Association of HLA-B*5701 genotypes and abacavir-induced hypersensitivity reaction: a sysyematic review and meta-analysis

OBJECTIVES: This study aimed to systematically review and quantitatively synthesize the association between HLA-B*5701 and abacavir-induced hypersensitivity reaction (ABC-HSR). METHODS: We searched for studies that investigated the association between HLA-B genotype and ABCHSR and provided information about the frequency of carriers of HLA-B genotypes among cases and controls. We then performed a meta-analysis with a random-effects model to pool the data and to investigate the sources of heterogeneity. RESULTS: From 1,026 articles identified, ten studies were included. Five using clinical manifestation as their diagnostic criteria, 409 and 1,883 subjects were included as cases and controls. Overall OR was 23.6 (95% CI = 15.4 – 36.3). Whereas, the another five studies using confirmed immunologic test as their diagnostic criteria, 110 and 1,968 subjects were included as cases and controls, respectively. The association of ABC-HSR was strong in this populations with HLA-B*5701. Overall OR was 1,056.2 (95% CI = 345.0 – 3,233.3). CONCLUSIONS: Using meta-analysis technique, the association between HLA-B*5701 and ABC-HSR is strong in the studies using immunologic confirmation to identify ABC-HSR. These results support the US FDA recommendations for screening HLA-B*5701 allele before initiating abacavir therapy

Relationship between the HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson Syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis

IMPORTANCE: The US Food and Drug Administration recommends screening for the HLA-B*1502 allele before initiation of carbamazepine therapy in patients of Asian ancestry, but there remains unclear evidence of a relationship between HLA-B*1502 and Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) among carbamazepine users, especially in some racial/ethnic populations. OBJECTIVE: To determine the relationship between the HLA-B*1502 allele and carbamazepine-induced SJS and TEN. DATA SOURCES: A comprehensive search of the following data sources was performed without language restriction from the inception of the database until January 8, 2013: EMBASE, PubMed, clinicaltrials.gov, Cochrane Library, IPA (International Pharmaceutical Abstracts), HuGENet (Human Genome Epidemiology Network), and CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the reference lists of identified studies. STUDY SELECTION: Inclusion criteria were studies that investigated the relationship between HLA-B*1502 and carbamazepine-induced SJS and TEN and that reported sufficient data for calculating the frequency of HLA-B*1502 carriers among cases and controls. The search yielded 525 articles, of which 16 met the inclusion criteria. The studies included 227 SJS or TEN cases, 602 matched control subjects, and 2949 population control subjects. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted the following data: study design, eligibility criteria, diagnostic criteria, patient demographics, genotype distribution, HLA-B genotyping technique, selection of cases and controls, dosage of carbamazepine and duration of use, and results of Hardy-Weinberg equilibrium in the control group. The Newcastle-Ottawa Scale was used to assess the quality of studies. The overall odds ratios (ORs) with corresponding 95% CIs were calculated using a random-effects model. The primary analysis was based on matched control studies. Subgroup analyses by race/ethnicity were also performed. MAIN OUTCOME AND MEASURE: The primary outcomewas carbamazepine-induced SJS and TEN. The outcome measure is given as an overall OR. RESULTS: The summary OR for the relationship between HLA-B*1502 and carbamazepine-induced SJS and TEN was 79.84 (95% CI, 28.45-224.06). Racial/ethnic subgroup analyses yielded similar findings for Han-Chinese (115.32; 18.17-732.13), Thais (54.43; 16.28-181.96), and Malaysians (221.00; 3.85-12 694.65). Among individuals of white or Japanese race/ethnicity, no patients with SJS or TEN were carriers of the HLA-B*1502 allele. CONCLUSIONS AND RELEVANCE: We found a strong relationship between the HLA-B*1502 allele and carbamazepine-induced SJS and TEN in Han-Chinese, Thai, and Malaysian populations. HLA-B*1502 screening in patients requiring carbamazepine therapy is warranted

Association of HLA-B*5801 allele and allopurinol-induced stevens johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis

