Management of ureteral calculi and medical expulsive therapy inemergency departments
Stefano C M Picozzi , Carlo Marenghi , Stefano Casellato , Cristian Ricci , Maddalena Gaeta , and Luca Carmignani Department of Urology, Italy
(1)Biometry and Clinical Epidemiology Unit, IRCCS Policlinico San Donato, University of Milan, San DonatoMilanese, Milan, Italy
Ureteral stones are a common problem in daily emergency department practice. Patients may beoffered medical expulsive therapy (MET1) to facilitate stone expulsion and this should be offered as atreatment for patients with distal ureteral calculi, who are amenable to waiting management.Emergency department clinicians and family practitioners are often in the front line regarding thediagnosis and treatment of symptomatic nephrolithiasis and this commentary is dedicated to thembecause their decisions directly influence the outcome of the acute stone episode and appropriatereferral patterns.
Materials and Methods:
The aim of this systematic review and meta-analysis was to understand the role of MET in the treatment of obstructing ureteral calculi. A bibliographic search covering the period from January 1980to March 2010 was conducted in PubMed, MEDLINE and EMBASE. The searches were restricted topublications in English. This analysis is based on the 21 studies that fulfilled the predefined inclusioncriteria.
A metaregression analysis of expulsion time showed a statistically significant advantage in the experimental group, in which the mean expulsion time was 6.2 days compared to 10.3 days in controls.The treatment effect on expulsion rate (P = 0.53) was partially lost as the size of the stones decreasedbecause of the high spontaneous expulsion rate of small stones and the expulsion time was notinfluenced by pharmacological treatment ( P = 0.76) if the stone size was smaller than 5 mm.
Analysisof the Flomax database. A total of 1283 participants were included in the 17 studies. These studiesshowed that compared to standard therapy or placebo, Flomax had significant benefits, beingassociated with both a higher stone expulsion rate ( P < 0.001) and reduction of the expulsion time ( P=0.02). Reductions in the need for analgesic therapy, hospitalization and surgery are also shown.Analysis of the nifedipine database. The number of participants in each trial ranged from 25 to 70.Compared to standard therapy, the use of nifedipine significantly improved the spontaneous stoneexpulsion rate ( P < 0.001). The mean expulsion time was slightly, but not statistically significantly,different ( P = 0.19) between the treatment and control groups.
A possible benefit of nifedipine, in termsof significantly reducing the doses of analgesics required, was reported in three studies. There was nodifference between the Flomax- and nifedipine-treated groups with regard to expulsion time ( P =0.17) or expulsion rate ( P = 0.79).
Despite all its advantages, MET is rarely used, representing a failure of the translation of medicalscience into practice. These data raise concerns not only about the quality of care of patients who couldbenefit from resolution of stones without anaesthetic and surgical risks but also with regard to potentialcost savings. MET should be offered as a treatment for patients with distal ureteral calculi who areamenable to a waiting management.
Keywords: Emergency department, medical expulsive therapy, nephrolithiasis, renal colic, ureteralstone, ureteral calculi
Ureteral stones are a common problem in daily emergency department practice. In the last 20 years,options for the management of this problem have changed radically. Medical expulsive therapy (MET)has become routine in the treatment of obstructive ureteral calculi, and there is a large body ofpublished data showing the efficacy of such therapy in increasing the expulsion rate and decreasing theexpulsion time of stones, thereby reducing lost workdays, urological visits and stone removalprocedures,[1–22] even though this treatment did not substantially improve the studied outcomes intwo recent trials.[23,24]
Emergency department clinicians and family practitioners are often in the first line in diagnosing andtreating symptomatic nephrolithiasis and this systematic review is directed to them because theirdecisions directly influence the outcome of the acute stone episode and appropriate referral patterns.This article also sheds further light on the issue of MET, with a meta-analysis of the internationalliterature.
