Extracorporeal Treatment in Phenytoin Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup

The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup conducted a systematic literature review using a standardized process to develop evidence-based recommendations on the use of extracorporeal treatment (ECTR) in patients with phenytoin poisoning. The authors reviewed all articles, extracted data, summarized findings, and proposed structured voting statements following a predetermined format. A 2-round modified Delphi method was used to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. 51 articles met the inclusion criteria. Only case reports, case series, and pharmacokinetic studies were identified, yielding a very low quality of evidence. Clinical data from 31 patients and toxicokinetic grading from 46 patients were abstracted. The workgroup concluded that phenytoin is moderately dialyzable (level of evidence = C) despite its high protein binding and made the following recommendations. ECTR would be reasonable in select cases of severe phenytoin poisoning (neutral recommendation, 3D). ECTR is suggested if prolonged coma is present or expected (graded 2D) and it would be reasonable if prolonged incapacitating ataxia is present or expected (graded 3D). If ECTR is used, it should be discontinued when clinical improvement is apparent (graded 1D). The preferred ECTR modality in phenytoin poisoning is intermittent hemodialysis (graded 1D), but hemoperfusion is an acceptable alternative if hemodialysis is not available (graded 1D). In summary, phenytoin appears to be amenable to extracorporeal removal. However, because of the low incidence of irreversible tissue injury or death related to phenytoin poisoning and the relatively limited effect of ECTR on phenytoin removal, the workgroup proposed the use of ECTR only in very select patients with severe phenytoin poisoning

Accuracy of Nasal Nitric Oxide Measurement as a Diagnostic Test for Primary Ciliary Dyskinesia: A Systematic Review and Meta-Analysis

RATIONALE: Primary ciliary dyskinesia (PCD) is a rare disorder causing chronic otosinopulmonary disease, generally diagnosed through evaluation of respiratory ciliary ultrastructure and/or genetic testing. Nasal nitric oxide (nNO) measurement is used as a PCD screening test because patients with PCD have low nNO levels, but its value as a diagnostic test remains unknown. OBJECTIVES: To perform a systematic review to assess the utility of nNO measurement (index test) as a diagnostic tool compared with the reference standard of electron microscopy (EM) evaluation of ciliary defects and/or detection of biallelic mutations in PCD genes. DATA SOURCES: Ten databases were searched for reference sources from database inception through July 29, 2016. DATA EXTRACTION: Study inclusion was limited to publications with rigorous nNO index testing, reference standard diagnostic testing with EM and/or genetics, and calculable diagnostic accuracy information for cooperative patients (generally >5 yr old) with high suspicion of PCD. SYNTHESIS: Meta-analysis provided a summary estimate for sensitivity and specificity and a hierarchical summary receiver operating characteristic curve. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess study quality, and Grading of Recommendations Assessment, Development, and Evaluation was used to assess the certainty of evidence. In 12 study populations (1,344 patients comprising 514 with PCD and 830 without PCD), using a reference standard of EM alone or EM and/or genetic testing, summary sensitivity was 97.6% (92.7-99.2) and specificity was 96.0% (87.9-98.7), with a positive likelihood ratio of 24.3 (7.6-76.9), a negative likelihood ratio of 0.03 (0.01-0.08), and a diagnostic odds ratio of 956.8 (141.2-6481.5) for nNO measurements. After studies using EM alone as the reference standard were excluded, the seven studies using an extended reference standard of EM and/or genetic testing showed a summary sensitivity of nNO measurements of 96.3% (88.7-98.9) and specificity of 96.4% (85.1-99.2), with a positive likelihood ratio of 26.5 (5.9-119.1), a negative likelihood ratio of 0.04 (0.01-0.12), and a diagnostic odds ratio of 699.3 (67.4-7256.0). Certainty of the evidence was graded as moderate. CONCLUSIONS: nNO is a sensitive and specific test for PCD in cooperative patients (generally >5 yr old) with high clinical suspicion for this disease. With a moderate level of evidence, this meta-analysis confirms that nNO testing using velum closure maneuvers has diagnostic accuracy similar to EM and/or genetic testing for PCD when cystic fibrosis is ruled out. Thus, low nNO values accompanied by an appropriate clinical phenotype could be used as a diagnostic PCD test, though EM and/or genetics will continue to provide confirmatory information

Anthropogenically induced adaptation to invade (AIAI): contemporary adaptation to human-altered habitats within the native range can promote invasions

Adaptive evolution is currently accepted as playing a significant role in biological invasions. Adaptations relevant to invasions are typically thought to occur either recently within the introduced range, as an evolutionary response to novel selection regimes, or within the native range, because of long-term adaptation to the local environment. We propose that recent adaptation within the native range, in particular adaptations to human-altered habitat, could also contribute to the evolution of invasive populations. Populations adapted to human-altered habitats in the native range are likely to increase in abundance within areas frequented by humans and associated with human transport mechanisms, thus enhancing the likelihood of transport to a novel range. Given that habitats are altered by humans in similar ways worldwide, as evidenced by global environmental homogenization, propagules from populations adapted to human-altered habitats in the native range should perform well within similarly human-altered habitats in the novel range. We label this scenario ‘Anthropogenically Induced Adaptation to Invade’. We illustrate how it differs from other evolutionary processes that may occur during invasions, and how it can help explain accelerating rates of invasions

