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    Beyond PSA testing for prostate cancer

    Doug Brooks, Ian N Olver and Adrian J Esterman
    Med J Aust 2018; 208 (10): . || doi: 10.5694/mja18.00324
    Published online: 4 June 2018

    Better biomarkers are needed to ensure early and accurate detection and prognosis of prostate cancer

    Prostate cancer is now the most common cancer diagnosed in men in Australia,1 and Australia has one of the highest incidence rates of prostate cancer in the world, with an estimated age-standardised rate of 119.2 per 100 000 men.2 Before 1960, the primary diagnostic test for prostate cancer was the prostatic acid phosphatase test. This was eventually replaced in the 1980s by the prostate-specific antigen (PSA) test.

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      Active surveillance of men with low risk prostate cancer: evidence from the Prostate Cancer Outcomes Registry–Victoria

      Melanie A Evans, Jeremy L Millar, Arul Earnest, Mark Frydenberg, Ian D Davis, Declan G Murphy, Paul Aidan Kearns and Sue M Evans
      Med J Aust 2018; 208 (10): . || doi: 10.5694/mja17.00559
      Published online: 28 May 2018

      Abstract

      Objective: To characterise the practice of active surveillance (AS) for men with low risk prostate cancer by examining the characteristics of those who commence AS, the rate of adherence to accepted AS follow-up protocols over 2 years, and factors associated with good adherence.

      Design, setting: Retrospective cohort study; analysis of data collected from 38 sites participating in the Prostate Cancer Outcomes Registry–Victoria.

      Participants: Men diagnosed with prostate cancer between August 2008 and December 2014 aged 75 years or less at diagnosis, managed by AS for at least 2 years, and with an ISUP grade group of 3 or less (Gleason score no worse than 4 + 3 = 7).

      Main outcome measures: Adherence to an AS schedule consisting of at least three PSA measurements and at least one biopsy in the 2 years following diagnosis.

      Results: Of 1635 men eligible for inclusion in the analysis, 433 (26.5%) adhered to the AS protocol. The significant predictor of adherence in the multivariate model was being diagnosed in a private hospital (v public hospital: adjusted odds ratio [aOR], 1.83; 95% CI, 1.42–2.37; P < 0.001). Significant predictors of non-adherence included being diagnosed by transurethral resection of the prostate (v transrectal ultrasound biopsy [TRUS]: OR, 0.54; 95% CI, 0.39–0.77; P < 0.001) or transperineal biopsy (v TRUS: OR, 0.32; 95% CI, 0.19–0.52; P < 0.001), and being 66 years of age or more at diagnosis (v < 55 years: OR, 0.65; 95% CI, 0.45–0.92; P = 0.015).

      Conclusion: Almost three-quarters of men who had prostate cancer with low risk of disease progression did not have follow-up investigations consistent with standard AS protocols. The clinical consequences of this shortcoming are unknown.

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      • 1 Monash University, Melbourne, VIC
      • 2 Alfred Health, Melbourne, VIC
      • 3 Monash Health, Melbourne, VIC
      • 4 Eastern Health Clinical School, Monash University, Melbourne, VIC
      • 5 The Peter MacCallum Cancer Centre, Melbourne, VIC
      • 6 University of Melbourne, Melbourne, VIC
      • 7 Barwon Health, Geelong, VIC
      • 8 Geelong Urology, Geelong, VIC


      Correspondence: sue.evans@monash.edu
      Acknowledgements: 

      Funding for this project has been provided by the Movember Foundation. Ian Davis is supported by a National Health and Medical Research Council Practitioner Fellowship (APP1102604). Sue Evans is supported by a Monash Partners Academic Health Science Centre Fellowship.

      Competing interests:

      No relevant disclosures.

      • 1. Bul M, Zhu X, Valdagni R, et al. Active surveillance for low-risk prostate cancer worldwide: the PRIAS study. Eur Urol 2013; 63: 597-603.
      • 2. Prostate Cancer Foundation of Australia; Cancer Council Australia PSA Testing Guidelines Expert Advisory Panel. PSA testing and early management of test-detected prostate cancer: active surveillance (Clinical practice guidelines). Jan 2016. http://wiki.cancer.org.au/australiawiki/index.php?oldid=122836 (viewed March 2017).
      • 3. Dall'Era MA, Cooperberg MR, Chan JM, et al. Active surveillance for early-stage prostate cancer: review of the current literature. Cancer 2008; 112: 1650-1659.
      • 4. National Institute for Health and Clinical Excellence. Prostate cancer: diagnosis and management (CG175). Jan 2014. http://www.nice.org.uk/guidance/cg175/resources/prostate-cancer-diagnosis-andmanagement-35109753913285 (viewed Feb 2017).
      • 5. Prostate Cancer Research International: Active Surveillance (PRIAS). Guideline and study for the expectant management of localized prostate cancer with curative intent: study protocol. Nov 2014. https://www.prias-project.org/uploads/pdfs/2014-11-27%20Protocol%20versie%205.0%20(FINAL).pdf (viewed March 2017).
      • 6. Mottet N, Bellmunt J, Briers E, et al. EAU/ESTRO/SIOG guidelines on prostate cancer. European Association of Urology, 2016. https://uroweb.org/wp-content/uploads/EAU-Guidelines-Prostate-Cancer-2016.pdf (viewed Feb 2017).
      • 7. National Comprehensive Cancer Network. Prostate cancer (NCCN clinical practice guidelines in oncology). Version 3.2016. May 2016. https://www.tri-kobe.org/nccn/guideline/urological/english/prostate.pdf (viewed Feb 2017).
      • 8. Klotz L. Active surveillance for men with low-risk, clinically localized prostate cancer. UpToDate; Aug 2016. http://www.uptodate.com/contents/active-surveillance-for-men-with-low-risk-clinically-localized-prostate-cancer#H12016 (viewed Feb 2017).
      • 9. Cheng JY. The Prostate Cancer Intervention Versus Observation Trial (PIVOT) in perspective. J Clin Med Res 2013; 5: 266-268.
      • 10. Hamdy FC, Donovan JL, Neal DE. 10-Year outcomes in localized prostate cancer. N Engl J Med 2017; 376: 180.
      • 11. Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 2012; 367: 203-213.
      • 12. Evans SM, Millar JL, Wood JM, et al. The Prostate Cancer Registry: monitoring patterns and quality of care for men diagnosed with prostate cancer. BJU Int 2013; 111: E158-E166.
      • 13. Sampurno F, Earnest A, Kumari PB, et al. Quality of care achievements of the Prostate Cancer Outcomes Registry–Victoria. Med J Aust 2016; 204: 319. <MJA full text>
      • 14. Womble PR, Montie JE, Ye ZJ, et al. Contemporary use of initial active surveillance among men in Michigan with low-risk prostate cancer. Eur Urol 2015; 67: 44-50.
      • 15. Cooperberg MR, Carroll PR. Trends in management for patients with localized prostate cancer, 1990–2013. JAMA 2015; 314: 80-82.
      • 16. Loeb S, Folkvaljon Y, Curnyn C, et al. Uptake of active surveillance for very-low-risk prostate cancer in Sweden. JAMA Oncol 2016; Oct 20: 1393-1398.
      • 17. Luckenbaugh AN, Auffenberg GB, Hawken SR, et al. Variation in guideline concordant active surveillance followup in diverse urology practices. J Urol 2017; 197: 621-626.
      • 18. Bokhorst LP, Alberts AR, Rannikko A, et al. Compliance rates with the Prostate Cancer Research International Active Surveillance (PRIAS) protocol and disease reclassification in noncompliers. Eur Urol 2015; 68: 814-821.
      • 19. Loeb S, Walter D, Curnyn C, et al. How active is active surveillance? Intensity of followup during active surveillance for prostate cancer in the United States. J Urol 2016; 196: 721-726.
      • 20. Kinsella N, Stattin P, Cahill D, et al. Factors influencing men's choice of and adherence to active surveillance for low-risk prostate cancer: a mixed-method systematic review. Eur Urol 2018; doi:10.1016/j.eururo.2018.02.026 [Epub ahead of print].
      • 21. Droz JP, Aapro M, Balducci L, et al. Management of prostate cancer in older patients: updated recommendations of a working group of the International Society of Geriatric Oncology. Lancet Oncol 2014; 15: e404-e414.
      • 22. Vyas L, Acher P, Kinsella J, et al. Indications, results and safety profile of transperineal sector biopsies (TPSB) of the prostate: a single centre experience of 634 cases. BJU Int 2014; 114: 32-37.
      • 23. Schoots IG, Petrides N, Giganti F, et al. Magnetic resonance imaging in active surveillance of prostate cancer: a systematic review. Eur Urol 2015; 67: 627-636.
      • 24. Chapple AB, Ziebland S, Brewster S, McPherson A. Patients’ perceptions of transrectal prostate biopsy: a qualitative study. Eur J Cancer Care (Engl) 2007; 16: 215-221.
      • 25. Roth H, Millar JL, Cheng AC, et al. The state of TRUS biopsy sepsis: readmissions to Victorian hospitals with TRUS biopsy-related infection over 5 year. BJU Int 2015; 116: 49-53.
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        Virtual medicine: how virtual reality is easing pain, calming nerves and improving health

        Brennan MR Spiegel
        Med J Aust 2018; 209 (6): . || doi: 10.5694/mja17.00540
        Published online: 21 May 2018

        Virtual reality is thought to create an immersive distraction that restricts the mind from processing pain

        Not so far in the future, doctors might prescribe a virtual beach vacation to calm aches and pains, in lieu of pharmacotherapy. Insurance companies might offer scenic tours of Icelandic fjords to lower blood pressure, instead of doubling up on drugs. Psychiatrists might treat social phobia by inviting patients to a virtual dinner party. Hospitals may immerse children in a fantastical playland while they receive chemotherapy.


        • Cedars-Sinai Health Services, Los Angeles, CA, United States


        Correspondence: Brennan.Spiegel@cshs.org
        Acknowledgements: 

        Support for this work is provided by the Marc and Sheri Rapaport Fund for Digital Health Sciences and Precision Health.

        Competing interests:

        I have received a research grant, administered by Cedars-Sinai Health Services, from appliedVR (Los Angeles, CA). I have no equity, royalty, board positions or other relevant financial relationships to disclose with appliedVR or any other company with a product or service mentioned in this article.