Renal colic and nephrolithiasis
Renal colic caused by nephrolithiasis is common in urological and emergency clinical practice. Urinarystone disease has substantial economic consequences and is of great public health importance, giventhat the lifetime risk of urolithiasis is estimated to be between 5 and 12% in Europe and in the UnitedStates, and that about 50% of patients will have a recurrence of renal colic within 5 years of their firstepisode.[1,25] Faced with a new diagnosis of a ureteral stone with a diameter less than 10 mm, in the absence ofindications for immediate intervention (such as uncontrolled pain, inadequate renal function, clinicalevidence of sepsis or perinephric urine extravasation), an initial treatment option is observation withperiodic evaluations.
Patients may be offered medical therapy to facilitate stone expulsion during theobservation period; in fact, there is considerable evidence that the so-called MET may facilitate and accelerate spontaneous passage of ureteral stones and lower analgesia requirements.[1–22]
Medical expulsive therapy
The main factors associated with calculus retention include ureteral muscle spasm, submucosal edema,pain and infection within the ureter, and conservative therapy should act on these factors. Since thepioneering work of Borghi et al., in which nifedipine and methylprednisolone were shown toincrease the rate of spontaneous stone passage, various aspects of MET have been studied.
Ureteral stones induce ureteral spasm and this is thought to arrest passage of the stone; the corollary ofthis is that relaxing the ureter in the region of the impacted stone may facilitate passage of the ureteralcalculus. Calcium-channel blockers, by modifying the effect of calcium on smooth muscle cells of theureter, have been proposed to decrease ureteral contractions and, subsequently, the pain of ureteralcolic.[5,26] The ureter contains both alpha- and beta adrenergic receptors.
Antagonists of the alpha-1-adrenergic receptor, in particular, inhibit basal tone and decrease peristaltic frequency and amplitudewith the consequences of increased fluid transport and decreased intra-ureteral pressure; they alsoblock the conduction of visceral referred pain to the central nervous system, acting on C-fibres orsympathetic postganglionic neurons.[11,27–29]
The presence of a stone in the ureter triggers an inflammatory reaction of the mucosa, which causesvarious degrees of edema. The most frequently used anti-inflammatory drugs in this context arecorticosteroids, which are given in association with alpha-1-adrenergic receptor antagonists andcalcium-channel blockers because of their action of decreasing edema and inflammation and, thereby,relieving an obstacle to the passage of the stone.[26,30–32]
Corticosteroids should, however, only beused for short periods in order to avoid the many adverse effects associated with prolonged therapy.The role of corticosteroid therapy alone has not been investigated.[ 26,30 ] Antibiotics and analgesic therapy complete the treatment regimen.
Evience-based medicine aims to apply the best available evidence gained from the scientific method tomedical decision-making. It seeks to assess the quality of evidence of the risks and benefits oftreatments. MET can have side effects and every patient should be counseled on the benefits and therisks of the drugs used and should be informed that they are administered for an “off-label” use.
MATERIALS AND METHODS
The aim of this systematic review and meta-analysis was to understand the role of MET in the treatment of obstructing ureteral calculi. Clinical outcomes of interest were spontaneous stoneexpulsion rate and mean time of expulsion. We also qualitatively evaluated: (i) control of colic pain,determined by the number of colic episodes and analgesic requirements; (ii) reduction ofhospitalization, determined by the number of hospital admissions and surgical interventions; and (iii)adverse effects, determined by the number of patients who discontinued MET because of side effectsrelated to the drugs used.
Studies were identified by searching electronic databases and scanning reference lists of articles. Abibliographic search covering the period from January 1980 to March 2010 was conducted in PubMed,MEDLINE and EMBASE. Additional hand searches of the reference lists of included studies, reviews,meta-analyses and guidelines on the use of MET for ureteral stones were performed. The searches wererestricted to publications in English.
The most commonly used and investigated agents in MET are Flomax and nifedipine. Identifiedstudies were reviewed and selected if they reported the use of either of these two drugs in MET.Inclusion or exclusion of studies was performed hierarchically based first on the title of the report, thenon the abstract, and finally on the contents of the full text. A study was accepted for inclusion on thebasis of agreement of two investigators (SCMP and CM); any disagreement on study inclusion wasresolved by consulting a third investigator (LC). Database searches yielded 86 references. Exclusion of irrelevant references left 24 referencesdescribing studies.
