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Global, regional, and national trends in liver disease-related mortality across 112 countries from 1990 to 2021, with projections to 2050: comprehensive analysis of the WHO Mortality Database
No full textBackground
Liver disease causes over two million deaths annually worldwide, comprising approximately 4% of all global fatalities. We aimed to analyze liver disease-related mortality trends from 1990 to 2021 using the World Health Organization (WHO) Mortality Database and forecast global liver disease-related mortality rates up to 2050.
Methods
This study examined age-standardized liver disease-related death rates from 1990 to 2021, employing data from the WHO Mortality Database across 112 countries across five continents. The rates over time were calculated using a locally weighted scatter plot smoother curve, with weights assigned based on the population of each country. Furthermore, this study projected liver disease-related mortality rates up to 2050 using a Bayesian age-period-cohort (BAPC) model. Additionally, a decomposition analysis was conducted to discern influencing factors such as population growth, aging, and epidemiological changes.
Results
The estimated global age-standardized liver disease-related mortality rates surged significantly from 1990 to 2021 across 112 countries, rising from 103.4 deaths per 1,000,000 people (95% confidence interval [CI], 88.16, 118.74) in 1990 to 173.0 deaths per 1,000,000 people (95% CI, 155.15, 190.95) in 2021. This upward trend was particularly pronounced in low- and middle-income countries, in Africa, and in populations aged 65 years and older. Moreover, age-standardized liver disease-related mortality rates were correlated with a lower Human Development Index (P
Conclusion
Global age-standardized liver disease-related mortality has increased significantly and continues to emerge as a crucial global public health issue. Further investigation into liver disease-related mortality rates in Africa is needed, and updating policies is necessary to effectively manage the global burden of liver disease.
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Defining military sexual trauma: establishing parameters and perspectives
No full textBackground: The term military sexual trauma [MST] is increasingly used to describe instances of sexual harassment/assault that occur between serving personnel during military service. However, in the absence of a clear universal definition, MST is an increasingly contested term, with confusion about its scope, application to differing jurisdictions and implications for responses and treatment.Objective: This editorial provides a universal definition of MST, decoupled from any national system or framework.Method: Drawing on existing international evidence about the nature and impact of MST.Results and Conclusion: We argue that MST terminology provides a unique framing which recognises the institutional nature of MST victimisation and situates the context, behaviours, and impact on a continuum of violence.</p
Effectiveness of hand reconstruction techniques for the treatment of postburn contractures of the hand: a systematic review
No full textIntroduction: Despite the multitude of preventative methods, postburn hand contractures are poorly controlled and often require surgery. However, there is no consensus on which hand reconstruction technique is most efficacious. This systematic review aims to compare the efficacy of available postburn hand contracture reconstruction techniques over the long term and to evaluate the quality of current literature. Effectiveness is assessed with functional improvement, increase of skin surface area, and scar quality/enhanced cosmesis.
Material and methods: Four medical databases/registries were searched (PubMed/MEDLINE, Scopus, Cochrane, EMBASE) alongside grey literature sources from December 2012 to November 2022 for randomized controlled trials and observational studies with ≥ 15 participants and ≥ 3-month follow-up. Exclusion criteria were acute burn management, non-burn/non-hand contractures, non-surgical management, other burn sequelae, nonEnglish studies, and outcomes reports, reviews, communications, editorials, letters, case reports, and nonhuman studies. Quality was assessed with the Joanna Briggs Institute checklist and GRADE.
Results: Seven observational studies (1310 patients) were eligible; three with a pre-/post-operative design and four comparative cohorts. Functional and aesthetic/scar quality outcomes for skin grafting and random or defined-vascularization flaps, complication rates and rehabilitation modalities were reported. No studies on dermal substitutes or utilising skin surface area measurements were identified. Significant risk of bias, indirectness and imprecision were noted in all studies, deriving from absence of randomization, blinding, or independent control groups; confounding; missing data; and subpar reporting. Owing to heterogeneity in outcome measures, meta-analysis was not possible.
