Epidemiology, Clinical Features and Antifungal Resistance Profile of Candida auris in Africa: Systematic Review

Candida auris since it discovery in 2009 is becoming a severe threat to human health due to its very quickly spread, its worldwide high resistance to systemic antifungal drugs. In resource-constrained settings where several conditions are met for its emergence and spread, this worrisome fungus could cause large hospital and/or community-based outbreaks. This review aimed to summarize the available data on C. auris in Africa focusing on its epidemiology and antifungal resistance profile. Major databases were searched for articles on the epidemiology and antifungal resistance profile of C. auris in Africa. Out of 2,521 articles identified 22 met the inclusion criteria. In Africa, nearly 89% of African countries have no published data on C. auris. The prevalence of C. auris in Africa was 8.74%. The case fatality rate of C. auris infection in Africa was 39.46%. The main C. auris risk factors reported in Africa were cardiovascular disease, renal failure, diabetes, HIV, recent intake of antimicrobial drugs, ICU admissions, surgery, hemodialysis, parenteral nutrition and indwelling devices. Four phylogenetic clades were reported in Africa, namely clades I, II, III and IV. Candida auris showed a pan-African very high resistance rate to fluconazole, moderate resistance to amphotericin B, and high susceptibility to echinocandins. Finally, C. auris clade-specific mutations were observed within the ERG2, ERG3, ERG9, ERG11, FKS1, TAC1b and MRR1 genes in Africa. This systematic review showed the presence of C. auris in the African continent and a worrying unavailability of data on this resilient fungus in most African countries.

Clinical Nurses’Research Capacity Building in Practice—A Systematic Review

The aim of this study was to identify and evaluate evidence of clinical nurses’ research capacity building in practice. A systematic review of studies of nurses’ research capacity building in practice was performed. The quality of the articles was evaluated and reflected on in accordance with the Quality Assessment and Validity Tool for Correlation Studies. The literature searches identified a total of 4748 abstracts and titles. Eight quantitative studies were included in the evaluation. Three themes emerged from the analysis: Failure to ensure research quality and standards, Developing a research culture and Collaboration and organization of research utilization. The first theme has one sub-theme: Lack of knowledge about how to increase research utilization. The second theme is based on three sub-themes: Ability to identify clinical problems, changing nurses’ attitudes to research and research supervision. Finally, the third theme has one sub-theme: Funding as a success factor. In conclusion, research capacity building requires the development of research competence to generate knowledge that enhances quality and patient safety. Nurse leaders are essential for establishing evidence-based practice and a research culture, thus enhancing nurses’ scientific attitudes and capacity.

Nanomaterials-mediated lysosomal regulation:a robust protein-clearance approach for the treatment of Alzheimer’s disease

Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the brain.Lysosomes,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular homeostasis.Some studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s disease.Restoring the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s disease.Currently,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and targeting.Recently,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical properties.This review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s disease.This review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal function.In conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s disease.The application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.

A Comparative Trial: The Safety and Clinical Efficacy of PEG 3350 and Liquid Paraffin in Management of Chronic Functional Constipation in Children

Background: Constipation is one of the most common problems in the pediatric age group. In the vast majority, chronic constipation is idiopathic or functional. In addition to education and behavioral changes, disimpaction and maintenance treatment with medications are the main pillars of successful outcome. The medications are variably effective and have potential side effects. Objectives: The current clinical trial was designed to evaluate clinical efficacy of polyethylene glycol (PEG) 3350 and liquid paraffin in chronic functional constipation. Besides, subjects were followed carefully for the side effects. Material and Methods: This study was involved 110 children suffering from chronic functional constipation. They were placed into two different groups, randomly. Each group was treated with PEG 3350 or liquid paraffin. The clinical efficacy and side effects were monitored. Results: After disimpaction with bisacodyl suppositories or combined with Mineral oil enemas in hard fecal impaction, maintenance therapy with PEG 3350 or liquid paraffin was started. The treatment duration and efficacies were not different between the two groups. Furthermore, serious adverse drug reaction was not observed. The family history of constipation and presence of incontinence were two worse prognostic factors. Conclusion: No difference was observed between PEG 3350 and liquid paraffin in chronic functional constipation in children in terms of their efficacies. They are safe and effective medications in this age group.

