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Care Burden and Coping Strategies among Caregivers of Paediatric HIV/AIDS in Northern Uganda: A Cross-Sectional Mixed-Method Study
Background. Family caregivers provide the bulk of care to children living with HIV. This places an enormous demand and care burden on the caregivers who often struggle to cope in various ways, some of which may be maladaptive. This may adversely affect their quality of care. Very little literature exists in resource-limited contexts on the burden of care experienced by caregivers on whom children living with HIV/AIDS depend for their long-term care. We assessed care burden and coping strategies among the caregivers of paediatric HIV/AIDS patients in Lira district, northern Uganda. Methods. A mixed-method cross-sectional study was conducted among 113 caregivers of paediatric HIV patients attending the ART clinic at a tertiary healthcare facility in Lira district, northern Uganda. A consecutive sampling method was used to select participants for the quantitative study, while 15 respondents were purposively sampled for the qualitative data. Quantitative data were collected using standard interviewer-administered questionnaires, while in-depth interview guides were used to collect qualitative data. Data were entered, cleaned, and analysed using SPSS version 23. Qualitative data were analysed thematically. Results. The majority of the caregivers, 65.5% (74), experienced mild-to-moderate burden. The mean burden scores significantly differed by caregivers’ age (), marital status (), average monthly income (), and child’s school attendance (). Accepting social support, seeking spiritual support, and reframing were the three most commonly used strategies for coping. Marital status and occupation were, respectively, positively and negatively correlated with information-seeking as a coping strategy, while monthly income was positively correlated with psychosocial support as a strategy. Seeking community support was negatively correlated with the duration of the child’s care. Conclusions. Our findings show that care burden is a common problem among the caregivers of children living with HIV in the study context
A Multilayered Dural Repair Technique Using Duragen for Early Cranioplasty Following Decompressive Craniotomy
Decompressive craniotomy is a neurosurgical emergency procedure in which a large skull bone is removed and the dura matter is extensively opened. Duraplasty is required to avoid cerebrospinal fluid (CSF) leakage during the decompressive craniotomy. DuraGen® is a safe and effective type I collagen matrix graft, which is frequently used in decompressive craniotomy procedures. Since DuraGen® does not require labor-intensive suturing, the operative time is shortened by DuraGen® closure with sufficient tightness preventing CSF leakage. Recently, early cranioplasty is preferred to achieve efficient rehabilitation after decompressive craniotomy. Although evidence of efficacy and safety of DuraGen® has been increasing in the management of duraplasty, no reports have previously discussed the condition of DuraGen® during the second surgery (cranioplasty) at this early timing. DuraGen®-derived neodura develops a mature dura 1 year post its placement, and the neodura remain fragile at this early time point. A deconstructed fragile neodura may result in postoperative CSF leakage. Here, we illustrated a multilayered dural repair technique with DuraGen® to avoid disruption of the fragile neodura during early cranioplasty
Systematic Review Comparing the Effectiveness of Robotic verse Laparoscopic Liver Surgery in Colorectal Liver Metastasis (CRLM)
Introduction: Colorectal cancer (CRC) is the third most common cancer in the world. The liver is the most common site of metastasis with 15 to 25% of patients presenting with synchronous colorectal liver metastasis (CRLM). This study is aimed at evaluating the long- and short-term outcomes of laparoscopic and robotic CRLM surgery, and directly comparing their respective effectiveness. Methodology: A literature search was performed and all studies that reported on operative characteristics, oncological outcomes for CRLM, morbidity or mortality and cost-effectiveness on robotic or laparoscopic surgery were included. The study design was in keeping with the PRISMA guidelines. Results: From the initial 606 manuscripts identified, 19 studies were included in the final qualitative analysis. A total of 1340 patients with 1194 LLR (Laparoscopic Liver Resection) and 146 RLR (Robotic Liver Resection) cases were analysed. Within the LLR group, the average tumour size excised was 32.1 mm compared to the RLR group of 33.8 mm. The average operative time in the LLR was 193 min, CI of 95% (147.4 min to 238.6 min) compared to RLR 257 min, CI of 95% (201.5 min to 313.8 min) with a p-value < 0.0001. Estimated blood loss was lower in the RLR group (210 mL) compared with the LLR group (246 mL). Conclusion: Despite the higher operative cost, RLRs do not result in statistically better treatment outcomes, with the exception of lower estimated blood loss and excision of larger CRLMs. Operative time and total complication rate are significantly more favourable with LLRs. Our study has shown that robotic liver surgery is safe and feasible in well-selected patient
How Much Knowledge and Awareness of Faecal Incontinence Is There in Primary Care?
