Category: Statistics

BMJ Glob Health. 2021 Sep;6(9):e005427. doi: 10.1136/bmjgh-2021-005427.

ABSTRACT

BACKGROUND: While it is now apparent clinical sequelae (long COVID) may persist after acute COVID-19, their nature, frequency and aetiology are poorly characterised. This study aims to regularly synthesise evidence on long COVID characteristics, to help inform clinical management, rehabilitation strategies and interventional studies to improve long-term outcomes.

METHODS: A living systematic review. Medline, CINAHL (EBSCO), Global Health (Ovid), WHO Global Research on COVID-19 database, LitCovid and Google Scholar were searched till 17 March 2021. Studies including at least 100 people with confirmed or clinically suspected COVID-19 at 12 weeks or more post onset were included. Risk of bias was assessed using the tool produced by Hoy et al. Results were analysed using descriptive statistics and meta-analyses to estimate prevalence.

RESULTS: A total of 39 studies were included: 32 cohort, 6 cross-sectional and 1 case-control. Most showed high or moderate risk of bias. None were set in low-income countries and few included children. Studies reported on 10 951 people (48% female) in 12 countries. Most included previously hospitalised people (78%, 8520/10 951). The longest mean follow-up time was 221.7 (SD: 10.9) days post COVID-19 onset. Over 60 physical and psychological signs and symptoms with wide prevalence were reported, most commonly weakness (41%; 95% CI 25% to 59%), general malaise (33%; 95% CI 15% to 57%), fatigue (31%; 95% CI 24% to 39%), concentration impairment (26%; 95% CI 21% to 32%) and breathlessness (25%; 95% CI 18% to 34%). 37% (95% CI 18% to 60%) of patients reported reduced quality of life; 26% (10/39) of studies presented evidence of reduced pulmonary function.

CONCLUSION: Long COVID is a complex condition with prolonged heterogeneous symptoms. The nature of studies precludes a precise case definition or risk evaluation. There is an urgent need for prospective, robust, standardised, controlled studies into aetiology, risk factors and biomarkers to characterise long COVID in different at-risk populations and settings.

PROSPERO REGISTRATION NUMBER: CRD42020211131.

PMID:34580069 | DOI:10.1136/bmjgh-2021-005427

Pancreatology. 2021 Sep 21:S1424-3903(21)00574-3. doi: 10.1016/j.pan.2021.09.010. Online ahead of print.

ABSTRACT

BACKGROUND: Maturity-onset diabetes of the young type 8 (MODY8 or CEL-MODY) is an inherited pancreatic disease characterized by chronic inflammation of the pancreas and diabetes. It is not known whether MODY8 patients have increased risk for developing pancreatic cancer. We investigated KRAS mutation load in duodenal juice from MODY8 patients, comparing with other groups of pancreatic disease.

METHODS: Droplet digital PCR (ddPCR) was used to detect KRAS codon 12/13/61 mutations in duodenal juice sampled from 11 MODY8 patients, nine healthy subjects and 100 patients clinically investigated due to suspected pancreatic disease.

RESULTS: KRAS mutations were detected in 4/11 patients with MODY8 (36%), 1/9 healthy subjects (11%), 15/44 patients with chronic pancreatitis (CP, 34%), 3/5 patients with pancreatic ductal adenocarcinoma (PDAC, 60%), 3/20 patients with acute pancreatitis (15%), 0/13 patients with other pancreatic disorders and 2/18 patients with nonpancreatic gastrointestinal disease (11%). Of the 28 positive juice samples, 25 (89%) had low-abundance mutations in codons 12/13, with a variant allele frequency (VAF) less than 1%. KRAS-positive patients with MODY8 or CP had significantly lower VAFs than patients with PDAC (Mann-Whitney U test; p = 0.041). Although the overall mutation detection rate was higher for subjects ≥50 years old (26%) than for younger subjects (15%), the difference was not statistically significant.

CONCLUSIONS: KRAS mutations were detectable in duodenal juice from MODY8 patients, but with low abundance and at the same frequency as in CP patients. The discriminative value of the analysis with regard to other pancreatic disease was limited.

PMID:34580018 | DOI:10.1016/j.pan.2021.09.010

J Am Pharm Assoc (2003). 2021 Sep 11:S1544-3191(21)00373-3. doi: 10.1016/j.japh.2021.09.003. Online ahead of print.

ABSTRACT

BACKGROUND: Although community pharmacists have been actively engaged in patient care, their role in deprescribing is still restricted.

OBJECTIVES: This study aimed to assess the effectiveness of a new educational approach designed to catalyze deprescribing in community pharmacies.