Case reports of extracorporeal treatments in poisoning: historical trends

There are currently limited data on the trends in case reporting of poisoned patients undergoing enhanced elimination with an extracorporeal treatment (ECTR). The present manuscript specifically reviews the longitudinal trends of reports according to technique, poison, and country of publication. To identify case reports of ECTR use in the management of poisoning, multiple databases were searched. There were no limitations on language and year of publication. All case reports describing individual patients undergoing ECTR with the intent of enhancing the elimination of a poison were included in the analysis. Since 1913, 2908 reports were identified. There were an increasing number of published reports with time except for a slight decrease during the 1990s. Hemodialysis was by far the most commonly used ECTR in poisoning, followed by hemoperfusion. The number of reported peritoneal dialyses decreased steadily since 1980s. Methanol, ethylene glycol, lithium, and salicylates remained among the most commonly reported poisons in every decade. The large majority of publications originated from either Europe or North America, and more specifically from the United States, Germany, the United Kingdom, and China. Despite the emerging apparition of new techniques, hemodialysis remains to this day the favoured ECTR in the treatment of poisoned patients

Extracorporeal blood purification for treating acute paraquat poisoning

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of extracorporeal blood purification techniques for treating paraquat poisoning.This project was supported by the UK National Institute for Health Research, through Cochrane Infrastructure funding to the Cochrane Injuries Group

Availability and cost of extracorporeal treatments for poisonings and other emergency indications: A worldwide survey

Background: Extracorporeal treatments (ECTRs) are used for different conditions, including replacement of organ function and poisoning. Current recommendations for ECTRs in various poisonings suggest that intermittent haemodialysis (IHD) is the most efficient technique. However, the practicality of these recommendations is poorly defined in view of limited information on availability and cost worldwide. Methods: A survey invitation to an Internet-based questionnaire was emailed between January 2014 and March 2015 to members of international societies to determine the availability, time to initiation and cost of ECTRs (including filters, dialysate, catheter, anticoagulant and nursing/physician salary). The median cost ratio of every ECTR compared with IHD performed in the same institution were presented. Results: The view rate was estimated at 28.1% (2532/9000), the participation rate was 40.1% (1015/2532) and the completion rate was 16.0% (162/1015). Respondents originated from 89 countries, and nearly three-fourths practiced in a tertiary care centre. A total of 162 respondents provided sufficient data for in-depth analysis. IHD was the most available acute ECTR (96.9%), followed by therapeutic plasma exchange (TPE; 68.3%), continuous renal replacement therapy (CRRT; 62.9%), peritoneal dialysis (PD; 44.8%), haemoperfusion (HP; 30.9%) and liver support devices (LSDs; 14.7%). IHD, CRRT and HP were the shortest to initiate (median60 min). The median cost ratios of each ECTR compared with IHD were 1.7 for CRRT and HP, 2.8 for TPE, 6.5 for LSDs and 1.4 for PD (P<0.001 for all). The median cost ratio of a 4-h IHD treatment compared with 1 day in the intensive care unit was 0.6 (P 0.2). Conclusions: IHD appears to be the most widely available ECTR worldwide and is at least 30% less expensive than other ECTRs. The superior efficacy of IHD for enhanced elimination, added to its lower cost and wider availability, strengthens its preference as the ECTR of choice in most cases of acute poisonin

Pneumocystis pneumonia in patients with inflammatory or autoimmune diseases: Usefulness of lymphocyte subtyping

Objectives: No consensus currently exists on the indications for Pneumocystis jirovecii prophylaxis in patients with inflammatory or autoimmune diseases. The main objective was to identify biomarkers associated with P. jirovecii pneumonia (PCP) in this population. Methods: A retrospective study was carried out at Beijing Union Medical College Hospital (2003–2014). All patients with an inflammatory or autoimmune disease presenting with acute onset of fever and respiratory symptoms were included. Results: A total of 123 patients were included, of whom 42% had confirmed PCP, 18% had possible PCP, and 40% were negative for PCP. Immunosuppressive conditions consisted mostly of diffuse connective tissue disease (50%) and primary nephropathy (20%). Immunosuppressive therapies consisted of corticosteroids (95%) with concomitant non-steroidal drugs (80%). Independent predictors of PCP were a CD3+ cell count <625 × 106/l, serum albumin <28 g/l, and PaO2/FiO2 <210. Furthermore, 90% of patients with PCP had a CD3+ cell count <750 × 106/l. Independent predictors of mortality were a CD8+ cell count <160 × 106/l and a PaO2/FiO2 <160. Conclusions: In patients with inflammatory and autoimmune conditions receiving immunosuppressive therapy, low CD3+ and CD8+ cell counts were strongly associated with PCP and its mortality. These results suggest that lymphocyte subtyping is a very useful tool to optimize the selection of patients needing prophylaxis

Treating ethylene glycol poisoning with alcohol dehydrogenase inhibition, but without extracorporeal treatments: a systematic review

International audienc