scholarly journals Problem-based learning in medical degree teaching: a scoping review

2021 ◽  
Author(s):  
Joan Carles Trullas ◽  
Carles Blay ◽  
Elisabet Sarri ◽  
Ramon Pujol
Keyword(s):  
Scoping Review ◽  
Postgraduate Medical Education ◽  
Small Sample Size ◽  
Meta Analysis ◽  
Scientific Evidence ◽  
Problem Based Learning ◽  
Knowledge Retention ◽  
Small Sample ◽  
Continuous Training ◽  
Randomized Design

Abstract Problem-based learning (PBL) is a pedagogical approach that shifts the role of the teacher to the student (student-centred) and is based on self-directed learning. Although PBL has been adopted in undergraduate and postgraduate medical education, the effectiveness of the method is still under discussion. We employed a scoping review to appraise available international evidence concerning to the effectiveness and usefulness of PBL methodology in undergraduate medical teaching programs. We applied the Arksey and O’Malley framework to undertake a scoping review. A search of literature published in English and Spanish identified one hundred and twenty four publications eligible for this review. Despite the fact that this review includes many studies, their design is heterogeneous and only a few provide a high scientific evidence methodology (randomized design and/or systematic review with meta-analysis). Furthermore, most are single-center experiences with small sample size and there are no large multi-center studies. PBL methodology obtains a high level of satisfaction, especially among students. It is more effective than other more traditional (or lecture-based methods) at improving social and communication skills, problem-solving and self-learning skills. Knowledge retention and academic performance are no worse (and in many studies are better) than with traditional methods. PBL is not universally widespread, probably because it requires greater human resources and continuous training for its implementation. More comparative and randomized studies and/or other systematic reviews and meta-analysis are required to determine which educational strategies are the most suitable for training the doctors of the future.

scholarly journals The incidence and prevalence of cardiovascular diseases in gout: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Peter Cox ◽  
Sonal Gupta ◽  
Sizheng Steven Zhao ◽  
David M. Hughes
Keyword(s):  
Systematic Review ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Cardiovascular Diseases ◽  
Small Sample Size ◽  
Meta Analysis ◽  
Random Effect ◽  
Small Sample ◽  
Future Research ◽  
Increased Risk

AbstractThe aims of this systematic review and meta-analysis were to describe prevalence of cardiovascular disease in gout, compare these results with non-gout controls and consider whether there were differences according to geography. PubMed, Scopus and Web of Science were systematically searched for studies reporting prevalence of any cardiovascular disease in a gout population. Studies with non-representative sampling, where a cohort had been used in another study, small sample size (< 100) and where gout could not be distinguished from other rheumatic conditions were excluded, as were reviews, editorials and comments. Where possible meta-analysis was performed using random-effect models. Twenty-six studies comprising 949,773 gout patients were included in the review. Pooled prevalence estimates were calculated for five cardiovascular diseases: myocardial infarction (2.8%; 95% confidence interval (CI)s 1.6, 5.0), heart failure (8.7%; 95% CI 2.9, 23.8), venous thromboembolism (2.1%; 95% CI 1.2, 3.4), cerebrovascular accident (4.3%; 95% CI 1.8, 9.7) and hypertension (63.9%; 95% CI 24.5, 90.6). Sixteen studies reported comparisons with non-gout controls, illustrating an increased risk in the gout group across all cardiovascular diseases. There were no identifiable reliable patterns when analysing the results by country. Cardiovascular diseases are more prevalent in patients with gout and should prompt vigilance from clinicians to the need to assess and stratify cardiovascular risk. Future research is needed to investigate the link between gout, hyperuricaemia and increased cardiovascular risk and also to establish a more thorough picture of prevalence for less common cardiovascular diseases.

scholarly journals DIAGNOSIS OF ENDOCRINE DISEASE: The diagnostic performance of adrenal biopsy: a systematic review and meta-analysis