METHODS: In this 4-month, randomized, controlled trial, 108 community pharmacies in Egypt were randomly and equally distributed to either the active or the control groups. Participants from the active group pharmacies received 31 deprescribing-related clinical case scenarios, designed according to the available deprescribing guideline and clinical experiences of an expert panel members, and delivered through WhatsApp. Then participants from both groups reported the incidence of potentially inappropriate medicines (PIMs), the frequency of deprescribing opportunities, and related pharmacist interventions.

RESULTS: Pharmacists from the active group reported a considerably higher incidence of PIMs (20.87%) than that reported by pharmacists from the control group (5.03%). In addition, they made 1326 deprescribing-related interventions, of which 1022 (77.07%) were accepted and 641 (48.34%) were significant interventions. The proportions of cessation of drug therapy, reducing the dose, and persuasion of patients to accept deprescribing pharmacist interventions in the active group were 37.85%, 22.09%, and 10.63%, respectively. In contrast, 150 of 268 deprescribing-related interventions (55.97%) in the active group were accepted. The clinical value and type of deprescribing decision were statistically significant determinants for the acceptance of deprescribing decisions. The mean time needed to persuade the patient about deprescribing and the cost saved per patient across the active and the control groups were 5.09 ± 3.54 minutes versus 10.03 ± 6.19 minutes and 17.88 ± 9.60 U.S. dollars versus 4.49 ± 2.44 U.S. dollars, respectively.

CONCLUSION: The intervention proposed improved the frequency and clinical value of deprescribing decisions.

PMID:34580032 | DOI:10.1016/j.japh.2021.09.003

J Pediatr Surg. 2021 Sep 17:S0022-3468(21)00599-6. doi: 10.1016/j.jpedsurg.2021.09.006. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the relationship between timing of re-introduction of feeds following surgery for Necrotising Enterocolitis (NEC) and important early outcomes.

METHODS: Secondary analysis of prospectively collected data from paediatric surgical units in UK/Ireland of infants who underwent laparotomy for NEC between 01/03/2013 and 28/02/2014. Multivariable logistic regression analysis was used to compare the relationship of early (≤ 7 days) and later (8-27 days) re-introduction of feeding after surgery on death or need for PN at 28 days, correcting for known cofounders.

RESULTS: 41/143 infants (29%) received early and 102/143 infants (71%) had delayed reintroduction of feeding. Infants in the early feeding group had a higher gestational age at birth, higher proportion of growth restriction, lower inotrope requirement, and weremore likely to have undergone primary anastomosis. Following adjustment there was no statistically significant difference detected in the rate of death or need for PN at 28 days, adjusted OR 0.4 (95% CI 0.2-1.1), noting the limited statistical power of this comparison.

CONCLUSIONS: There is no evidence from this study to support a minimum period of 7 days nil by mouth post laparotomy for infants with NEC. Early feed reintroduction following laparotomy for NEC is safe in appropriate cases.

LEVEL OF EVIDENCE: Level II – Treatment Study Group; Prospective comparative study.

PMID:34579967 | DOI:10.1016/j.jpedsurg.2021.09.006

Curr Probl Cancer. 2021 Sep 20:100792. doi: 10.1016/j.currproblcancer.2021.100792. Online ahead of print.

ABSTRACT

To assess the recurrence of high-grade vaginal intraepithelial neoplasia (VAIN) after various treatments and to determine the factors affecting recurrence. A retrospective cohort study was conducted in patients with a histologic diagnosis of high-grade VAIN who underwent treatment between 1986 and 2013. Recurrence rates, life table analysis of recurrence-free intervals following treatment, and factors affecting recurrence were analyzed. Of the 104 included patients, the mean age was 50.8± 13.4 years; 21.1% and 78.8% had VAIN2 and VAIN3, respectively. Overall, the recurrence rate of high-grade VAIN was 33.2 incidence density rate (IDR)% per year, and the median time to recurrence was 23.6 months. Observation, topical treatment, laser vaporization, electrosurgical ablation, electrosurgical excision, knife excision, and radiation were associated with recurrence rates of 65.4, 70.0, 38.0, 22.6, 43.1, 18.5, and 0 IDR% per year, respectively. The median times to recurrence for each treatment were 16.2, 18.8, 26.5, >35.8, 6.6, 39.8, and >57.3 months, respectively, but the differences in recurrence-free intervals among treatments were not statistically significant (P = 0.06). Patients in the treatment intervention group were less likely to experience recurrence than those in the untreated group (HR = 0.44, CI: 0.23-0.87, P = 0.018). A history of pelvic radiation was associated with a higher risk of recurrence (OR = 4.14, 95% CI: 1.06-16.16, P = 0.030). Although treatments for high-grade VAIN significantly decreased the risk of recurrence, approximately one-third of patients had recurrence after therapy. No treatment modality was superior to the others with respect to the recurrence rate. A history of radiation therapy was associated with higher recurrence.