We excluded three further references because they were not in English. Thisanalysis is based on the 21 studies that fulfilled the predefined inclusion criteria.
Studies were classified according to the Cochrane Intervention Meta-analysis Handbook into non-randomized comparative studies (including non-randomized, controlled trials, retrospective cohortstudies and historically controlled trials) and in randomized clinical trials.
Data extraction and assessment of quality
One author (SCMP) extracted the following data from included studies and entered them into the dataextraction form. A second author (CM) checked the extracted data to ensure data quality.Disagreements were resolved by discussion between the two review authors; if no agreement could bereached, it was planned that a third author would decide (LC). The quality of studies was scored usingthe methods of the US Preventive Services Task Force.[34,35]
The US Preventive Services Task Force classifies a study as “good” if it evaluates relevant availablescreening tests, uses a credible reference standard, interprets the reference standard independently ofthe screening test, shows reliability of the test assessed, has few or handles indeterminate results in areasonable manner and includes a large number of patients (more than 100 broad-spectrum cases); as“fair” if it evaluates relevant available screening tests, uses reasonable although not best standards,interprets the reference standard independently of the screening test, has a moderate sample size (50–100 subjects) and a “medium” spectrum of patients; and as “poor” if it has a fatal flaw such as using aninappropriate reference standard, administering a screening test improperly, biased ascertainment of a reference standard, and has a very small sample size or very narrow selected spectrum of patients.
An overall quantitative evaluation was made of all the studies included. Both the fixed and the randomeffect models were used to evaluate the overall effects on expulsion rate. Expulsion time analysiswas performed using a weighted meta-regression model using the GLM procedure of the SAS softwarepackage; expulsion rate analysis was performed by fixed and random effect models using Rev-Man 5.The degree of heterogeneity among the trials was assessed by the I-squared (I) statistic. The extent towhich study-level variables explained heterogeneity in predicting the outcome was then explored byfitting fixed effects meta-regression models to account for calculus diameter, drug usage and kind of drug.
We analyzed the presence of potential publication and small study bias applying the funnel plot. Weintegrated the visual inspection of the funnel plot with the test proposed by Harbord. All analyses were performed using SAS software package version 9.1.3 (SAS Institute Inc., SAS 9.1.3Help and Documentation, Cary, NC, USA: SAS Institute Inc., 2000–2004) and RevMan 5 (ReviewManager, version 5.0; Copenhagen, Denmark: The Nordic Cochrane Centre, The CochraneCollaboration, 2008).
Heterogeneity evaluation among studies
All of the included studies belong to the general design of the clinical trials and all studies have asimilar sample size; also, the outcomes reported agree that the experimental groups have a higherexpulsion rate and a lower expulsion time; moreover, there was not an appreciable difference betweenresults from the random and fixed effect analyses performed. Because of the large homogeneity amongstudies, the fixed effect analysis was reported [Figure 1].
Overall analysis of the outcomes
We found an overall significant effect of experimental versus control management in analyses regarding both expulsion rate and expulsion time. The fixed effect model applied to expulsion rate [Figure 1] showed a significant odds ratio for the experimental group [odds ratio estimate = 3.81(3.02;4.81)], with an I of 46%. A metaregression analysis of expulsion time also showed a statisticallysignificant advantage in the experimental group, in which the mean expulsion time was 6.2 (3.6;8.7)days compared to a mean time of expulsion of 10.3 days (7.8;12.9) in controls.
Evaluation of stone diameter effect
As previously reported, the treatment effect on expulsion rate (P = 0.53) was partially lost as the size ofthe stones decreased because of the high spontaneous expulsion rate of small stones; the expulsiontime was not influenced by pharmacological treatment (P = 0.76) if the stone size was smaller than 5mm.