Machine learning in data abstraction: A computable phenotype for sepsis and septic shock diagnosis in the intensive care unit

BACKGROUND With the recent change in the definition(Sepsis-3 Definition)of sepsis and septic shock,an electronic search algorithm was required to identify the cases for data automation.This supervised machine learning method would help screen a large amount of electronic medical records(EMR)for efficient research purposes.AIM To develop and validate a computable phenotype via supervised machine learning method for retrospectively identifying sepsis and septic shock in critical care patients.METHODS A supervised machine learning method was developed based on culture orders,Sequential Organ Failure Assessment(SOFA)scores,serum lactate levels and vasopressor use in the intensive care units(ICUs).The computable phenotype was derived from a retrospective analysis of a random cohort of 100 patients admitted to the medical ICU.This was then validated in an independent cohort of 100 patients.We compared the results from computable phenotype to a gold standard by manual review of EMR by 2 blinded reviewers.Disagreement was resolved by a critical care clinician.A SOFA score≥2 during the ICU stay with a culture 72 h before or after the time of admission was identified.Sepsis versions as V1 was defined as blood cultures with SOFA≥2 and Sepsis V2 was defined as any culture with SOFA score≥2.A serum lactate level≥2 mmol/L from 24 h before admission till their stay in the ICU and vasopressor use with Sepsis-1 and-2 were identified as Septic Shock-V1 and-V2 respectively.RESULTS In the derivation subset of 100 random patients,the final machine learning strategy achieved a sensitivity-specificity of 100%and 84%for Sepsis-1,100%and 95%for Sepsis-2,78%and 80%for Septic Shock-1,and 80%and 90%for Septic Shock-2.An overall percent of agreement between two blinded reviewers had a k=0.86 and 0.90 for Sepsis 2 and Septic shock 2 respectively.In validation of the algorithm through a separate 100 random patient subset,the reported sensitivity and specificity for all 4 diagnoses were 100%-100%each.CONCLUSION Supervised machine learning for identification of sepsis and septic shock is reliable and an efficient alternative to manual chart review.

Molecular detection of oxacillinase genes and typing of clinical isolates of Acinetobacter baumannii in Tehran, Iran

Objective:To determine patterns of antimicrobial resistance,analyze the prevalence of oxacillinase and molecular typing of strains of Acinetobacter baumannii(A.baumannii).Methods:A total of 121 strains of A.baumannii were obtained from patients admitted to Imam Hossein and Imam Khomeini Hospitals,Tehran,Iran,from January 2016 to November 2018.Antimicrobial susceptibility testing was performed by Kirby-Bauer disc diffusion method according to the Clinical and Laboratory Standards Institute recommendations.The presence of oxacillinase genes was assessed by polymerase chain reaction(PCR).To determine clonal relatedness,all isolates were subjected to repetitive sequence-based PCR(REP-PCR).Results:The isolates were obtained from 56(46.3%)males and 65(53.7%)females with the mean age of 39.5 years.Colistin with 100.0%sensitivity rate had the highest effect,while ceftriaxone with 16.5%sensitivity rate had the least effect on A.baumannii isolates.In addition,96(79.3%)and 99(81.8%)isolates were resistant to imipenem and meropenem,respectively.A total of 109 isolates(90.0%)exhibited multiple drug resistance with 10 different resistotypes.In total,75(75.7%)of carbapenem resistant isolates were positive for blaOXA-23-like,and 14(14.1%)for blaOXA-24-like gene.The five main clones A,B,C,D,and E were detected in 25(25.2%),36(36.4%),10(10.1%),8(8.0%),and 6(6.1%)of isolates,respectively.Conclusions:Carbapenem-resistant A.baumannii strains are high in the current study.To control the spread of carbapenem-resistant A.baumannii strains,regular monitoring programs are needed.