        • 1. Dascal J, Reid M, IsHak WW, et al. Virtual reality and medical inpatients: a systematic review of randomized, controlled trials. Innov Clin Neurosci 2017; 14: 14-21.
        • 2. Malloy KM, Milling LS. The effectiveness of virtual reality distraction for pain reduction: a systematic review. Clin Psychol Rev 2010; 30: 1011-1018.
        • 3. Hoffman HG, Doctor JN, Patterson DR, et al. Virtual reality as an adjunctive pain control during burn wound care in adolescent patients. Pain 2000; 85: 305-309.
        • 4. Hoffman HG, Garcia-Palacios A, Patterson DR, et al. The effectiveness of virtual reality for dental pain control: a case study. Cyberpsychol Behav 2001; 4: 527-535.
        • 5. Hoffman HG, Patterson DR, Carrougher GJ. Use of virtual reality for adjunctive treatment of adult burn pain during physical therapy: a controlled study. Clin J Pain 2000; 16: 244-250.
        • 6. Hoffman HG, Patterson DR, Carrougher GJ, Sharar SR. Effectiveness of virtual reality-based pain control with multiple treatments. Clin J Pain 2001; 17: 229-235.
        • 7. Rizzo AA, Difede J, Rothbaum BO, et al. VR PTSD exposure therapy results with active duty OIF/OEF combatants. Stud Health Technol Inform 2009; 142: 277-282.
        • 8. Maples-Keller JL, Bunnell BE, Kim SJ, Rothbaum BO. The use of virtual reality technology in the treatment of anxiety and other psychiatric disorders. Harv Rev Psychiatry 2017; 25: 103-113.
        • 9. Maples-Keller JL, Price M, Rauch S, et al. Investigating relationships between PTSD symptom clusters within virtual reality exposure therapy for OEF/OIF veterans. Behav Ther 2017; 48: 147-155.
        • 10. Maples-Keller JL, Yasinski C, Manjin N, Rothbaum BO. Virtual reality-enhanced extinction of phobias and post-traumatic stress. Neurotherapeutics 2017; 14: 554-563.
        • 11. Bordnick PS, Traylor AC, Carter BL, Graap KM. A feasibility study of virtual reality-based coping skills training for nicotine dependence. Res Soc Work Pract 2012; 22: 293-300.
        • 12. Bordnick PS, Traylor A, Copp HL, et al. Assessing reactivity to virtual reality alcohol based cues. Addict Behav 2008; 33: 743-756.
        • 13. Bordnick PS, Graap KM, Copp HL, et al. Virtual reality cue reactivity assessment in cigarette smokers. Cyberpsychol Behav 2005; 8: 487-492.
        • 14. Li A, Montaño Z, Chen VJ, Gold JI. Virtual reality and pain management: current trends and future directions. Pain Manag 2011; 1: 147-157.
        • 15. Carrougher GJ, Hoffman HG, Nakamura D, et al. The effect of virtual reality on pain and range of motion in adults with burn injuries. J Burn Care Res 2009; 30: 785-791.
        • 16. Furman E, Jasinevicius TR, Bissada NF, et al. Virtual reality distraction for pain control during periodontal scaling and root planing procedures. J Am Dent Assoc 2009; 140: 1508-1516.
        • 17. Garrett B, Taverner T, Masinde W, et al. A rapid evidence assessment of immersive virtual reality as an adjunct therapy in acute pain management in clinical practice. Clin J Pain 2014; 30: 1089-1098.
        • 18. Gold JI, Kim SH, Kant AJ, et al. Effectiveness of virtual reality for pediatric pain distraction during i.v. placement. Cyberpsychol Behav 2006; 9: 207-212.
        • 19. Sato K, Fukumori S, Matsusaki T, et al. Nonimmersive virtual reality mirror visual feedback therapy and its application for the treatment of complex regional pain syndrome: an open-label pilot study. Pain Med 2010; 11: 622-629.
        • 20. Sarig-Bahat H, Weiss PL, Laufer Y. Neck pain assessment in a virtual environment. Spine (Phila Pa 1976) 2010; 35: E105-E112.
        • 21. Tashjian VC, Mosadeghi S, Howard AR, et al. Virtual reality for management of pain in hospitalized patients: results of a controlled trial. JMIR Ment Health 2017; 4: e9.
        • 22. McCaul KD, Malott JM. Distraction and coping with pain. Psychol Bull 1984; 95: 516-533.
        • 23. Mosadeghi S, Reid MW, Martinez B, et al. Feasibility of an immersive virtual reality intervention for hospitalized patients: an observational cohort study. JMIR Ment Health 2016; 3: e28.
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          Impact of ethnicity on the natural history of Parkinson disease

          Anna Sauerbier, Azman Aris, Ee Wei Lim, Kalyan Bhattacharya and K Ray Chaudhuri
          Med J Aust 2018; 208 (9): . || doi: 10.5694/mja17.01074
          Published online: 21 May 2018

          Summary

           

          • Parkinson disease (PD) affects people of all races and ethnicity worldwide.
          • PD is a multineurotransmitter and multisystem disorder and our current concept of the natural history of PD has changed considerably over the past decades.
          • Many aspects of this heterogeneous condition still remain unexplained; one aspect that is poorly studied is the role of ethnicity and manifest motor and non-motor PD.
          • Some preliminary data suggest that the prodromal risk of developing PD, clinical symptom expression and the experience of living with the condition may vary between different ethnic groups.
          • Several factors might play a role in the influence of ethnicity on PD, such as pharmacogenetics, sociocultural aspects and environmental exposures.
          • Increased knowledge on the role of ethnicity in PD may help shed light on the symptom expression and treatment response of PD, address inequalities in health care delivery worldwide and improve the delivery of personalised medicine.

           


          • 1 Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
          • 2 Parkinson's Foundation Centre of Excellence, King's College Hospital NHS Foundation Trust, London, UK
          • 3 National Neuroscience Institute, Singapore
          • 4 RG Kar Medical College and Hospital, Kolkata, India


          Correspondence: annasauerbier@nhs.net
          Acknowledgements: 

          We acknowledge the support of the Movement Disorder Society Non-Motor PD Study Group and the Non-Motor PD Early Career Subgroup, and of the National Institute for Health Research (NIHR) London South Clinical Research Network and the NIHR Biomedical Research Centre. Anna Sauerbier has received funding from Parkinson’s UK and the Kirby Laing Foundation. This article represents independent collaborative research part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London.

          Competing interests:

          No relevant disclosures.

