality ratios (SMRs) for cancers were selected for meta-analysis. The SMR results from individual study were combined for all cancers, leukemia and lymphoma to estimate the summary SMRs and 95% confidence intervals (CIs) with random-effects model. To adjust for healthy worker effect, the relative SMRs (rSMR=SMRx/SMRnot x) were calculated using observed and expected counts for the specific cause of interest (i.e., all cancers and leukemia) and observed and expected counts for all the other causes of mortality. Then, the rSMR results were combined to estimate the summary rSMRs and 95% confidence intervals.

RESULTS: The SMRs for all causes among semiconductor industry workers ranged from 0.25 to 0.80, which reflects significant healthy worker effects. Remarkable difference was found between the summary SMRs and the summary rSMRs. The summary SMR for all cancers was 0.70 (95% CI=0.63-0.79) whereas the summary rSMR was 1.38 (1.20-1.59). The summary SMR for leukemia was 0.88 (0.72-1.08), and the summary rSMR was 1.38 (1.20-1.59).

CONCLUSION: Our results suggest that the adjustment for the healthy worker effect (i.e., rSMR) may be useful in meta-analyses of cohort studies reporting SMRs.

PMID:34525505 | DOI:10.4178/epih.e2021057

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Microneedling-assisted topical tranexamic acid solution versus 4% hydroquinone for treating melasma: A split-face randomized study

J Cosmet Dermatol. 2021 Sep 15. doi: 10.1111/jocd.14440. Online ahead of print.

ABSTRACT

BACKGROUND: Melasma, also known as chloasma or mask of pregnancy, is a common, acquired, hyperpigmentary disorder usually affecting females. Tranexamic acid (TA), a derivative of amino acid lysine, has shown promising results over the past few years when used along with other therapies and when used as a stand-alone therapy.

AIM OF THE WORK: In this study, we aimed to evaluate and compare the effectiveness of topically applied tranexamic acid after microneedling versus topically applied hydroquinone (HQ) 4% alone in patients with melasma.

PATIENTS AND METHODS: Fifty selected patients were divided randomly according to the random number allocation method into two groups (25 patients each) of A (topical 4% hydroquinone, nightly application) and B (microneedling + topical 4% TA, every other week).

RESULTS: After eight weeks of treatment, the mean modified MASI score of the HQ treated side changed from 6.604 ± 4.02 to 3.032 ± 1.19 with a mean decrease percentage of 54.8% ± 19.4%. This reduction in modified MASI score was found to be statistically significant, (p < 0.001). MASI score of group B (TA +microneedling) changed from 6.348 ± 3.84 to 3.712 ± 1.19 with mean decrease percentage of 57.4% ± 23.4% which was also statistically significant, (p < 0.001).

CONCLUSION: We demonstrated safety and efficacy of both used modalities and with minimal side effects. Topical HQ application achieved minimal non-significant higher satisfactory results among raters and subjects.

PMID:34525492 | DOI:10.1111/jocd.14440

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Pain and mortality among older adults in Korea

Epidemiol Health. 2021 Sep 7:e2021058. doi: 10.4178/epih.e2021058. Online ahead of print.

ABSTRACT

OBJECTIVES: With the rising elderly population subject to chronic disease, pain becomes crucial to understand and design an appropriate approach to it. While pain is a noted mortality risk factor, limited studies exists due to various causes of pain and subjectivity of pain expression. This study aims to examine the relationship between pain and mortality, controlling for other disease and socio-cultural factors.

METHODS: We used 6,258 community-dwelling individuals aged 45 years or older – population with highest prevalence of pain, using the Korean Longitudinal Study of Aging (2006-2016) data and the Cox proportional-hazards model. Further subgroup analyses were conducted by gender and education level to examine differences in the relationship between pain and mortality.

RESULTS: The adjusted hazard ratios of mortality were 1.16 (95%CI: 1.00-1.34, Model 1) and 1.12 (95%CI: 0.97-1.29, Model 2) for the individuals in pain depending on the models used, where additional socio-cultural factors were accounted for in Model 2. Importantly, for individuals in severe pain, they were significantly higher with 1.23 (95%CI: 1.08-1.41, Model 1) and 1.16 (95%CI: 1.02-1.32, Model 2). Further subgroup analyses showed that while both male and more educated individuals were less likely to report pain, their severe pain were more associated with mortality, for example 1.29 (95%CI: 1.08-1.55, Model 2) for male and 1.62 (95%CI: 1.15-2.28, Model 2) for more educated individuals.