2016 ◽  
Vol 175 (2) ◽  
pp. R65-R80 ◽  
Author(s):  
Irina Bancos ◽  
Shrikant Tamhane ◽  
Muhammad Shah ◽  
Danae A Delivanis ◽  
Fares Alahdab ◽  
...  
Keyword(s):  
Systematic Review ◽  
Diagnostic Performance ◽  
Small Sample Size ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Small Sample ◽  
Cochrane Central Register ◽  
Moderate Risk ◽  
Adrenal Biopsy ◽  
Adrenocortical Carcinomas

ObjectiveTo perform a systematic review of published literature on adrenal biopsy and to assess its performance in diagnosing adrenal malignancy.MethodsMedline In-Process and Other Non-Indexed Citations, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trial were searched from inception to February 2016. Reviewers extracted data and assessed methodological quality in duplicate.ResultsWe included 32 observational studies reporting on 2174 patients (39.4% women, mean age 59.8 years) undergoing 2190 adrenal mass biopsy procedures. Pathology was described in 1621/2190 adrenal lesions (689 metastases, 68 adrenocortical carcinomas, 64 other malignancies, 464 adenomas, 226 other benign, 36 pheochromocytomas, and 74 others). The pooled non-diagnostic rate (30 studies, 2013 adrenal biopsies) was 8.7% (95%CI: 6–11%). The pooled complication rate (25 studies, 1339 biopsies) was 2.5% (95%CI: 1.5–3.4%). Studies were at a moderate risk for bias. Most limitations related to patient selection, assessment of outcome, and adequacy of follow-up. Only eight studies (240 patients) could be included in the diagnostic performance analysis with a sensitivity and specificity of 87 and 100% for malignancy, 70 and 98% for adrenocortical carcinoma, and 87 and 96% for metastasis respectively.ConclusionsEvidence based on small sample size and moderate risk of bias suggests that adrenal biopsy appears to be most useful in the diagnosis of adrenal metastasis in patients with a history of extra-adrenal malignancy. Adrenal biopsy should only be performed if the expected findings are likely to alter the management of the individual patient and after biochemical exclusion of catecholamine-producing tumors to help prevent potentially life-threatening complications.

Mesenchymal Stem Cell Therapy for Acetaminophen-Related Liver Injury: A Systematic Review and Meta-Analysis of Experimental Studies in Vivo

2021 ◽  
Vol 16 ◽  
Author(s):  
Li Wang ◽  
Yiwen Zhang ◽  
Jiajun Zhong ◽  
Yuan Zhang ◽  
Shuisheng Zhou ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cell ◽  
Liver Injury ◽  
Mesenchymal Stem Cell ◽  
Small Sample Size ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Small Sample ◽  
Control Group

Objective: The efficacy of mesenchymal stem cell (MSC) therapy in acetaminophen-induced liver injury has been investigated in animal experiments, but individual studies with a small sample size cannot be used to draw a clear conclusion. Therefore, we conducted a systematic review and meta-analysis of preclinical studies to explore the potential of using MSCs in acetaminophen-induced liver injury. Methods: Eight databases were searched for studies reporting the effects of MSCs on acetaminophen hepatoxicity. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. SYRCLE’s risk of bias tool for animal studies was applied to assess the methodological quality. A meta-analysis was performed by using RevMan 5.4 and STATA/SE 16.0 software. Results: Eleven studies involving 159 animals were included according to PRISMA statement guidelines. Significant associations were found for MSCs with the levels of alanine transaminase (ALT) (standardized mean difference (SMD) − 2.58, p < 0.0001), aspartate aminotransferase (AST) (SMD − 1.75, p = 0.001), glutathione (GSH) (SMD 3.7, p < 0.0001), superoxide dismutase (SOD) (SMD 1.86, p = 0.022), interleukin 10 (IL-10) (SMD 5.14, p = 0.0002) and tumor necrosis factor-α (TNF-α) (SMD − 4.48, p = 0.011) compared with those in the control group. The subgroup analysis showed that the tissue source of MSCs significantly affected the therapeutic efficacy (p < 0.05). Conclusion: Our meta-analysis results demonstrate that MSCs could be a potential treatment for acetaminophen-related liver injury.

scholarly journals Approaches to multidrug-resistant organism prevention and control in long-term care facilities for older people: a systematic review and meta-analysis

