Category: Statistics

Orphanet J Rare Dis. 2023 Jul 24;18(1):209. doi: 10.1186/s13023-023-02803-5.

ABSTRACT

BACKGROUND: Agalsidase beta, an enzyme replacement therapy for Fabry disease, is dosed biweekly at 1 mg/kg body weight, with increasing infusion rates based on tolerability. The US label specifies ≥ 90-min infusions for all patients; the US and EU labels require ≤ 15 mg/hr infusions in patients < 30 kg. The Japanese label allows infusions up to 30 mg/hr, allowing < 90-min dosing for some patients weighing < 45 kg. Japanese post-marketing data were analyzed for rate of infusion-associated reactions (IARs), adverse events (AEs), and serious AEs (SAEs) based on infusion rate and patient attributes (weight, antibody status).

RESULTS: Data were available for 436 reduced-duration infusions (< 90 min) and 2242 standard infusions (≥ 90 min). SAEs were rare (0.6%), and the frequency of all safety events decreased over the treatment course. Little impact of infusion duration on safety outcomes was observed: IARs and AEs were numerically more common when infusion duration was ≥ 90 min compared to < 90 min (IARs: 2.0% vs 0.9%; AEs: 2.9% vs 1.4%), while the rate of SAEs was similar (0.4% vs 0.5%). IAR, AE, and SAE frequencies decreased significantly with increasing infusion rates, and this trend was consistent in patients < 30 kg. Safety events tended to be less frequent in patients < 30 kg vs those ≥ 30 kg (IARs: 1.8% vs 2.1%; AEs: 2.3% vs 3.6%; SAEs: 0.0% vs 0.6%), although the differences were not statistically significant. IARs occurred in < 1% of all infusions in the < 30 kg group, 84% of which were < 90 min. More anti-agalsidase beta antibody-positive patients experienced IARs (41.9% vs 30.7%; P = 0.0445) and AEs (61.1% vs 49.3%; P = 0.0497) vs antibody-negative patients; however, there was no significant difference in the frequency of SAEs. In patients with available data, no changes in antibody status were observed after infusion durations were reduced to < 90 min.

CONCLUSIONS: The results of this post-hoc analysis demonstrated no significant impact of infusion duration on safety outcomes, and no significant difference in outcomes between patients of different weights. These findings suggest that infusion times in patients who are tolerating treatment can, with careful monitoring, be gradually decreased.

PMID:37488580 | DOI:10.1186/s13023-023-02803-5

BMC Psychiatry. 2023 Jul 24;23(1):534. doi: 10.1186/s12888-023-04685-0.

ABSTRACT

BACKGROUND: Depression is an important public health burden, its risk of occurrence is associated with vitamin D deficiency and may also increase with age, while serum vitamin D levels are closely related to age.

OBJECTIVE: The purpose of this study was to evaluate whether vitamin D and age are associated with depression after adjustment for each other.

MATERIALS AND METHODS: We extracted data from NHANES 2013-2018, including demographic characteristics, depression level, vitamin D level, physical activity, and body measures. A total of 15,156 adults aged 20 years or older (mean age 49.81 ± 17.67 years, 7301 males and 7855 females) were included. Depression was screened by PHQ-9. Vitamin D deficiency was defined by a serum vitamin D level < 30nmol/L. We performed binary logistic regression models to analyze the association between vitamin D, age and depression, respectively.

RESULTS: Vitamin D levels were negatively associated with depression (P < 0.001). Vitamin D had a significant effect on depression (OR = 0.776, 95%CI: 0.682-0.884, P < 0.001), the effect remained significant after adjusted for confounding variables (OR = 0.761, 95%CI: 0.663-0.874, P < 0.001). Age was positively associated with depression (P < 0.001) and had a significant effect on depression (OR = 1.079, 98%CI: 1.032-1.128, P = 0.001), the effect remained significant after adjusted for confounding variables (OR = 1.092, 95%CI: 1.040-1.146, P < 0.001). Age and vitamin D levels were positively correlated (P < 0.001), and older age had a significant effect on vitamin D level (OR = 1.526, 95%CI: 1.416-1.645, P < 0.001), the effect remained significant after adjusted for confounding variables (OR = 1.371, 95%CI: 1.263-1.487, P < 0.001). In addition, the prevalence of depression was higher in females (2312/7855, 29.43%) than in males (1571/7301, 21.52%), and the difference was statistically significant (P < 0.001).

