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Pelvic organ prolapse affects between 5% and 10%of women, and is strongly associated with increasingage, as shown by its prevalence of 40% in womenolder than 50 years.1 The disorder is one of the mostcommon indications for gynaecological surgery in olderwomen, and the estimated lifetime cumulative risk ofsurgery is 7–11%.2 In addition to the surgical proceduresavailable for prolapse, conservative treatments includeintravaginal pessaries, avoidance of activities thatincrease pressure on the pelvic oor, weight loss, andpelvic oor muscle training.

Pelvic oor muscle training is an established treatmentfor some pelvic oor disorders, including urinary andfaecal incontinence. Such training is often combined withother behavioural approaches, such as urge suppressionstrategies, and can improve urinary urgency, frequency,3 and nocturia.4 In fact, the International Consultation onIncontinence recommends pelvic oor muscle trainingas the rst-line treatment for stress, urge, or mixedincontinence in women of all ages.5 The 2011 American

Urological Association guideline for diagnosis andtreatment of overactive bladder in adults recommendsthat behavioural treatments, including pelvic oor muscletraining, be the rst treatments offered to all women,and men, with overactive bladder.6 Although pelvic oormuscle training is used clinically to treat prolapse, littleempirical evidence is available for its effectiveness.7,8

In The Lancet, Suzanne Hagen and colleagues9 reportresults from their Pelvic Organ Prolapse PhysiotherapY(POPPY) trial, a 25-site, randomised controlled trialcomparing one-to-one individualised pelvic oormuscle training with a lifestyle advice leaet (control) inwomen with symptomatic stage I, II, or III prolapse, asconrmed by objective assessment. The intervention wasdelivered to newly diagnosed women by women’s healthphysiotherapists in ve in-person visits over 16 weeks.Notably, the intervention was not limited to daily pelvicoor muscle exercise. Women were taught to precontractpelvic oor muscles during activities that increase intra-abdominal pressure. Thus, in addition to the possible

Pelvic oor muscle training for pelvic organ prolapse

heterogeneity and susceptibility across different riskgroups and regions.

Despite major improvements in air quality in the past50 years, the data from Beelen and colleagues’ reportdraw attention to the continuing effects of air pollutionon health. These data, along with the ndings fromother large cohort studies, suggest that further publicand environmental health policy interventions arenecessary and have the potential to reduce morbidityand mortality across Europe. Movement towards morestringent guidelines, as recommended by WHO, shouldbe an urgent priority.

Jeremy P Langrish, *Nicholas L MillsUniversity of Edinburgh/British Heart Foundation Centre forCardiovascular Science, University of Edinburgh, Edinburgh,EH16 4SB, UKnick.mills@ed.ac.ukWe declare that we have no conicts of interest.

1 Committee on the Medical Effects of Air Pollution. Long-term exposure toair pollution: effect on mortality. London: Health Protection Agency, 2009.

2 Pope CA 3rd, Ezzati M, Dockery DW. Fine-particulate air pollution and lifeexpectancy in the United States.N Engl J Med 2009; 360: 376–86.

3 Brook RD, Rajagopalan S, Pope CA 3rd, et al. Particulate matter air pollutionand cardiovascular disease. An update to the scientic statement from theAmerican Heart Association.Circulation 2010; 121: 2331–78.

4 Shah AS, Langrish JP, Nair H, et al. Global association of air pollution and heart

failure: a systematic review and meta-analysis.Lancet 2013;382: 1039–48. 5 Pope C, Burnett R, Thun M, et al. Lung cancer, cardiopulmonary mortality,and long-term exposure to ne particulate air pollution. JAMA 2002;287: 1132–41.

6 Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burdenof disease and injury attributable to 67 risk factors and risk factor clustersin 21 regions, 1990–2010: a systematic analysis for the Global Burden ofDisease Study 2010.Lancet 2012;380: 2224–60.

7 Zhang LW, Chen X, Xue XD, et al. Long-term exposure to high particulatematter pollution and cardiovascular mortality: a 12-year cohort study infour cities in northern China.Environ Int 2014; 62: 41–47.

8 Yang G, Wang Y, Zeng Y, et al. Rapid health transition in China, 1990–2010:ndings from the Global Burden of Disease Study 2010.Lancet2013;381: 1987–2015.

9 Beelen R, Raaschou-Nielsen O, Stafoggia M, et al. Effects of long-termexposure to air pollution on natural-cause mortality: an analysis of22 European cohorts within the multicentre ESCAPE project.Lancet2013;published online Dec 9. http://dx.doi.org/10.1016/S0140-6736(13)62158-3.

10 Raaschou-Nielsen O, Andersen ZJ, Beelen R, et al. Air pollution and lungcancer incidence in 17 European cohorts: prospective analyses from theEuropean Study of Cohorts for Air Pollution Effects (ESCAPE).Lancet Oncol2013; 14: 813–22.

11 Hoek G, Krishnan RM, Beelen R, et al. Long-term air pollution exposure andcardio- respiratory mortality: a review.Environ Health 2013;12: 43.

