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Medicine Correspondence Blog

The Medicine Correspondence Blog allows authors to post Letters to the Editors, Reviews, and other editorial writings that are not considered original research.

Thursday, March 7, 2019

We read with interest the recent paper by Lin and colleagues (1) and while we commend them on their care of a critically ill patient, we have concerns regarding the interpretation of their plasma exchange data.  While many of the critical parameters needed to evaluate the efficacy of plasma exchange (PE), such as patient weight, are omitted or not explicitly stated in the report,(2) enough data are available to provide an approximation. Using a “best-case” estimate of the volume of distribution of thallium at 3L/kg and an assumed patient weight of 50kg we can deduce the following:

Blood [thallium] at the first PE (on figure 1) = 280ng/mL = 280mcg/L

Total body content of thallium at the time of the 1st PE: 50kg x 3L/kg x 280mcg/L = 42,000 mcg = 42mg

[Thallium] in effluent at the 1st PE (on figure 1) = 120ng/mL = 120mcg/L

Effluent volume during the 1st PE (as stated in the supplemental material) = 1.95L

Amount of thallium removed by the 1st PE = 1.95L x 120mcg/L = 234mcg = 0.234mg

Percentage of thallium removed during 1st exchange = 0.234mg/42mg = 0.55%

According to EXTRIP’s criteria for “dialyzability”, these results are considered “non-dialyzable”.(3) Given these data, we conclude that plasma exchange was inconsequential. The interpretation of a decreasing blood thallium concentration as evidence of the efficacy of plasma exchange is misleading due to the large volume of distribution of thallium, and the cumulative effects of endogenous clearance and to prussian blue. As noted by the authors the benefit of plasma exchange is most evident for toxins that are highly protein bound and thallium has no protein binding.(4) While we agree that the precise role of intermittent hemodialysis and hemoperfusion is not entirely determined in patients with thallium poisoning (5) we argue that this report speaks strongly against the use of plasma exchange. Intermittent hemodialysis in this case might have removed more thallium, at lower cost, and risk to the patient.


Author Correspondence

Robert S. Hoffman, MD, Division of Medical Toxicology, NYU School of Medicine, USA

Marc Ghannoum, MD FRCP, Department of Medicine University of Montreal, Verdun Hospital, Canada

Sophie Gosselin, MD FRCP, Emergency Department Hôpital Charles-Lemoyne, Canada


References

[1] Lin G, Yuan L, Bai L, Liu Y, Wang Y, Qiu Z. Successful treatment of a patient with severe thallium poisoning in a coma using Prussian blue and plasma exchange: A case report. Medicine (Baltimore). 2019;98(8):e14629.  

[2] Lavergne V, Ouellet G, Bouchard J, et al. Guidelines for reporting case studies on extracorporeal treatments in poisonings: methodology. Semin Dial. 2014;27(4):407-414.  

[3] Lavergne V, Nolin TD, Hoffman RS, et al. The EXTRIP (EXtracorporeal TReatments In Poisoning) workgroup: guideline methodology. Clin Toxicol (Phila). 2012;50(5):403-413.

[4] Ghannoum M, Hoffman RS, Gosselin S, Nolin TD, Lavergne V, Roberts DM. Use of
extracorporeal treatments in the management of poisonings. Kidney Int. 2018;94(4):682-688. 

[5] Ghannoum M, Nolin TD, Goldfarb DS, et al. Extracorporeal Treatments in Poisoning Workgroup. Extracorporeal treatment for thallium poisoning: recommendations from the EXTRIP Workgroup. Clin J Am Soc Nephrol. 2012;7(10):1682-1690.



Tuesday, February 12, 2019

I was greatly interested in the systematic review and meta-analysis by Lanaro et al. suggesting osteopathic manipulative treatment is clinically effective in reducing the length of stay (LOS) and costs in a large population of preterm infants.[1] Within this review my attention was drawn to Lanaro et al. use of a fixed effect model for calculating their primary outcome: length of hospital stay (LOS). They included five studies (n= 1306, 645 preterm were allocated in the OMT group and 661 to the control group) in their meta-analysis. The application of a fixed effect model depends on two assumptions that should be met: 1. One believes that all the studies included in the analysis are functionally equivalent and 2. that one has the goal to compute a common effect size for the identified population, and not to generalize to other populations.[2] An example for such a case would be a pharmaceutical company that uses thousand patients to compare a drug versus a placebo. The company might run a series of trials which can be considered identical in the sense that it is reasonable to assume that any variables that have an impact on the outcome should be the same across them. Further, we assume that the patients, the treatment dose, the outcomes measures and the timepoints are essentially the same. In that instance since all the studies share a common effect and the first condition is met. It also meets the second goal because the goal of the analysis which is to see if the drug works in the population from which the patients were drawn.[3]