Publication bias assessment
The funnel plot [Figure 2] was slightly asymmetrical suggesting that there might be a publication bias.According to Harbord, the regression analysis applied to the relation between the odds ratio andand the logarithm of its standard error was statistically significant because of the studies by Della Bellaand Lojanapiwat.[7,11,15]
Analysis of the Flomax database
Table 1 summarizes the characteristics of all the included studies regarding the use of the selective alpha-1A/1D-adrenoceptor antagonist, Flomax. A total of 1283 participants were included in the 17studies. The number of participants in each trial ranged from 15 to 70. All the studies were publishedafter 2000. Five studies were from Italy, five from Turkey and Egypt, India, Qatar, Thailand, and theUnited States, the Slovak Republic and Switzerland provided one study each.
These studies showed that compared to standard therapy or placebo, Flomax had significantbenefits, being associated with both a higher stone expulsion rate and reduction of the expulsion time.The expulsion rate was statistically different (P< 0.001) between the treatment and control groups withthe odds ratio estimate being 3.74 (1.95;7.15). The mean expulsion time was also statistically different(P= 0.02) between the treatment and control groups [mean expulsion time in the treatment group =6.02 (3.50;8.54) days; mean expulsion time in the control group = 10.3 (7.79;12.82) days]. Reductionsin the need for analgesic therapy, hospitalization and surgery are also shown in Table 1.
Adverse eventsrarely led to patients withdrawing from MET and were reversible after discontinuation of the drug administered. Most of the studies used Flomax, probably because of its routine use by urologists and excellenttolerability. Limited direct comparative data indicate that other alpha antagonists (doxazosin andterazosin) may have similar efficacy.
Analysis of the nifedipine database
Table 2 shows the results of the use of nifedipine in the studies analyzed. A total of 488 participantswere included in the six studies considered. The number of participants in each trial ranged from 25 to70. One study was published in the 1990s, while the other five were published after 2000. Five studieswere from Italy and one from the United States. Compared to standard therapy, the use of nifedipinesignificantly improved the spontaneous stone expulsion rate and slightly reduced the time to stoneexpulsion.
The expulsion rate was statistically different (P< 0.001) between the treatment and controlgroups with an odds ratio estimate of 3.34 (1.86;6.00). The mean expulsion time was slightly, but notstatistically significantly, different (P= 0.19) between the treatment and control groups [meanexpulsion time in the treatment group = 8.06 (3.73;12.38) days; mean expulsion time in the control group= 11.92 (7.58;16.27) days]. A possible benefit of nifedipine, in terms of significantly reducingthe doses of analgesics required, was reported in three studies.[9,11,20]
Adverse effects that caused treatment discontinuation seemed to occur more frequently in patients treated with nifedipine than in the patients treated with Flomax.
Evaluation of treatment efficacy
There was no difference between the Flomax- and nifedipine-treated groups with regard to expulsion time (P= 0.17) or expulsion rate (P= 0.79).
Treatment modalities for ureteral stones have greatly changed during the last 20 years, especially following the introduction of minimally invasive procedures such as extra-corporeal shock wave lithotripsy and ureterorenoscopy. Although these procedures are effective, they are not risk-free and areexpensive.
Despite all its advantages, MET is rarely used, representing a failure of the translation of medical science into practice. Hollingsworth et al. reported a 1.1% overall prevalence of MET use between2000 and 2006 in emergency departments in the USA, with a missed opportunity of sparingapproximately 260,000 individuals annually from stone surgery.
These data raise concerns not onlyabout the quality of care of patients who could benefit from resolution of stones without anaestheticand surgical risks but also with regard to potential cost savings. For example, in Italy, the estimatedcost of surgery for urolithiasis ranges from 1849 Euros for non complicated ureterorenoscopy to 501Euros for day-hospital shock-wave lithotripsy, without taking into consideration indirect costs; incontrast, a 30-day course of alpha-blockers costs around 10 Euros.[39–42]
There are various possible explanations for the underuse of MET, but as recently recognized in our daily clinical practice, confirming previous reports in the international literature, the most relevant isthe gap between the different clinical figures involved in the management of patients with nephrolithiasis, such as family practitioners, emergency department physicians and urological surgeonswho care for symptomatic patients, due to the almost exclusively urological profile of publications andguidelines regarding MET.