2022 ◽  
Vol 11 (1) ◽  
Author(s):  
Valerie Wing Yu Wong ◽  
Ying Huang ◽  
Wan In Wei ◽  
Samuel Yeung Shan Wong ◽  
Kin On Kwok
Keyword(s):  
Small Sample Size ◽  
Meta Analysis ◽  
Small Sample ◽  
Risk Of Bias ◽  
Source Control ◽  
Resistant Organism ◽  
Routine Practice ◽  
Post Intervention ◽  
Term Care ◽  
Mrsa Colonization

Abstract Background Despite clear evidence of benefits in acute-care hospitals, controversy over the effectiveness of IPC measures for MDROs is perceptible and evidence-based practice has not been established. Objective To investigate the effects of IPC interventions on MDRO colonization and infections in LTCFs. Data sources Ovid MEDLINE, EMBASE, and CINAHL from inception to September 2020. Eligibility criteria Original and peer-reviewed articles examining the post-intervention effects on MDRO colonization and infections in LTCFs. Interventions (i) Horizontal interventions: administrative engagement, barrier precautions, education, environmental cleaning, hand hygiene, performance improvement, and source control; and (ii) vertical intervention: active surveillance plus decolonization. Study appraisal and synthesis We employed a random-effects meta-analysis to estimate the pooled risk ratios (pRRs) for methicillin-resistant Staphylococcus aureus (MRSA) colonization by intervention duration; and conducted subgroup analyses on different intervention components. Study quality was assessed using Cochrane risk of bias tools. Results Of 3877 studies identified, 19 were eligible for inclusion (eight randomized controlled trials (RCTs)). Studies reported outcomes associated with MRSA (15 studies), vancomycin-resistant Enterococci (VRE) (four studies), Clostridium difficile (two studies), and Gram-negative bacteria (GNB) (two studies). Eleven studies were included in the meta-analysis. The pRRs were close to unity regardless of intervention duration (long: RR 0.81 [95% CI 0.60–1.10]; medium: RR 0.81 [95% CI 0.25–2.68]; short: RR 0.95 [95% CI 0.53–1.69]). Vertical interventions in studies with a small sample size showed significant reductions in MRSA colonization while horizontal interventions did not. All studies involving active administrative engagement reported reductions. The risk of bias was high in all but two studies. Conclusions Our meta-analysis did not show any beneficial effects from IPC interventions on MRSA reductions in LTCFs. Our findings highlight that the effectiveness of interventions in these facilities is likely conditional on resource availability—particularly decolonization and barrier precautions, due to their potential adverse events and uncertain effectiveness. Hence, administrative engagement is crucial for all effective IPC programmes. LTCFs should consider a pragmatic approach to reinforce standard precautions as routine practice and implement barrier precautions and decolonization to outbreak responses only.

Abstract 181: A Systematic Review of Interventions to Increase tPA Administration

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Mollie McDermott ◽  
Lesli E Skolarus ◽  
James F Burke
Keyword(s):  
Systematic Review ◽  
Public Education ◽  
Small Sample Size ◽  
Case Reports ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Fixed Effect Model ◽  
Small Sample ◽  
Eligibility Criteria ◽  
Design Elements

Introduction: Rates of tPA administration remain low nationally and globally despite its demonstrated efficacy. We performed a systematic review and meta-analysis of interventions to increase the rate of tPA administration. Methods: We searched PubMed and EMBASE to identify all studies (excluding case reports) published between 1995 and January 8, 2015 documenting interventions to increase the utilization of tPA. We screened each study with pre-specified inclusion and exclusion criteria. Design elements and study data were extracted from eligible studies. The principal summary measure was the percentage change in rate of tPA administration. Fixed and random effects meta-analytic models were built to summarize the effect of intervention compared to control as well as intervention subtypes. Results: Our search yielded 1457 results of which 25 met eligibility criteria. We identified 13 pre-post studies and 11 randomized or quasi-experimental studies. Included studies utilized EMS (n=14), telemedicine (n=6), and public education (n=5). Intervention settings included urban (n=13), rural (n=4), and combined (n=4). In a fixed effect model, tPA administration was significantly higher in the intervention arm across all studies that limited enrollment to ischemic stroke patients (n=14) with a risk ratio (RR) of 1.71. Interventions involving EMS were associated with an increased rate of tPA administration with a RR of 1.51, (95% CI: 1.43-1.59, p<0.0001); promoting public education RR = 2.62, (95% CI: 1.54-4.43, p<0.01); and utilizing telemedicine RR = 2.97, (95% CI: 2.61-3.39, p<0.0001). Conclusions: Interventions to increase tPA use appear to have considerable efficacy. Comparative inferences between intervention types are limited by small sample size and intervention heterogeneity.