CONCLUSIONS: Vitamin D deficiency and older age are both associated with higher risk of depression, while older age is a protective factor for vitamin D deficiency.

PMID:37488550 | DOI:10.1186/s12888-023-04685-0

BMC Public Health. 2023 Jul 24;23(1):1420. doi: 10.1186/s12889-023-16150-4.

ABSTRACT

BACKGROUND: The workplace can be affected negatively by hazardous alcohol use, and intervening at an early stage remains a challenge. Recently, a multi-component alcohol prevention program, Alcohol Policy and Managers’ skills Training (hereafter, ‘APMaT’), was delivered at the organizational level. In a previous outcome evaluation, APMaT appeared to be effective at the managerial level. The current study takes a step further by aiming to evaluate the effectiveness of APMaT in decreasing the alcohol risk level among employees.

METHODS: Data from 853 employees (control: n = 586; intervention: n = 267) were gathered through a cluster-randomized study. To analyze changes in the odds of hazardous alcohol use among employees, multilevel logistic regression was applied using group (control vs. intervention), time (baseline vs. 12-month follow-up), and the multiplicative interaction term (group × time) as the main predictors. The intervention effect was further adjusted for sociodemographic characteristics and policy awareness.

RESULTS: No statistically significant difference was observed in the odds of hazardous alcohol use, although employees in the intervention group showed a larger decrease compared to the control group. This remained even after adjusting for several factors, including the sociodemographic factors and policy awareness.

CONCLUSIONS: The findings are insufficient to determine the effectiveness of APMaT at the employee level at the current stage of the evaluation. Future studies should strive to identify issues with implementation processes in workplace-based alcohol interventions.

TRIAL REGISTRATION: The trial was retrospectively registered on 11/10/2019; ISCRTN ID: ISRCTN17250048.

PMID:37488547 | DOI:10.1186/s12889-023-16150-4

BMC Psychiatry. 2023 Jul 24;23(1):535. doi: 10.1186/s12888-023-04822-9.

ABSTRACT

BACKGROUND: Schizophrenia is a chronic, complex, and severe mental disorder and caregivers having knowledge about it can help improve patient adherence to treatment. This study aims to translate the Knowledge About Schizophrenia Test (KAST) into a Chinese Mandarin version and test it among caregivers to validate its reliability and reproducibility, as well as to determine its associated sociodemographic factors and clinical factors.

METHODS: The project surveyed 160 patients with schizophrenia and their caregivers at four community health facilities in Beijing, China, from January 2022 to February 2022. All patients and caregivers completed the sociodemographic questionnaire, and caregivers also completed the Chinese-version KAST, and 143 of these caregivers completed the Chinese-version KAST again 2-4 weeks later.

RESULTS: The mean (SD) of the caregiver score was 11.49 (± 3.13). After item analysis, there was acceptable internal consistency among the 17 items in the Chinese version (KR-20 coefficient 0.702). The intraclass correlation coefficient in the retest (0.686) was statistically significant. Gender, educational attainment, marital status, relationship with the patient, and occupational status were associated with the KAST score.

CONCLUSION: The findings demonstrate that the Chinese-version KAST is a reliable and reproducible instrument that can measure knowledge about schizophrenia and is valid to be applied in schizophrenia research.

PMID:37488539 | DOI:10.1186/s12888-023-04822-9

BMC Psychiatry. 2023 Jul 24;23(1):531. doi: 10.1186/s12888-023-04912-8.

