Family Practice Advance Access originally published online on July 8, 2005
Family Practice 2005 22(5):523-528; doi:10.1093/fampra/cmi055
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Do herpes zoster patients receive antivirals? A Dutch national survey in general practice
a Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, b Pain Clinic, Department of Anaesthesiology, Division Perioperative Care and Emergency Medicine, University Medical Center Utrecht and c NIVEL (Netherlands Institute for Health Services Research), Utrecht, The Netherlands
Correspondence to W Opstelten, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85060, 3500 AB Utrecht, The Netherlands; Email: w.opstelten{at}med.uu.nl
Received 2 November 2004; Accepted 21 April 2005.
Opstelten W, van Essen GA, Moons KGM, van Wijck AJM, Schellevis FG, Kalkman CJ and Verheij TJM. Do herpes zoster patients receive antivirals? A Dutch national survey in general practice. Family Practice 2005; 22: 523–528.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionDeclarationReferences |
|---|
Background. The main complications of herpes zoster (HZ) are postherpetic neuralgia and, in case of HZ ophthalmicus, eye disorders. Antiviral treatment may modify the course of disease and reduce the risk of complications.
Objective. To assess which doctors' and patients' characteristics were related to prescription of antiviral therapy for HZ.
Methods. Ninety general practices (358 008 patients) in The Netherlands registered all patient contacts in a database for one year as part of the Second Dutch National Survey of General Practice. The present study used ICPC code S70 to search that database for patients with a new diagnosis of HZ. The full-text medical records of the selected patients were then reviewed and the potential determinants for the prescription of antiviral drugs (including characteristics of patients, GPs, and practices) analysed using multilevel logistic regression modelling.
Results. Of the 1129 patients diagnosed with HZ (incidence 3.2/1000 patients/year), 22.5% received antiviral drugs. Independent determinants for prescription of antiviral therapy were age [45–54 years: adjusted odds ratio (OR) 2.9 (95% CI 1.6–5.0); 55–64 years: OR 4.2 (95% CI 2.4–7.6); 65–74 years: OR 5.1 (95% CI 2.7–9.6); 
75 years: OR 8.1 (95% CI 4.4–15.1)], ophthalmic localisation of the shingles (OR 3.2, 95% CI 1.6–6.7), and the presence of asthma/COPD (OR 1.6, 95% CI 1.0–2.6). GPs who reported to strongly adhere to professional guidelines prescribe more frequently antiviral drugs (OR 1.9, 95% CI 1.2–3.1).
Conclusions. A minority of HZ patients were prescribed antiviral treatment. Increasing age, ophthalmic localisation, presence of asthma/COPD, and adherence to professional guidelines were factors favouring prescription. More information on the determinants of GPs' treatment decisions is necessary for successful implementation of HZ guidelines.
Keywords. Guidelines, herpes zoster, incidence, primary care, treatment.
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionDeclarationReferences |
|---|
Herpes zoster (HZ) or shingles is a common disease, with a reported incidence varying from 2.2 to 3.4/1000 persons/year.1,2 As this incidence increases with age, HZ is frequently seen in ageing populations. HZ is caused by a localised infection with the varicella zoster virus and represents a recrudescence of the virus in sensory ganglia where it has remained dormant since the primary infection (chickenpox). It causes substantial acute and chronic morbidity, the commonest long-term complication being persistent pain. This so-called postherpetic neuralgia (PHN), which may persist for several months to years, can have a high impact on a patient's quality of life. The risk of developing PHN increases with age. Because the results of PHN treatment have been rather disappointing,3 clinicians advocate that the management of acute HZ be focused not only on immediate pain relief, but also on reducing the risk of PHN development. Another complication of HZ comprises ophthalmologic problems. Without antiviral therapy, half of the patients with HZ ophthalmicus (HZO) will develop eye disorders such as conjunctivitis, keratitis, and uveitis, some of which some are potentially sight threatening.4
To date, several international guidelines and recommendations have been issued on HZ treatment.51115 A central issue in these is the prescription of antiviral drugs for prevention of zoster-related complications. They are preferably administered within 72 hours of rash onset and routinely in cases of immunosuppression and/or HZO for patients >505,791215 or >606101114 years of age, and in severe cases irrespective of age. Additional recommendations include local therapies (e.g. zinc oxide containing local applications) and the addition of oral steroids or tricyclic antidepressants to alleviate acute symptoms. Empirical evidence about their pre-emptive efficacy however is still equivocal.16 In this paper we focus on the prescription of antiviral drugs.