Efficacy of heavy eccentric calf training for treating mid-portion Achilles tendinopathy: a systematic review and meta-analysis

2019 ◽  
Vol 53 (17) ◽  
pp. 1070-1077 ◽  
Author(s):  
Myles Calder Murphy ◽  
Mervyn J Travers ◽  
Paola Chivers ◽  
James Robert Debenham ◽  
Sean Iain Docking ◽  
...  
Keyword(s):  
Systematic Review ◽  
Natural History ◽  
Small Sample Size ◽  
Meta Analysis ◽  
Achilles Tendinopathy ◽  
Small Sample ◽  
Current Evidence ◽  
Eligibility Criteria ◽  
Exercise Interventions ◽  
And Function

ObjectiveTo assess the effectiveness of heavy eccentric calf training (HECT) in comparison with natural history, traditional physiotherapy, sham interventions or other exercise interventions for improvements in pain and function in mid-portion Achilles tendinopathy.DesignA systematic review and meta-analysis were conducted as per the PRISMA guidelines.Data sourcesPUBMED, CINAHL (Ovid) and CINAHL (EBSCO) were searched from inception until 24 September 2018.Eligibility criteriaRandomised controlled trials comparing HECT to natural history, sham exercise, traditional physiotherapy and other exercise interventions were included. Primary outcome assessing pain and function was the Victorian Institute of Sports Assessment-Achilles.ResultsSeven studies met the inclusion criteria. This review suggests HECT may be superior to both natural history, mean difference (MD) (95% CI) of 20.6 (11.7 to 29.5, one study) and traditional physiotherapy, MD (95% CI) of 17.70 (3.75 to 31.66, two studies). Following removal of one study, at high risk of bias, due to pre-planned sensitivity analysis, this review suggests HECT may be inferior to other exercise interventions, MD (95% CI) of −5.65 (-10.51 to −0.79, three studies). However, this difference is unlikely to be clinically significant.ConclusionCurrent evidence suggests that HECT may be superior to natural history and traditional physiotherapy while HECT may be inferior to other exercise interventions. However, due to methodological limitations, small sample size and a lack of data we are unable to be confident in the results of the estimate of the effect, as the true effect is likely to be substantially different.Systematic review registryPROSPERO registration number: CRD4201804493Protocol referenceThis protocol has been published open access: Murphy M, Travers MJ, Gibson, W. Is heavy eccentric calf training superior to natural history, sham rehabilitation, traditional physiotherapy and other exercise interventions for pain and function in mid-portion Achilles tendinopathy? Systematic Reviews 2018; 7: 58

scholarly journals Deficiencies in Scientific Evidence for Medical Management of Gender Dysphoria

2019 ◽  
Vol 87 (1) ◽  
pp. 34-42 ◽  
Author(s):  
Paul W. Hruz
Keyword(s):  
Gender Identity ◽  
Gender Dysphoria ◽  
Small Sample Size ◽  
Scientific Evidence ◽  
Prospective Trial ◽  
Scientific Data ◽  
Small Sample ◽  
Sex Characteristics ◽  
Biological Sex