          • 1. Halliday G, Lees A, Stern M. Milestones in Parkinson’s disease–clinical and pathologic features. Mov Disord 2011; 26: 1015-1021.
          • 2. Titova N, Padmakumar C, Lewis SJG, Chaudhuri KR. Parkinson’s: a syndrome rather than a disease? J Neural Transm (Vienna) 2017; 124: 907-914.
          • 3. Khedr EM, Al Attar GS, Kandil MR, et al. Epidemiological study and clinical profile of Parkinson’s disease in the Assiut Governorate, Egypt: a community-based study. Neuroepidemiology 2012; 38: 154-163.
          • 4. Wang SJ, Fuh JL, Teng EL, et al. A door-to-door survey of Parkinson’s disease in a Chinese population in Kinmen. Arch Neurol 1996; 53: 66-71.
          • 5. Chaudhuri KR, Hu MT, Brooks DJ. Atypical parkinsonism in Afro-Caribbean and Indian origin immigrants to the UK. Mov Disord 2000; 15: 18-23.
          • 6. Caparros-Lefebvre D, Elbaz A. Possible relation of atypical parkinsonism in the French West Indies with consumption of tropical plants: a case-control study. Caribbean Parkinsonism Study Group. Lancet 1999; 354: 281-286.
          • 7. Caparros-Lefebvre D, Steele J. Atypical parkinsonism on Guadeloupe, comparison with the parkinsonism-dementia complex of Guam, and environmental toxic hypotheses. Environ Toxicol Pharmacol 2005; 19: 407-413.
          • 8. Aharon-Peretz J, Rosenbaum H, Gershoni-Baruch R. Mutations in the glucocerebrosidase gene and Parkinson’s disease in Ashkenazi Jews. N Engl J Med 2004; 351: 1972-1977.
          • 9. Louis ED, Barnes LF, Ford B, et al. Ethnic differences in essential tremor. Arch Neurol 2000; 57: 723-727.
          • 10. Sharafaddinzadeh N, Moghtaderi A, Majdinasab N, et al. The influence of ethnicity on the characteristics of multiple sclerosis: a local population study between Persians and Arabs. Clin Neurol Neurosurg 2013; 115: 1271-1275.
          • 11. Hardiman O, Al-Chalabi A, Brayne C, et al. The changing picture of amyotrophic lateral sclerosis: lessons from European registers. J Neurol Neurosurg Psychiatry 2017; 88: 557-563.
          • 12. Burchard EG, Ziv E, Coyle N, et al. The importance of race and ethnic background in biomedical research and clinical practice. N Engl J Med 2003; 348: 1170-1175.
          • 13. Bower JH. Understanding Parkinson disease in sub Saharan Africa: a call to action for the international neurologic community. Parkinsonism Relat Disord 2017; 41: 1-2.
          • 14. Erro R, Brigo F, Tamburin S, et al. Nutritional habits, risk, and progression of Parkinson disease. J Neurol 2018; 265: 12-23.
          • 15. de Rijk MC, Tzourio C, Breteler MM, et al. Prevalence of parkinsonism and Parkinson’s disease in Europe: the EUROPARKINSON Collaborative Study. European Community Concerted Action on the Epidemiology of Parkinson’s disease. J Neurol Neurosurg Psychiatry 1997; 62: 10-15.
          • 16. Muangpaisan W, Mathews A, Hori H, Seidel D. A systematic review of the worldwide prevalence and incidence of Parkinson’s disease. J Med Assoc Thai 2011; 94: 749-755.
          • 17. Pringsheim T, Jette N, Frolkis A, Steeves TD. The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord 2014; 29: 1583-1590.
          • 18. Kessler II. Epidemiologic studies of Parkinson’s disease. 3. A community-based survey. Am J Epidemiol 1972; 96: 242-254.
          • 19. Seo WK, Koh SB, Kim BJ, et al. Prevalence of Parkinson’s disease in Korea. J Clin Neurosci 2007; 14: 1155-1157.
          • 20. Schrag A, Ben-Shlomo Y, Quinn NP. Cross sectional prevalence survey of idiopathic Parkinson’s disease and parkinsonism in London. BMJ 2000; 321: 21-22.
          • 21. Seijo-Martinez M, Castro del Rio M, Rodríguez Alvarez J, et al. Prevalence of parkinsonism and Parkinson’s disease in the Arosa Island (Spain): a community-based door-to-door survey. J Neurol Sci 2011; 304: 49-54.
          • 22. Okada K, Kobayashi S, Tsunematsu T. Prevalence of Parkinson’s disease in Izumo City, Japan. Gerontology 1990; 36: 340-344.
          • 23. Lanska DJ. The geographic distribution of Parkinson’s disease mortality in the United States. J Neurol Sci 1997; 150: 63-70.
          • 24. Masalha R, Kordysh E, Alpert G, et al. The prevalence of Parkinson’s disease in an Arab population, Wadi Ara, Israel. Isr Med Assoc J 2010; 12: 32-35.
          • 25. Lombard A, Gelfand M. Parkinson’s disease in the African. Centr Afr J Med 1978; 24: 5-8.
          • 26. Mayeux R, Marder K, Cote LJ, et al. The frequency of idiopathic Parkinson’s disease by age, ethnic group, and sex in northern Manhattan, 1988-1993. Am J Epidemiol 1995; 142: 820-827.
          • 27. Moriwaka F, Tashiro K, Itoh K, et al. Prevalence of Parkinson’s disease in Hokkaido, the northernmost island of Japan. Intern Med 1996; 35: 276-279.
          • 28. Jendroska K, Olasode BJ, Daniel SE, et al. Incidental Lewy body disease in black Africans. Lancet 1994; 344: 882-883.
          • 29. Dorsey ER, Constantinescu R, Thompson JP, et al. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology 2007; 68: 384-386.
          • 30. Wright Willis A, Evanoff BA, Lian M, et al. Geographic and ethnic variation in Parkinson disease: a population-based study of US Medicare beneficiaries. Neuroepidemiology 2010; 34: 143-151.
          • 31. Zhang Z-X, Anderson DW, Huang J-B, et al. Prevalence of Parkinson’s disease and related disorders in the elderly population of greater Beijing, China. Mov Disord 2003; 18: 764-772.
          • 32. Zhang L, Nie ZY, Liu Y, et al. The prevalence of PD in a nutritionally deficient rural population in China. Acta Neurol Scand 2005; 112: 29-35.
          • 33. Surathi P, Jhunjhunwala K, Yadav R, Pal PK. Research in Parkinson’s disease in India: a review. Ann Indian Acad Neurol 2016; 19: 9-20.
          • 34. Dotchin C, Walker R. Racial differences in the diagnosis of Parkinson’s disease–not just a North American issue [letter]. Mov Disord 2010; 25: 2255-2256; author reply 6-7.
          • 35. Dahodwala N, Siderowf A, Xie M, et al. Racial differences in the diagnosis of Parkinson’s disease. Mov Disord 2009; 24: 1200-1205.
          • 36. Kontis V, Bennett JE, Mathers CD, et al. Future life expectancy in 35 industrialised countries: projections with a Bayesian model ensemble. Lancet 2017; 389: 1323-1335.
          • 37. Calne DB. Is “Parkinson’s disease” one disease? J Neurol Neurosurg Psychiatry 1989; Suppl: 18-21.
          • 38. Korczyn AD. Parkinson’s disease: one disease entity or many? In: Przuntek H, Müller T, editors. Diagnosis and treatment of Parkinson’s disease — state of the art. Vienna: Springer, 1999; pp 107-111.
          • 39. Langston JW. The Parkinson’s complex: parkinsonism is just the tip of the iceberg. Ann Neurol 2006; 59: 591-596.
          • 40. Hu MT, Chaudhuri KR, Jarosz J, et al. An imaging study of parkinsonism among African-Caribbean and Indian London communities. Mov Disord 2002; 17: 1321-1328.
          • 41. Caparros-Lefebvre D, Sergeant N, Lees A, et al. Guadeloupean parkinsonism: a cluster of progressive supranuclear palsy-like tauopathy. Brain 2002; 125(Pt 4): 801-811.
          • 42. Lannuzel A, Ruberg M, Michel PP. Atypical parkinsonism in the Caribbean island of Guadeloupe: etiological role of the mitochondrial complex I inhibitor annonacin. Mov Disord 2008; 23: 2122-2128.
          • 43. Mulder DW, Kurland LT, Iriarte LL. Neurologic diseases on the island of Guam. U S Armed Forces Med J 1954; 5: 1724-1739.
          • 44. Steele JC. Parkinsonism-dementia complex of Guam. Mov Disord 2005; 20 Suppl 12: S99-S107.
          • 45. Uitti RJ, Berry K, Yasuhara O, et al. Neurodegenerative ‘overlap’ syndrome: clinical and pathological features of Parkinson’s disease, motor neuron disease, and Alzheimer’s disease. Parkinsonism Relat Disord 1995; 1: 21-34.
          • 46. Zhang ZX, Anderson DW, Lavine L, Mantel N. Patterns of acquiring parkinsonism-dementia complex on Guam. 1944 through 1985. Arch Neurol 1990; 47: 1019-1024.
          • 47. Kuzuhara S. [ALS and parkinsonism-dementia complex of Kii peninsula] [Japanese]. Ryoikibetsu Shokogun Shirizu 1999(27 Pt 2): 335-338.
          • 48. Okumiya K, Wada T, Fujisawa M, et al. Amyotrophic lateral sclerosis and parkinsonism in Papua, Indonesia: 2001-2012 survey results. BMJ Open 2014; 4: e004353.
          • 49. Caparros-Lefebvre D, Steele J, Kotake Y, Ohta S. Geographic isolates of atypical Parkinsonism and tauopathy in the tropics: possible synergy of neurotoxins. Mov Disord 2006; 21: 1769-1771.
          • 50. Angibaud G, Gaultier C, Rascol O. Atypical parkinsonism and Annonaceae consumption in New Caledonia. Mov Disord 2004; 19: 603-604.
          • 51. de Bie RM, Gladstone RM, Strafella AP, et al Manganese-induced Parkinsonism associated with methcathinone (Ephedrone) abuse. Arch Neurol 2007; 64: 886-889.
          • 52. Chaudhuri KR, Martinez-Martin P, Brown RG, et al. The metric properties of a novel non-motor symptoms scale for Parkinson’s disease: Results from an international pilot study. Mov Disord 2007; 22: 1901-1911.
          • 53. Sauerbier A, Jitkritsadakul O, Titova N, et al. Non-motor symptoms assessed by Non-Motor Symptoms Questionnaire and Non-Motor Symptoms Scale in Parkinson’s disease in selected Asian populations. Neuroepidemiology 2017; 49: 1-17.
          • 54. Barone P, Antonini A, Colosimo C, et al. The PRIAMO study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson’s disease. Mov Disord 2009; 24: 1641-1649.
          • 55. Cheon SM, Ha MS, Park MJ, Kim JW. Nonmotor symptoms of Parkinson’s disease: prevalence and awareness of patients and families. Parkinsonism Relat Disord 2008; 14: 286-290.
          • 56. Maïga B, Koné A, Landouré G, et al. Non-motor signs in patients with Parkinson’s disease at the University Hospital of Point “G”, Mali. eNeurologicalSci 2016; 3: 35-36.
          • 57. Wang G, Hong Z, Cheng Q, et al. Validation of the Chinese non-motor symptoms scale for Parkinson’s disease: results from a Chinese pilot study. Clin Neurol Neurosurg 2009; 111: 523-526.
          • 58. Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967; 17: 427-442.
          • 59. Li H, Zhang M, Chen L, et al. Nonmotor symptoms are independently associated with impaired health-related quality of life in Chinese patients with Parkinson’s disease. Mov Disord 2010; 25: 2740-2746.
          • 60. Sellami L, Kacem I, Nasri A, et al. Evaluation of an Arabic version of the non-motor symptoms scale in Parkinson’s disease. Neurol Sci 2016; 37: 963-968.
          • 61. Branson CO, Ferree A, Hohler AD, Saint-Hilaire M-H. Racial disparities in Parkinson disease: a systematic review of the literature. Adv Parkinsons Dis 2016; 5: 87-96.
          • 62. Chan JC, Malik V, Jia W, et al. Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA 2009; 301: 2129-2140.
          • 63. Mischley LK, Lau RC, Bennett RD. Role of diet and nutritional supplements in Parkinson's disease progression. Oxid Med Cell Longev 2017; 2017: 6405278.
          • 64. Alcalay RN, Gu Y, Mejia-Santana H, et al. The association between Mediterranean diet adherence and Parkinson’s disease. Mov Disord 2012; 27: 771-774.
          • 65. Ho SC, Woo J, Lee CM. Epidemiologic study of Parkinson’s disease in Hong Kong. Neurology 1989; 39: 1314-1318.
          • 66. Pan S, Stutzbach J, Reichwein S, et al. Knowledge and attitudes about Parkinson’s disease among a diverse group of older adults. J Cross Cult Gerontol 2014; 29: 339-352.
          • 67. National Research Council Panel on Race, EHealth in Later Life The National Academies Collection: Reports funded by National Institutes of Health. In: Anderson NB, Bulatao RA, Cohen B, editors. Critical perspectives on racial and ethnic differences in health in late life. Washington (DC): National Academies Press (US), 2004.
          • 68. Huang T, Shu Y, Cai Y-D. Genetic differences among ethnic groups. BMC Genomics 2015; 16: 1093.
          • 69. Fung HC, Chen CM, Hardy J, et al. A common genetic factor for Parkinson disease in ethnic Chinese population in Taiwan. BMC Neurol 2006; 6: 47.
          • 70. Gopalai AA, Lim SY, Chua JY, et al. LRRK2 G2385R and R1628P mutations are associated with an increased risk of Parkinson’s disease in the Malaysian population. Biomed Res Int 2014; 2014: 867321.
          • 71. Inzelberg R, Hassin-Baer S, Jankovic J. Genetic movement disorders in patients of Jewish ancestry. JAMA Neurol 2014; 71: 1567-1572.
          • 72. Huang CL, Wu-Chou YH, Lai SC, et al. Contribution of glucocerebrosidase mutation in a large cohort of sporadic Parkinson’s disease in Taiwan. Eur J Neurol 2011; 18: 1227-1232.
          • 73. Barkhuizen M, Anderson DG, Grobler AF. Advances in GBA-associated Parkinson’s disease–Pathology, presentation and therapies. Neurochem Int 2016; 93: 6-25.
          • 74. Alcalay RN, Mirelman A, Saunders-Pullman R, et al. Parkinson disease phenotype in Ashkenazi Jews with and without LRRK2 G2019S mutations. Mov Disord 2013; 28: 1966-1971.
          • 75. Brockmann K, Srulijes K, Pflederer S, et al. GBA-associated Parkinson’s disease: reduced survival and more rapid progression in a prospective longitudinal study. Mov Disord 2015; 30: 407-411.
          • 76. McLeod HL, Syvanen AC, Githang’a J, et al. Ethnic differences in catechol O-methyltransferase pharmacogenetics: frequency of the codon 108/158 low activity allele is lower in Kenyan than Caucasian or South-west Asian individuals. Pharmacogenetics 1998; 8: 195-199.
          • 77. Dotchin C, Walker R. The management of Parkinson’s disease in sub-Saharan Africa. Expert Rev Neurother 2012; 12: 661-666.
          • 78. Hemming JP, Gruber-Baldini AL, Anderson KE, et al. Racial and socioeconomic disparities in parkinsonism. Arch Neurol 2011; 68: 498-503.
          • 79. Lewey J, Choudhry NK. The current state of ethnic and racial disparities in cardiovascular care: lessons from the past and opportunities for the future. Curr Cardiol Rep 2014; 16: 530.
          • 80. Nagashayana N, Sankarankutty P, Nampoothiri MR, et al. Association of L-DOPA with recovery following Ayurveda medication in Parkinson’s disease. J Neurol Sci 2000; 176: 124-127.
          • 81. Sauerbier A, Lenka A, Aris A, Pal PK. Nonmotor symptoms in Parkinson's disease: gender and ethnic differences. Int Rev Neurobiol 2017; 133: 417-446.
          • 82. Rana AQ, Athar A, Owlia A, et al. Impact of ethnicity on non-motor symptoms of Parkinson’s disease. J Parkinsons Dis 2012; 2: 281-285.
          • 83. Titova N, Chaudhuri KR. Personalized medicine in Parkinson’s disease: time to be precise. Mov Disord 2017; 32: 1147-1154.
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            Non-motor Parkinson disease: new concepts and personalised management