ABSTRACT

OBJECTIVE: The aim was to determine the prevalence of depressive disorder and associated psychological factors among adolescents living with HIV/AIDS.

METHODS: One hundred and five adolescents with HIV were assessed for self-esteem, internalized HIV stigma and diagnosed of depressive disorder. Chi square and t tests were used to test associations and hierarchical logistic regression used to identify independent risk factors for depression.

RESULTS: The mean age of participants was 16.5 (± 1.97) years and 55.2% were males. Mean stigma scores were significantly higher in those with depressive disorder (16.53 ± 3.85) when compared with those without (13.42 ± 3.464) and this difference was statistically significant (t = 3.17, p = 0.01). The mean self-esteem scores were significantly lower in participants with depressive disorder (17.53 ± 4.69) compared to those without depressive disorder (19.71 ± 3.86), though not significant (t = 1.96, p = 0.053). Depressive disorder was further significantly associated with female sex, being in romantic relationship, decline in work output due to HIV and HIV stigma. Independent risk factors were sex and HIV stigma.

CONCLUSION: Depressive disorder is common among adolescents living with HIV infection in Nigeria. The association between HIV stigma and depression, thus suggests the need for prevention strategies targeting the impacts of HIV infection among adolescents.

PMID:37488523 | DOI:10.1186/s12888-023-04912-8

BMC Psychiatry. 2023 Jul 24;23(1):533. doi: 10.1186/s12888-023-05015-0.

ABSTRACT

BACKGROUND: In Uganda, cognitive impairment in older persons aged ≥ 60 years is often undiagnosed due to inadequate appreciation of the condition compounded with limitations of trained human resource able to conduct appropriate cognitive evaluations. Use of Community Health Workers (CHWs) especially in hard-to-reach communities can be an important link for older persons to the health facilities where they can receive adequate evaluations and interventions for cognitive challenges. The aim of the study was to assess the feasibility of screening for cognitive impairment among older persons and referral by CHWs in Wakiso district, Uganda.

METHODS: This was a sequential explanatory mixed methods study. The CHWs received a one-day training on causes, signs and symptoms, and management of cognitive impairment and screened older persons ≥ 60 years for cognitive impairment using the Alzheimer’s Disease scale 8 (AD8). Psychiatric clinical officers (PCOs) administered the AD8 and the Mini Mental State Examination to the older persons after assessment by the CHWs who then referred them for appropriate clinical care. We conducted Kappa statistic for agreement between the CHWs and PCOs and compared raw scores of the CHWs to Experts scores using Bland Altman and pair plots and corresponding analyses. We also conducted focus group discussions for the older persons, caregivers and CHWs.

RESULTS: We collected data from 385 older persons. We involved 12 CHWs and 75% were females, majority were married (58.3%) with at least a secondary education (66.7%). There was 96.4% (CI 94.5-98.2%) agreement between PCOs and CHWs in identifying cognitive impairment with the PCOs identifying 54/385 (14.0: 95%CI 10.7-17.9%) older persons compared to 58/385 (15.1: 95%CI 11.6-19.0%) identified by CHWs. Of the 58 identified to have cognitive impairment by the CHWs, 93.1% were referred for care. The average difference between the score of the expert and that of the CHW was – 0.042 with a 95% CI of -1.335 to 1.252. Corresponding Bland Altman and pair plots showed high agreement between the measurements although CHWs scored higher values with increasing scores.

CONCLUSION: CHWs can be trained to identify and refer older persons with cognitive impairment in the communities.

PMID:37488506 | DOI:10.1186/s12888-023-05015-0

BMC Pregnancy Childbirth. 2023 Jul 24;23(1):535. doi: 10.1186/s12884-023-05840-x.