PMID:34579973 | DOI:10.1016/j.currproblcancer.2021.100792

Br J Anaesth. 2021 Aug 30:S0007-0912(21)00546-8. doi: 10.1016/j.bja.2021.07.033. Online ahead of print.

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies, particularly those preventing interaction between the viral spike receptor-binding domain and the host angiotensin-converting enzyme 2 receptor, may prevent viral entry into host cells and disease progression.

METHODS: We performed a systematic review, meta-analysis, trial sequential analysis (TSA), and meta-regression of RCTs to evaluate the benefit of convalescent plasma for COVID-19. The primary outcome was 28-30 day mortality. Secondary outcomes included need for mechanical ventilation and ICU admission. Data sources were PubMed, Embase, MedRxiv, and the Cochrane library on July 2, 2021.

RESULTS: We identified 17 RCTs that recruited 15 587 patients with 8027 (51.5%) allocated to receive convalescent plasma. Convalescent plasma use was not associated with a mortality benefit (24.7% vs 25.5%; odds ratio [OR]=0.94 [0.85-1.04]; P=0.23; I²=4%; TSA adjusted confidence interval [CI], 0.84-1.05), or reduction in need for mechanical ventilation (15.7% vs 15.4%; OR=1.01 [0.92-1.11]; P=0.82; I²=0%; TSA adjusted CI, 0.91-1.13), or ICU admission (22.4% vs 16.7%; OR=0.80 [0.21-3.09]; P=0.75; I²=63%; TSA adjusted CI, 0.0-196.05). Meta-regression did not reveal association with titre of convalescent plasma, timing of administration, or risk of death and treatment effect (P>0.05). Risk of bias was high in most studies.

CONCLUSIONS: In patients with COVID-19, there was no clear mortality benefit associated with convalescent plasma treatment. In patients with mild disease, convalescent plasma did not prevent either the need for mechanical ventilation or ICU admission.

CLINICAL TRIAL REGISTRATION: CRD42021234201 (PROSPERO).

PMID:34579942 | DOI:10.1016/j.bja.2021.07.033

Encephale. 2021 Sep 24:S0013-7006(21)00168-8. doi: 10.1016/j.encep.2021.05.004. Online ahead of print.

ABSTRACT

BACKGROUND: Suicide is a leading yet underestimated cause of death in the world and in France. The goal of our study was to determine the impact at 3 months of a large-scale simulation program on suicide risk assessment for first-year medical residents.

METHODS: All the first-year medical residents participated in the simulation program that included a session on suicide risk assessment. The scenario was carried out by a standardized patient (professional actor) who had a normal check-up at the ER after a chest pain. He verbalized suicidal thoughts to an ER nurse due to a recent divorce and social difficulties, who then reported it to the resident. The latter had to assess suicide risk on his own. The QECS “Questionnaire de connaissances relatives au suicide” was used to assess knowledge of suicide before the training session (T0) and 3 months later (T1). A pre/post comparison was performed with a paired t-test.

RESULTS: 420 residents participated in this study. A total of 273 matching questionnaires was obtained. A statistically significant theoretical knowledge improvement was found at 3 months of the session for all the residents.

LIMITATIONS: The absence of a control group and data loss were some of the major limitations of our study. Another limitation corresponds to the lack of additional questions, such as levels of interest, former and recent training, level of experience, attitudes, and self-competency in suicide risk assessment before and after the simulation program that could have helped to interpret the obtained results and their variation. Moreover, the exact effects of this increased knowledge on clinical practice has not been measured in our study.

CONCLUSION: This is an unprecedented, large-scale attempt in France to allow all the medical residents to practice suicide risk assessment. This simulation-based training had a positive impact at 3 months on the knowledge of suicide in medical residents.

PMID:34579939 | DOI:10.1016/j.encep.2021.05.004

Clin Radiol. 2021 Sep 24:S0009-9260(21)00429-3. doi: 10.1016/j.crad.2021.09.004. Online ahead of print.

ABSTRACT

AIM: To determine whether quantitative parameters derived from conventional diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) correlate with the Ki67 proliferation status in musculoskeletal tumours.