            Nataliya Titova and K Ray Chaudhuri
            Med J Aust 2018; 208 (9): . || doi: 10.5694/mja17.00993
            Published online: 21 May 2018

            Summary

             

            • Most patients with Parkinson disease (PD) have non-motor symptoms (NMS), and on average these can range from four to 19 different symptoms.
            • NMS dominate the prodromal phase of PD and some may serve as clinical biomarkers of PD.
            • NMS can be dopaminergic, non-dopaminergic, of genetic origin or drug induced.
            • Clinical assessment of NMS should include the NMS Questionnaire (completed by patients) for screening, as recommended by the International Parkinson and Movement Disorders Society and other international societies.
            • The total number of NMS in a patient with PD constitutes the NMS burden, which can be graded using validated cut-off scores on the NMS Questionnaire and Scale and can be used as an outcome measure in clinical trials.
            • Despite NMS burden having a major effect on the quality of life of patients and carers, a large European study showed that NMS are often ignored in the clinic.
            • The syndromic nature of PD is underpinned by non-motor subtypes which are likely to be related to specific dysfunction of cholinergic, noradrenergic, serotonergic pathways in the brain, not just the dopaminergic pathways.
            • NMS can be treated by dopaminergic and non-dopaminergic strategies, but further robust studies supported by evidence from animal models are required.
            • The future of modern treatment of PD needs to be supported by the delivery of personalised medicine.

             


            • 1 Pirogov Russian National Research Medical University, Moscow, Russia
            • 2 Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK


            Correspondence: nattitova@yandex.ru
            Acknowledgements: 

            We thank the National Institute of Health Research Biomedical Research Centre and the Institute of Psychiatry, Psychology and Neuroscience at Kings College London for supporting research cited in this article, and the MDS Non-Motor Parkinson’s Disease Study Group.

            Competing interests:

            No relevant disclosures.

            • 1. Parkinson J. An essay on the shaking palsy. Lond Med Phys J 1817; 38.
            • 2. Korczyn AD. Parkinson’s disease: one disease entity or many? J Neural Transm 1999; 56: 107-111.
            • 3. Langston JW. The Parkinson’s complex: parkinsonism is just the tip of the iceberg. Ann Neurol 2006; 59: 591-596.
            • 4. Titova N, Padmakumar C, Lewis SJG, et al. Parkinson’s: a syndrome rather than a disease? J Neural Transm (Vienna) 2017; 124: 907-914.
            • 5. Chaudhuri, KR, Healy DG, Schapira AHV. Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol 2006; 5: 235-245.
            • 6. Martinez-Martin P, Rodriguez-Blazquez C, Kurtis MM, NMSS Validation Group. The impact of non-motor symptoms on health-related quality of life of patients with Parkinson’s disease. Mov Disord 2011; 26: 399-406.
            • 7. Chaudhuri KR, Rojo JM, Schapira AHV, et al. A proposal for a comprehensive grading of Parkinson’s disease severity combining motor and non-motor assessments: meeting an unmet need. PLoS One 2013; 8: e57221.
            • 8. Chaudhuri KR, Sauerbier A, Rojo J, et al. The burden of non-motor symptoms in Parkinson’s disease using a self-completed non-motor questionnaire: a simple grading system. Parkinsonism Relat Disord 2015; 21: 287-291.
            • 9. Titova N, Chaudhuri KR. Personalized medicine in Parkinson’s disease: time to be precise. Mov Disord 2017; 32: 1147-1154.
            • 10. Alves G, Forsaa E, Pedersen KF, et al. Epidemiology of Parkinson’s disease. J Neurol 2008; 255(Suppl 5): 18-32.
            • 11. Titova N, Qamar MA, Chaudhuri KR. Biomarkers of Parkinson’s disease: an introduction. Int Rev Neurobiol 2017; 132: 183-196.
            • 12. Chaudhuri KR, Odin P. The challenge of non-motor symptoms in Parkinson’s disease. Prog Brain Res 2010; 184: 325-341.
            • 13. Berg D, Postuma RB, Adler CH, et al. MDS research criteria for prodromal Parkinson’s disease. Mov Disord 2015; 30: 1600-1611.
            • 14. Doppler K, Jentschke HM, Schulmeyer L, et al. Dermal phospho-alpha-synuclein deposits confirm REM sleep behaviour disorder as prodromal Parkinson’s disease. Acta Neuropathol 2017; 133: 535-545.
            • 15. Katunina E, Titova N. The epidemiology of nonmotor symptoms in Parkinson’s disease (cohort and other studies). Int Rev Neurobiol 2017; 133: 91-110.
            • 16. Todorova A, Jenner P, Chaudhuri KR. Non-motor Parkinson’s: integral to motor Parkinson’s, yet often neglected. Pract Neurol 2014; 14: 310-322.
            • 17. Barone P, Antonini A, Colosimo C, et al. The PRIAMO study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson’s disease. Mov Disord 2009; 24: 1641-1649.
            • 18. Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 2008; 79: 368-376.
            • 19. Martinez-Martin P, Rodriguez-Blazquez C, Abe K, et al. International study on the psychometric attributes of the non-motor symptoms scale in Parkinson disease. Neurology 2009; 73: 1584-1591.
            • 20. Schrag A, Jahanshahi M, Quinn N. What contributes to quality of life in patients with Parkinson’s disease? J Neurol Neurosurg Psychiatry 2000; 69: 308-312.
            • 21. Hagell P, Nordling S, Reimer J, et al. Resource use and costs in a Swedish cohort of patients with Parkinson’s disease. Mov Disord 2002; 17: 1213-1220.
            • 22. Braak H, Del Tredici K, Rub U, et al. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 2003; 24: 197-211.
            • 23. Braak H, Ghebremedhin E, Rub U, et al. Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 2004; 318: 121-134.
            • 24. Postuma RB, Iranzo A, Hogl B, et al. Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: a multicenter study. Ann Neurol 2015; 77: 830-839.
            • 25. Hassan A, Wu SS, Schmidt P, et al. The profile of long-term Parkinson’s disease survivors with 20 years of disease duration and beyond. J Parkinsons Dis 2015; 5: 313-319.
            • 26. Titova N, Martinez-Martin P, Katunina E, et al. Advanced Parkinson’s or “complex phase” Parkinson’s disease? Re-evaluation is needed. J Neural Transm 2017; 124: 1529-1537.
            • 27. Jellinger KA. Neuropathobiology of non-motor symptoms in Parkinson disease. J Neural Transm (Vienna) 2015; 122: 1429-1440.
            • 28. Jellinger KA. Neuropathology of sporadic Parkinson's disease: evaluation and changes of concepts. Mov Disord 2012; 27: 8-30.
            • 29. Titova N, Schapira AHV, Chaudhuri KR, et al. Nonmotor symptoms in experimental models of Parkinson’s disease. Int Rev Neurobiol 2017; 133: 63-89.
            • 30. Chaudhuri KR, Martinez-Martin P, Schapira AHV, et al. International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson’s disease: the NMSQuest study. Mov Disord 2006; 21: 916-923.
            • 31. Chaudhuri KR, Martinez-Martin P, Brown RG, et al. The metric properties of a novel non-motor symptoms scale for Parkinson’s disease: results from an international pilot study. Mov Disord 2007; 22: 1901-1911.
            • 32. Martinez-Martin P, Chaudhuri KR, Rojo-Abuin JM, et al. Assessing the non-motor symptoms of Parkinson’s disease: MDS-UPDRS and NMS Scale. Eur J Neurol 2015; 22: 37-43.
            • 33. Titova NV, Chaudhuri KR. Non-motor symptoms of Parkinson’s disease: the submerged part of the iceberg. Ann Clin Exp Neurol 2017; 11(4): 5-18.
            • 34. Sauerbier A, Qamar MA, Rajah T, et al. New concepts in the pathogenesis and presentation of Parkinson’s disease. Clin Med (Lond) 2016; 16: 365-370.
            • 35. Martinez-Martin P, Ray Chaudhuri K. Comprehensive grading of Parkinson’s disease using motor and non-motor assessments: addressing a key unmet need. Expert Rev Neurother 2018; 18: 41-50.
            • 36. Storch A, Schneider CB, Wolz M, et al. Nonmotor fluctuations in Parkinson disease: severity and correlation with motor complications. Neurology 2013; 80: 800-809.
            • 37. Erro R, Vitale C, Amboni M, et al. The heterogeneity of early Parkinson’s disease: a cluster analysis on newly diagnosed untreated patients. PLoS One 2013; 8: e70244.
            • 38. Pont-Sunyer C, Hotter A, Gaig C, et al. The onset of nonmotor symptoms in Parkinson’s disease (the ONSET PD study). Mov Disord 2015: 30; 229-237.
            • 39. Sauerbier A, Jenner P, Todorova A, et al. Non motor subtypes and Parkinson’s disease. Parkinsonism Relat Disord 2016; 22(Suppl 1): 41-46.
            • 40. Zis P, Martinez-Martin P, Sauerbier A, et al. Non-motor symptoms burden in treated and untreated early Parkinson’s disease patients: argument for non-motor subtypes. Eur J Neurol 2015; 22: 1145-1150.
            • 41. Marras C, Chaudhuri KR. Nonmotor features of Parkinson’s disease subtypes. Mov Disord 2016; 31: 1095-1102.
            • 42. Williams-Gray CH, Evans JR, Goris A, et al. The distinct cognitive syndromes of Parkinson’s disease: 5 year follow-up of the CamPaIGN cohort. Brain 2009; 132(Pt 11): 2958-2969.
            • 43. Weintraub D, Simuni T, Caspell-Garcia C, et al.; Parkinson’s Progression Markers Initiative Cognitive performance and neuropsychiatric symptoms in early, untreated Parkinson’s disease. Mov Disord 2015; 30: 919-927.
            • 44. Shimada H, Hirano S, Shinotoh H, et al. Mapping of brain acetylcholinesterase alterations in Lewy body disease by PET. Neurology 2009; 73: 273-278.
            • 45. Gjerløff T, Fedorova T, Knudsen K, et al. Imaging acetylcholinesterase density in peripheral organs in Parkinson’s disease with 11C-donepezil PET. Brain 2015; 138(Pt 3): 653-663.
            • 46. O’Callaghan C, Lewis SJG. Cognition in Parkinson’s disease. Int Rev Neurobiol 2017; 133: 557-583.
            • 47. Muralidharan V, Balasubramani PP, Chakravarthy VS, et al. A neurocomputational model of the effect of cognitive load on freezing of gait in Parkinson’s disease. Front Hum Neurosci 2017; 10: 649.
            • 48. Espay AJ, LeWitt PA, Kaufmann H. Norepinephrine deficiency in Parkinson’s disease: the case for noradrenergic enhancement. Mov Disord 2014; 29: 1710-1719.
            • 49. Pavese N, Metta V, Bose SK, et al. Fatigue in Parkinson’s disease is linked to striatal and limbic serotonergic dysfunction. Brain 2010; 133: 3434-3443.
            • 50. Seppi K, Weintraub D, Coelho M, et al. The Movement Disorder Society Evidence-Based Medicine Review Update: treatments for the non-motor symptoms of Parkinson’s disease. Mov Disord 2011; 26(Suppl 3): S42-80.
            • 51. Schrag A, Sauerbier A, Chaudhuri KR. New clinical trials for nonmotor manifestations of Parkinson’s disease. Mov Disord 2015; 30: 1490-1504.
            • 52. Titova N, Jenner P, Chaudhuri KR. The future of Parkinson’s treatment - personalised and precision medicine. Eur Neurol Rev 2017; 12: 15-16.
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              Psychotropic drug prescribing in residential aged care homes