Faecal incontinence (FI) is a debilitating symptom with a likely underreported incidence in the general population. Postpartum or postmenopausal women are at increased risk of this. General Practitioners (GPs) have a vital role in screening patient groups with FI. Knowledge of the underlying diseases associated with FI is important for all clinicians who have contact with this patient group. An online questionnaire (Survey MonkeyTM, San Mateo, CA, USA) was sent to GPs in Wales and England through a deanery, social media and GP educational groups. Questions: A total of 250 participants completed the questionnaire—195 GPs and 55 GPSTs. Two-thirds had no coloproctology experience, but 70% had worked in obstetrics and gynaecology. In total, 70% had no formal FI training and 75% felt insufficiently informed about FI. A total of 80% felt that GPs need specific training on FI. A third of respondents used the 6-week postnatal check to assess maternal bowel function and most did not appreciate faecal urgency as a symptom. Patients should be asked about FI symptoms by GPs, particularly those populations at increased risk. Our GP survey participants were enthusiastic for more education on the treatment options and where to signpost patients with F
The establishment of a prognostic scoring model based on the new tumor immune microenvironment classification in acute myeloid leukemia
The high degree of heterogeneity brought great challenges to the diagnosis and treatment of acute myeloid leukemia (AML). Although several different AML prognostic scoring models have been proposed to assess the prognosis of patients, the accuracy still needs to be improved. As important components of the tumor microenvironment, immune cells played important roles in the physiological functions of tumors and had certain research value. Therefore, whether the tumor immune microenvironment (TIME) can be used to assess the prognosis of AML aroused our great interest.
Methods
The patients’ gene expression profile from 7 GEO databases was normalized after removing the batch effect. TIME cell components were explored through Xcell tools and then hierarchically clustered to establish TIME classification. Subsequently, a prognostic model was established by Lasso-Cox. Multiple GEO databases and the Cancer Genome Atlas dataset were employed to validate the prognostic performance of the model. Receiver operating characteristic (ROC) and the concordance index (C-index) were utilized to assess the prognostic efficacy.
Results
After analyzing the composition of TIME cells in AML, we found infiltration of ten types of cells with prognostic significance. Then using hierarchical clustering methods, we established a TIME classification system, which clustered all patients into three groups with distinct prognostic characteristics. Using the differential genes between the first and third groups in the TIME classification, we constructed a 121-gene prognostic model. The model successfully divided 1229 patients into the low and high groups which had obvious differences in prognosis. The high group with shorter overall survival had more patients older than 60 years and more poor-risk patients (both P< 0.001). Besides, the model can perform well in multiple datasets and could further stratify the cytogenetically normal AML patients and intermediate-risk AML population. Compared with the European Leukemia Net Risk Stratification System and other AML prognostic models, our model had the highest C-index and the largest AUC of the ROC curve, which demonstrated that our model had the best prognostic efficacy.
Conclusion
A prognostic model for AML based on the TIME classification was constructed in our study, which may provide a new strategy for precision treatment in AML
Dynamic changes of functional fitness, antibodies to SARS-CoV-2 and immunological indicators within 1 year after discharge in Chinese health care workers with severe COVID-19: a cohort study
Background
Few studies had described the health consequences of patients with coronavirus disease 2019 (COVID-19) especially in those with severe infections after discharge from hospital. Moreover, no research had reported the health consequences in health care workers (HCWs) with COVID-19 after discharge. We aimed to investigate the health consequences in HCWs with severe COVID-19 after discharge from hospital in Hubei Province, China.
Methods
We conducted an ambidirectional cohort study in “Rehabilitation Care Project for Medical Staff Infected with COVID-19” in China. The participants were asked to complete three physical examinations (including the tests of functional fitness, antibodies to SARS-CoV-2 and immunological indicators) at 153.4 (143.3, 164.8), 244.3 (232.4, 259.1), and 329.4 (319.4, 339.3) days after discharge, respectively. Mann-Whitney U test, Kruskal-Wallis test, t test, one-way ANOVA, χ2, and Fisher’s exact test were used to assess the variance between two or more groups where appropriate.