ABSTRACT

BACKGROUND: International and national New Zealand (NZ) research has identified women of South Asian ethnicity at increased risk of perinatal mortality, in particular stillbirth, with calls for increased perinatal research among this ethnic group. We aimed to analyse differences in pregnancy outcomes and associated risk factors between South Asian, Māori, Pacific and NZ European women in Aotearoa NZ, with a focus on women of South Asian ethnicity, to ultimately understand the distinctive pathways leading to adverse events.

METHODS: Clinical data from perinatal deaths between 2008 and 2017 were provided by the NZ Perinatal and Maternal Mortality Review Committee, while national maternity and neonatal data, and singleton birth records from the same decade, were linked using the Statistics NZ Integrated Data Infrastructure for all births. Pregnancy outcomes and risk factors for stillbirth and neonatal death were compared between ethnicities with adjustment for pre-specified risk factors.

RESULTS: Women of South Asian ethnicity were at increased risk of stillbirth (aOR 1.51, 95%CI 1.29-1.77), and neonatal death (aOR 1.51, 95%CI 1.17-1.92), compared with NZ European. The highest perinatal related mortality rates among South Asian women were between 20-23 weeks gestation (between 0.8 and 1.3/1,000 ongoing pregnancies; p < 0.01 compared with NZ European) and at term, although differences by ethnicity at term were not apparent until ≥ 41 weeks (p < 0.01). No major differences in commonly described risk factors for stillbirth and neonatal death were observed between ethnicities. Among perinatal deaths, South Asian women were overrepresented in a range of metabolic-related disorders, such as gestational diabetes, pre-existing thyroid disease, or maternal red blood cell disorders (all p < 0.05 compared with NZ European).

CONCLUSIONS: Consistent with previous reports, women of South Asian ethnicity in Aotearoa NZ were at increased risk of stillbirth and neonatal death compared with NZ European women, although only at extremely preterm (< 24 weeks) and post-term (≥ 41 weeks) gestations. While there were no major differences in established risk factors for stillbirth and neonatal death by ethnicity, metabolic-related factors were more common among South Asian women, which may contribute to adverse pregnancy outcomes in this ethnic group.

PMID:37488505 | DOI:10.1186/s12884-023-05840-x

BMC Cancer. 2023 Jul 24;23(1):693. doi: 10.1186/s12885-023-10981-5.

ABSTRACT

BACKGROUND: Radiation therapy (XRT) causes numerous biological changes in tumor microenvironment. Radiation vascular response, due to endothelial disruption, can influence treatment outcomes in a dose-dependent manner. Ultrasound-stimulated microbubbles (USMB) have also been demonstrated to create a vascular response in the tumor microenvironment and enhance tumor response when used in combination with XRT. Single doses of 8-10 Gy are known to induce activation of acid sphingomyelinase (ASMase)-induced ceramide production, causing vascular damage. Destruction of vasculature results in endothelial apoptosis followed by tumor cell death. The effect of tumor response is known to be synergistic by 10-fold higher cell kill observed when USMB is combined with radiation.

METHODS: In this study, we used an USMB approach in combination with conventional low dose fractionated radiation to enhance endothelial cell responses to XRT in human PC3 prostate cancer xenograft model. Mice were divided into untreated, USMB therapy, fractionated XRT, and combined USMB therapy followed by XRT (USMB + XRT) groups. USMB therapy was delivered twice per week in the USMB-alone and combined USMB + XRT treatment groups over four weeks. Radiation treatments were delivered in fractions of 2 Gy/day (total 40 Gy in 20 fractions, BED₁₀ = 48 Gy) in the XRT-alone and combined USMB + XRT groups. The treatment outcome was evaluated using histopathology, power Doppler, and immunohistochemistry assays.

RESULTS: Tumor growth assessment showed that sizes of tumors increased in the control and the single treatment groups over a treatment period of four weeks, but significantly decreased with the combined treatments of USMB + XRT. Immunohistochemical analysis indicated a statistically significant vascular disruption in mice that received treatment involving a full 4-week schedule of combined (USMB + XRT) treatments. A statistically significant increase in vascular disruption was demonstrated through CD68 and trichrome fibrosis staining. Changes in local perfusion assessed using high-frequency power Doppler imaging demonstrated attenuated blood flow in the combined group.