              Gerard J Byrne
              Med J Aust 2018; 208 (9): . || doi: 10.5694/mja18.00037
              Published online: 21 May 2018

              Individualised psychosocial interventions are needed as alternatives to pharmacological sedation

              Sedating psychotropic drugs, including antipsychotics and benzodiazepines, are commonly prescribed in residential aged care facilities (RACFs), despite extensive evidence of their limited efficacy for treating behavioural and psychological symptoms in older people and of their potential for eliciting serious adverse effects, including death.1 As a consequence, efforts are afoot in many countries to minimise the use of these medications in RACFs. In this issue of the MJA, Westbury and colleagues2 report findings from the RedUSe study of a multi-component intervention designed to reduce the prescribing of sedative medications in Australian RACFs. This uncontrolled investigation employed four complementary interventions in 150 nursing homes: psychotropic medication audits by a local champion nurse; RACF staff education sessions conducted by a pharmacist using benchmarked local data and incorporating training in non-pharmacological interventions; interdisciplinary prescribing reviews for each RACF resident; and academic detailing for prescribers. This intervention sequence was repeated twice, 3 months apart. Data for 12 157 RACF residents collected at baseline, 3 months and 6 months indicated that prescribing of antipsychotics and benzodiazepine had decreased significantly following the intervention: the prevalence of antipsychotic use dropped from 21.6% of residents at baseline to 18.9% at 6 months, and that of benzodiazepines from 22.2% to 17.6%. For 39% of RACF residents taking antipsychotics or benzodiazepines at baseline, medication was ceased or the dosage reduced at 6 months.


              • University of Queensland, Brisbane, QLD


              Correspondence: gerard.byrne@uq.edu.au
              Competing interests:

              No relevant disclosures.

              • 1. Ma H, Huang Y, Cong Z, et al. The efficacy and safety of atypical antipsychotics for the treatment of dementia: a meta-analysis of randomized, placebo-controlled trials. J Alzheimers Dis 2014; 42: 915-937.
              • 2. Westbury JL, Gee P, Ling T, et al. RedUSe: reducing antipsychotic and benzodiazepine prescribing in residential aged care facilities. Med J Aust 2018; 108: 398-403.
              • 3. Ballard C, Lana MM, Theodoulou M, et al. A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial). PLoS Med 2008; 5: e76.
              • 4. Devanand DP, Mintzer J, Schultz SK, et al. Relapse risk after discontinuation of risperidone in Alzheimer’s disease. N Engl J Med 2012; 367: 1497-1507.
              • 5. Ballard C, Orrell M, YongZhong S, et al. Impact of antipsychotic review and nonpharmacological intervention on antipsychotic use, neuropsychiatric symptoms, and mortality in people with dementia living in nursing homes: a factor cluster-randomized controlled trial by the Well-Being and Health for People with Dementia (WHELD) Program. Am J Psychiatry 2016; 173: 252-262.
              • 6. Scales K, Zimmerman S, Miller SJ. Evidence-based nonpharmacological practices to address behavioural and psychological symptoms of dementia. Gerontologist 2018; 58: S88-S102.
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                Tremor: a simple four-step approach to clinical assessment

                Andre Loiselle
                Med J Aust 2018; 208 (9): . || doi: 10.5694/mja18.00115
                Published online: 21 May 2018

                Tremor is the most common movement disorder encountered in clinical practice.1-3 It is defined as an involuntary, rhythmic and oscillatory movement of a body part. Tremors tend to be relatively constant in frequency but variable in amplitude,1 which may happen due to exaggeration of the physiological tremor or due to a tremor disorder. If significant enough, it may lead to medical presentation.


                • John Hunter Hospital, Newcastle, NSW


                Series Editors

                Balakrishnan (Kichu) R Nair

                Simon O'Connor

                Competing interests:

                No relevant disclosures.

                • 1. Jankovic J, Fahn S. Physiologic and pathologic tremors. Diagnosis, mechanism, and management. Ann Intern Med 1980; 93: 460-465.
                • 2. Sirisena D, Williams D. My hands shake — classification and treatment of tremor. Aust Fam Physician 2009; 38: 678-683.
                • 3. Crawford P, Zimmerman E. Differentiation and diagnosis of tremor. Am Fam Physician 2011; 83; 697-702.
                • 4. Thenganatt MA, Louis ED. Distinguishing essential tremor from Parkinson’s disease: bedside tests and laboratory evaluations. Expert Rev Neurother 2012; 12: 687-696.
                • 5. Cohen O, Pullman S, Jurewicz E, et al. Rest tremor in patients with essential tremor: prevalence, clinical correlates, and electrophysiologic characteristics. Arch Neurol 2003; 60: 405-410.
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                  Identifying genes in Parkinson disease: state of the art

                  Elaine GY Chew, Jia Nee Foo and Eng-King Tan
                  Med J Aust 2018; 208 (9): . || doi: 10.5694/mja17.01254
                  Published online: 21 May 2018

                  Recent studies are expanding our understanding of the genetic basis of Parkinson disease

                  Parkinson disease (PD) is a common neurodegenerative disorder which manifests as bradykinesia, movement rigidity and tremors in affected individuals. Our understanding of the genetic basis of PD has been steadily increasing since the initial report of α-synuclein mutations two decades ago.1 Mutations implicated in familial PD fully account for monogenic inheritance and point to potential functional mechanisms underlying PD.2,3 However, most sporadic PD cannot be accounted for by known familial PD genes, with the late-onset nature of PD making further linkage studies challenging. Genome-wide association and whole exome sequencing studies have implicated a growing list of mutations and genes in PD, which are expected to provide new insights into potential pathways involved in PD pathogenicity.


                  • 1 Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore
                  • 2 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
                  • 3 National Neuroscience Institute, Singapore
                  • 4 Duke–NUS Medical School, Singapore


                  Acknowledgements: 

                  Eng-King Tan acknowledges funding from the National Medical Research Council Singapore under the Singapore Translational Research Investigator Award and the Translational and Clinical Research Flagship Programme (NMRC/TCR/013-NNI/2014); Duke–NUS Medical School; and the Singapore Millennium Foundation. Jia Nee Foo is a Singapore National Research Foundation Fellow (NRF-NRFF2016-03).

                  Competing interests:

                  No relevant disclosures.

                  • 1. Polymeropoulos MH, Lavedan C, Leroy E, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 1997; 276: 2045-2047.
                  • 2. Singleton AB, Farrer MJ, Bonifati V. The genetics of Parkinson’s disease: progress and therapeutic implications. Mov Disord 2013; 28: 14-23.
                  • 3. Mohan M, Mellick GD. Role of the VPS35 D620N mutation in Parkinson’s disease. Parkinsonism Relat Disord 2017; 36: 10-18.
                  • 4. Chang D, Nalls MA, Hallgrimsdottir IB, et al. A meta-analysis of genome-wide association studies identifies 17 new Parkinson’s disease risk loci. Nat Genet 2017; 49: 1511-1516.
                  • 5. Nalls MA, Pankratz N, Lill CM, et al. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nat Genet 2014; 46: 989-993.
                  • 6. International Parkinson's Disease Genomics Consortium (IPDGC); Wellcome Trust Case Control Consortium 2 (WTCCC2). A two-stage meta-analysis identifies several new loci for Parkinson’s disease. PLOS Genet 2011; 7: e1002142.
                  • 7. Robak LA, Jansen IE, van Rooij J, et al. Excessive burden of lysosomal storage disorder gene variants in Parkinson’s disease. Brain 2017; 140: 3191-3203.
                  • 8. Siitonen A, Nalls MA, Hernandez D, et al. Genetics of early-onset Parkinson’s disease in Finland: exome sequencing and genome-wide association study. Neurobiol Aging 2017; 53: 195.e197-195.e110.
                  • 9. Jansen IE, Ye H, Heetveld S, et al. Discovery and functional prioritization of Parkinson’s disease candidate genes from large-scale whole exome sequencing. Genome Biol 2017; 18: 22.
                  • 10. Chartier-Harlin MC, Dachsel JC, Vilarino-Guell C, et al. Translation initiator EIF4G1 mutations in familial Parkinson disease. Am J Hum Genet 2011; 89: 398-406.
                  • 11. Vilarino-Guell C, Wider C, Ross OA, et al. VPS35 mutations in Parkinson disease. Am J Hum Genet 2011; 89: 162-167.
                  • 12. Vilarino-Guell C, Rajput A, Milnerwood AJ, et al. DNAJC13 mutations in Parkinson disease. Hum Mol Genet 2014; 23: 1794-1801.
                  • 13. Funayama M, Ohe K, Amo T, et al. CHCHD2 mutations in autosomal dominant late-onset Parkinson’s disease: a genome-wide linkage and sequencing study. Lancet Neurol 2015; 14: 274-282.
                  • 14. Deng HX, Shi Y, Yang Y, et al. Identification of TMEM230 mutations in familial Parkinson’s disease. Nat Genet 2016; 48: 733-739.
                  • 15. Farrer MJ, Milnerwood AJ, Follett J, Guella I. TMEM230 is not a gene for Parkinson disease. bioRxiv 2017. doi:10.1101/097030.
                  • 16. Ibanez L, Dube U, Budde J, et al. TMEM230 in Parkinson’s disease. Neurobiol Aging 2017; 56: 212.e211-212.e213.
                  • 17. Nichols N, Bras JM, Hernandez DG, et al. EIF4G1 mutations do not cause Parkinson’s disease. Neurobiol Aging 2015; 36: 2444.e2441-2444.e2444.
                  • 18. Mok KY, Sheerin U, Simon-Sanchez J, et al. Deletions at 22q11.2 in idiopathic Parkinson’s disease: a combined analysis of genome-wide association data. Lancet Neurol 2016; 15: 585-596.
                  • 19. Butcher NJ, Kiehl TR, Hazrati LN, et al. Association between early-onset Parkinson disease and 22q11.2 deletion syndrome: identification of a novel genetic form of Parkinson disease and its clinical implications. JAMA Neurol 2013; 70: 1359-1366.
                  • 20. Jo J, Xiao Y, Sun Alfred X, et al. Midbrain-like organoids from human pluripotent stem cells contain functional dopaminergic and neuromelanin-producing neurons. Cell Stem Cell 2016; 19: 248-257.
                  • 21. Monzel AS, Smits LM, Hemmer K, et al. Derivation of human midbrain-specific organoids from neuroepithelial stem cells. Stem Cell Reports 2017; 8: 1144-1154.
                  • 22. Kumari U, Tan EK. LRRK2 in Parkinson’s disease: genetic and clinical studies from patients. FEBS J 2009; 276: 6455-6463.
                  • 23. Sidransky E, Nalls MA, Aasly JO, et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson’s disease. N Engl J Med 2009; 361: 1651-1661.
                  • 24. Espay AJ, Brundin P, Lang AE. Precision medicine for disease modification in Parkinson disease. Nat Rev Neurol 2017; 13: 119.
                  • 25. Payami H. The emerging science of precision medicine and pharmacogenomics for Parkinson’s disease. Mov Disord 2017; 32: 1139-1146.
                  • 26. Bae T, Tomasini L, Mariani J, et al. Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis. Science 2018; 359: 550-555.
                  • 27. Lodato MA, Rodin RE, Bohrson CL, et al. Aging and neurodegeneration are associated with increased mutations in single human neurons. Science 2018; 359: 555-559.
                  • 28. Poduri A, Evrony GD, Cai X, Walsh CA. Somatic mutation, genomic variation, and neurological disease. Science 2013; 341: 1237758.
                  • 29. Kennedy SR, Loeb LA, Herr AJ. Somatic mutations in aging, cancer and neurodegeneration. Mech Ageing Dev 2012; 133: 118-126.
                  • 30. Ammal Kaidery N, Tarannum S, Thomas B. Epigenetic landscape of Parkinson’s disease: emerging role in disease mechanisms and therapeutic modalities. Neurotherapeutics 2013; 10: 698-708.
                  • 31. Jakubowski JL, Labrie V. Epigenetic biomarkers for Parkinson’s disease: from diagnostics to therapeutics. J Parkinsons Dis 2016; 7: 1-12.
                  • 32. Migdalska-Richards A, Daly L, Bezard E, Schapira AH. Ambroxol effects in glucocerebrosidase and alpha-synuclein transgenic mice. Ann Neurol 2016; 80: 766-775.
                  • 33. Chan SL, Tan E-K. Targeting LRRK2 in Parkinson’s disease: an update on recent developments. Expert Opin Ther Targets 2017; 21: 601-610.
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                    Clinical Oncology Society of Australia position statement on exercise in cancer care