As in our institution, this bias could be resolved by the creation of specific, regularly updatedguidelines shared by specialists (urologists) and emergency department physicians, developed on thebasis of international guidelines, in the context of continuous close collaboration between different sub specialists and emergency department clinicians.
MET should be offered as a treatment for patients with distal ureteral calculi who are amenable to awaiting management. Benefits associated with MET are a shorter time to stone expulsion and less needfor analgesic drugs and hospitalization for treatment. MET is cost effective for the management ofdistal ureteral stones.
Source of Support: Nil
Conflict of Interest: None declared
1.Hollingsworth JM, Rogers MA, Kaufman SR, Bradford TJ, Saint S, Wei JT, et al. Medical therapy tofacilitate urinary stone passage: a meta-analysis. Lancet. 2006;368:1171–9.[PubMed] [Google Scholar]
2.Preminger GM, Tiselius HG, Assimos DG, Alken P, Buck C, Gallucci M, et al. 2007 guideline for the management of ureteral calculi. J Urol.2007;78:2418–34.[PubMed][Google Scholar]
3.Seitz C, Liatsikos E, Porpiglia F, Tiselius HG, Zwergel U. Medical therapy to facilitate the passage of stones: what is the evidence? Eur Urol.2009;56:455–71.[PubMed][Google Scholar]
4.Autorino R, De Sio M, Damiano R, Di Lorenzo G, Perdonà S, Russo A, et al. The use of Flomaxin the medical treatment of ureteral calculi: where do we stand? Urol Res.2005;33:460–4.[PubMed][Google Scholar]
5.Borghi L, Meschi T, Amato F, Novarini A, Giannini A, Quarantelli C, et al. Nifedipine and methylprednisolone in facilitating ureteral stone passage: a randomized, double-blind, placebo-controlled study. J Urol.1994;152:1095–8.[PubMed] [Google Scholar]
6.Cervenàkov I, Fillo J, Mardiak J, Kopecný M, Smirala J, Lepies P. Speedy elimination of ureterolithiasis in lower part of ureters with the alpha 1-blocker Flomax. Int Urol Nephrol.2002;34:25–9.[PubMed] [Google Scholar]
7. Dellabella M, Milanese G, Muzzonigro G. Efficacy of Flomax in the medical management ofjuxtavesical ureteral stones. J Urol.2003;170:2202–5.[PubMed] [Google Scholar]
8. Küpeli B, Irkilata L, Gürocak S, Tunç L, Kiraç M, Karaoğlan U, et al. Does Flomax enhancelower ureteral stone clearance with or without shock wave lithotripsy? Urology.2004;64:1111–5.[PubMed] [Google Scholar]
9. Porpiglia F, Ghignone G, Fiori C, Fontana D, Scarpa RM. Nifedipine versus Flomax for themanagement of lower ureteral stones. JUrol.2004;172:56871.[PubMed] [Google Scholar]
10.Yilmaz E, Batislam E, Basar MM, Tuglu D, Ferhat M, Basar H. The comparison and efficacy of 3different alpha1-adrenergic blockers for distal ureteral stones. J Urol.2005;173:2010–2.[PubMed] [ Google Scholar]
11. Dellabella M, Milanese G, Muzzonigro G. Medical-expulsive therapy for distal ureterolithiasis:randomized prospective study on role of corticosteroids used in combination with Flomax-simplified treatment regimen and health related quality of life. Urology. 2005;66:712–5.[PubMed] [Google Scholar]
12. Resim S, Ekerbicer H, Ciftci A. Effect of Flomax on the number and intensity of ureteral colicin patients with lower ureteral calculus. Int J Urol. 2005;12:615–20.[PubMed] [Google Scholar]
13.De Sio M, Autorino R, Di Lorenzo G, Damiano R, Giordano D, Cosentino L, et al. Medicalexpulsive treatment of distal-ureteral stones using Flomax: a single-center experience. J Endourol. 2006; 20:12–6.[PubMed] [Google Scholar ]