Conclusions: No consensus remains on the superiority of a single reconstruction technique. Meticulous preoperative planning and intensive rehabilitation are vital. A stepwise approach, considering individual patient and contracture characteristics and the limitations of each technique, should be followed. Well-designed and conducted future studies, utilizing reliable and validated contracture description methods and outcome assessment, are now imperative. </p
The Relationship Between Dehydration and Etiologic Subtypes of Major Neurocognitive Disorder in Older Patients
No full textPurpose
Studies investigating associations between etiologic subtypes of major neurocognitive disorder (MND) and dehydration frequency are lacking. The aim of this study was to investigate the prevalence and risk factors of dehydration among older adults with and without MND (dementia), and across different etiologic subtypes of MND.
Methods
This cross-sectional study included adults aged ≥ 65 years old from one geriatric outpatient clinic. Dehydration was defined as a calculated [1,86 × (Na + K) + 1,15 × glucose + urea + 14] plasma osmolarity of > 295 mOsm/L.Clinical characteristics and measures of comprehensive geriatric assessments of patients with dehydration and normohydration were compared. MND was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders—Fifth Edition criteria. The underlying etiologic subtypes were determined by specific diagnostic criteria.
Results
Of the 1377 patients 72% were female, the mean age was 80 ± 8 years, and 575 had dementia. Dehydration was more common in patients with dementia than those without dementia (58% vs. 53%, p = 0.044). The prevelance of dehydration was 57%, 62%, 54%, 57% and 68% in Alzheimer’s disease, Parkinson’s disease dementia, fronto-temporal dementia, dementia with Lewy bodies, and vascular dementia, respectively (p ≥ 0.05). MND was associated with dehydration (OR 1.26, 95% CI 1.01–1.57; p = 0.037) after adjustment for age and sex. In multivariable analysis, among patients with dementia, hypertension, DM, CKD, and dysphagia were more common while mean Mini-Mental State Examination score was lower in those who had dehydration versus no dehydration in older patients with dementia (p
Conclusion
Dehydration is slightly associated with the presence of MND independent of age and sex. However, dehydration is also quite common in older patients without cognitive disorders. Therefore, hydration status should be monitored in older adults irrespective of neurocognitive status. Hypertension, DM, CKD, dysphagia and severity of cognitive dysfunction were associated with dehydration in patients with dementia. The prevalence of dehydration is highest in patients with vascular dementia.</p
The Experience of Embodiment Scale: An Examination of its Psychometric Properties in Women From the Republic of Cyprus
No full textThe Experience of Embodiment Scale (EES) is a recently developed instrument that assesses experiences of living in the body. Here, we prepared a novel Greek translation of the EES and examined its psychometric properties. We initially prepared a Greek translation of the EES using a 5-step procedure recommended for test adaptation studies. Next, in a cross-sectional study, we asked a sample of 933 women from Cyprus to complete the Greek EES, alongside additional, previously validated measures assessing body appreciation, psychological well-being (self-esteem, life satisfaction), eating restriction, perfectionism, and internalisation of appearance ideals. Our analyses showed that EES factorial models based on confirmatory factor analysis (CFA) roundly had poor fit. Conversely, models based on exploratory structural equation modelling (ESEM) – which accounts for the fact that EES items cross-load across factors – had adequate fit to the data. Additionally, we found that both higher-order and bifactor-ESEM models that controlled for the uniqueness of negatively worded items had adequate fit. The bifactor-ESEM model had the best fit of all the models tested, and was invariant across ethnicity (Greeks and Greek-Cypriots) and was unaffected by differential item functioning based on age and body mass index. Additionally, construct validity of the final, optimal model was adequate, especially for its G-factor, as indicated by significant associations with additional constructs in expected directions. These results suggest that a bifactor-ESEM model of the Greek EES has adequate psychometric properties. Our work highlights important psychometric issues relating to the manner in which the EES should (or could) be conceptualised and modelled, which should be considered more fully in future work.</p
Gene therapy for choroideremia using an adeno-associated viral vector encoding Rab escort protein 1: the REGENERATE open-label trial
No full textChoroideremia is an X-linked inherited retinal degeneration that begins in childhood with nyctalopia and loss of peripheral vision, and gradually progresses to blindness in adulthood. Choroideremia is caused by null mutations in the CHM gene, which encodes Rab escort protein 1. Objective Assessment of the efficacy and safety of a single subretinal injection of an adeno-associated virus serotype 2 vector encoding Rab escort protein 1 in patients with choroideremia. Design Multicentre open-label clinical trial of a gene therapy for choroideremia using an adeno-associated virus serotype 2-Rab escort protein 1 vector. Setting This study (NCT02407678) was conducted at two NHS eye hospitals in the UK. Participants Males aged 18 years or above, having a clinical diagnosis of choroideremia with genetic confirmation of CHM gene mutation or molecular confirmation of Rab escort protein 1 protein deficiency and having best corrected visual acuity better than or equal to 6/60 (20/200; LogMAR 1.0). Intervention Adeno-associated virus serotype 2-Rab escort protein 1 vector suspension (1 × 1012 vector particles per ml) was supplied by Nightstar Therapeutics (London, UK), now