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Interventions for preventing and ameliorating cognitive deficits in adults treated with cranial irradiation

Cochrane Database Syst Rev. 2022 Nov 25;11:CD011335. doi: 10.1002/14651858.CD011335.pub3.

ABSTRACT

BACKGROUND: Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of pharmacological and non-pharmacological treatment of cognitive deficits in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 12, 2014.

OBJECTIVES: To assess the effectiveness of interventions for preventing or ameliorating cognitive deficits in adults treated with cranial irradiation.

SEARCH METHODS: For this review update we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE via Ovid, Embase via Ovid, and PsycInfo via Ovid to 12 September 2022.

SELECTION CRITERIA: We included randomised controlled (RCTs) trials that evaluated pharmacological or non-pharmacological interventions in cranial irradiated adults, with objective cognitive functioning as a primary or secondary outcome measure.

DATA COLLECTION AND ANALYSIS: Two review authors (MK, JD) independently extracted data from selected studies and carried out a risk of bias assessment. Cognitive function, fatigue and mood outcomes were reported. No data were pooled.

MAIN RESULTS: Eight studies met the inclusion criteria and were included in this updated review. Six were from the original version of the review, and two more were added when the search was updated. Nineteen further studies were assessed as part of this update but did not fulfil the inclusion criteria. Of the eight included studies, four studies investigated “prevention” of cognitive problems (during radiotherapy and follow-up) and four studies investigated “amelioration” (interventions to treat cognitive impairment as a late complication of radiotherapy). There were five pharmacological studies (two studies on prevention and three in amelioration) and three non-pharmacological studies (two on prevention and one in amelioration). Due to differences between studies in the interventions being evaluated, a meta-analysis was not possible. Studies in early radiotherapy treatment phase (five studies) Pharmacological studies in the “early radiotherapy treatment phase” were designed to prevent or ameliorate cognitive deficits and included drugs used in dementia (memantine) and fatigue (d-threo-methylphenidate hydrochloride). Non-pharmacological studies in the “early radiotherapy treatment phase” included a ketogenic diet and a two-week cognitive rehabilitation and problem-solving programme. In the memantine study, the primary cognitive outcome of memory at six months did not reach significance, but there was significant improvement in overall cognitive function compared to placebo, with similar adverse events across groups. The d-threo-methylphenidate hydrochloride study found no statistically significant difference between arms, with few adverse events. The study of a calorie-restricted ketogenic diet found no effect, although a lower than expected calorie intake in the control group complicates interpretation of the results. The study investigating the utility of a rehabilitation program did not carry out a statistical comparison of cognitive performance between groups. Studies in delayed radiation or late effect phase (four studies) The “amelioration” pharmacological studies to treat cognitive complications of radiotherapy included drugs used in dementia (donepezil) or psychostimulants (methylphenidate and modafinil). Non-pharmacological measures included cognitive rehabilitation and problem solving (Goal Management Training). These studies included patients with cognitive problems at entry who had “stable” brain cancer. The donepezil study did not find an improvement in the primary cognitive outcome of overall cognitive performance, but did find improvement in an individual test of memory, compared to placebo; adverse events were not reported. A study comparing methylphenidate with modafinil found improvements in cognitive function in both the methylphenidate and modafinil arms; few adverse events were reported. Another study comparing two different doses of modafinil combined treatment arms and found improvements across all cognitive tests, however, a number of adverse events were reported. Both studies were limited by a small sample size. The Goal Management Training study suggested a benefit of the intervention, a behavioural intervention that combined mindfulness and strategy training, on executive function and processing speed. There were a number of limitations across studies and few were without high risks of bias.

AUTHORS’ CONCLUSIONS: In this update, limited additional evidence was found for the treatment or amelioration of cognitive deficits in adults treated with cranial irradiation. As concluded in the original review, there is supportive evidence that memantine may help prevent cognitive deficits for adults with brain metastases receiving cranial irradiation. There is supportive evidence that donepezil, methylphenidate and modafinil may have a role in treating cognitive deficits in adults with brain tumours who have been treated with cranial irradiation; patient withdrawal affected the statistical power of these studies. Further research that tries to minimise the withdrawal of consent, and subsequently reduce the requirement for imputation procedures, may offer a higher certainty of evidence. There is evidence from only a single small study to support non-pharmacological interventions in the amelioration of cognitive deficits. Further research is required.

PMID:36427235 | DOI:10.1002/14651858.CD011335.pub3

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Point-of-care lung ultrasound in the assessment of COVID-19: results of a UK multicentre service evaluation

Acute Med. 2022;21(3):131-138. doi: 10.52964/AMJA.0912.