Results
Of 333 HCWs with severe COVID-19, the HCWs’ median age was 36.0 (31.0, 43.0) years, 257 (77%) were female, and 191 (57%) were nurses. Our research found that 70.4% (114/162), 48.9% (67/137), and 29.6% (37/125) of the HCWs with severe COVID-19 were considered to have not recovered their functional fitness in the first, second, and third functional fitness tests, respectively. The HCWs showed improvement in muscle strength, flexibility, and agility/dynamic balance after discharge in follow-up visits. The seropositivity of IgM (17.0% vs. 6.6%) and median titres of IgM (3.0 vs. 1.4) and IgG (60.3 vs. 45.3) in the third physical examination was higher than that in the first physical examination. In the third physical examination, there still were 42.1% and 45.9% of the HCWs had elevated levels of IL-6 and TNF-α, and 11.9% and 6.3% of the HCWs had decreased relative numbers of CD3+ T cells and CD4+ T cells.
Conclusion
The HCWs with severe COVID-19 showed improvement in functional fitness within 1 year after discharge, active intervention should be applied to help their recovery if necessary. It is of vital significance to continue monitoring the functional fitness, antibodies to SARS-CoV-2 and immunological indicators after 1 year of discharge from hospital in HCWs with severe COVID-1
Validity of observational evidence on putative risk and protective factors: appraisal of 3744 meta-analyses on 57 topics
The validity of observational studies and their meta-analyses is contested. Here, we aimed to appraise thousands of meta-analyses of observational studies using a pre-specified set of quantitative criteria that assess the significance, amount, consistency, and bias of the evidence. We also aimed to compare results from meta-analyses of observational studies against meta-analyses of randomized controlled trials (RCTs) and Mendelian randomization (MR) studies.
Methods
We retrieved from PubMed (last update, November 19, 2020) umbrella reviews including meta-analyses of observational studies assessing putative risk or protective factors, regardless of the nature of the exposure and health outcome. We extracted information on 7 quantitative criteria that reflect the level of statistical support, the amount of data, the consistency across different studies, and hints pointing to potential bias. These criteria were level of statistical significance (pre-categorized according to 10−6, 0.001, and 0.05 p-value thresholds), sample size, statistical significance for the largest study, 95% prediction intervals, between-study heterogeneity, and the results of tests for small study effects and for excess significance.
Results
3744 associations (in 57 umbrella reviews) assessed by a median number of 7 (interquartile range 4 to 11) observational studies were eligible. Most associations were statistically significant at P < 0.05 (61.1%, 2289/3744). Only 2.6% of associations had P < 10−6, ≥1000 cases (or ≥20,000 participants for continuous factors), P < 0.05 in the largest study, 95% prediction interval excluding the null, and no large between-study heterogeneity, small study effects, or excess significance. Across the 57 topics, large heterogeneity was observed in the proportion of associations fulfilling various quantitative criteria. The quantitative criteria were mostly independent from one another. Across 62 associations assessed in both RCTs and in observational studies, 37.1% had effect estimates in opposite directions and 43.5% had effect estimates differing beyond chance in the two designs. Across 94 comparisons assessed in both MR and observational studies, such discrepancies occurred in 30.8% and 54.7%, respectively
Impact of replacing sedentary behaviour with other movement behaviours on depression and anxiety symptoms: a prospective cohort study in the UK Biobank
Sedentary behaviour is potentially a modifiable risk factor for depression and anxiety disorders, but findings have been inconsistent. To assess the associations of sedentary behaviour with depression and anxiety symptoms and estimate the impact of replacing daily time spent in sedentary behaviours with sleep, light, or moderate to vigorous physical activity, using compositional data analysis methods.
Methods
We conducted a prospective cohort study in 60,235 UK Biobank participants (mean age: 56; 56% female). Exposure was baseline daily movement behaviours (accelerometer-assessed sedentary behaviour and physical activity, and self-reported total sleep). Outcomes were depression and anxiety symptoms (Patient Health Questionnaire-9 and Generalised Anxiety Disorders-7) at follow-up.
Results
Replacing 60 min of sedentary behaviour with light activity, moderate-to-vigorous activity, and sleep was associated with lower depression symptom scores by 1.3% (95% CI, 0.4–2.1%), 12.5% (95% CI, 11.4–13.5%), and 7.6% (95% CI, 6.9–8.4%), and lower odds of possible depression by 0.95 (95% CI, 0.94–0.96), 0.75 (95% CI, 0.74–0.76), and 0.90 (95% CI, 0.90–0.91) at follow-up.