In the case of the meta-analysis of Lanaro et al. the use of a fixed effect model is inappropriate for the meta-analysis. The study population arises form different clinics and from two different countries. The studies used different treatment techniques, different treatment durations and different frequencies of treatment. Control group conditions also differed across the trials. These reasons make it unlikely that a fixed effect model is the right choice for the analysis. A further indication of the heterogeneity between included studies is found in the relatively high I² value of I²=61%[4], which can be considered moderate to high.[5]

A more appropriate model for the meta-analysis of the studies is a random effects meta-analysis because it does not assume a common effect size.[6] Recreating the analysis (using RevMan Version 5.2.6) with a random effects model the overall effect is no longer statistically significant (p = 0.08) [see figure 1]. This significantly alters the conclusion that osteopathic manipulative treatment does reduce LOS and costs in preterm infants.

Authors should choose models whose assumptions best fit the research question and those assumptions should be considered in the interpretation of the data.

I would like to thank Dr Neil OConnell for his comments on this letter.


Author Correspondence

Tobias Saueressig, Dipl.-Volkswirt, PT

Email: t.saueressig@gmx.de

Tel: 0049-202-27249596

Website: https://physiomeetsscience.com


References

[1] Lanaro, Diego, et al. "Osteopathic manipulative treatment showed reduction of length of stay and costs in preterm infants: A systematic review and meta-analysis." Medicine 96.12 (2017).

[2] Borenstein, Michael, et al. Introduction to meta-analysis. John Wiley & Sons, 2011.

[3] Borenstein, Michael, et al. Introduction to meta-analysis. John Wiley & Sons, 2011.

[4] Lanaro, Diego, et al. "Osteopathic manipulative treatment showed reduction of length of stay and costs in preterm infants: A systematic review and meta-analysis." Medicine 96.12 (2017).

[5] Higgins, Julian PT, et al. "Measuring inconsistency in meta-analyses." BMJ: British Medical Journal 327.7414 (2003): 557.

[6] Borenstein, Michael, et al. Introduction to meta-analysis. John Wiley & Sons, 2011.

Monday, February 4, 2019

​I read with interest a recent article on systematic review and meta-analysis regarding the efficacy of pigtail catheters for pneumothorax by Fang et al. (1), and found several mistakes in the study. The authors stated that "the meta-analysis was based on 16 articles with a total of 1067 patients" in the abstract and showed "16 included articles" in Figure 1. However, there were "17 included studies" in the results and in Table 1, and the authors stated that "In this systematic review and meta-analysis of 1124 cases of pneumothorax from 18 articles…". Moreover, two of the articles (references No. 19 and 21 of the article) listed in Table 1 included patients with pleural effusion (2) and with pleural effusion, empyema, and anterior mediastinal collection (3) in addition to those with pneumothorax. These mistakes are obvious and question the validity of the meta-analysis.


Author Correspondence

Hui-Ling Huang, NP, Department of Intensive Care Medicine, Chi Mei Medical Center, Taiwan

Email: ling890765@gmail.com

Telephone: +886-6-2812811 ext 57106


References

[1] Fang M, Liu G, Luo G, Wu T. Does pigtail catheters relieve pneumothorax?: A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 2018 Nov;97(47):e13255. doi: 10.1097/MD.0000000000013255.

[2] Cantin L, Chartrand-Lefebvre C, Lepanto L, et al. Chest tube drainage under radiological guidance for pleural effusion and pneumothorax in a tertiary care university teaching hospital: review of 51 cases. Can Respir J 2005;12:29–33.

[3] Gammie JS, Banks MC, Fuhrman CR, et al. The pigtail catheter for pleural drainage: a less invasive alternative to tube thoracostomy. JSLS 1999;3:57–61.