Relationship between Changes in Functional Capacity and Anthropometric, Clinical and Psychological Indicators in Cardiac Patients Participating in Cardiac Rehabilitation Program

Background: Cardiac rehabilitation (CR) is a multifaceted treatment that can increase the survival and quality of life of cardiac patients by increasing their functional capacity (FC). In this study, we aimed to investigate the FC changes of cardiac patients after the CR program in different subgroups in terms of anthropometric, clinical, and psychological indices. Materials and Methods: This is a descriptive retrospective study that has been derived from the results of a Cohort study at the Rehabilitation Research Center of the Cardiovascular Research Institute of Isfahan (Iran), from 2006 to 2017. In this study, the dependent variable is functional capacity changes based on Mets obtained in exercise testing at the beginning and end of the CR program. Independent variables included age, sex, dyslipidemia, diabetes, smoking, and Body mass index, type of intervention, depression, and EF. Results: The sample size is 1250 cardiovascular patients, of which 917 (73.5%) are male and 331 (26.5%) are female. Functional capacity after the CR program significantly increased in all age, gender, body mass index, hypertension, hyperlipidemia, diabetes, smoking, depression, EF, and type of operation performed (angioplasty or open-heart surgery) subgroups, (p < 0.001). Using multiple linear regression analysis, a significant relationship was found between Mets changes and only the variables of gender, depression, and EF. Conclusion: The results of this study show the importance of rehabilitation programs in the secondary prevention of cardiovascular disease in different subgroups and factors such as gender, level of primary depression, and EF less than 35 are the most important factors affecting functional capacity increase after CR program in heart patients.

Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial

Objective: To evaluate different doses of ivermectin in adult patients with mild COVID-19 and to evaluate the effect of ivermectin on mortality and clinical consequences.Methods: A randomized, double-blind, placebo-controlled, multicenter clinical trial was performed at five hospitals. A total of 180 mild hospitalized patients with COVID-19 confirmed by PCR or chest image tests were enrolled and allocated to six arms including hydroxychloroquine 200 mg twice per day, placebo plus hydroxychloroquine 200 mg twice per day, single dose ivermectin(200 μg/kg), three low interval doses of ivermectin(200, 200, 200 μg/kg), single dose ivermectin(400 μg/kg), and three high interval doses of ivermectin(400, 200, 200 μg/kg). The primary endpoint of this trial was all-cause of mortality or clinical recovery. The radiographic findings, hospitalization and low O_2 saturation duration, and hematological variables of blood samples were analyzed. Results: A total of 16.7%(5/30) and 20.0%(6/30) patients died in arms treated with hydroxychloroquine 200 mg twice per day and placebo plus hydroxychloroquine 200 mg twice per day, respectively, and a reduction in mortality rate in patients receiving ivermectin treatment to 0%, 10%, 0% and 3.3% for arms 1-4 were observed. Risk of mortality was also decreased about 15% in the ivermectin treated arms. Conclusions: Ivermectin as an adjunct reduces the rate of mortality, time of low O_2 saturation, and duration of hospitalization in adult COVID-19 patients. The improvement of other clinical parametersshows that ivermectin, with a wide margin of safety, had a high therapeutic effect on COVID-19.

Post-transplant biliary complications using liver grafts from deceased donors older than 70 years:Retrospective case-control study

BACKGROUND The shortage of liver grafts and subsequent waitlist mortality led us to expand the donor pool using liver grafts from older donors.AIM To determine the incidence,outcomes,and risk factors for biliary complications(BC)in liver transplantation(LT)using liver grafts from donors aged>70 years.METHODS Between January 1994 and December 31,2019,297 LTs were performed using donors older than 70 years.After excluding 47 LT for several reasons,we divided 250 LTs into two groups,namely post-LT BC(n=21)and without BC(n=229).This retrospective case-control study compared both groups.RESULTS Choledocho-choledochostomy without T-tube was the most frequent technique(76.2%in the BC group vs 92.6%in the non-BC group).Twenty-one patients(8.4%)developed BC(13 anastomotic strictures,7 biliary leakages,and 1 nonanastomotic biliary stricture).Nine patients underwent percutaneous balloon dilation and nine required a Rouxen-Y hepaticojejunostomy because of dilation failure.The incidence of post-LT complications(graft dysfunction,rejection,renal failure,and non-BC reoperations)was similar in both groups.There were no significant differences in the patient and graft survival between the groups.Moreover,only three deaths were attributed to BC.While female donors were protective factors for BC,donor cardiac arrest was a risk factor.CONCLUSION The incidence of BC was relatively low on using liver grafts>70 years.It could be managed in most cases by percutaneous dilation or Roux-en-Y hepaticojejunostomy,without significant differences in the patient or graft survival between the groups.