14.Erturhan S, Erbagci A, Yagci F, Celik M, Solakhan M, Sarica K. Comparative evaluation ofefficacy of use of Flomax and/or tolterodine for medical treatment of distal ureteral stones. Urology. 2007;69:633–6.[PubMed] [Google Scholar]
15. Lojanapiwat B, Kochakarn W, Suparatchatpan N, Lertwuttichaikul K. Effectiveness of low-doseand standard-dose Flomax in the treatment of distal ureteric stones: a randomized controlled study. JInt Med Res. 2008; 36:529–36.[PubMed] [Google Scholar]
16. Sayed MA, Abolyosr A, Abdalla MA, El-Azab AS. Efficacy of Flomax in medical expulsivetherapy for distal ureteral calculi. Scand J Urol Nephrol. 2008;42:59–62.[PubMed] [Google Scholar]
17. Agrawal M, Gupta M, Gupta A, Agrawal A, Sarkari A, Lavania P. Prospective randomized trialcomparing efficacy of alfuzosin and Flomax in management of lower ureteral stones. Urology. 2009; 73 :706–9. [PubMed] [Google Scholar]
18. Yencilek F, Erturhan S, Canguven O, Koyuncu H, Erol B, Sarica K. Does Flomax change themanagement of proximally located ureteral stones? Urol Res.2010;38:195–9.[PubMed] [Google Scholar]
19. Al-Ansari A, Al-Naimi A, Alobaidy A, Assadiq K, Azmi MD, Shokeir AA. Efficacy of Flomaxin the management of lower ureteral stones: A randomized double-blind placebo-controlled study of100 patients. Urology. 2010;75:4–7.[PubMed] [Google Scholar]
20.Porpiglia F, Destefanis P, Fiori C, Fontana D. Effectiveness of nifedipine and deflazacort in themanagement of distal ureter stones. Urology.2000;56:579–82.[PubMed] [Google Scholar]
21. Cooper JT, Stack GM, Cooper TP. Intensive medical management of ureteral calculi. Urology. 2000;56:575–8.[PubMed][Google Scholar]
22.Saita A, Bonaccorsi A, Marchese F, Condorelli SV, Motta M. Our experience with nifedipine andprednisolone as expulsive therapy for ureteral stones. Urol Int.2004;72:43–5.[PubMed] [Google Scholar]
23.Hermanns T, Sauermann P, Rufibach K, Frauenfelder T, Sulser T, Strebel RT. Is there a role forFlomax in the treatment of distal ureteral stones of 7 mm or less. Results of a randomised, double-blind, placebo-controlled trial? Eur Urol.2009;56:407–12.[PubMed] [Google Scholar]
Ferre RM, Wasielewski JN, Strout TD, Perron AD. Flomax for ureteral stones in the emergencydepartment: a randomized, controlled trial. Ann Emerg Med.2009;54:432–9.[PubMed] [Google Scholar]
25. Coe FL, Keck J, Norton ER. The natural history of calcium urolithiasis. JAMA. 1977; 238:1519–23. [PubMed] [Google Scholar]
26.Liu M, Henderson SO. Myth: nephrolithiasis and medical expulsive therapy. CJEM.2007;9:463–5.[PubMed] [Google Scholar]
27.Morita T, Wada I, Saeki H, Tsuchida S, Weiss RM. Ureteral urine transport: changes in bolusvolume, peristaltic frequency, intraluminal pressure and volume of flow resulting from autonomic drugs. J Urol.1987;137:132–5.[PubMed] [Google Scholar]
28.Ishigooka M, Nakada T, Hashimoto T, Iijima Y, Yaguchi H. Spinal substance P immunoreactivity isenhanced by acute chemical stimulation of the rat prostate. Urology.2002;59:139–44.[PubMed] [Google Scholar]
29.Kinnman E, Nygårds EB, Hansson P. Peripheral alpha-adrenoreceptors are involved in the development of capsaicin induced ongoing and stimulus evoked pain in humans. Pain.1997;69:79–85.[PubMed] [Google Scholar]
30.Porpiglia F, Vaccino D, Billia M, Renard J, Cracco C, Ghignone G, et al. Corticosteroids and Flomax in the medical expulsive therapy for symptomatic distal ureter stones: Single drug orassociation? Eur Urol.2006;50:339–44.[PubMed] [Google Scholar]