12 Nawrot TS, Perez L, Kunzli N, Munters E, Nemery B. Public healthimportance of triggers of myocardial infarction: a comparative riskassessment. Lancet 2011;377: 732–40.

13 Langrish JP, Bosson J, Unosson J, et al. Cardiovascular effects of particulateair pollution exposure: time course and underlying mechanisms. J Intern Med2012; 272: 224–39.

14 Mills NL, Donaldson K, Hadoke PW, et al. Adverse cardiovascular effectsof air pollution.Nat Clin Pract Cardiovasc Med 2009; 6: 36–44.

PublishedOnlineNovember 28, 2013

http://dx.doi.org/10.1016/S0140-6736(13)62372-7

This online publicationhas been corrected. The

corrected version rstappeared at thelancet.

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improvement in structural support at rest, 10 treatment

involved changes in muscle function, requiring women tobe more vigilant and intentional in their daily activities.

Women who received pelvic oor muscle trainingreported fewer prolapse symptoms (dened as asignicantly greater reduction in the pelvic organ prolapsesymptom score [POP-SS]) than those in the control group,at both 6 months (between-group difference in changefrom baseline 2·84, 95% CI 2·05–3·63) and 12 months, thetrial’s primary endpoint (1·52, 0·42–2·59), after treatment.One of the challenges in interpretation of these ndings isin understanding the meaning for patients of a 1·5-point

difference in symptom scores. The POP-SS is a validatedmethod consisting of seven items addressing frequencyof prolapse symptoms and yielding a total score between0 and 28. Although the effect size might not seem large,it exceeds the minimally important change establishedfor this method, 11 showing its importance to patients.Furthermore, signicant outcomes were shown forseveral secondary endpoints. For example, more womenin the intervention group than the control group reportedthat their prolapse was ‘better’ at both 6 months (52%vs 17%) and 12 months (57% vs 45%), and a smaller

proportion had sought further treatment by 12 months(24%vs50%), showing less residual symptom burden.Hagen and colleagues’ ndings would have been more

compelling had the objective measures, based on thepelvic organ prolapse quantication (POP-Q) system,shown signicant treatment effects. More women in theintervention group had improvement in prolapse stageat 6 months but this fell short of statistical signicance,possibly because the trial was not powered to detectdifferences in this measure. The intervention tested inthe trial could be accommodated by the UK NationalHealth Service. A more intensive programme of pelvicoor muscle training might achieve enough connectivetissue change to be detected in the POP-Q. Nevertheless,the POP-Q results do not diminish the importance ofthe primary ndings, because symptom severity drivestreatment seeking and is not highly correlated withprolapse stage.12,13

In interpretation of the ndings, we should alsoconsider the within-group variability in outcomes. Inthe pelvic oor muscle training group, 57% of womenreported that they were better, leaving 43% who saidthey were worse or the same. This shows that thereare subgroups of responders and non-responders.

Identication of the characteristics of these groups toenable selection of responders would be ideal, but isbeyond present knowledge. In view of the safety andreasonable cost of the intervention, a rational approachwould be to offer a trial of pelvic oor muscle training toany woman with stage I–III prolapse who is motivated to

engage in the treatment.Historically, behavioural and physical treatmentshave been criticised for having inadequate durability.As with so many other studies, the magnitude of thetreatment effect in Hagen and colleagues’ study seemsto diminish between 6–12 months. This decrease shouldnot necessarily be attributed to waning effectivenessof the muscle training itself. In interpretation of thesendings, we should consider that the control groupcontinued to improve over time, decreasing the gapbetween the groups, most likely because half of thesewomen sought prolapse treatment outside the trial. Alsonoteworthy is that only 66% of participants completedthe 12 month assessment, suggesting the possibilityof selective attrition. Finally, although this trial reportsgood adherence (78%) at 12 months, the ndings are areminder of the diffi culties in maintenance of the effects ofa behavioural intervention over time. Increased attentionshould be given to the development of interventions thatimprove adherence, helping women sustain their exerciseregimen and behavioural changes long term.

POPPY makes an important contribution bystrengthening the evidence base for pelvic oor muscletraining in women with prolapse. In addition to the

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Melioidosis, dubbed the Vietnamese time bomb1 afterreports of lengthy disease latency in war veterans, iscaused by Burkholderia pseudomallei and manifestsas acute, subacute, or chronic disease. Bacteraemicdisease especially when associated with pneumoniais the most lethal form, especially if associated withseptic shock, but infection with or without abscessformation can occur in any organ system. Althoughmost presentations occur soon after exposure, theorganism’s ability to evade host immune mechanismsand to survive and multiply in phagocytes2 gives rise tolatency—latency of up to 62 years has been reported.3 Seroprevalence rates vary widely but are highest innortheast Thailand, where most children show evidenceof exposure.4 It remains unclear how many of thosewith serological evidence of exposure harbour latentB pseudomalleiwith the potential for subsequentactivation. Several risk factors cause some people tohave an increased risk of melioidosis, with diabetesbeing the most common. 5