Replacing 60 min of sedentary behaviour with moderate-to-vigorous activity and sleep was associated with lower anxiety symptom scores by 6.6% (95% CI, 5.5–7.6%) and 4.5% (95% CI, 3.7–5.2%), and lower odds of meeting the threshold for a possible anxiety disorder by 0.90 (95% CI, 0.89–0.90) and 0.97 (95%CI, 0.96–0.97) at follow-up. However, replacing 60 min of sedentary behaviour with light activity was associated with higher anxiety symptom scores by 4.5% (95% CI, 3.7–5.3%) and higher odds of a possible anxiety disorder by 1.07 (95% CI, 1.06–1.08).
Conclusions
Sedentary behaviour is a risk factor for increased depression and anxiety symptoms in adults. Replacing sedentary behaviour with moderate-to-vigorous activity may reduce mental health risks, but more work is necessary to clarify the role of light activit
Tuberculosis related disability: a systematic review and meta-analysis
The sustainable development goals aim to improve health for all by 2030. They incorporate ambitious goals regarding tuberculosis (TB), which may be a significant cause of disability, yet to be quantified. Therefore, we aimed to quantify the prevalence and types of TB-related disabilities.
Methods
We performed a systematic review of TB-related disabilities. The pooled prevalence of disabilities was calculated using the inverse variance heterogeneity model. The maps of the proportions of common types of disabilities by country income level were created.
Results
We included a total of 131 studies (217,475 patients) that were conducted in 49 countries. The most common type of disabilities were mental health disorders (23.1%), respiratory impairment (20.7%), musculoskeletal impairment (17.1%), hearing impairment (14.5%), visual impairment (9.8%), renal impairment (5.7%), and neurological impairment (1.6%). The prevalence of respiratory impairment (61.2%) and mental health disorders (42.0%) was highest in low-income countries while neurological impairment was highest in lower middle-income countries (25.6%). Drug-resistant TB was associated with respiratory (58.7%), neurological (37.2%), and hearing impairments (25.0%) and mental health disorders (26.0%), respectively.
Conclusions
TB-related disabilities were frequently reported. More uniform reporting tools for TB-related disability and further research to better quantify and mitigate it are urgently needed.
Prospero registration number
CRD4201914748
Combined homologous recombination repair deficiency and immune activation analysis for predicting intensified responses of anthracycline, cyclophosphamide and taxane chemotherapy in triple-negative breast cancer
Triple-negative breast cancer (TNBC) is a clinically aggressive disease with abundant variants that cause homologous recombination repair deficiency (HRD). Whether TNBC patients with HRD are sensitive to anthracycline, cyclophosphamide and taxane (ACT), and whether the combination of HRD and tumour immunity can improve the recognition of ACT responders are still unknown.
Methods
Data from 83 TNBC patients in The Cancer Genome Atlas (TCGA) was used as a discovery cohort to analyse the association between HRD and ACT chemotherapy benefits. The combined effects of HRD and immune activation on ACT chemotherapy were explored at both the genome and the transcriptome levels. Independent cohorts from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO) were adopted to validate our findings.
Results
HRD was associated with a longer ACT chemotherapy failure-free interval (FFI) with a hazard ratio of 0.16 (P = 0.004) and improved patient prognosis (P = 0.0063). By analysing both HRD status and ACT response, we identified patients with a distinct TNBC subtype (ACT-S&HR-P) that showed higher tumour lymphocyte infiltration, IFN-γ activity and NK cell levels. Patients with ACT-S&HR-P had significantly elevated immune inhibitor levels and presented immune activation associated with the increased activities of both innate immune cells and adaptive immune cells, which suggested treatment with immune checkpoint blockade as an option for this subtype. Our analysis revealed that the combination of HRD and immune activation enhanced the efficiency of identifying responders to ACT chemotherapy (AUC = 0.91, P = 1.06e−04) and synergistically contributed to the clinical benefits of TNBC patients. A transcriptional HRD signature of ACT response-related prognostic factors was identified and independently validated to be significantly associated with improved survival in the GEO cohort (P = 0.0038) and the METABRIC dataset (P < 0.0001).
Conclusions
These findings highlight that HR deficiency prolongs FFI and predicts intensified responses in TNBC patients by combining HRD and immune activation, which provides a molecular basis for identifying ACT responders