Although there is discussion on the benefit of antiviral drugs in immunocompetent HZ patients, at present they provide the greatest opportunity for reducing the risk of complications. Especially patients at high risk for developing HZ complications are assumed to benefit by these drugs. Since PHN is still a prevalent disorder in general practice17 and since there is a need to improve rational prescription of antiviral medication, we wondered to what extent HZ patients are prescribed antiviral therapy in primary care and which factors determine this prescription. We used data from a large prospective national database to determine the actual management of acute HZ in general practice and patients' and physicians' factors related to the prescription of antiviral treatment.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionDeclarationReferences |
|---|
Patients and setting
The data used in this study were derived from the Second Dutch National Survey of General Practice, carried out by The Netherlands Institute for Health Services Research (NIVEL) in 2001; 195 GPs in 104 practices were initially recruited to participate in the study. Data from 14 practices were excluded from the present analysis because (a) the registration of patient contacts and prescriptions appeared inadequate in 10 practices and (b) software problems hindered registration in 4 practices. Therefore, our analyses pertained to 186 GPs serving 358 008 patients. The participating GPs and practices were representative of Dutch GPs and practices except for the type of practice: solo-practices were underrepresented in the study population. This dynamic population cohort had a rather stable size and its age and sex ratios were comparable with those of the general Dutch population.18 The GPs recorded all physician–patient contacts during a 12-month period. The GPs used a computerised medical record system and diagnoses were coded according to the ICPC. ICPS code S70 (‘herpes zoster’) was used in the present study to search the database for all HZ patients. The full-text medical records of the selected patients were then reviewed. Since the 1-year observation window precluded a follow-up analysis of all of the patients, only data related to the first contact of each patient, during which HZ was diagnosed, were analysed.
Data collection
Outcome. We recorded for each HZ patient the treatment that was administered, including prescription of medication (notably antivirals, steroids, and amitriptyline) and whether or not the patient was referred to secondary care.
Determinants. Information regarding possible determinants of HZ treatment decisions was registered for each HZ patient. Based on clinical reasoning and the existing literature we selected the following potential determinants of HZ treatment, categorised in three groups: patient characteristics, GP characteristics, and practice characteristics. Patient characteristics comprised age, gender, duration of symptoms, localisation of the rash, presence of severe pain, and co-morbidity. For presence of severe pain the concomitant prescription of analgesics was used as a proxy.19 Relevant co-morbidity included the presence of diabetes mellitus, chronic pulmonary disease (asthma/COPD), and malignancy. Since only the current co-morbidity might be relevant for the treatment of HZ, we included only these diseases, if a physician–patient contact took place during the registration year. GP characteristics included gender, years since certification, part-time/full-time working, self-reported adherence to professional guidelines, and willingness to receive representatives of pharmaceutical companies. Practice characteristics included level of urbanization and practice type (solo versus group practice).