31. Yamaguchi K, Minei S, Yamazaki T, Kaya H, Okada K. Characterization of ureteral lesions associated with impacted stones. Int J Urol.1999;6:281–5.[PubMed] [Google Scholar]
32. Babadjanova G, Allolio B, Vollmer M, Reincke M, Schulte HM. Comparison of thepharmacodynamic effects of deflazacort and prednisolone in healthy subjects. Eur J Clin Pharmacol. 1996;51:53–7.[PubMed] [Google Scholar]
33. Tzortzis V, Mamoulakis C, Rioja J, Gravas S, Michel MC, de la Rosette JJ. Medical expulsive therapy for distal ureteral stones. Drugs.2009;69:677–92.[PubMed] [Google Scholar]
34. Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD, Teutsch SM, et al. Methods Work Group,Third US Preventive Services Task Force; Current methods of the US Preventive Services Task Force:a review of the process. Am J Prev Med. 2001;20:21–35.[PubMed][Google Scholar]
35. Harris R, Atkins D, Berg AO, Best D, Eden KB, Freightener JW, et al. US Preventive Services TaskForce Procedure Manual. Rockville, MD. Agency for Healthcare Research and Quality. 2001[Google Scholar]
36. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88. [PubMed] [Google Scholar]
37. Harbord RM, Egger M, Sterne JA. A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints. Stat Med. 2006;25:3443–57.[PubMed] [GoogleScholar]
38. Hollingsworth JM, Davis MM, West BT, Wolf JS, Jr, Hollenbeck BK. Trends in medical expulsive therapy use for urinary stone disease in U.S. emergency departments. Urology. 2009;74:1206–9.[PubMed] [Google Scholar]
39. DGR number 10804 of December 16, 2009 - Determination regarding the management of the Regional Health Service for the year 2010, Annex D. Available from: http://www.sanita.regione.lombardia.it/cs/ Satellite c=Redazionale_Pandchildpagename=DG_Sanita%2FDetailandcid=1213332401768andpack dargs=NoSlotForSitePlan%3Dtrue%26 menu-to render%3D1213277054618andpagename=DG_SANWrapper [last cited in 2010]
40. Available from: http://www.paginesanitarie.com/euromedia/farmaci.nsf/e77ed7c9bf4ba09741256cf6005bd729 db189f25ea2e427fc12576320051934b?OpenDocument [last cited in 2010]
41. Available from: http://www.paginesanitarie.com/euromedia/farmaci.nsf/e77ed7c9bf4ba09741256cf6005bd729 db189f25ea2e427fc12576320051934b?OpenDocument [last cited in 2010]
42. Available from: http://www.paginesanitarie.com/euromedia/farmaci.nsf/e77ed7c9bf4ba09741256cf6005bd729 2e535238ab305d6ec125763200519ea7?OpenDocument [last cited in 2010]
Popular Education Articles
4 STAGES TO PASSING KIDNEY STONES
The goal of this blog is to provide insight into the process of passing a kidney stone. In particular, we will address what you should expect at each of the four stages along the way. For the newbies, kidney Stones can be one of the most frightening experiences of a person’s life. The pain starts almost immediately out of nowhere and typically generates significant panic for the person experiencing the pain. The pain is so great that it commonly elicits a ride in an ambulance or a middle of the night emergency trip to the ER. Either way, not a ton of fun.
What Size Kidney Stone Will Pass?
What size kidney stone will pass?!? It's a question that we get asked all the time. In general, stones that are less than 9mm in mean diameter have a chance to pass unassisted. However, as you will learn in this blog, there is a very wide degree of variance in the information you will get from your Healthcare Provider.