Background: Despite some studies suggesting a possible association between human leukocyte antigen, HLA-B*5801 and allopurinol induced Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), the evidence of association and its magnitude remain inconclusive. This study aims to systematically review and meta-analyze the association between HLA-B*5801 allele and allopurinol-induced SJS/TEN.Methods: A comprehensive search was performed in databases including MEDLINE, Pre-MEDLINE, Cochrane Library, EMBASE, International Pharmaceutical Abstracts (IPA), CINAHL, PsychInfo, the WHO International, Clinical Trial Registry, and ClinicalTrial.gov from their inceptions to June 2011. Only studies investigating association between HLA-B*5801 with allopurinol-induced SJS/TEN were included. All studies were extracted by two independent authors. The primary analysis was the carrier frequency of HLA-B*5801 comparison between allopurinol-induced SJS/TEN cases and each comparative group. The pooled odds ratios were calculated using a random effect model.Results: A total of 4 studies with 55 SJS/TEN cases and 678 matched-controls (allopurinol-tolerant control) was identified, while 5 studies with 69 SJS/TEN cases and 3378 population-controls (general population) were found. SJS/TEN cases were found to be significantly associated with HLA-B*5801 allele in both groups of studies with matched-control (OR 96.60, 95%CI 24.49-381.00, p < 0.001) and population-control (OR 79.28, 95%CI 41.51-151.35, p < 0.001). Subgroup analysis for Asian and Non-Asian population yielded similar findings.Conclusion: We found a strong and significant association between HLA-B*5801 and allopurinol-induced SJS/TEN. Therefore, HLA-B*5801 allele screening may be considered in patients who will be treated with allopurinol

The diagnostic accuracy of isothermal nucleic acid point-of-care tests for human coronaviruses: A systematic review and meta-analysis

Many recent studies reported coronavirus point-of-care tests (POCTs) based on isothermal amplification. However, the performances of these tests have not been systematically evaluated. Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy was used as a guideline for conducting this systematic review. We searched peer-reviewed and preprint articles in PubMed, BioRxiv and MedRxiv up to 28 September 2020 to identify studies that provide data to calculate sensitivity, specificity and diagnostic odds ratio (DOR). Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was applied for assessing quality of included studies and Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) was followed for reporting. We included 81 studies from 65 research articles on POCTs of SARS, MERS and COVID-19. Most studies had high risk of patient selection and index test bias but low risk in other domains. Diagnostic specificities were high (&gt; 0.95) for included studies while sensitivities varied depending on type of assays and sample used. Most studies (n = 51) used reverse transcription loop-mediated isothermal amplification (RT-LAMP) to diagnose coronaviruses. RT-LAMP of RNA purified from COVID-19 patient samples had pooled sensitivity at 0.94 (95% CI: 0.90–0.96). RT-LAMP of crude samples had substantially lower sensitivity at 0.78 (95% CI: 0.65–0.87). Abbott ID Now performance was similar to RT-LAMP of crude samples. Diagnostic performances by CRISPR and RT-LAMP on purified RNA were similar. Other diagnostic platforms including RT- recombinase assisted amplification (RT-RAA) and SAMBA-II also offered high sensitivity (&gt; 0.95). Future studies should focus on the use of un-bias patient cohorts, double-blinded index test and detection assays that do not require RNA extraction

Additive synergism between asbestos and smoking in lung cancer risk: a systematic review and meta-analysis