part of Biogen Inc. (Cambridge, MA, USA). Up to 0.1 ml of adeno-associated virus serotype 2-Rab escort protein 1 vector suspension, corresponding to a dose of up to 1 × 1011 vector particles, was administered to the treated eye by subretinal injection. Selection of treated eyes was randomised in participants having relatively symmetrical retinal degeneration. Main outcome measures The primary safety-related outcome was change from baseline in best corrected visual acuity in treated eyes at 24 months post treatment, with prospective efficacy evaluated by comparative change from baseline in best corrected visual acuity in treated and untreated contralateral (control) eyes. Secondary outcomes included comparative change from baseline in mean retinal sensitivity (microperimetry) and retinal anatomy (area of autofluorescence) in treated and control eyes. Visual assessments were conducted by masked assessors. Results The primary efficacy-related outcome (comparative change from baseline in best corrected visual acuity in treated and control eyes at 24 months post treatment) was not statistically different between treated eyes (−2.63 letters, standard error of the mean 2.76) and control eyes (+2.67 letters, standard error of the mean 0.768) in all 30 participants (p = 0.08). Greater loss of visual fields, possibly surgery-induced, was observed in treated eyes. Six serious adverse events were reported in the treated eyes of four participants: one surgery-related and two inflammation-related serious adverse events involving clinically significant decreases in best corrected visual acuity, and three serious adverse events in one participant involving reduction in central retinal sensitivity, but with best corrected visual acuity remaining stable. Limitations No evidence of possible efficacy of the intervention was observed, as a meaningful difference in comparative change from baseline in best corrected visual acuity in treated and control eyes was not discernible at 24 months post treatment. As choroideremia is a very slow degeneration, best corrected visual acuity in control eyes did not decline significantly during the assessment period. Conclusion Although this study has not presented evidence that reduction in visual fields caused by the intervention would be justified by the possible rescue of best corrected visual acuity, a more definitive assessment may be provided by long-term monitoring of trial participants in an observational study (NCT03584165). Trial registration This study is registered as ISRCTN15602229 (www.isrctn.com/) and NCT02407678 (https://clinicaltrials.gov/). Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/66/35) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 9. See the NIHR Funding and Awards website for further award information.</p
Book Review: Turtles of the World
No full textTurtles are perhaps the reptiles with the best public image. People love marine turtles, and all species are instantly recognizable due to their distinctive carapace, which comes in a myriad of shapes, sizes, and colours. They are adapted to many environments including oceans, lakes, forests and deserts. I am sure that if you are of a similar age to myself, you may remember the cultural phenomenon that surrounded four of these crime-fighting animals named after four of the Renaissance greats. However, based almost entirely on the geography of where I grew up, my experience with turtles is quite limited. Unfortunately, we have no native species in the United Kingdom (except the occasional vagrant marine turtle), although I do have some experience with introduced sliders which were once a popular pet – due to the aforementioned ninjas. There are currently more than 350 species known to science and so I was looking for a book to act as a quick guide to species that I have clearly overlooked. I therefore picked up a copy of Turtles of the World: A Guide to Every Family to help fill in some of those large gaps in my knowledge, hoping the information would be in an accessible and user-friendly format.</p
Mechanisms of sensitivity and resistance to CDK4/CDK6 inhibitors in hormone receptor-positive breast cancer treatment
No full textCell cycle dysregulation is a hallmark of cancer that promotes eccessive cell division. Cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6) are key molecules in the G1-to-S phase cell cycle transition and are crucial for the onset, survival, and progression of breast cancer (BC). Small-molecule CDK4/CDK6 inhibitors (CDK4/6i) block phosphorylation of tumor suppressor Rb and thus restrain susceptible BC cells in G1 phase. Three CDK4/6i are approved for the first-line treatment of patients with advanced/metastatic hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) BC in combination with endocrine therapy (ET). Though this has improved the clinical outcomes for survival of BC patients, there is no established standard next-line treatment to tackle drug resistance. Recent studies suggest that CDK4/6i can modulate other distinct effects in both BC and breast stromal compartments, which may provide new insights into aspects of their clinical activity. This review describes the biochemistry of the CDK4/6-Rb-E2F pathway in HR+ BC, then discusses how CDK4/6i can trigger other effects in BC/breast stromal compartments, and finally outlines the mechanisms of CDK4/6i resistance that have emerged in recent preclinical studies and clinical cohorts, emphasizing the impact of these findings on novel therapeutic opportunities in BC.</p
Pharmacological non-hormonal treatment options for male infertility: a systematic review and network meta-analysis
No full textAbstract
Background
Male factor infertility affect up to 50% of couples unable to conceive spontaneously. Several non-hormonal pharmacological treatments have been proposed to boost spermatogenesis and increase chances of conception in men with infertility. Still, no clear evidence exists on the most effective treatment strategy.
