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Pelvic organ prolapse aff ects between 5% and 10% of women, and is strongly associated with increasing age, as shown by its prevalence of 40% in women older than 50 years.1 The disorder is one of the most common indications for gynaecological surgery in older women, and the estimated lifetime cumulative risk of surgery is 7–11%.2 In addition to the surgical procedures available for prolapse, conservative treatments include intravaginal pessaries, avoidance of activities that increase pressure on the pelvic fl oor, weight loss, and pelvic fl oor muscle training.

Pelvic fl oor muscle training is an established treatment for some pelvic fl oor disorders, including urinary and faecal incontinence. Such training is often combined with other behavioural approaches, such as urge suppression strategies, and can improve urinary urgency, frequency,3 and nocturia.4 In fact, the International Consultation on Incontinence recommends pelvic fl oor muscle training as the fi rst-line treatment for stress, urge, or mixed incontinence in women of all ages.5 The 2011 American

Urological Association guideline for diagnosis and treatment of overactive bladder in adults recommends that behavioural treatments, including pelvic fl oor muscle training, be the fi rst treatments off ered to all women, and men, with overactive bladder.6 Although pelvic fl oor muscle training is used clinically to treat prolapse, little empirical evidence is available for its eff ectiveness.7,8

In The Lancet, Suzanne Hagen and colleagues9 report results from their Pelvic Organ Prolapse PhysiotherapY (POPPY) trial, a 25-site, randomised controlled trial comparing one-to-one individualised pelvic fl oor muscle training with a lifestyle advice leafl et (control) in women with symptomatic stage I, II, or III prolapse, as confi rmed by objective assessment. The intervention was delivered to newly diagnosed women by women’s health physiotherapists in fi ve in-person visits over 16 weeks. Notably, the intervention was not limited to daily pelvic fl oor muscle exercise. Women were taught to precontract pelvic fl oor muscles during activities that increase intra-abdominal pressure. Thus, in addition to the possible

Pelvic fl oor muscle training for pelvic organ prolapse

heterogeneity and susceptibility across diff erent risk groups and regions.

Despite major improvements in air quality in the past 50 years, the data from Beelen and colleagues’ report draw attention to the continuing eff ects of air pollution on health. These data, along with the fi ndings from other large cohort studies, suggest that further public and environmental health policy interventions are necessary and have the potential to reduce morbidity and mortality across Europe. Movement towards more stringent guidelines, as recommended by WHO, should be an urgent priority.

Jeremy P Langrish, *Nicholas L MillsUniversity of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, EH16 4SB, UKnick.mills@ed.ac.uk

We declare that we have no confl icts of interest.

1 Committee on the Medical Eff ects of Air Pollution. Long-term exposure to air pollution: eff ect on mortality. London: Health Protection Agency, 2009.

2 Pope CA 3rd, Ezzati M, Dockery DW. Fine-particulate air pollution and life expectancy 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 pollution and cardiovascular disease. An update to the scientifi c statement from the American 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 fi ne particulate air pollution. JAMA 2002; 287: 1132–41.

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

7 Zhang LW, Chen X, Xue XD, et al. Long-term exposure to high particulate matter pollution and cardiovascular mortality: a 12-year cohort study in four 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: fi ndings from the Global Burden of Disease Study 2010. Lancet 2013; 381: 1987–2015.

9 Beelen R, Raaschou-Nielsen O, Stafoggia M, et al. Eff ects of long-term exposure to air pollution on natural-cause mortality: an analysis of 22 European cohorts within the multicentre ESCAPE project. Lancet 2013; 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 lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Eff ects (ESCAPE). Lancet Oncol 2013; 14: 813–22.

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

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

13 Langrish JP, Bosson J, Unosson J, et al. Cardiovascular eff ects of particulate air pollution exposure: time course and underlying mechanisms. J Intern Med 2012; 272: 224–39.