Individuals who experience a gender identity that is discordant with biological sex are increasingly presenting to physicians for assistance in alleviating associated psychological distress. In contrast to prior efforts to identify and primarily address underlying psychiatric contributors to gender dysphoria, interventions that include uncritical social affirmation, use of gonadotropin-releasing hormone agonists to suppress normally timed puberty, and administration of cross-sex steroid hormones to induce desired secondary sex characteristics are now advocated by an emerging cohort of transgender medicine specialists. For patients with persistent gender dysphoria, surgery is offered to alter the appearance of breasts and genital organs. Efforts to address ethical concerns regarding this contentious treatment paradigm are dependent upon reliable evidence on immediate and long-term risks and benefits. Although strong recommendations have been made for invasive and potentially irreversible interventions, high-quality scientific data on the effects of this approach are generally lacking. Limitations of the existing transgender literature include general lack of randomized prospective trial design, small sample size, recruitment bias, short study duration, high subject dropout rates, and reliance on “expert” opinion. Existing data reveal significant intervention-associated morbidity and raise serious concern that the primary goal of suicide prevention is not achieved. In addition to substantial moral questions, adherence to established principles of evidence-based medicine necessitates a high degree of caution in accepting gender-affirming medical interventions as a preferred treatment approach. Continued consideration and rigorous investigation of alternate approaches to alleviating suffering in people with gender dysphoria are warranted. Summary: This paper provides an overview of what is currently known about people who experience a gender identity that differs from their biological sex and the associated desire to engage the medical profession in alleviating associated discomfort and distress. The scientific evidence used to support current recommendations for affirming one’s preferred gender, halting normally timed puberty, administering cross-sex hormones, and surgically altering primary and secondary sexual traits are summarized and critically evaluated. Serious deficits in understanding the cause of this condition, the reasons for the marked increase in people presenting for medical care, together with immediate and long-term risks relative to benefit of medical intervention are exposed.

Efficacy and safety of colistin loading dose: a meta-analysis

2020 ◽  
Vol 75 (7) ◽  
pp. 1689-1698
Author(s):  
Ioannis Bellos ◽  
Vasilios Pergialiotis ◽  
Maximos Frountzas ◽  
Konstantinos Kontzoglou ◽  
Georgios Daskalakis ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Meta Analysis ◽  
Treatment Success ◽  
Small Sample ◽  
High Dose ◽  
Loading Dose ◽  
Efficacy And Safety ◽  
Optimal Dosing ◽  
Retrospective Cohort Studies ◽  
Dosing Strategy

Abstract Objectives Colistin represents a polypeptide used for the treatment of MDR microorganisms, although the optimal dosing strategy is under investigation. The present meta-analysis aims to determine whether the administration of a colistin loading dose in patients receiving high-dose maintenance regimens changes the rates of treatment success and the risk of nephrotoxicity. Methods Medline, Scopus, CENTRAL, Clinicaltrials.gov and Google Scholar were systematically searched from inception to 18 November 2019. Studies were considered eligible if they reported clinical outcomes among patients receiving high-dose colistin therapy with and without the administration of a loading dose. Meta-analysis was performed by fitting a random-effects model. Results Eight (three prospective and five retrospective cohort) studies were included, comprising 1115 patients. The administration of a colistin loading dose was associated with significantly higher microbiological [risk ratio (RR) = 1.23, 95% CI = 1.10–1.39] but not clinical (RR = 1.04, 95% CI = 0.87–1.24) success. No significant associations were calculated for nephrotoxicity (RR = 1.31, 95% CI = 0.90–1.91) and mortality (RR = 1.03, 95% CI = 0.82–1.29) risk. The results remained stable after adjustments for small sample size, credibility ceilings, publication bias and risk of bias. Conclusions Observational evidence suggests that the administration of a colistin loading dose in patients receiving high maintenance dosage regimens is significantly associated with higher rates of microbiological response, but does not change clinical cure, mortality or nephrotoxicity risk. The dosing regimen that would provide the optimal balance between treatment efficacy and safety needs to be determined by future randomized controlled trials.

scholarly journals Acupuncture for Chronic Pain-Related Insomnia: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Fushui Liu ◽  
Jianyu You ◽  
Qi Li ◽  
Ting Fang ◽  
Mei Chen ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Sample Size ◽  
Small Sample Size ◽  
Meta Analysis ◽  
Sham Acupuncture ◽  
Small Sample ◽  
Control Group ◽  
Large Sample Size ◽  
Cure Rate ◽  
Significant Difference