ABSTRACT

BACKGROUND: Coronavirus disease 2019 has had a dramatic impact on the delivery of acute care globally. Accurate risk stratification is fundamental to the efficient organisation of care. Point-of-care lung ultrasound offers practical advantages over conventional imaging with potential to improve the operational performance of acute care pathways during periods of high demand. The Society for Acute Medicine and the Intensive Care Society undertook a collaborative evaluation of point-of-care imaging in the UK to describe the scope of current practice and explore performance during real-world application.

METHODS: A retrospective service evaluation was undertaken of the use of point-of-care lung ultrasound during the initial wave of coronavirus infection in the UK. We report an evaluation of all imaging studies performed outside the intensive care unit. An ordinal scale was used to measure the severity of loss of lung aeration. The relationship between lung ultrasound, polymerase chain reaction for SARS-CoV-2 and 30-day outcomes were described using logistic regression models.

RESULTS: Data were collected from 7 hospitals between February and September 2020. In total, 297 ultrasound examinations from 295 patients were recorded. Nasopharyngeal swab samples were positive in 145 patients (49.2% 95%CI 43.5-54.8). A multivariate model combining three ultrasound variables showed reasonable discrimination in relation to the polymerase chain reaction reference (AUC 0.77 95%CI 0.71-0.82). The composite outcome of death or intensive care admission at 30 days occurred in 83 (28.1%, 95%CI 23.3-33.5). Lung ultrasound was able to discriminate the composite outcome with a reasonable level of accuracy (AUC 0.76 95%CI 0.69-0.83) in univariate analysis. The relationship remained statistically significant in a multivariate model controlled for age, sex and the time interval from admission to scan Conclusion: Point-of-care lung ultrasound is able to discriminate patients at increased risk of deterioration allowing more informed clinical decision making.

PMID:36427211 | DOI:10.52964/AMJA.0912

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Contemporary management of atrial fibrillation and the predicted vs. absolute risk of ischaemic stroke despite treatment: a report from ESC-EHRA EORP-AF Long-Term General Registry

Europace. 2022 Nov 25:euac214. doi: 10.1093/europace/euac214. Online ahead of print.

ABSTRACT

BACKGROUND: Risk stratification in patients with atrial fibrillation (AF) is important to facilitate guideline-directed therapies. The Calculator of Absolute Stroke Risk (CARS) scheme enables an individualized estimation of 1-year absolute risk of stroke in AF. We aimed to investigate the predicted and absolute risks of ischaemic stroke, and evaluate whether CARS (and CHA2DS2-VASc score) may be useful for identifying high risk patients with AF despite contemporary treatment.

METHODS: We utilized the EORP-AF General Long-Term Registry which prospectively enrolled patients with AF from 250 centres across 27 participating European countries. Patients with sufficient data to determine CARS and CHA2DS2-VASc score, and reported outcomes of ischaemic stroke were included in this analysis. The primary outcome of ischaemic stroke was recorded over a 2-year follow-up period.

RESULTS: A total of 9444 patients were included (mean age 69.1 [±11.4] years; 3776 [40.0%] females). There was a high uptake (87.9%) of anticoagulation therapy, predominantly with vitamin K antagonist (50.0%). Over a mean follow-up period of 24 months, there were a total of 101 (1.1%) ischaemic stroke events. In the entire cohort, the median CARS and absolute annual risks of ischaemic stroke were 2.60 (IQR 1.60-4.00) and 0.53% (95%CI 0.43-0.64%), respectively. There was no statistical difference between the predictive performance of CARS and CHA2DS2-VASc score (0.621 [95%CI 0.563-0.678] vs. 0.626 [95%CI 0.573-0.680], P = 0.725).

CONCLUSION: Contemporary management of AF was associated with a low risk of ischaemic stroke. CARS and CHA2DS2-VASc score may be useful to identify high risk patients despite treatment who may benefit from more aggressive treatment and follow-up.

PMID:36427202 | DOI:10.1093/europace/euac214

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Criteria Associated with Treatment Decisions in Juvenile Idiopathic Arthritis with a Focus on Ultrasonography: Results from the JIRECHO Cohort

Rheumatol Ther. 2022 Nov 23. doi: 10.1007/s40744-022-00512-2. Online ahead of print.

ABSTRACT

BACKGROUND: The treatment of children with juvenile idiopathic arthritis (JIA) to prevent disability is a major challenge in paediatric rheumatology. The presence of synovitis, which is difficult to detect in children, is associated with structural damage. Musculoskeletal ultrasonography (MSUS) can be used in patients with JIA to reveal subclinical synovitis.