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

Published OnlineNovember 28, 2013

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

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Comment

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improvement in structural support at rest,10 treatment involved changes in muscle function, requiring women to be more vigilant and intentional in their daily activities.

Women who received pelvic fl oor muscle training reported fewer prolapse symptoms (defi ned as a signifi cantly greater reduction in the pelvic organ prolapse symptom score [POP-SS]) than those in the control group, at both 6 months (between-group diff erence in change from baseline 2·84, 95% CI 2·05–3·63) and 12 months, the trial’s primary endpoint (1·52, 0·42–2·59), after treatment. One of the challenges in interpretation of these fi ndings is in understanding the meaning for patients of a 1·5-point diff erence in symptom scores. The POP-SS is a validated method consisting of seven items addressing frequency of prolapse symptoms and yielding a total score between 0 and 28. Although the eff ect size might not seem large, it exceeds the minimally important change established for this method,11 showing its importance to patients. Furthermore, signifi cant outcomes were shown for several secondary endpoints. For example, more women in the intervention group than the control group reported that 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% vs 50%), showing less residual symptom burden.

Hagen and colleagues’ fi ndings would have been more compelling had the objective measures, based on the pelvic organ prolapse quantifi cation (POP-Q) system, shown signifi cant treatment eff ects. More women in the intervention group had improvement in prolapse stage at 6 months but this fell short of statistical signifi cance, possibly because the trial was not powered to detect diff erences in this measure. The intervention tested in the trial could be accommodated by the UK National Health Service. A more intensive programme of pelvic fl oor muscle training might achieve enough connective tissue change to be detected in the POP-Q. Nevertheless, the POP-Q results do not diminish the importance of the primary fi ndings, because symptom severity drives treatment seeking and is not highly correlated with prolapse stage.12,13

In interpretation of the fi ndings, we should also consider the within-group variability in outcomes. In the pelvic fl oor muscle training group, 57% of women reported that they were better, leaving 43% who said they were worse or the same. This shows that there are subgroups of responders and non-responders.

Identifi cation of the characteristics of these groups to enable selection of responders would be ideal, but is beyond present knowledge. In view of the safety and reasonable cost of the intervention, a rational approach would be to off er a trial of pelvic fl oor muscle training to any woman with stage I–III prolapse who is motivated to engage in the treatment.

Historically, behavioural and physical treatments have been criticised for having inadequate durability. As with so many other studies, the magnitude of the treatment eff ect in Hagen and colleagues’ study seems to diminish between 6–12 months. This decrease should not necessarily be attributed to waning eff ectiveness of the muscle training itself. In interpretation of these fi ndings, we should consider that the control group continued to improve over time, decreasing the gap between the groups, most likely because half of these women sought prolapse treatment outside the trial. Also noteworthy is that only 66% of participants completed the 12 month assessment, suggesting the possibility of selective attrition. Finally, although this trial reports good adherence (78%) at 12 months, the fi ndings are a reminder of the diffi culties in maintenance of the eff ects of a behavioural intervention over time. Increased attention should be given to the development of interventions that improve adherence, helping women sustain their exercise regimen and behavioural changes long term.

POPPY makes an important contribution by strengthening the evidence base for pelvic fl oor muscle

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Melioidosis, dubbed the Vietnamese time bomb1 after reports of lengthy disease latency in war veterans, is caused by Burkholderia pseudomallei and manifests as acute, subacute, or chronic disease. Bacteraemic disease especially when associated with pneumonia is the most lethal form, especially if associated with septic shock, but infection with or without abscess formation can occur in any organ system. Although most presentations occur soon after exposure, the organism’s ability to evade host immune mechanisms and to survive and multiply in phagocytes2 gives rise to latency—latency of up to 62 years has been reported.3 Seroprevalence rates vary widely but are highest in northeast Thailand, where most children show evidence of exposure.4 It remains unclear how many of those with serological evidence of exposure harbour latent B pseudomallei with the potential for subsequent activation. Several risk factors cause some people to have an increased risk of melioidosis, with diabetes being the most common.5