For those with culture-conrmed melioidosis, treat-ment recommendations include an initial intensiveintravenous course of at least 10 days with ceftazidimeor a carbapenem.5 This course is followed by a so-calledoral eradication phase of at least 3 months. The initialclinical response might indicate a need to modify theduration of the intensive phase, but the optimumantibiotic regimen and duration for eradication areuncertain. Recurrent melioidosis was noted in 13%of patients treated in Australia,6 but its prevalencehas fallen over the past decade, possibly attributed toimproved compliance, choice, and dosing of antibioticregimens.7 Higher rates of recurrence in Thailand havebeen associated with inadequate duration of treatment. 8

In The Lancet, Ploenchan Chetchotisakd andcolleagues present ndings from the MERTH trial,9 inwhich they enrolled 626 patients with melioidosis,randomly allocating them to receive trimethoprim-sulfamethoxazole alone (the recommended regimenin Australia) or trimethoprim-sulfamethoxazole

Melioidosis: rening management of a tropical time bomb

effectiveness of muscle training, the trial also shows the

potential for prevention of prolapse symptoms throughlifelong attention to pelvic oor muscle exercise, andpossibly intentional use of muscles to protect the pelvicoor during physical strain, such as that inicted byheavy lifting. The results of this trial should encourageclinicians to refer women to physiotherapists, and toother health-care professionals who can implementbehavioural and physical therapies for prolapse in arange of health-care settings.

Kathryn L Burgio

University of Alabama at Birmingham and the Birmingham/Atlanta Geriatric Research, Education, and Clinical Center,Birmingham, AL 35244, USAkburgio@uabmc.eduI declare that I have no conicts of interest.

Copyright © Burgio. Open Access article distributed under the terms of CC BY-NC-SA.

1 Hendrix SL, Clark A, Nygaard I, Aragaki A, Barnabei V, McTiernan A. Pelvicorgan prolapse in the Women’s Health Initiative: gravity and gravidity. Am J Obstet Gynecol2002 ;186: 1160–66.

2 Bergstrom JO, Colling JC, Clark AL. Epidemiology of surgically managedpelvic organ prolapse and urinary incontinence.Obstet Gynecol1997;89: 501–06.

3 Burgio KL, Goode PS, Johnson TM, et al. Behavioral versus drug treatmentfor overactive bladder in men: the male overactive bladder treatment inveterans (MOTIVE) trial. J Am Geriatr Soc 2011;59: 2209–16.

4 Johnson TM, Markland AD, Goode PS, et al. Effi cacy of adding behavioral

treatment or antimuscarinic drug therapy to alpha-blocker therapy in menwith nocturia. Br J Urol Int 2013;110: 100–08.5 Moore K, Dumoulin C, Bradley C, et al. Adult conservative management.

In Abrams P, Cardozo L, Khoury S, Wein A, eds. Incontinence, 5th InternationalConsultation on Incontinence. Plymbridge: Health Publications,2013: 1101–27.

6 Gormley EA, Lightner DJ, Burgio KL, et al, American Urological Association,Society of Urodynamics, Female Pelvic Medicine & UrogenitalReconstruction. Diagnosis and treatment of overactive bladder(non-neurogenic) in adults: AUA/SUFU guideline. J Urol2012;188: 2455–63.

7 Brækken IH, Majida M, Engh ME, Bø K. Can pelvic oor muscle trainingreverse pelvic organ prolapse and reduce prolapse symptoms? An assessor-blinded, randomized, controlled trial. Am J Obstet Gynecol2010;203: 170.e1–e7.

8 Kashyap R, Jain V, Singh A. Comparative effect of 2 packages of pelvic oormuscle training on the clinical course of stage I-III pelvic organ prolapse.Int J Gynaecol Obstet2013; 121: 69–73.

9 Hagen S, Stark D, Glazener C, et al, on behalf of the POPPY TrialCollaborators. Individualised pelvic oor muscle training in women withpelvic organ prolapse (POPPY): a multicentre randomised controlled trial.Lancet2013; published online Nov 28.http://dx.doi.org/10.1016/S0140-6736(13)61977-7.

10 Bo K. Pelvic oor muscle training is effective in treatment of female stressurinary incontinence, but how does it work?Int Urogynecol J Pelvic Flood Dysfunct 2004; 15: 76–84.

11 Hagen S, Glazener C, Cook J, Herbison P, Toozs-Hobson P. Further propertiesof the pelvic organ prolapse symptom score: minimally important changeand test-retest reliability. Neurourol Urodyn2010; 29: 1055–56.

12 Ellerkmann RM, Cundiff GW, Melick CF, Nihira MA, Leffl er K, Bent AE.Correlation of symptoms with location and severity of pelvic organprolapse. Am J Obstet Gynecol2001; 185: 1332–37.

13 Mouritsen OL, Larsen JP. Symptoms, bother and POPQ in women referredwith pelvic organ prolapse.Int Urogynecol J Pelvic Floor Dysfunct2003;14: 122–27.

PublishedOnlineNovember 25, 2013

http://dx.doi.org/10.1016/S0140-6736(13)62143-1

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the terms of CC BY

Burkholderia pseudomallei

E y e o f S c i e n c e / S c i e n c e P h o t o L i b r a r y