OBJECTIVE: The primary aim was to determine whether the use of MSUS was associated with therapeutic modification in patients with JIA. The secondary aim was to identify other factors associated with therapeutic decisions.

METHODS: We conducted an observational study based on the JIRECHO multi-centre cohort, which was developed to provide a systematic MSUS follow-up for patients with JIA. Follow-up occurred every 6 months and included clinical and MSUS examinations. We included children who underwent MSUS of the elbows, wrists, second metacarpophalangeal joints, knees and ankles, which was performed by expert sonographers. Clinical and biological data, disease activity scores and information on therapeutics were collected.

RESULTS: A total of 185 visits concerning 112 patients were recorded. Three groups were defined according to the therapeutic decision: escalation (22%, n = 40), de-escalation (14%, n = 26) or stable (64%, n = 119). In the “therapeutic escalation” group: the presence of ultrasonographic synovitis in B-mode and the presence of grade 2 or 3 synovitis in B-mode were not significantly more frequent than in the “stable therapeutic or de-escalation” group (80% versus 65%, p = 0.06; 33% versus 19%, p = 0.06), and the patient’s and physician’s visual analogue scale (VAS) scores, the clinical JADAS and the C-reactive protein level were significantly higher, but only physician’s VAS score remained in the model of logistic regression. In the “therapeutic de-escalation” group: there was no difference in the presence of US synovitis compared with the “stable therapeutic or escalation” group (62% versus 69%, p = 0.48).

CONCLUSION: Even though US synovitis tended to be more frequent in patients with therapeutic escalation, the study did not show that the presence of synovitis in MSUS was statistically associated with therapeutic modifications in patients with JIA. Treatment remained stable despite the presence of US synovitis.

PMID:36427176 | DOI:10.1007/s40744-022-00512-2

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Early risk assessment in paediatric and adult household contacts of confirmed tuberculosis cases by novel diagnostic tests (ERASE-TB): protocol for a prospective, non-interventional, longitudinal, multicountry cohort study

BMJ Open. 2022 Jul 19;12(7):e060985. doi: 10.1136/bmjopen-2022-060985.

ABSTRACT

INTRODUCTION: The WHO End-TB Strategy calls for the development of novel diagnostics to detect tuberculosis (TB) earlier and more accurately. Better diagnostics, together with tools to predict disease progression, are critical for achieving WHO End-TB targets. The Early Risk Assessment in TB Contacts by new diagnoStic tEsts (ERASE-TB) study aims to evaluate novel diagnostics and testing algorithms for early TB diagnosis and accurate prediction of disease progression among household contacts (HHCs) exposed to confirmed index cases in Mozambique, Tanzania and Zimbabwe.

METHODS AND ANALYSIS: A total of 2100 HHCs (aged ≥10 years) of adults with microbiologically-confirmed pulmonary TB will be recruited and followed up at 6-month intervals for 18-24 months. At each time point, a WHO symptom screen and digital chest radiograph (dCXR) will be performed, and blood and urine samples will be collected. Individuals screening positive (WHO symptom screen or dCXR) will be requested to provide sputum for Xpert MTB/Rif Ultra. At baseline, HHCs will also be screened for HIV, diabetes (HbA1c), chronic lung disease (spirometry), hypertension and anaemia. Study outcomes will be coprevalent TB (diagnosed at enrolment), incident TB (diagnosed during follow-up) or no TB at completion of follow-up. Novel diagnostics will be validated using fresh and biobanked samples with a nested case-control design. Cases are defined as HHCs diagnosed with TB (for early diagnosis) or with incident TB (for prediction of progression) and will be matched by age, sex and country to HHCs who remain healthy (controls). Statistical analyses will include assessment of diagnostic accuracy by constructing receiver operating curves and calculation of sensitivity and specificity.

ETHICS AND DISSEMINATION: ERASE-TB has been approved by regulatory and ethical committees in each African country and by each partner organisation. Consent, with additional assent for participants <18 years, is voluntary. Attestation by impartial witnesses is sought in case of illiteracy. Confidentiality of participants is being maintained throughout. Study findings will be presented at scientific conferences and published in peer-reviewed international journals.

TRIAL REGISTRATION NUMBER: NCT04781257.Cite Now.

PMID:36427173 | DOI:10.1136/bmjopen-2022-060985

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Prevalence of dog erythrocyte antigen 1 in a population of dogs tested in California

J Vet Emerg Crit Care (San Antonio). 2022 Nov 25. doi: 10.1111/vec.13263. Online ahead of print.

ABSTRACT

BACKGROUND: Multiple studies have evaluated the breed-specific prevalence of dog erythrocyte antigen (DEA) 1 in various geographic regions. However, few large-scale studies exist that describe breed prevalence of DEA 1 in the United States.