                    Prue Cormie, Morgan Atkinson, Lucy Bucci, Anne Cust, Elizabeth Eakin, Sandra Hayes, Alexandra L McCarthy, Andrew Murnane, Sharni Patchell and Diana Adams
                    Med J Aust 2018; 209 (4): . || doi: 10.5694/mja18.00199
                    Published online: 7 May 2018

                    Abstract

                    Introduction: Clinical research has established exercise as a safe and effective intervention to counteract the adverse physical and psychological effects of cancer and its treatment. This article summarises the position of the Clinical Oncology Society of Australia (COSA) on the role of exercise in cancer care, taking into account the strengths and limitations of the evidence base. It provides guidance for all health professionals involved in the care of people with cancer about integrating exercise into routine cancer care.

                    Main recommendations: COSA calls for:

                    • exercise to be embedded as part of standard practice in cancer care and to be viewed as an adjunct therapy that helps counteract the adverse effects of cancer and its treatment;
                    • all members of the multidisciplinary cancer team to promote physical activity and recommend that people with cancer adhere to exercise guidelines; and
                    • best practice cancer care to include referral to an accredited exercise physiologist or physiotherapist with experience in cancer care.

                    Changes in management as a result of the guideline: COSA encourages all health professionals involved in the care of people with cancer to:

                    • discuss the role of exercise in cancer recovery;
                    • recommend their patients adhere to exercise guidelines (avoid inactivity and progress towards at least 150 minutes of moderate intensity aerobic exercise and two to three moderate intensity resistance exercise sessions each week); and
                    • refer their patients to a health professional who specialises in the prescription and delivery of exercise (ie, accredited exercise physiologist or physiotherapist with experience in cancer care).

                    • 1 Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, VIC
                    • 2 Youth Cancer Services South Australia and Northern Territory, Adelaide, SA
                    • 3 Peter MacCallum Cancer Centre, Melbourne
                    • 4 Cancer Epidemiology and Prevention Research Group, University of Sydney, Sydney, NSW
                    • 5 Melanoma Institute Australia, Sydney, NSW
                    • 6 University of Queensland, Brisbane, QLD
                    • 7 Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD
                    • 8 University of Auckland, Auckland, NZ
                    • 9 Macarthur Cancer Therapy Centre, South Western Sydney Local Health District, Sydney, NSW


                    Correspondence: prue.cormie@acu.edu.au
                    Acknowledgements: 

                    This position statement was developed with the support of the COSA Council and Exercise and Cancer Group. We acknowledge the feedback provided by the COSA members and affiliated organisations throughout the national consultation process. We also acknowledge the contribution of COSA staff who assisted in the development of the position statement. Anne Cust is supported by National Health and Medical Research Council and Cancer Institute NSW Career Development Fellowships. Sandra Hayes receives fellowship funding from Cancer Council Queensland.

                    Competing interests:

                    No relevant disclosures.

                    • 1. Winters-Stone KM, Neil SE, Campbell KL. Attention to principles of exercise training: a review of exercise studies for survivors of cancers other than breast. Br J Sports Med 2014; 48: 987-995.
                    • 2. Sasso JP, Eves ND, Christensen JF, Koelwyn GJ, Scott J, Jones LW. A framework for prescription in exercise-oncology research. J Cachexia Sarcopenia Muscle 2015; 6: 115-124.
                    • 3. Cormie P, Zopf EM, Zhang X, Schmitz KH. The impact of exercise on cancer mortality, recurrence, and treatment-related adverse effects. Epidemiol Rev 2017; 39: 71-92.
                    • 4. Courneya KS, Friedenreich CM, editors. Physical activity and cancer. London: Springer; 2011.
                    • 5. Mishra SI, Scherer RW, Snyder C, et al. Exercise interventions on health-related quality of life for people with cancer during active treatment. Cochrane Database Syst Rev 2012; 8: CD008465.
                    • 6. Mishra SI, Scherer RW, Geigle PM, et al. Exercise interventions on health-related quality of life for cancer survivors. Cochrane Database Syst Rev 2012; 8: CD007566.
                    • 7. Craft LL, Vaniterson EH, Helenowski IB, et al. Exercise effects on depressive symptoms in cancer survivors: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 2012; 21: 3-19.
                    • 8. Cramp F, Daniel J. Exercise for the management of cancer-related fatigue in adults. Cochrane Database Syst Rev 2010; 11: CD006145.
                    • 9. Gardner JR, Livingston PM, Fraser SF. Effects of exercise on treatment-related adverse effects for patients with prostate cancer receiving androgen-deprivation therapy: a systematic review. J Clin Oncol 2014; 32: 335-346.
                    • 10. Speck RM, Courneya KS, Masse LC, et al. An update of controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. J Cancer Surviv 2010; 4: 87-100.
                    • 11. Cheema BS, Kilbreath SL, Fahey PP, et al. Safety and efficacy of progressive resistance training in breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat 2014; 148: 249-268.
                    • 12. Meneses-Echávez J, González-Jiménez E, Ramírez-Vélez R. Effects of supervised exercise on cancer-related fatigue in breast cancer survivors: a systematic review and meta-analysis. BMC Cancer 2015; 15: 77.
                    • 13. Brown JC, Huedo-Medina TB, Pescatello LS, et al. Efficacy of exercise interventions in modulating cancer-related fatigue among adult cancer survivors: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2011; 20: 123-133.
                    • 14. Bourke L, Boorjian SA, Briganti A, et al. Survivorship and improving quality of life in men with prostate cancer. Eur Urol 2015; 68: 374-383.
                    • 15. Tomlinson D, Diorio C, Beyene J, Sung L. Effect of exercise on cancer-related fatigue: a meta-analysis. Am J Phys Med Rehabil 2014; 93: 675-686.
                    • 16. Hanson ED, Wagoner CW, Anderson T, Battaglini CL. The independent effects of strength training in cancer survivors: a systematic review. Curr Oncol Rep 2016; 18: 31.
                    • 17. Strasser B, Steindorf K, Wiskemann J, Ulrich CM. Impact of resistance training in cancer survivors: a meta-analysis. Med Sci Sports Exerc 2013; 45: 2080-2090.
                    • 18. Des Guetz G, Uzzan B, Bouillet T, et al. Impact of physical activity on cancer-specific and overall survival of patients with colorectal cancer. Gastroenterol Res Pract 2013; 2013: 1-6.
                    • 19. Friedenreich CM, Neilson HK, Farris MS, Courneya KS. Physical activity and cancer outcomes: a precision medicine approach. Clin Cancer Res 2016; 22: 4766-4775.
                    • 20. Ibrahim EM, Al-Homaidh A. Physical activity and survival after breast cancer diagnosis: meta-analysis of published studies. Med Oncol 2010; 28: 753-765.
                    • 21. Je Y, Jeon JY, Giovannucci EL, Meyerhardt JA. Association between physical activity and mortality in colorectal cancer: a meta-analysis of prospective cohort studies. Int J Cancer 2013; 133: 1905-1913.
                    • 22. Lahart IM, Metsios GS, Nevill AM, Carmichael AR. Physical activity, risk of death and recurrence in breast cancer survivors: a systematic review and meta-analysis of epidemiological studies. Acta Oncol 2015; 54 635-654.
                    • 23. Li T, Wei S, Shi Y, et al. The dose-response effect of physical activity on cancer mortality: findings from 71 prospective cohort studies. Br J Sports Med 2015; 50: 339-345.
                    • 24. Otto SJ, Korfage IJ, Polinder S, et al. Association of change in physical activity and body weight with quality of life and mortality in colorectal cancer: a systematic review and meta-analysis. Support Care Cancer 2015; 23: 1237-1250.
                    • 25. Schmid D, Leitzmann MF. Association between physical activity and mortality among breast cancer and colorectal cancer survivors: a systematic review and meta-analysis. Ann Oncol 2014; 25: 1293-1311.
                    • 26. Wu W, Guo F, Ye J, et al. Pre- and post-diagnosis physical activity is associated with survival benefits of colorectal cancer patients: a systematic review and meta-analysis. Oncotarget 2016; 7: 52095-52103.
                    • 27. Zhong S, Jiang T, Ma T, et al. Association between physical activity and mortality in breast cancer: a meta-analysis of cohort studies. Eur J Epidemiol 2014; 29: 391-404.
                    • 28. Schmitz KH, Courneya KS, Matthews C, et al. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc 2010; 42: 1409-1426.
                    • 29. Rock CL, Doyle C, Demark-Wahnefried W, et al. Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin 2012; 62: 242-274.
                    • 30. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Survivorship. Fort Washington, PA: NCCN, 2016. https://www.nccn.org/professionals/physician_gls/pdf/survivorship.pdf (viewed Aug 2017).
                    • 31. ASCO Cancer Survivorship Committee. Providing high quality survivorship care in practice: an ASCO guide. American Society of Clinical Oncology, 2014. https://phpa.health.maryland.gov/cancer/cancerplan/SiteAssets/SitePages/PNN/20140523ASCOsurvivorship.pdf (viewed Aug 2017).
                    • 32. Campbell A, Stevinson C, Crank H. The BASES Expert Statement on exercise and cancer survivorship. J Sports Sci 2012; 30: 949-952.
                    • 33. Hayes SC, Spence RR, Galvao DA, Newton RU. Australian Association for Exercise and Sport Science position stand: optimising cancer outcomes through exercise. J Sci Med Sport 2009; 12: 428-434.
                    • 34. Eakin EG, Youlden DR, Baade PD, et al. Health behaviors of cancer survivors: data from an Australian population-based survey. Cancer Causes Control 2007; 18: 881-894.
                    • 35. Short CE, James EL, Girgis A, et al. Main outcomes of the Move More for LifeTrial: a randomised controlled trial examining the effects of tailored-print and targeted-print materials for promoting physical activity among post-treatment breast cancer survivors. Psychooncology 2015; 24: 771-778.
                    • 36. Galvao DA, Newton RU, Gardiner RA, et al. Compliance to exercise-oncology guidelines in prostate cancer survivors and associations with psychological distress, unmet supportive care needs, and quality of life. Psychooncology 2015; doi:10.1002/pon.3882. [Epub ahead of print].
                    • 37. Blaney JM, Lowe-Strong A, Rankin-Watt J, et al. Cancer survivors’ exercise barriers, facilitators and preferences in the context of fatigue, quality of life and physical activity participation: a questionnaire-survey. Psychooncology 2013; 22: 186-194.
                    • 38. McGowan EL, Speed-Andrews AE, Blanchard CM, et al. Physical activity preferences among a population-based sample of colorectal cancer survivors. Oncol Nurs Forum 2013; 40: 44-52.
                    • 39. Harrington JM, Schwenke DC, Epstein DR. Exercise preferences among men with prostate cancer receiving androgen-deprivation therapy. Oncol Nurs Forum 2013; 40: E358-E367.
                    • 40. Jones LW, Courneya KS. Exercise counseling and programming preferences of cancer survivors. Cancer Pract 2002; 10: 208-215.
                    • 41. Jones LW, Guill B, Keir ST, et al. Exercise interest and preferences among patients diagnosed with primary brain cancer. Support Care Cancer 2006; 15: 47-55.
                    • 42. Karvinen KH, Courneya KS, Campbell KL, et al. Exercise preferences of endometrial cancer survivors: a population-based study. Cancer Nurs 2006; 29: 259-265.
                    • 43. Karvinen KH, Courneya KS, Venner P, North S. Exercise programming and counseling preferences in bladder cancer survivors: a population-based study. J Cancer Surviv 2007; 1: 27-34.
                    • 44. Karvinen KH, Raedeke TD, Arastu H, Allison RR. Exercise programming and counseling preferences of breast cancer survivors during or after radiation therapy. Oncol Nurs Forum 2011; 38: E326-E334.
                    • 45. Vallance J, Lavallee C, Culos-Reed N, Trudeau M. Rural and small town breast cancer survivors’ preferences for physical activity. Int J Behav Med 2013; 20: 522-528.
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                      Developmental dysplasia of the hip: addressing evidence gaps with a multicentre prospective international study