Ultrasound-guided erector spine plane block (ESPB) utilization in managing refractory renal colic pain in the emergency department

Due to the acute and terrible pain that patients with renal colic experience,the most essential therapeutic priority for these patients in the emergency department(ED)is to reduce pain.[1]Although numerous medications are utilized to reduce pain in patients with acute renal colic,no therapy has yet been developed to totally and quickly relieve pain.[2,3]Intravenous opioids and nonsteroidal anti-inflammatory drugs(NSAIDs)are commonly administered intravenously to control pain in these patients in the ED;however,the need for frequent monitoring for possible complications and relatively slow-acting features render these strategies undesirable.

Experiences of Social Isolation in Older Hospitalized Patients with COVID-19 and Their Close Relatives: A Qualitative Study

Background: Proximity between older patients and their close relatives is essential during hospitalisation. During the first wave of the pandemic, the Danish Patient Safety Authority restricted no hospital visitors. Aim: To explore how older patients with COVID-19 and their close relatives experienced physical separation during hospitalization. Method: A qualitative study using semi-structured interviews and thematic analysis was employed. Findings: Six interviews were conducted: three patients with a mean age of 81 years and three close relatives—two daughters and one spouse. The patients felt boredom, loneliness, and a sense of imprisonment, yet they felt safe and satisfied. Isolation was known beforehand from the media. Close relatives emphasised that information, involvement, and collaboration with hospital staff were crucial. Conclusion: Although older patients with COVID-19 and their close relatives widely accept their situation during hospitalization, they experience negative consequences from social isolation.

The Role of Mitochondrial VDAC2 in the Survival and Proliferation of T-Cell Acute Lymphoblastic Leukemia Cells

Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with aberrant T-cell developmental arrest. Individuals with relapsed T-ALL have limited therapeutic alternatives and poor prognosis. The mitochondrial function is critical for the T-cell viability. The voltage-dependent anion channel 2 (VDAC2) in the mitochondrial outer membrane, interacts with pro-apoptotic BCL-2 proteins and mediates the apoptosis of several cancer cell lines. Objective: The aim of the current study is to explore the role of VDAC2 in T-ALL cell survival and proliferation. Methods: Publicly available datasets of RNA-seq results were analyzed for expression of VDAC isoforms and T-ALL cell lines were treated with a VDAC2 small molecular inhibitor erastin. A VDAC2 RNA interference (siRNA) was delivered to T-ALL cell lines using a retroviral vector. Functional assays were performed to investigate the VDAC2 siRNA impacts on cell proliferation, apoptosis and survival of T-ALL cells. Results: Our analysis found a high expression of VDAC2 mRNA in various T-ALL cell lines. Public datasets of T-ALL RNA-seq also showed that VDAC2 is highly expressed in T-ALL (116.2 ± 36.7), compared to control groups. Only two T-ALL cell lines showed sensitivity to erastin (20 μM) after 48 hours of incubation, including Jurkat (IC50 = 3.943 μM) and Molt4 (IC50 = 3.286 μM), while another two T-ALL cells (CUTLL1 and RPMI 8402) had unstable IC50. However, five T-ALL cell lines (LOUCY, CCRF-CEM, P12-ICHI, HPB-ALL, and PEER cells) showed resistance to erastin. On the contrary, all T-ALL cell lines genetically inhibited with VDAC2 siRNA led to more than 80% decrease in VDAC2 mRNA levels, and a Conclusion: VDAC2 is highly expressed in T-ALL cells. The inhibition of VDAC2 significantly decreased cell viability, increased apoptosis, reduced cell proliferation and caused cell cycle sub-G1 arrest of T-ALL cells.