For those with culture-confi rmed melioidosis, treat-ment recommendations include an initial intensive intravenous course of at least 10 days with ceftazidime or a carbapenem.5 This course is followed by a so-called oral eradication phase of at least 3 months. The initial clinical response might indicate a need to modify the duration of the intensive phase, but the optimum antibiotic regimen and duration for eradication are uncertain. Recurrent melioidosis was noted in 13% of patients treated in Australia,6 but its prevalence has fallen over the past decade, possibly attributed to improved compliance, choice, and dosing of antibiotic regimens.7 Higher rates of recurrence in Thailand have been associated with inadequate duration of treatment.8

In The Lancet, Ploenchan Chetchotisakd and colleagues present fi ndings from the MERTH trial,9 in which they enrolled 626 patients with melioidosis, randomly allocating them to receive trimethoprim-sulfamethoxazole alone (the recommended regimen in Australia) or trimethoprim-sulfamethoxazole

Melioidosis: refi ning management of a tropical time bomb

training in women with prolapse. In addition to the eff ectiveness of muscle training, the trial also shows the potential for prevention of prolapse symptoms through lifelong attention to pelvic fl oor muscle exercise, and possibly intentional use of muscles to protect the pelvic fl oor during physical strain, such as that infl icted by heavy lifting. The results of this trial should encourage clinicians to refer women to physiotherapists, and to other health-care professionals who can implement behavioural and physical therapies for prolapse in a range of health-care settings.

Kathryn L BurgioUniversity of Alabama at Birmingham and the Birmingham/Atlanta Geriatric Research, Education, and Clinical Center, Birmingham, AL 35244, USAkburgio@uabmc.edu

I declare that I have no confl icts of interest.

1 Hendrix SL, Clark A, Nygaard I, Aragaki A, Barnabei V, McTiernan A. Pelvic organ prolapse in the Women’s Health Initiative: gravity and gravidity. Am J Obstet Gynecol 2002; 186: 1160–66.

2 Bergstrom JO, Colling JC, Clark AL. Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence. Obstet Gynecol 1997; 89: 501–06.

3 Burgio KL, Goode PS, Johnson TM, et al. Behavioral versus drug treatment for overactive bladder in men: the male overactive bladder treatment in veterans (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 men with 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 International Consultation 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 & Urogenital Reconstruction. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. J Urol 2012; 188: 2455–63.

7 Brækken IH, Majida M, Engh ME, Bø K. Can pelvic fl oor muscle training reverse pelvic organ prolapse and reduce prolapse symptoms? An assessor-blinded, randomized, controlled trial. Am J Obstet Gynecol 2010; 203: 170.e1–e7.

8 Kashyap R, Jain V, Singh A. Comparative eff ect of 2 packages of pelvic fl oor muscle training on the clinical course of stage I-III pelvic organ prolapse. Int J Gynaecol Obstet 2013; 121: 69–73.

9 Hagen S, Stark D, Glazener C, et al, on behalf of the POPPY Trial Collaborators. Individualised pelvic fl oor muscle training in women with pelvic organ prolapse (POPPY): a multicentre randomised controlled trial. Lancet 2013; published online Nov 28. http://dx.doi.org/10.1016/S0140-6736(13)61977-7.

10 Bo K. Pelvic fl oor muscle training is eff ective in treatment of female stress urinary 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 properties of the pelvic organ prolapse symptom score: minimally important change and test-retest reliability. Neurourol Urodyn 2010; 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 organ prolapse. Am J Obstet Gynecol 2001; 185: 1332–37.

13 Mouritsen OL, Larsen JP. Symptoms, bother and POPQ in women referred with pelvic organ prolapse. Int Urogynecol J Pelvic Floor Dysfunct 2003; 14: 122–27.

Published OnlineNovember 25, 2013

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

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Copyright © Fisher et al. Open Access article distributed under

the terms of CC BY

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