DISCUSSION AND CONCLUSIONS: This work demonstrates the efficacy of using USMB as a radiation sensitizer in a mouse model of human PC3 tumor xenograft. This radiation treatment enhancement modality has the advantage of targeting tumor vasculature with ultrasound stimulation that can be implemented prior to radiation treatment.

PMID:37488490 | DOI:10.1186/s12885-023-10981-5

Tissue Cell. 2023 Jul 13;84:102162. doi: 10.1016/j.tice.2023.102162. Online ahead of print.

ABSTRACT

Peripheral nerve injury is one of the common disabling clinical conditions and around 50% of the cases end up in permanent impairment. Due to the lack of effective treatment options regenerative medicine employing stem cells is being evaluated. The presented study evaluated and compared regeneration potential of mesenchymal stem cells (MSCs) derived from bone marrow (BM) and adipose tissue (AD) in acute rabbit sciatic nerve injury (axonotmesis) model. A total of n = 54 grey giant rabbits were made subject of the study and divided equally into 3 groups: Control, BM-MSCs in Collagen I and AD-MSCs in Collagen I as per the treatment given. Iliac crest BM and omental AD was harvested from the same donor for isolation and culture of MSCs. The repair of sciatic nerve injury was evaluated on days 60 and 90. The clinical and histopathological scores and SEM morphology was better in cell treated groups as compared to the control. Morphology and histological studies revealed injured nerve in different levels of regenerative process. Gene expression was more than double for N-Cadherin in cell treated groups as compared to the control, especially at day 60. Between cell treated groups, BM-MSCs group showed better response as compared to the AD-MSCs, although statistically non-significant (p > 0.05). Incomplete nerve regeneration observed under various diagnostic parameters was in compliance to the incomplete clinical recovery at day 90. It was concluded that MSCs may improve sciatic nerve healing but fall short of complete regeneration at day 90, although BM-MSCs may have an edge over AD-MSCs.

PMID:37487256 | DOI:10.1016/j.tice.2023.102162

Retina. 2023 Jul 17. doi: 10.1097/IAE.0000000000003896. Online ahead of print.

ABSTRACT

PURPOSE: To study the status of retinal pigment epithelium (RPE) in non-exudative and active choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nAMD).

METHODS: Only treatment-naïve nAMD patients were enrolled in this prospective case-control study, including 17 eyes with non-exudative CNV (six males and 11 females, 74.9 ± 10.0 years) and 28 eyes with active CNV (eight males and 20 females, 69.3 ± 6.8 years). All patients received a comprehensive ophthalmic examination, optical coherence tomography (OCT), dark-field scanning laser ophthalmoscopy (DF-SLO), and fundus autofluorescence (FAF). The status of RPE was assessed with ImageJ software as the brightness of the CNV region on transillumination OCT, DF-SLO, and FAF images. CNV vessel density was measured based on OCT angiography.

RESULTS: The brightness of CNV region in non-exudative CNV was statistically significantly lower than in active CNV with both OCT transillumination (p = 0.004) and DF-SLO (p = 0.0015). No difference in brightness of CNV region between non-exudative and active CNV was found based on FAF (p = 0.44). The vessel density of non-exudative CNV was statistically significantly higher than that of active CNV with a median value of 64.5% (95% confidential interval (CI) 53.4 – 79.0 %) and 55.3% (95% CI 52.2 – 60.0%), respectively (p = 0.05).

CONCLUSION: Multimodal imaging revealed substantial alteration of RPE in active CNV but not in non-exudative CNV which correlates with the higher vessel density of non-exudative CNV.

PMID:37487237 | DOI:10.1097/IAE.0000000000003896