Smoking and asbestos exposure are important risks for lung cancer. Several epidemiological studies have linked asbestos exposure and smoking to lung cancer. To reconcile and unify these results, we conducted a systematic review and meta-analysis to provide a quantitative estimate of the increased risk of lung cancer associated with asbestos exposure and cigarette smoking and to classify their interaction. Five electronic databases were searched from inception to May, 2015 for observational studies on lung cancer. All case-control (N = 10) and cohort (N = 7) studies were included in the analysis. We calculated pooled odds ratios (ORs), relative risks (RRs) and 95% confidence intervals (CIs) using a random-effects model for the association of asbestos exposure and smoking with lung cancer. Lung cancer patients who were not exposed to asbestos and non-smoking (A-S-) were compared with; (i) asbestos-exposed and non-smoking (A+S-), (ii) non-exposure to asbestos and smoking (A-S+), and (iii) asbestos-exposed and smoking (A+S+). Our meta-analysis showed a significant difference in risk of developing lung cancer among asbestos exposed and/or smoking workers compared to controls (A-S-), odds ratios for the disease (95% CI) were (i) 1.70 (A+S-, 1.31-2.21), (ii) 5.65; (A-S+, 3.38-9.42), (iii) 8.70 (A+S+, 5.8-13.10). The additive interaction index of synergy was 1.44 (95% CI = 1.26-1.77) and the multiplicative index = 0.91 (95% CI = 0.63-1.30). Corresponding values for cohort studies were 1.11 (95% CI = 1.00-1.28) and 0.51 (95% CI = 0.31-0.85). Our results point to an additive synergism for lung cancer with co-exposure of asbestos and cigarette smoking. Assessments of industrial health risks should take smoking and other airborne health risks when setting occupational asbestos exposure limits

Assessing clinical evidence of drug interactions between citrus juices and cyclosporine

Background: Previous studies have demonstrated that grapefruit juice increased the bioavailability of cyclosporine;however, the results from the literature are inconsistent. Other citrus fruits such as pomelo or orange juice had variable effects on the bioavailability of cyclosporine.Objective: To assess the effect of grapefruit juice and other types of citrus juice on oral bioavailability of cyclosporine in humans using meta-Analysis.Methods: We conducted a meta-Analysis of placebo-controlled studies evaluating the effects of citrus juices on bioavailability of cyclosporine. The studies were identified in PubMed, Cochrane CENTRAL, CINAHL, ISI Web of Knowledge, Psych Info International, Pharmaceutical Abstract (IPA), and reference lists of relevant papers. The weighted-mean difference (WMD) was calculated for net changes in the area under the curve (AUC) of cyclosporine. All studies conducted as placebo-controlled crossover studies in humans to compare the effect of citrus juices and control (drinking water) on AUC of cyclosporine and/or Cmin,ss were reviewed. All studies included were evaluated and extracted independently, and discrepancies were resolved through discussion.Results: Eighteen studies were identified. A subgroup analysis suggested that grapefruit juice significantly increased AUC of cyclosporine (WMD = 1762.5 ng·h/ml, 95%CI = 1178.9-2346.0 ng·h/ml, p > 0.001). While a meta-Analysis of all other types of citrus juices (tangerine juice, Seville orange juice, sweet orange juice, and citrus soda) except pomelo juice revealed no effect on the AUC of cyclosporine (WMD = -181.0 ng·h/ml,95%CI = -582.8-220.9 ng·h/ml, p > 0.5), a study of pomelo juice indicated a significant increase in the AUC of cyclosporine.Conclusions: Grapefruit juice intake increases oral bioavailability of cyclosporine in both healthy volunteers and renal transplant patients, whereas all other types of citrus juices may not have an influence on the oral bioavailability of cyclosporine. Current evidence suggests that pomelo juice may be able to increase cyclosporine oral bioavailability