                      Emily K Schaeffer, IHDI Study Group and Kishore Mulpuri
                      Med J Aust 2018; 208 (8): . || doi: 10.5694/mja18.00154
                      Published online: 7 May 2018

                      Summary

                       

                      • There is a lack of high quality evidence available to guide clinical practice in the treatment and management of developmental dysplasia of the hip (DDH).
                      • Evidence has been limited by persistent confusion on diagnostic and classification terminology, variability in surgeon decision making and a reliance on single centre, retrospective studies with small patient numbers.
                      • To address gaps in knowledge regarding screening, diagnosis and management of DDH, the International Hip Dysplasia Institute began a multicentre, international prospective study on infants with hips dislocated at rest.
                      • This review discusses the current state of screening, diagnostic and management practices in DDH and addresses important unanswered questions that will be critical in identifying best practices and optimising patient outcomes.
                      • There is insufficient evidence to support universal ultrasound screening; instead, selective screening should be performed by 6–8 weeks of age on infants with risk factors of breech presentation, family history, or history of clinical hip instability. Follow-up of infants with risk factors and normal initial screening should be considered to at least 6 months of age.
                      • Brace treatment is a sensible first-line treatment for management of dislocated hips at rest in infants < 6 months of age.
                      • Early operative reduction may be considered as there is insufficient evidence to support a protective role for the ossific nucleus in the development of avascular necrosis.

                       


                      • 1 BC Children's Hospital, Vancouver, Canada
                      • 2 University of British Columbia, Vancouver, Canada
                      • 3 Orlando Health Center, Orlando, FL, USA


                      Correspondence: kmulpuri@cw.bc.ca
                      Acknowledgements: 

                      We thank members of the IHDI Study Group for their intellectual and data contributions to the IHDI and IHDR studies; and Niamul Quader for supplying the image and data for Box 3.

                      Competing interests:

                      We have received funding for research support from the registry seed grant, the IHDI, the Children’s Hospital Research Institute and the I'm a HIPpy Foundation.