KEY FINDINGS: From January 2000 to October 2020, 6469 dogs had their RBC antigen type determined and were included in the study. The overall prevalence of DEA 1 in all dogs was 61.2%. Of 50 breeds with sample sizes ≥20, 8 breeds had a high prevalence (≥90%) of DEA 1-positive blood type: Basset Hound, Bernese Mountain Dog, Brittany, Dachshund, Miniature Pinscher, Miniature Schnauzer, Pug, and Rottweiler. Four breeds had a high prevalence (≥90%) of DEA 1-negative blood type: Boxer, English Bulldog, Flat-Coated Retriever, and French Bulldog. Numerous breeds with a sample size <20 and ≥5 were found to have 100% prevalence of a DEA 1 blood type, although these findings need to be confirmed with a larger sample size. No statistical difference in any breed based on sex was found. The results in this study are consistent with previously reported data in other countries.

SIGNIFICANCE: Knowledge of regional breed differences in DEA 1 prevalence can help to improve selection and recruitment of appropriate blood donor dogs.

PMID:36427164 | DOI:10.1111/vec.13263

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Have public environmental appeals inspired green total factor productivity? empirical evidence from Baidu Environmental Search Index

Environ Sci Pollut Res Int. 2022 Nov 24. doi: 10.1007/s11356-022-23993-8. Online ahead of print.

ABSTRACT

Literatures focus on whether formal environmental regulatory policies can effectively stimulate green total factor productivity (GTFP), but generally ignore the role of informal institutions such as public environmental appeals. This paper uses inter-provincial panel data and Non-Radial Slacks-Based Measure (SBM) model to measure GTFP. With the Baidu Environmental Search Index presenting the public environmental appeals, the dynamic panel System Generalized Method of Moments (SYS-GMM) and Differenced Generalized Method of Moments (DIFF-GMM) methods are used to explore the effect, transmission mechanism and conditions of the public’s environmental demands on green total factor productivity. The study concludes that public environmental appeals are beneficial to improve GTFP, and this result still holds after endogenous and robustness tests. The mechanism results show that the green technology innovation effect is an important mechanism for public environmental appeals to improve GTFP. In addition, public environmental appeals of different pollutants and different locations have heterogeneous effects on GTFP. In addition, the public wealth level, human capital level, and government institutional environment play an important role in the impact of public environmental appeals on GTFP.

PMID:36427122 | DOI:10.1007/s11356-022-23993-8

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Prognostic significance of microinvasion with ductal carcinoma in situ of the breast: a meta-analysis

Breast Cancer Res Treat. 2022 Nov 24. doi: 10.1007/s10549-022-06800-3. Online ahead of print.

ABSTRACT

PURPOSE: Ductal carcinoma in situ (DCIS) associated with invasive carcinoma ≤ 1 mm in size is defined as DCIS with microinvasion (DCIS/microinvasion) rather than as invasive breast carcinoma. The number of patients with microinvasion accounts for < 1% of all breast cancer in published studies. As the numbers are limited, the prognostic significance of DCIS/microinvasion has not been clearly elucidated. This meta-analysis aimed to investigate the survival differences between patients with DCIS/microinvasion and those with pure DCIS.

METHODS: A meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was performed. We searched three electronic databases (MEDLINE, Cochrane Library, and EMBASE) and included observational studies published in English that contained survival details of patients with either DCIS or DCIS/microinvasion.

RESULTS: This study identified 26 studies that described the clinicopathological characteristics of patients in both the DCIS and DCIS/microinvasion groups. Survival differences were evaluated in 10 of 26 studies. Disease-free survival and loco-regional recurrence-free survival were significantly shorter in patients with DCIS/microinvasion than in those with DCIS (Hazard ratio, 1.52; 95% confidence interval, 1.11-2.08; p = 0.01 and hazard ratio, 2.53; 95% confidence interval, 1.45-4.41; p = 0.001, respectively). Both overall survival and distant metastasis-free survival tended to be shorter in patients with DCIS/microinvasion than in patients with DCIS (Hazard ratio, 1.63; 95% CI, 0.63-4.23; p = 0.31 and hazard ratio, 1.85; 95% confidence interval, 0.74-4.66; p = 0.19, respectively) but the difference was not statistically significant.

CONCLUSION: Our meta-analysis suggests that DCIS/microinvasion may display more aggressive biological and clinical behavior than pure DCIS, highlighting the potential need for closer follow-up and consideration of adjuvant treatment strategies in DCIS patients with microinvasive disease.