Investigation of litigation in trauma orthopaedic surgery

BACKGROUND It has been said that the number of orthopaedic claims has increased in the last few years. Investigation through the most prevalent cause would help to prevent further cases.AIM To review the cases of medical complaints in orthopedic patients who had been involved in a traumatic accident.METHODS A retrospective multi-center review of trauma orthopaedic-related malpractice lawsuits from 2010 to 2021 was conducted utilizing the regional medicolegal database. Defendant and plaintiff characteristics along with fracture location, allegations, and litigation outcomes were investigated.RESULTS A total of 228 claims referred to trauma-related conditions with a mean age of 31.29 ± 12.56 were enrolled. The most common injuries were at hand, thigh, elbow, and forearm, respectively.Likewise, the most common alleged complication was related to malunion or nonunion. In 47% of the cases, the main problem that led to the complaint was the inappropriate or insufficient explanation to the patient, and in 53%, there was a problem in the surgery. Eventually, 76% of the complaints resulted in a defense verdict, and 24% resulted in a plaintiff verdict.CONCLUSION Surgical treatment of hand injuries and surgery in non-educational hospitals received the most complaints. The majority of litigation outcomes were caused by a physician’s failure to fully explain and educate the traumatic orthopedic patients and technological errors.

BMI-Adjusted Tube Current in Chest CT and Comparison of Lifetime Attributable Risk (LAR) of Breast Cancer in Two Different BMI-Based Protocols

Possible strategies to reduce radiation dose during CT scanning have been investigated over recent decades;here the optimization of the tube current and its link with patient’s cancer incidence are being evaluated. 154 consecutive trauma patients with the need for chest CT scan were included. Two different BMI-adjusted CT protocols at a fixed voltage tube and the same scan length were applied. Dose estimation parameters like CT dose index (CTDI), dose length product (DLP) and effective breast dose were calculated. Breast surface dose was obtained by using thermoluminescence dosimeters (TLDs) and eventually, the life attributable risk (LAR) of cancer incidence was estimated. The mean effective dose was 4.87 ± 2.3 mSv and 5.12 ± 2.8 mSv for patients who were scanned with tube currents of 120 mAs and 200 mAs, respectively. There was no significant difference between organ surface doses for females but in males it was notable. The risk of cancer incidence is lower for protocol 1 in comparison with protocol 2. Optimizing tube current of 120 mAs reduced breast surface dose up to 50% in comparison with the tube current of 200 mAs. In trauma patients, using lower tube current based on BMI has notable impact on the absorbed dose in the breast and can reduce the breast cancer risk by nearly 33.6% for women.

Comparison of the Use of Conventional and Antibiotic-Coated Tracheal Tubes and EVAC on the Incidence of Ventilator-Associated Pneumonia (VAP)

Ventilator-associated pneumonia (VAP) is one of the most important hospital infections in hospitalized patients, which is associated with increased mortality and patient costs. The tracheal tube itself seems to be a major risk factor for VAP. Contaminated secretions pass through the endotracheal tube and reach the lungs. Also, bacteria form a bacterial biofilm on the tracheal tube and are transferred from there to the lungs. Different tracheal tube designs have been produced to overcome these cases. The purpose of this study is to investigate the effect of an Evac tracheal tube covered with antibiotics and normal on the incidence of pneumonia caused by the ventilator. Research method: 180 patients were randomly intubated in three groups of 60 people with three types of tracheal tubes, Evac and Bactiguard. Clinical examinations, endotracheal tube aspiration culture, and chest radiography were obtained from the patients and the incidence of VAP was calculated based on the CPIS standard. The relationship between the type of endotracheal tube and the incidence of VAP and the length of stay in the intensive care unit (ICU) and being discharged alive from the ICU were investigated. Findings and conclusions: The average incidence of VAP for the group of patients intubated with a conventional tracheal tube was 50%, EVAC was 45% and Bactiguard was 40%. The results showed that there is no significant relationship between the incidence of ventilator-induced pneumonia and the type of tracheal tube. The incidence of ventilator-induced pneumonia was not significantly reduced by suctioning subglottic secretions and Bactiguard tracheal tubes. It seems that using one method alone is not effective in reducing ventilator-induced pneumonia.