Surgery for congenital Browns syndrome

Die operative Behandlung des kongenitalen Brown-Syndroms zeigt oft unbefriedigende Ergebnisse. In dieser Arbeit wurde der Effekt der Obliquus-superior-Rücklagerung retrospektiv untersucht. Da zum spontanen Verlauf des kongenitalen Brown-Syndroms nur spärliche Berichte vorliegen, wurden auch Patienten mit kongenitalem Brown-Syndrom, die nicht operiert wurden, in einem definierten Zeitraum nachuntersucht, um spontane Verbesserungen hinsichtlich der Motilität und Schielwinkel zu erfassen. Die Befunde wurden anhand der Krankenakten von Patienten ausgewertet, von denen 27 (Gruppe A) wegen eines kongenitalen Brown-Syndroms operiert und 18 (Gruppe B) lediglich beobachtet wurden. Die Operationsindikation zur Rücklagerung der Obliquus-superior-Sehne wurde bei einer manifesten Vertikaldeviation im Geradeausblick mit kompensatorischer Kopfzwangshaltung und deutlichem Hebungsdefizit in Adduktion des betroffenen Auges gestellt, wenn die Störung spontan nicht rückläufig war. Die Schielwinkel wurden in beiden Gruppen mit dem einseitigen bzw. simultanen und dem alternierenden Prismenabdecktest gemessen, die maximale monokulare Exkursion nach Führungsbewegungen und die Kopfzwangshaltung mit einem Goniometer bei Fernfixation bestimmt. Die Messungen in der Gruppe A erfolgten 1 Tag präoperativ, innerhalb von 3 Monaten früh postoperativ und bei 13 Patienten spät postoperativ nach 1,5-10 Jahren. Der Beobachtungszeitraum der Gruppe B betrug 1,5-11 Jahre ab der ersten Vorstellung. Die Patienten der Gruppe A wurden im Alter von 4-45 (Median 7) Jahren operiert, 14 waren männlich, 16-mal war das rechte Auge betroffen. Acht Patienten wiesen eine Eso-, einer eine Exotropie auf, bei einem Patienten wurde eine kombinierte Konvergenzoperation und bei einem eine kombinierte Divergenzoperation gleichzeitig mit der Rücklagerung des Obliquus superior durchgeführt. Präoperativ betrug der Tieferstand des betroffenen Auges in Primärposition 0-12° (Median 7°). Die Hebung in Adduktion war mindestens 10° unter, höchstens 15° über die Mittellinie (Median 0°) möglich und in Abduktion mit 10-35° (Median 25°) deutlich besser. Neunzehn Patienten nahmen eine Kopfzwangshaltung ein. Die Rücklagerungsstrecke betrug zwischen 6 bis 14 mm, 4-mal mit zusätzlicher freier Schlinge (6-0 Polyester). Am Ende der Operation war die passive Hebung in Adduktion wesentlich gebessert. Postoperativ war der Tieferstand auf 0-6° (Median 1°) reduziert. Zwölf Patienten nahmen postoperativ noch eine geringe Kopfzwangshaltung ein. Die aktive Hebungsfähigkeit war trotz freier passiver Motilität initial nur gering besser (5° unter bis 15° über Mittellinie, Median 5°). Bei der Spätkontrolle waren der residuelle Tieferstand (0-4°, Median 0°) und die aktive Hebung deutlich verbessert (5-35° über Mittellinie, Median 15°). Nur ein Patient zeigte noch eine geringe Kopfzwangshaltung. Die 18 Patienten der Gruppe B wurden im Alter von 2-9 Jahren in unserer Klinik untersucht, davon waren 8 männlich, das rechte Auge war 11-mal betroffen. Bei der ersten Untersuchung betrug der Tieferstand in Primärposition 0-14° (Median 0°), die Hebungsfähigkeit des betroffenen Auges war auf 10° unter bis 15° über die Mittellinie (Median 0°) eingeschränkt. In Abduktion wiesen nur 2 Patienten ein Hebungsdefizit auf. Sieben Patienten nahmen eine Kopfzwangshaltung ein. Nach 1,5-11 Jahren bestand bei 2 Patienten ein Tieferstand in Primärposition, die Hebungsfähigkeit war bei 10 Patienten deutlich verbessert, bei 6 Patienten unverändert. Zwei Patienten nahmen eine Kopfzwangshaltung ein. Die Rücklagerung der Obliquus-superior-Sehne erwies sich somit als effektives und sicheres Verfahren zur Behandlung des kongenitalen Brown-Syndroms. Das Höhenschielen im Geradeausblick und damit die Kopfzwangshaltung werden unmittelbar reduziert. Die Hebungsfähigkeit verbessert sich mit Verzögerung, bleibt allerdings nicht selten auch langfristig eingeschränkt. Die Variabilität der Operationseffekte ist vermutlich auf die heterogene Ätiologie des Brown-Syndroms zurückzuführen. Aufgrund der möglichen Spontanheilung sollte die Indikation zur Operation erst nach einer Beobachtungszeit von ca. 2 Jahren und nur dann gestellt werden, wenn die Störung nicht spontan rückläufig ist.Various surgical