Wednesday, January 2, 2019

We read with great interest the article titled "A systematic review and meta-analysis of vessel controlling devices for renal pedicle ligation in laparoscopic live donor nephrectomy"  by Liu et al.1  The authors did a meta-analysis to compare outcomes of  Hem-o-Lok clips and staplers for vascular control in laparoscopic donor nephrectomy (LDN). We have several objections about this study.

Firstly, authors found greater amount of estimated blood loss in Hem-o-Lok clips than stapler. Ideally living kidney donors are healthy people without any known diseases. Putting these individuals at risk by surgical complications such as bleeding or prolonged surgery is not acceptable.

Secondly, authors found that Hem-o-Lok clips result in longer warm ischemia times than stapler. It is known that longer warm ischemia time causes increased rate of acute rejection. Each acute rejection episode in turn decreases the life span of the kidney graft regardless of the postoperative creatinine levels.2

The conclusion derived from this particular meta-analysis should not be to prefer Hem-o-Lok clips based only on cost because live donor and graft safety is of paramount importance in LDN.


Author Correspondence

Baris D.Yildiz, M.D, Ankara Numune Teaching Hospital General Surgery, Sihhiye, Ankara, Turkey

Email: baris104@yahoo.com

Telephone: 90-5324454655


References

[1] Liu Y, Huang Z, Chen Y, Liao B, Luo D, Gao X, Wang K, Li H. Staplers or clips?: A systematic review and meta-analysis of vessel controlling devices for renal pedicle ligation in laparoscopic live donor nephrectomy. Medicine (Baltimore). 2018 Nov;97(45):e13116.

[2] Soulsby RE, Evans LJ, Rigg KM, Shehata M.Warm ischemic time during laparoscopic live donor nephrectomy:effects on graft function.Transplant Proc.2005 Mar;37(2):620-2.

Thursday, November 8, 2018

With interest we read the systematic review of Song et al1, aiming to investigate the clinical outcomes of early enteral nutrition (<48 hours) in severe acute pancreatitis. We would like to address two methodological issues that may have influenced outcomes.

The authors recognize that enteral nutrition may have beneficial effects on the intestinal barrier function. Surprisingly, however, the authors created a control-group which included studies on enteral and studies on parenteral nutrition. The favorable results of early enteral nutrition in this meta-analysis could have very well occurred due to the detrimental effects of the parenteral nutrition in the control group.

Furthermore, in the meta-analysis focusing on the outcomes of systemic infections and gastro-intestinal symptoms, the authors have added up all the different events, as reported in the original article, not taking into account that these events could have occurred concurrently (i.e. multiple events in a single patient). This will introduce bias and may lead to overestimation of the effect of the intervention studies in the meta-analysis.

By preservation of the gut barrier function and reduction of bacterial translocation, enteral nutrition has the potential benefit of reducing complications in acute pancreatitis. Therefore, the use of parenteral nutrition should be discouraged, and only be used if enteral nutrition is not possible.

Therefore, we would like to emphasize the conclusions of the only multicenter randomized controlled trial that truly compared early enteral feeding (<24h) vs delayed enteral feeding (on demand >72h): enteral tube feeding can be limited to patients with predicted severe pancreatitis who have inadequate intake after 72 hours after onset of symptoms. Initiating enteral feeding within 24 hours of start of symptoms did not improve outcomes2


Author Correspondence

Sven M. van Dijkm, Department of Surgery, Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam and Department of Research & Development, St. Antonius Hospital, Nieuwegein

Olaf J. Bakker, Department of Surgery, St. Antonius Hospital, Nieuwegein

Hjalmar C. van Santvoort, Department of Surgery, St. Antonius Hospital, Nieuwegein and Department of Surgery, University Medical Center Utrecht, Utrecht

Marc G. Besselink, Department of Surgery, Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam


References

[1] Song J, Zhong Y, Lu X, et al. Enteral nutrition provided within 48 hours after admission in severe acute pancreatitis: a systematic review and meta-analysis. Medicine. 97(34):e11871, August 2018.

[2] Bakker OJ, van Brunschot S, van Santvoort HC, et al. Early versus on-demand nasoenteric tube feeding in acute pancreatitis. N Engl J Med 2014;371:1983-1993