PMID:36427119 | DOI:10.1007/s10549-022-06800-3

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Relationship between nocturnal enuresis and sleep in children and adolescents

Pediatr Nephrol. 2022 Nov 24. doi: 10.1007/s00467-022-05818-5. Online ahead of print.

ABSTRACT

BACKGROUND: Nocturnal enuresis (NE) is a multifactorial and complex condition. One less understood factor in its pathophysiology is the enuretic inability to wake up when the bladder is full (impaired arousal).

OBJECTIVE: We aimed to investigate the relationship between sleep and NE in children and adolescents.

METHODS: A systematic review was performed following the PRISMA guidelines, and the electronic databases MEDLINE (via PubMed) and SCOPUS were searched until March 2022. Eligibility criteria were studies that recruited patients aged five-17 years with a diagnosis of NE according to the International Child Continence Society (ICCS), Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5), or International Classification Criteria of Sleep Disorders-Third edition (ICSD-3) who had their sleep assessed using validated questionnaires and/or polysomnography. The tool used to analyze the risk of bias in the included studies was the risk of bias in non-randomized studies of exposure.

RESULTS: Of 1582 citations screened, nine were included, giving 1685 participants, 581 with NE. All studies were observational and half had a low risk of bias. Four studies evaluated sleep by questionnaires only; two used questionnaires and polysomnography; two used only polysomnography, and one used sleep logs and actigraphy. Sleep questionnaires showed that children with enuresis had more sleep problems than controls, especially parasomnias, breathing disorders, and daytime sleepiness. Among the polysomnography parameters, the sleep stage architecture and periodic limb movements during sleep had conflicting data between the two studies.

LIMITATIONS: The studies evaluated sleep through heterogeneous tools. They used different questionnaires; even those considered by polysomnography did not record the same channels.

CONCLUSION: It seems that enuretic children and adolescents sleep differently from those who are non-enuretic. More studies are needed to clarify the best way to assess sleep and better understand this relationship. The review protocol was registered with PROSPERO, CRD42021266338. There was no funding.

PMID:36427087 | DOI:10.1007/s00467-022-05818-5

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Classic IL-6 signaling is associated with poor outcomes in burn patients

Shock. 2022 Nov 28. doi: 10.1097/SHK.0000000000002051. Online ahead of print.

ABSTRACT

BACKGROUND: Interleukin (IL)-6 is a multifunctional cytokine with both a pro- and anti-inflammatory role. In many studies, IL-6 increases rapidly after burn injury and is associated with poor outcomes. However, there are two aspects to IL-6; it can signal via its soluble IL-6 Receptor (sIL-6R), which is referred to as trans-signalling and is regarded as the proinflammatory pathway. The role of sIL-6R post-burn injury has yet to be explored in its entirety. We hypothesized that patients with a lower ratio of IL-6 to sIL-6R would have worse outcomes.

METHODS: Patients admitted to our burn centre within seven days of injury were included in this study. Patients were divided into two groups based on IL-6 and sIL-6R levels measured within the first seven days post-burn injury. Patients were in the high ratio group if their IL-6:sIL-6R ratio was ≥0.185. Clinical outcomes included organ biomarkers, morbidities, and hospital length of stay. Groups were compared using Student’s t-test, Mann-Whitney U, and Fisher’s exact test as appropriate; a P value of <0.05 was considered statistically significant.

RESULTS: We studied 86 patients with a median age of 50 (36 – 66) and a median total body surface area (TBSA) burn of 18% (10 – 31). There were 40 patients categorized with a low IL-6:sIL-6R ratio and 46 patients with a high IL-6:sIL-6R ratio. Patients in the high IL-6:sIL-6R ratio group had a significantly greater TBSA burn (p < 0.001) and a significantly greater proportion of patients with inhalation injury (p = 0.001). Levels of IL-6 were significantly higher in patients with a high IL-6:sIL-6R ratio (p < 0.0001). However, levels of sIL-6R were not significantly different among the low and high groups (p = 0.965). Mortality was significantly greater in the high IL-6:sIL-6R ratio group (3% vs. 26%; p = 0.002).

CONCLUSIONS: Interestingly, patients with a higher ratio of IL-6:sIL-6R had significantly greater mortality. Using sIL-6R as a marker for the proinflammatory immune response, we expected patients with a lower IL-6:sIL-6R ratio to have poor outcomes, typically associated with a hyperinflammatory or exaggerated immune response. However, the absolute value of sIL-6R did not differ. This suggests that classical signalling of IL-6 via its membrane-bound receptor, with an anti-inflammatory function, is essential.

PMID:36427079 | DOI:10.1097/SHK.0000000000002051