Objectives. Acupuncture has been widely used to relieve chronic pain-related insomnia (CPRI). However, the efficacy of acupuncture for CPRI is uncertain. The purpose of this study was to evaluate the efficacy of acupuncture for CPRI. Methods. Seven electronic databases were searched from inception to December 2018. Randomized controlled trials (RCTs) were included if acupuncture was compared to sham acupuncture or conventional drug therapies for treating CPRI. Two reviewers screened each study and extracted data independently. Statistical analyses were conducted by RevMan 5.3 software. Results. A total of nine studies involving 944 patients were enrolled. The pooled analysis indicated that acupuncture treatment was significantly better than control group in improving effective rate (OR = 8.09, 95%CI = [4.75, 13.79], P < 0.00001) and cure rate (OR = 3.17, 95%CI = [2.35, 4.29], P < 0.00001), but subgroup analysis showed that there was no statistically significant difference between acupuncture and sham acupuncture in improving cure rate (OR =10.36, 95% CI [0.53, 201.45], P=0.12) based on one included study. In addition, meta-analysis demonstrated that acupuncture group was superior to control group in debasing PSQI score (MD = -2.65, 95%CI = [-4.00, -1.30], P = 0.0001) and VAS score (MD = -1.44, 95%CI = [-1.58, -1.29], P < 0.00001). And there was no significant difference in adverse events (OR =1.73, 95%CI = [0.92, 3.25], P =0.09) between the two groups. Conclusions. Acupuncture therapy is an effective and safe treatment for CPRI, and this treatment can be recommended for the management of patients with CPRI. Due to the low quality and small sample size of the included studies, more rigorously designed RCTs with high quality and large sample size are recommended in future.

scholarly journals The CES1 Gene rs2244613 Minor Allele Impact on the Safety Profile of Dabigatran Etexilate: Meta-Analysis

2020 ◽  
Vol 16 (5) ◽  
pp. 699-705
Author(s):  
S. P. Abdullaev ◽  
K. B. Mirzaev ◽  
P. O. Bochkov ◽  
I. N. Sychev ◽  
D. A. Sychev
Keyword(s):  
Fixed Effects ◽  
Small Sample Size ◽  
Meta Analysis ◽  
Dabigatran Etexilate ◽  
Equilibrium Concentration ◽  
Small Sample ◽  
Heterogeneity Test ◽  
Russian Science Citation Index ◽  
Study Results ◽  
Ces1 Gene

Aim. A meta-analysis of studies on the CES1 gene c.1168-33A>C polymorphism (rs2244613) carriage influence on the equilibrium concentration and the risk of bleeding during dabigatran taking.Material and methods. The search was carried out in the Russian Science Citation Index, Google Academy, Medline PubMed, Embase databases. The meta-analysis included patients who according to the indications (atrial fibrillation, stroke, joint orthopedic surgery) were prescribed dabigatran in various doses. The association was identified in rs2244613 allele C carriers (genotypes AC and CC) and non-carriers (genotype AA). Quantitative synthesis was performed using OpenMetaAnalyst software. In statistical analysis the fixed effects model was used to estimate the influence of the allele C carriage on the any bleeding frequency and the random effects model was used to estimate the influence on the equilibrium plasma concentration level of dabigatran. The homogeneity of the analyzed studies was verified by Cochrane Q-test.Results. The analysis resulted in selection of 5 works matching all meta-analysis inclusion/exclusion criteria. All selected works included 2030 patients in total. The carriage of the rs2246613 allele C was associated with reduction of risk of any bleeding during dabigatran taking (risk ratio [RR] 0.732, 95% confidence interval [CI] 0.629-0.851; p<0.001). The heterogeneity test did not reveal any reliable differences between the study results (Q=2.183; p=0.535). The level of equilibrium residual concentration of dabigatran was not statistically significant lower for the carriers of C allele of the rs2244613 (mean difference -69.324, 95%CI -236.687-98.039; p=0.417). This might be related to the small sample size and the number of studies included in the meta-analysis. The heterogeneity test did not reveal statistically significant differences between studies (Q=0.388; I2=0%, p=0.534).Conclusion. The carriage of minor C allelic variant of rs2244613 reduces the risk of any bleeding during dabigatran taking, however, no significant association with decrease in dabigatran concentration was found.

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