Objective
We aimed to compare the effectiveness of non-hormonal pharmacological treatment options for men with infertility using a systematic review and network meta-analysis.
Methods
We searched MEDLINE, EMBASE, and CENTRAL until October 2023 for randomised/quasi-randomised trials that evaluated any non-hormonal pharmacological treatment options for men with idiopathic semen abnormalities or those with hypogonadism. We performed pairwise and network meta-analyses using a random effect model. We assessed risk of bias, heterogeneity, and network inconsistency. We calculated the mean rank and the surface under the cumulative ranking curve (SUCRA) for each intervention the maximum likelihood to achieve each of reported outcomes. We reported primarily on sperm concentration and other important semen and biochemical outcomes using standardised mean difference (SMD) and 95% confidence-intervals(CI).
Results
We included 14 randomised trials evaluating four treatments (Clomiphene citrate, Tamoxifen, Aromatase inhibitors, anti-oxidants) and their combinations in 1342 men. The overall quality of included trials was low. Sperm concentration improved with clomiphene compared to anti-oxidants (SMD 2.15, 95%CI 0.78–3.52), aromatase inhibitor (SMD 2.93, 95%CI 1.23–4.62), tamoxifen (SMD − 1.96, 95%CI -3.57; -0.36) but not compared to placebo (SMD − 1.53, 95%CI -3.52- 0.47). Clomiphene had the highest likelihood to achieve the maximum change in sperm concentration (SUCRA 97.4). All treatments showed similar effect for sperm motility, semen volume, and normal sperm morphology. FSH levels showed significant improvement with clomiphene vs.anti-oxidant (SMD 1.48, 95%CI 0.44–2.51) but not compared to placebo. The evidence networks for LH and testosterone suffered from significant inconsistency (p = 0.01) with similar trend of improvement with clomiphene compared to other treatments but not compared to placebo.
Conclusion
There is insufficient evidence to support the routine use of Clomiphene, tamoxifen, and aromatase inhibitors to optimise semen parameters in men with infertility. Future randomised trials are needed to confirm the efficacy of clomiphene in improving fertility outcomes in men.
PROSPERO
CRD42023430179.</p
Form and matter of regular geometrical bodies in Luca Pacioli’s Summa (1494) and Compendium de divina proportione (1498)
No full textLuca Pacioli (ca. 1447–1517) is widely considered a central figure in the Italian Renaissance, particularly in the history of practical mathematics. The perspectival representations of geometrical bodies that Leonardo da Vinci drew for Pacioli’s Compendium de divina proportione are, in turn, often singled out to illustrate the relationships between the visual arts and mathematics in the late fifteenth century. Yet despite increasing scholarly attention, the philosophical framework of Pacioli’s works deserves to be further explored. This paper discusses how Pacioli ably developed his arguments on regular geometrical bodies by relying on a predominantly Aristotelian philosophical framework. In this way, Pacioli established correlations among the quantitative, material, and formal properties of regular geometrical bodies, concluding with the visualisation of their (geometrically defined) form at the level of the intellect.</p
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