MATERIALS AND METHODS: Twenty-eight patients with musculoskeletal tumours diagnosed via surgical specimen histological analysis who underwent standard DWI, IVIM, and DCE were reviewed retrospectively. The mean standard DWI (apparent diffusion coefficient [ADC]), IVIM (pure diffusion coefficient [D], pseudo-diffusion coefficient [D∗] and perfusion fraction [ƒ]), and DCE (volume transfer constant [K^trans], rate constant [K_ep], and extravascular extracellular volume fraction [V_e]) parameters were measured and correlated with the Ki67 index. The Ki67 value was categorised as high (>20%) or low (≤20%).

RESULTS: The ADC and D values correlated negatively with the Ki67 index (r=-0.711∼-0.699, p<0.001), whereas the K^trans and K_ep values correlated positively with the Ki67 index (r=0.389-0.434, p=0.021, 0.041). The ADC and D values were lower (p<0.001), whereas the K^trans and K_ep values were higher (p=0.011, 0.005) in musculoskeletal tumours with a high Ki67 status than in those in a low status. The ADC and D demonstrated the largest area under the receiver-operating characteristic curve (AUC = 0.953), which is statistically bigger than the AUC of K^trans and K_ep (0.784 and 0.802, respectively).

CONCLUSION: ADC, D, K^trans, and K_ep correlate with the Ki67 index. ADC and D are the strongest quantitative parameters for predicting Ki67 status.

PMID:34579866 | DOI:10.1016/j.crad.2021.09.004

Encephale. 2021 Sep 24:S0013-7006(21)00173-1. doi: 10.1016/j.encep.2021.05.006. Online ahead of print.

ABSTRACT

Philosophy of Mind is currently one of the most prolific fields of research in philosophy and has witnessed a progressive hybridization with cognitive science. It focuses on fundamental questions to neuroscience and psychiatry, such as the nature of mental states and cognitive processes, or the relationships between mental states and the world. Anticipating the accumulation of experimental data from neuroscience, it provides a framework for the generation of theories in cognitive science. Philosophy of mind has thus laid the foundations of the conceptual space within which cognitive sciences have spread: a large part of contemporary theories in cognitive science result from a hybridization of conceptions forged by philosophers of mind and data produced by neuroscientists. Yet contemporary psychiatry is still reluctant to feed on the philosophy of mind, other than through the fragments that emerge from neuroscience. In this paper, we describe the evolution of contemporary philosophy of mind, and we detail its contributions around three central themes for psychiatry: naturalization of mind, mental causality, and subjectivity of mental states. We show how philosophy of mind provide the conceptual framework to link different levels of explanation in psychiatry: from biological to functional, from neurophysiology to cognition, from matter to mind.

PMID:34579938 | DOI:10.1016/j.encep.2021.05.006

Klin Monbl Augenheilkd. 2021 Sep 27. doi: 10.1055/a-1525-2588. Online ahead of print.

ABSTRACT

BACKGROUND: The role of CD133 und ABCB5 is discussed in treatment resistance in several types of cancer. The objective of this study was to evaluate whether CD133⁺/ABCB5⁺ colocalization differs in untreated, in beam radiation treated, and in chemotherapy treated retinoblastoma specimens. Additionally, CD133, ABCB5, sphingosine kinase 1, and sphingosine kinase 2 gene expression was analyzed in WERI-RB1 (WERI RB1) and etoposide-resistant WERI RB1 subclones (WERI ETOR).

METHODS: Active human untreated retinoblastoma specimens (n = 12), active human retinoblastoma specimens pretreated with beam radiation before enucleation (n = 8), and active human retinoblastoma specimens pretreated with chemotherapy before enucleation (n = 7) were investigated for localization and expression of CD133 and ABCB5 by immunohistochemistry. Only specimens with IIRC D, but not E, were included in this study. Furthermore, WERI RB1 and WERI ETOR cell lines were analyzed for CD133, ABCB5, sphingosine kinase 1, and sphingosine kinase 2 by the real-time polymerase chain reaction (RT-PCR).

RESULTS: Immunohistochemical analysis revealed the same amount of CD133⁺/ABCB5⁺ colocalization islets in untreated and treated human retinoblastoma specimens. Quantitative RT-PCR analysis showed a statistically significant upregulation of CD133 in WERI ETOR (p = 0.002). No ABCB5 expression was detected in WERI RB1 and WERI ETOR. On the other hand, SPHK1 (p = 0.0027) and SPHK2 (p = 0.017) showed significant downregulation in WERI ETOR compared to WERI RB1.

CONCLUSIONS: CD133⁺/ABCB5⁺ co-localization islets were noted in untreated and treated human retinoblastoma specimens. Therefore, we assume that CD133⁺/ABCB5⁺ islets might play a role in retinoblastoma genesis, but not in retinoblastoma treatment resistance.

PMID:34571550 | DOI:10.1055/a-1525-2588