CONCLUSION: Pain showed a statistically significant relationship with the mortality risk. Family members or medical staff need to pay proper attention to it, especially severe pain from male and highly educated individuals.

PMID:34525504 | DOI:10.4178/epih.e2021058

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Autopsy-Based Pulmonary and Vascular Pathology: Pulmonary Endotheliitis and Multi-Organ Involvement in COVID-19 Associated Deaths

Respiration. 2021 Sep 15:1-11. doi: 10.1159/000518914. Online ahead of print.

ABSTRACT

BACKGROUND: Findings from autopsies have provided evidence on systemic microvascular damage as one of the underlying mechanisms of Coronavirus disease 2019 (CO-VID-19). The aim of this study was to correlate autopsy-based cause of death in SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients with chest imaging and severity grade of pulmonary and systemic morphological vascular pathology.

METHODS: Fifteen SARS-CoV-2 positive autopsies with clinically distinct presentations (age 22-89 years) were retrospectively analyzed with focus on vascular, thromboembolic, and ischemic changes in pulmonary and in extrapulmonary sites. Eight patients died due to COVID-19 associated respiratory failure with diffuse alveolar damage in various stages and/or multi-organ failure, whereas other reasons such as cardiac decompensation, complication of malignant tumors, or septic shock were the cause of death in 7 further patients. The severity of gross and histopathological changes was semi-quantitatively scored as 0 (absent), 1 (mild), and 3 (severe). Severity scores between the 2 groups were correlated with selected clinical parameters, initial chest imaging, autopsy-based cause of death, and compared using Pearson χ2 and Mann-Whitney U tests.

RESULTS: Severe pulmonary endotheliitis (p = 0.031, p = 0.029) and multi-organ involvement (p = 0.026, p = 0.006) correlated significantly with COVID-19 associated death. Pulmonary microthrombi showed limited statistical correlation, while tissue necrosis, gross pulmonary embolism, and bacterial superinfection did not differentiate the 2 study groups. Chest imaging at hospital admission did not differ either.

CONCLUSIONS: Extensive pulmonary endotheliitis and multi-organ involvement are characteristic autopsy features in fatal CO-VID-19 associated deaths. Thromboembolic and ischemic events and bacterial superinfections occur frequently in SARS-CoV-2 infection independently of outcome.

PMID:34525475 | DOI:10.1159/000518914

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Rapid Risk Stratification of Acute Ischemic Stroke Patients in the Emergency Department: The Incremental Prognostic Role of Left Atrial Reservoir Strain

J Stroke Cerebrovasc Dis. 2021 Sep 12;30(11):106100. doi: 10.1016/j.jstrokecerebrovasdis.2021.106100. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine the prognostic value of positive global left atrial strain (LA-GSA+), measured by two-dimensional speckle tracking echocardiography (2D-STE) in a population of acute ischemic stroke (AIS) patients without atrial fibrillation (AF), in the setting of Emergency Department (ED).

METHODS: All consecutive AIS patients with sinus rhythm on ECG and without AF history entered this prospective study. All patients underwent complete blood tests and transthoracic echocardiography implemented with 2D-STE analysis of LA strain parameters within 6-12 h after symptoms onset. At 6-months follow-up, we evaluated the composite endpoint of all-cause mortality plus cardiovascular re-hospitalizations.

RESULTS: A total of 102 AIS patients (76.4 ± 10.8 yrs, 47% males) were prospectively included. LA-GSA+ was markedly reduced in AIS patients (20.8 ± 7.7%), without any statistically significant difference between the stroke subtypes. At 6-months follow-up, 7 deaths and 27 re-hospitalizations occurred. On multivariate Cox regression analysis, variables independently associated with outcome were: LA-GSA+ (per unit) (HR 0.29, 95% CI 0.19-0.39) and C-reactive protein (CRP) (per 0.1 mg/dl) (HR 1.45, 95% CI 1.15-1.75) as continuous variables; statin therapy (HR 0.45, 95%CI 0.28-0.62), and type 2 diabetes (HR 1.65, 95% CI 1.15-2.35) as categorical variables. A LA-GSA+ ≤20.0% predicted the occurrence of the above-mentioned outcome at 6-months follow-up with 94% sensitivity and 81% specificity (AUC=0.84). Interestingly, GSA+ showed a strong inverse correlation with CRP levels (r = -0.86).

CONCLUSIONS: A LA-GSA+ ≤20% reflects a more advanced atrial cardiomyopathy and might provide a rapid and reliable prognostic risk stratification of AIS patients without AF history in the setting of ED.

PMID:34525440 | DOI:10.1016/j.jstrokecerebrovasdis.2021.106100