                      • 1. Godward S, Dezateux C. Surgery for congenital dislocation of the hip in the UK as a measure of outcome of screening. Lancet 1998; 351: 1149-1152.
                      • 2. Tibrewal S, Gulati V, Ramachandran M. The Pavlik method: a systematic review of current concepts. J Pediatr Orthop B 2013; 22: 516-520.
                      • 3. Bialik V, Bialik GM, Blazer S, et al. Developmental dysplasia of the hip: a new approach to incidence. Pediatrics 1999; 103: 93-99.
                      • 4. Jackson JC, Runge MM, Nye NS. Common questions about developmental dysplasia of the hip. Am Fam Physician 2014; 90: 843-850.
                      • 5. Engesæter IØ, Lie SA, Lehmann TG, et al. Neonatal hip instability and risk of total hip replacement in young adulthood. Acta Orthop 2008; 79: 321-326.
                      • 6. Wedge JH, Wasylenko MJ. The natural history of congenital dislocation of the hip: a critical review. Clin Orthop Relat Res 1978; 137: 154-162.
                      • 7. Karmazyn BK, Gunderman RB, Coley BD, et al. ACR Appropriateness Criteria® on developmental dysplasia of the hip—child. J Am Coll Radiol 2009; 6: 551-557.
                      • 8. Shorter D, Hong T, Osborn DA. Cochrane Review: screening programmes for developmental dysplasia of the hip in newborn infants. Evid Based Child Health 2013; 8: 11-54.
                      • 9. Narayanan U, Mulpuri K, Sankar WN, et al. Reliability of a new radiographic classification for developmental dysplasia of the hip. J Pediatr Orthop 2015; 35: 478.
                      • 10. Tönnis D. Congenital dysplasia and dislocation of the hip in children and adults. Berlin: Springer-Verlag, 1987.
                      • 11. Atalar H, Sayli U, Yavuz OY, et al. Indicators of successful use of the Pavlik harness in infants with developmental dysplasia of the hip. Int Orthop 2007; 31: 145-150.
                      • 12. Harding MG, Harcke HT, Bowen JR, et al. Management of dislocated hips with Pavlik harness treatment and ultrasound monitoring. J Pediatr Orthop 1997; 17: 189-198.
                      • 13. Lerman JA, Emans JB, Millis MB, et al. Early failure of Pavlik harness treatment for developmental hip dysplasia: clinical and ultrasound predictors. J Pediatr Orthop 2001; 21: 348-353.
                      • 14. Viere RG, Birch JG, Herring JA, et al. Use of the Pavlik harness in congenital dislocation of the hip. An analysis of failures of treatment. J Bone Joint Surg Am 1990; 72: 238-244.
                      • 15. Upasani VV, Bomar JD, Matheney TH, et al. Evaluation of brace treatment for infant hip dislocation in a prospective cohort: defining the success rate and variables associated with failure. J Bone Joint Surg Am 2016; 98: 1215-1221.
                      • 16. Engesaeter LB, Furnes O, Havelin LI. Developmental dysplasia of the hip–good results of later total hip arthroplasty: 7135 primary total hip arthroplasties after developmental dysplasia of the hip compared with 59774 total hip arthroplasties in idiopathic coxarthrosis followed for 0 to 15 years in the Norwegian Arthroplasty Register. J Arthroplasty 2008; 23: 235-240.
                      • 17. Dezateux C, Rosendahl K. Developmental dysplasia of the hip. Lancet 2007; 369: 1541-1552.
                      • 18. American Academy of Orthopaedic Surgeons. Detection and nonoperative management of pediatric developmental dysplasia of the hip in infants up to six months of age: evidence-based clinical practice guideline. Rosemount, IL: AAOS, 2014. https://www.aaos.org/research/guidelines/DDHGuidelineFINAL.pdf (viewed Feb 2018).
                      • 19. Weinstein SL. Natural history of congenital hip dislocation (CDH) and hip dysplasia. Clin Orthop Relat Res 1987; 225: 62-76.
                      • 20. Azzopardi T, Van Essen P, Cundy PJ, et al. Late diagnosis of developmental dysplasia of the hip: an analysis of risk factors. J Pediatr Orthop B 2011; 20: 1-7.
                      • 21. Jacobsen S, Rømer L, Søballe K. The other hip in unilateral hip dysplasia. Clin Orthop Relat Res 2006; 446: 239-246.
                      • 22. Laborie LB, Markestad TJ, Davidsen H, et al. Selective ultrasound screening for developmental hip dysplasia: effect on management and late detected cases. A prospective survey during 1991–2006. Pediatr Radiol 2014; 44: 410-424.
                      • 23. Rosendahl K, Markestad T, Lie RT. Ultrasound in the early diagnosis of congenital dislocation of the hip: the significance of hip stability versus acetabular morphology. Pediatr Radiol 1992; 22: 430-433.
                      • 24. Abu Hassan FO, Shannak A. Associated risk factors in children who had late presentation of developmental dysplasia of the hip. J Child Orthop 2007; 1: 205-210.
                      • 25. Palocaren T, Rogers K, Haumont T, et al. High failure rate of the Pavlik harness in dislocated hips: is it bilaterality? J Pediatr Orthop 2013; 33: 530-535.
                      • 26. Borowski A, Thawrani D, Grissom L, et al. Bilaterally dislocated hips treated with the Pavlik harness are not at a higher risk for failure. J Pediatr Orthop 2009; 29: 661-665.
                      • 27. Rosendahl K, Markestad T, Lie RT. Ultrasound screening for developmental dysplasia of the hip in the neonate: the effect on treatment rate and prevalence of late cases. Pediatrics 1994; 94: 47-52.
                      • 28. Sewell MD, Rosendahl K, Eastwood DM. Developmental dysplasia of the hip. BMJ 2009; 339: b4454.
                      • 29. Graf R. Classification of hip joint dysplasia by means of sonography. Arch Orthop Trauma Surg 1984; 102: 248-255.
                      • 30. Holen KJ, Tegnander A, Eik-Nes SH, Terjesen T. The use of ultrasound in determining the initiation of treatment in instability of the hip in neonates. J Bone Joint Surg Br 1999; 81: 846-851.
                      • 31. Terjesen T, Bredland T, Berg V. Ultrasound for hip assessment in the newborn. Bone Joint J 1989; 71: 767-773.
                      • 32. Holen KJ, Tegnander A, Terjesen T, et al. Ultrasonography of clinically unstable hips: a prospective study of 143 neonates at birth and early follow-up. Acta Orthop Scand 1997; 68: 527-532.
                      • 33. Bialik V, Bialik GM, Wiener F. Prevention of overtreatment of neonatal hip dysplasia by the use of ultrasonography. J Pediatr Orthop B 1998; 7: 39-42.
                      • 34. Hadlow VI. Neonatal screening for congenital dislocation of the hip. A prospective 21-year survey. J Bone Joint Surg Br 1988; 70: 740-743.
                      • 35. Synder M, Harcke HT, Domzalski M. Role of ultrasound in the diagnosis and management of developmental dysplasia of the hip: an international perspective. Orthop Clin North Am 2006; 37: 141-147.
                      • 36. Szulc W. The frequency of occurrence of congenital dysplasia of the hip in Poland. Clin Orthop Relat Res 1991; 272: 100-102.
                      • 37. von Kries R, Ihme N, Oberle D, et al. Effect of ultrasound screening on the rate of first operative procedures for developmental hip dysplasia in Germany. Lancet 2003; 362: 1883-1887.
                      • 38. Mahan ST, Katz JN, Kim YJ. To screen or not to screen? A decision analysis of the utility of screening for developmental dysplasia of the hip. J Bone Joint Surg Am 2009; 91: 1705.
                      • 39. Sharpe P, Mulpuri K, Chan A, Cundy PJ. Differences in risk factors between early and late diagnosed developmental dysplasia of the hip. Arch Dis Child Fetal Neonatal Ed 2006; 91: F158-F162.
                      • 40. Shipman SA, Helfand M, Moyer VA, Yawn BP. Screening for developmental dysplasia of the hip: a systematic literature review for the US Preventive Services Task Force. Pediatrics 2006; 117: e557-e576.
                      • 41. Tredwell SJ. Neonatal screening for hip joint instability. Its clinical and economic relevance. Clin Orthop Relat Res 1992; 281: 63-68.
                      • 42. Shaw BA, Segal LS. Evaluation and referral for developmental dysplasia of the hip in infants. Pediatrics 2016; 138: e20163107.
                      • 43. Jaremko JL, Mabee M, Swami VG, et al. Potential for change in US diagnosis of hip dysplasia solely caused by changes in probe orientation: patterns of alpha-angle variation revealed by using three-dimensional US. Radiology 2014; 273: 870-878.
                      • 44. Cheng E, Mabee M, Swami VG, et al. Ultrasound quantification of acetabular rounding in hip dysplasia: reliability and correlation to treatment decisions in a retrospective study. Ultrasound Med Biol 2015; 41: 56-63.
                      • 45. Quader N, Hodgson A, Mulpuri K, et al. Towards reliable automatic characterization of neonatal hip dysplasia from 3D ultrasound images. In: Ourselin S, Joskowicz L, Sabuncu M, et al, editors. Medical Image Computing and Computer-Assisted Intervention – MICCAI 2016. Lecture Notes in Computer Science, vol. 9900. Springer: 2016: 602-609. https://link.springer.com/chapter/10.1007/978-3-319-46720-7_70 (viewed Mar 2018).
                      • 46. Quader N, Hodgson AJ, Mulpuri K, et al. A 3D femoral head coverage metric for enhanced reliability in diagnosing hip dysplasia. In: Descoteaux M, Maier-Hein L, Franz A, et al, editors. Medical Image Computing and Computer-Assisted Intervention – MICCAI 2017. Lecture Notes in Computer Science, vol. 10433. Springer: 2017: 100-107. https://link.springer.com/chapter/10.1007/978-3-319-66182-7_12 (viewed Mar 2018).
                      • 47. Ilfeld FW, Westin GW, Makin MY. Missed or developmental dislocation of the hip. Clin Orthop Relat Res 1986; 203: 276-281.
                      • 48. Lennox IA, McLauchlan J, Murali R. Failures of screening and management of congenital dislocation of the hip. J Bone Joint Surg Br 1993; 75: 72-75.
                      • 49. Sink EL, Ricciardi BF, Torre KD, Price CT. Selective ultrasound screening is inadequate to identify patients who present with symptomatic adult acetabular dysplasia. J Child Orthop 2014; 8: 451-455.
                      • 50. Imrie M, Scott V, Stearns P, et al. Is ultrasound screening for DDH in babies born breech sufficient? J Child Orthop 2010; 4: 3-8.
                      • 51. Sankar WN, Gornitzky AL, Clarke NM, et al. Closed reduction for developmental dysplasia of the hip: Early-term results from a prospective, multicenter cohort. J Pediatr Orthop 2016; doi:10.1097/BPO0000000000000895 [Epub ahead of print].
                      • 52. Schaeffer EK, Mulpuri K, Sankar WN, et al. Open reduction for developmental dysplasia of the hip: early outcomes from a multi-centre, international prospective cohort study [abstract]. J Child Orthop 2017; 11 (Suppl 1): S164.
                      • 53. Narayanan U, Mulpuri K, Sankar WN, et al. Reliability of a new radiographic classification for developmental dysplasia of the hip. J Pediatr Orthop 2015; 35: 478-484.
                      • 54. United Nations DESA/Population Division. World populations prospects 2017. Data query. https://esa.un.org/unpd/wpp/DataQuery/ (viewed Feb 2018).
                      • 55. United Nations Department of Economic and Social Affairs. Statistics Division. UN data. https://unstats.un.org/sdgs/ (viewed Feb 2018).
                      • 56. Rebello G, Joseph B. Late presentation of developmental dysplasia of the hip in children from southwest India – will screening help? Ind J Orthop 2003; 37: 210-214.
                      • 57. Guille JT, Pizzutillo PD, MacEwen GD. Developmental dysplasia of the hip from birth to six months. J Am Acad Orthop Surg 2000; 8: 232-242.
                      • 58. Heikkilä E, Ryöppy S, Louhimo L. Late diagnosis in congenital dislocation of the hip. Acta Orthop Scand 1984; 55: 256-260.
                      • 59. Inoue T, Naito M, Nomiyama H. Treatment of developmental dysplasia of the hip with the Pavlik harness: factors for predicting unsuccessful reduction. J Pediatr Orthop B 2001; 10: 186-191.
                      • 60. Riad JP, Cundy P, Gent RJ, et al. Longitudinal study of normal hip development by ultrasound. J Pediatr Orthop 2005; 25: 5-9.
                      • 61. Quader N, Hodgson AJ, Mulpuri K, et al. Automatic evaluation of scan adequacy and dysplasia metrics in 2-D ultrasound images of the neonatal hip. Ultrasound Med Biol 2017; 43: 1252-1262.
                      • 62. Swaroop VT, Mubarak SJ. Difficult-to-treat Ortolani-positive hip: improved success with new treatment protocol. J Pediatr Orthop 2009; 29: 224-230.
                      • 63. Novais EN, Hill MK, Carry PM, Heyn PC. Is age or surgical approach associated with osteonecrosis in patients with developmental dysplasia of the hip? A meta-analysis. Clin Orthop Relat Res 2016; 474: 1166-1177.
                      • 64. Mulpuri K, Schaeffer EK, Kelley SP, et al. What is the impact of center variability in a multicenter international prospective observational study on developmental dysplasia of the hip? Clin Orthop Relat Res 2016; 474: 1138-1145.
                      • 65. Mulpuri K, Schaeffer EK, Andrade J, et al. What risk factors and characteristics are associated with late-presenting dislocations of the hip in Infants? Clin Orthop Relat Res 2016; 474: 1131-1137.
                      • 66. Studer K, Williams N, Antoniou G, et al. Increase in late diagnosed developmental dysplasia of the hip in South Australia: risk factors, proposed solutions. Med J Aust 2016; 204: 240. <MJA full text>
                      • 67. Kalamchi A, MacEwen GD. Avascular necrosis following treatment of congenital dislocation of the hip. J Bone Joint Surg Am 1980; 62: 876-888.
                      • 68. Kruczynski J. Avascular necrosis of the proximal femur in developmental dislocation of the hip. Incidence, risk factors, sequelae an MR imaging for diagnosis and prognosis. Acta Orthop Scand Suppl 1996; 67(S268): 3-48.
                      • 69. Senaran H, Bowen JR, Harcke HT. Avascular necrosis rate in early reduction after failed Pavlik harness treatment of developmental dysplasia of the hip. J Pediatr Orthop 2007; 27: 192-197.
                      • 70. Konigsberg DE, Karol LA, Colby S, O’Brien S. Results of medial open reduction of the hip in infants with developmental dislocation of the hip. J Pediatr Orthop 2003; 23: 1-9.
                      • 71. Mankey MG, Arntz GT, Staheli LT. Open reduction through a medial approach for congenital dislocation of the hip. A critical review of the Ludloff approach in sixty-six hips. J Bone Joint Surg Am 1993; 75: 1334-1345.
                      • 72. Salter RB, Kostuk J, Dallas S. Avascular necrosis of the femoral head as a complication of treatment for congenital dislocation of the hip in young children: a clinical and experimental investigation. Can J Surg 1969; 12: 44-61.
                      • 73. Clarke NMP. Blood supply and proximal femoral epiphyseal deformity in congenital dislocation of the hip. In Uhtoff HK, Wiley JJ, editors. Behaviour of the growth plate. New York: Raven Press, 1998.
                      • 74. Segal LS, Boal DK, Borthwick L. Avascular necrosis after treatment of DDH: the protective influence of the ossific nucleus. J Pediatr Orthop 1999; 19: 177-184.
                      • 75. Luhmann SJ, Bassett GS, Gordon JE, et al. Reduction of a dislocation of the hip due to developmental dysplasia: Implications for the need for future surgery. J Bone Joint Surg Am 2003; 85: 239-243.
                      • 76. Ogden JA. Treatment positions for congenital dysplasia of the hip. J Pediatr 1975; 86: 732-734.
                      • 77. Dhar S, Taylor JF, Jones WA. Early open reduction for congenital dislocation of the hip. J Bone Joint Surg Br 1990; 72: 175-180.
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