Diabetic nephropathy and inflammation

Diabetic nephropathy(DN) is the leading cause of end-stage renal failure worldwide. Besides, diabetic nephropathy is associated with cardiovascular disease, and increases mortality of diabetic patients. Several factors are involved in the pathophysiology of DN, including metabolic and hemodynamic alterations, oxidative stress, and activation of the renin-angiotensin system. In recent years, new pathways involved in the development and progression of diabetic kidney disease have been elucidated; accumulated data have emphasized the critical role of inflammation in the pathogenesis of diabetic nephropathy. Expression of cell adhesion molecules, growth factors, chemokines and pro-inflammatory cytokines are increased in the renal tissues of diabetic patients, and serum and urinary levels of cytokines and cell adhesion molecules, correlated with albuminuria. In this paper we review the role of inflammation in the development of diabetic nephropathy, discussing some of the major inflammatory cytokines involved in the pathogenesis of diabetic nephropathy, including the role of adipokines, and take part in other mediators of inflammation, as adhesion molecules.

Alterations of glutathione S-transferase and matrix metalloproteinase-9 expressions are early events in esophageal carcinogenesis

AIM: To investigate the role of glutathione S-transferase (GST) and matrix metalloproteinase-9 (MMP-9) expres-sions in the development and progression of reflux es-ophagitis-Barrett’s metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.METHODS: GST and MMP-9 expressions were analyzed in 51 paraffin-embedded tissue samples by immunohisto-chemistry including patients with reflux esophagitis (n = 7), Barrett’s metaplasia (n = 14), Barrett and esophagi-tis (n = 8), Barrett and dysplasia (n = 7), esophageal adenocarcinoma (n = 8) and a control group without any histological changes (n = 7). Immunostaining was determined semiquantitatively. Statistical analysis with one-way ANOVA, LSD test and correlation analysis were performed. P value of < 0.05 was considered significant.RESULTS: GST expression was significantly higher while MMP-9 expression was significantly lower in control group compared to Barrett’s metaplasia and the other groups. No major changes were observed between Bar-rett, esophagitis, and Barrett and concomitant esophagi-tis. Barrett and concomitant dysplasia, and adenocarci-noma revealed a significant lower expression of GST and higher levels of MMP-9 compared to all other groups. Adenocarcinoma showed almost no expression of GST and significantly higher levels of MMP-9 than Barrett and concomitant dysplasia. Alterations of GST and MMP-9 were inversely correlated (r = - 0.82).CONCLUSION: Decreased GST and increased ex-pression of MMP-9 in Barrett’s metaplasia-dysplasia-adenocarcinoma sequence as compared to normal tissue suggest their association with esophageal tumorigenesis. Loss of GST and gain of MMP-9 in Barrett with dyspla-sia compared to non-dysplastic metaplasia indicate that these alterations may be early events in carcinogenesis. Quantification of these parameters in Barrett’s esopha-gus might be useful to identify patients at higher risk for progression to cancer.

Incidence and mortality of acute and chronic pancreatitis in the Netherlands:A nationwide record-linked cohort study for the years 1995-2005

AIM:To analyze trends in incidence and mortality of acute pancreatitis(AP) and chronic pancreatitis(CP) in the Netherlands and for international standard populations.METHODS:A nationwide cohort is identified through record linkage of hospital data for AP and CP,accumulated from three nationwide Dutch registries:the hospital discharge register,the population register,and the death certificate register.Sex-and age-group specific incidence rates of AP and CP are defined for the period 2000-2005 and mortality rates of AP and CP for the period 1995-2005.Additionally,incidence and mortality rates over time are reported for Dutch and international(European and World Health Organization) standard populations.RESULTS:Incidence of AP per 100000 persons per year increased between 2000 and 2005 from 13.2(95%CI:12.6-13.8) to 14.7(95%CI:14.1-15.3).Incidence of AP for males increased from 13.8(95%CI:12.9-14.7) to 15.2(95%CI:14.3-16.1),for females from 12.7(95%CI:11.9-13.5) to 14.2(95%CI:13.4-15.1).Irregular patterns over time emerged for CP.Overall mean incidence per 100000 persons per year was 1.77,for males 2.16,and for females 1.4.Mortality for AP fluctuated during 1995-2005 between 6.9 and 11.7 per million persons per year and was almost similar for males and females.Concerning CP,mortality for males fluctuated between 1.1(95%CI:0.6-2.3) and 4.0(95%CI:2.8-5.8),for females between 0.7(95%CI:0.3-1.6) and 2.0(95%CI:1.2-3.2).Incidence and mortality of AP and CP increased markedly with age.Standardized rates were lowest for World Health Organization standard population.CONCLUSION:Incidence of AP steadily increased while incidence of CP fluctuated.Mortality for both AP and CP remained fairly stable.Patient burden and health care costs probably will increase because of an ageing Dutch population.