procedures were reported for congenital (true) Brown’s syndrome. There are only few reports on the spontaneous course of the Brown’s syndrome. In this retrospective study, the effects of superior oblique tendon recession were evaluated and the spontaneous development of ocular motility was observed in another group of patients. The files of 27 patients (group A) were evaluated who received surgery for congenital Brown’s syndrome in our department and the files of 18 patients (group B) whose spontaneous course was observed. Recession of the superior oblique tendon was performed when there was a significant elevation deficit in adduction with hypotropia in straight gaze and an abnormal head posture and if these findings did not improve spontaneously. Squint angles (simultaneous and alternate prism and cover test), monocular motility and the abnormal head posture at distance fixation were assessed. Measurements in group A were performed 1 day before and about 3 month after surgery. Thirteen patients were examined 2-10 years after surgery. In group B the time interval under review ranged from 1.5 to 11 years after the first consultation. At the time of surgery, the patients of group A (n=27) were 4-45 years (median 7 years) old. Fourteen patients were male and 14 were female. In 16 cases the right eye was concerned. Eight patients had additional esotropia, one patient was exotropic. In two cases surgery for eso/exotropia was performed simultaneously. The preoperative vertical deviation in straight gaze was 0-12 deg (median 7 deg). Elevation of the concerned eye was restricted to 10 deg below midline up to 15 deg above midline (median 0 deg) in adduction and to 10-35 deg (median 25 deg) in abduction. Nineteen patients had an abnormal head posture. The superior oblique tendon was recessed by 6-14 mm, in 4 patients with an additional loop (6-0 Polyester). The forced duction test showed free elevation in adduction of the concerned eye. Postoperatively, the vertical deviation in straight gaze was 0-6 deg (median 1 deg). Twelve Patients showed low abnormal head posture. In spite of free passive motility at the end of surgery, the monocular elevation in adduction was only slightly improved to -5 to 15 deg (median 5 deg). At the final check-up, hypotropia in straight gaze was 0-4 deg (median 0 deg), elevation in adduction (5-35 deg, median 15) was significantly improved, and only one patient still had an abnormal head posture. Patients in group B (n =18) were 2-9 years old at the first consultation. Eight patients were male and 10 female. In 11 cases the right eye was concerned. The vertical deviation in primary position was 0-14 deg (median 0°). Elevation in adduction of the concerned eye was restricted to -10 below midline to 15 deg above midline (median 0°). In abduction, 2 patients showed an elevation deficiency. Seven patients had abnormal head posture. At the late control after 1.5-11 years, 6 patients were hypotropic in straight gaze, 10 patients showed significant, 6 patients showed no improvement of elevation in adduction. Only 2 patients still had abnormal head posture. Recession of the superior oblique tendon is an effective and safe surgical procedure for congenital Brown’s syndrome. Both vertical deviation in straight gaze and abnormal head posture improved immediately after surgery, while active elevation in adduction improved with delay and did not regularly become normal. The effect of the procedure was individually variable. Presumably, this variability is caused by the heterogeneous etiology of Brown’s syndrome rather than by the surgical technique. The decision to operate should be made carefully and an observation period of about 2 years should be awaited because spontaneous improvement is possible

Effect of the Exposure to Asbestos (A) and/or Cigarette Smoking (S) on Lung Cancer Risk in Case-Control Studies, Stratified by smoking levels.

<p>Effect of the Exposure to Asbestos (A) and/or Cigarette Smoking (S) on Lung Cancer Risk in Case-Control Studies, Stratified by smoking levels.</p

Characteristics of studies included in the meta-analysis.

<p>*All studies are occupational exposures</p><p>**NOS = Newcastle Ottawa-Scale</p><p>Characteristics of studies included in the meta-analysis.</p