Prevalence and risk factors of methotrexate hepatoxicity in Asian patients with psoriasis

AIM: To establish the prevalence of liver fibrosis and to evaluate the possible risk factors for fibrosis and progression in Asian with psoriasis treated with methotrexate (MTX) based on liver histology. METHODS: Patients with psoriasis treated with MTX referred to the Department of Gastroenterology, Tan Tock Seng Hospital for liver biopsy were identified and retrospectively studied. Patient case notes and electronic records were retrieved from the hospital database and relevant data collated. Histological changes of liver biopsies were staged according to Roengik score. The factors assessed were age, gender, ethnicity, cumulative dose of MTX, presence of comorbid conditions such as diabetes, hypertension, hyperlipidemia, and ethanol use. We also assessed the histological change in those with multiple liver biopsies. Statistical analysis was performed using Stata V.9.2. RESULTS: There were altogether 59 patients (median age 50 years old, range 22-81 years old, male, 88%) with 98 biopsies liver biopsies; 6 normal [median cumulative dose (MCD), 2285 mg]; 62 gradeⅠ (MCD 2885 mg), 23 grade Ⅱ (MCD 1800 mg) and 7 grade Ⅲ (MCD 1500 mg). There was no grade Ⅳ or cirrhosis. The prevalence of liver fibrosis (grade Ⅲ) was 12%. Of the factors assessed, diabetes (P=0.001) and hypertension (P=0.003) were significant for fibrosis on univariate analysis but not on multivariate analysis. Of the 26 patients who had more than one biopsy (median 2, range 2-6), 57.7% (n=15) were stable, 34.6% (n=9) had progression and 7.7% (n=2) had regression of histological grades. On univariate analysis, nonChinese ethnicity (P=0.031), diabetes (P=0.018), and hyperlipidemia (P=0.011) were predictive of progression of grades, but these were not significant on multivariate analysis. CONCLUSION: Liver fibrosis in Asian psoriatic population on MTX is comparable to the West. Cumulative dose was not associated with liver fibrosis. Metabolic syndrome is important factors.

International NeuroAIDS: prospects of HIV-1 associated neurological com-plications

Neurological complications associated with HIV-1/AIDS are being recognized with a high frequency that parallels the increased number of AIDS cases. The early infiltration by HIV-1 into the nervous system can cause primary and/or secondary neurological complications. The most common neurocognitive disorder is AIDS Dementia Complex (ADC). In developing countries of Asia the three most opportunistic infections are tuberculosis (TB), cryptococcosis, and Pneumocystis carinii pneumonia. Therefore, it is expected that secondary neurological complications due to TB and cryptococcosis will be the most common cause of morbility and mortality in HIV-1/AIDS cases in China. Research of NeuroAIDS in China is necessary to understand the impact and the biology of HIV-1 in the nervous system. Future studies would include, the molecular epidemiology and the description of opportunistic infections associated to HIV-1; the neuropathological description of primary and secondary HIV-1 complications in different groups; the HIV-1 neurot- ropism and immune response studies for China’s unique HIV-1 strains and recombinant forms derived from the nervous system, including experimental models such as the use of transgenic rats; and the study of potential resistant virus, primarily when the anti-retroviral therapy (ART) has not full access in the brain.