Data analysis
Data were analysed using SPSS for Windows, version 12.0 (SPSS Inc, Chicago, IL, USA). Incidence rates of HZ were standardized to the European standard population.20 We first quantified the frequencies of the different types of management administered to HZ patients. Next, we assessed the univariate association of each potential determinant and the prescription of antiviral treatment (yes/no). Finally, we performed a multilevel logistic regression analysis (using MIXOR version 2.021) to assess which potential determinants were independently associated with the prescription of antiviral treatment. As the study included various practices and as the number of HZ patients and type of prescribed treatment could substantially differ across practices, a multilevel (rather than conventional) logistic regression was performed to adjust for potential clustering.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionDeclarationReferences |
|---|
Incidence of HZ
There were 1129 patients, who contacted their physician for acute HZ (ICPC code S70.01) during the 12-month registration period. This number represents an incidence of 3.2/1000 patients/year [95% confidence interval (CI) 3.0–3.3] and, standardized to the standard European population, 3.3/1000 patients/year (95% CI 3.2–3.5). Moreover, the incidence increased with age. The incidence in persons aged
65 years amounted 6.7/1000 patients/year (95% CI 6.0–7.5). A total of 45% of all HZ patients were aged 55 or more.
Types of management
Antivirals were prescribed to 254 (22.5%) HZ patients during the first consultation for HZ, while 18 (1.6%) patients received amitriptyline, and only one corticosteroids. Eleven (1.0%) patients were referred to an anaesthesiologist and 7 (0.6%) to an ophthalmologist.
Determinants of antiviral prescription
In univariate analysis, both patient characteristics (notably age, ophthalmic localisation, pain, diabetes, asthma/COPD, and malignancy) and GP characteristics appeared to be determinants for the prescription of antiviral medicines (Table 1).
|
In the multilevel logistic regression analysis notably age and ophthalmic localisation independently determined the prescription of antiviral drugs (Table 1). Also the presence of asthma/COPD influenced this treatment prescription. GPs who reported to adhere strongly to professional guidelines prescribed more frequently antiviral drugs than their colleagues who complied less with guidelines.
The multilevel logistic model showed a good fit (–2 Log Likelihood of 219.669 with df = 19, yielding a P-value <0.001).
The affected dermatome could not be traced in 516 patients (Table 1). However, as shown in Table 2, there were no significant differences between HZ patients with and HZ patients without a known affected dermatome (except for the level of urbanization). Hence, we may assume that the 516 patients with unknown affected dermatome were no selected subsample of the total population.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionDeclarationReferences |
|---|
This large observational study on HZ in primary care revealed (1) that the HZ incidence corresponds with that reported in previous studies; (2) that only a minority of patients receive treatment that may reduce the risk of developing complications; and (3) that only higher age, ophthalmic localisation, presence of asthma/COPD, and strong adherence to professional guidelines independently predicted the prescription of antiviral treatment.
Some potential limitations of this study need to be addressed in order to appreciate the results. First, this kind of study is prone to registration inadequacy. All GPs participating in the present study, however, were highly motivated and had received special training in diagnostic coding before the start of the survey. Moreover, since HZ is regarded as an indicator for the reliability of registration morbidity in general practice, the observed HZ incidence in this study supports the adequacy of registration. Second, data on some of the relevant risk factors for PHN, such as pain severity and rash localisation, were incomplete. For example, information about the severity of pain was missing from almost all medical records of HZ patients and the localisation of HZ had not been registered in almost half of the records. We used the prescription of analgesics as a proxy for clinically relevant pain. It could be questioned whether this is plausible since patients may use over-the-counter medication. In The Netherlands, however, more potent analgesics are only available on doctor's prescription. In general, there were no differences between the characteristics of HZ patients with a known localisation of affected dermatomes and those without known localisation. Therefore, we are convinced that the results of the multilevel analysis can be generalised to the entire study population. Third, in most patients the duration of HZ rash before the consultation had not been recorded. Therefore, patients could have consulted their GP too late for effective antiviral treatment. However, preliminary data from a large randomised clinical trial on the prevention of PHN in elderly patients in primary care indicated that more than 50% of the HZ patients contact their GP within 72 hours from the onset of the rash.22 Finally, because this study only analysed the first physician–patient contact in the HZ episodes, it has a cross-sectional character and cannot reveal any change in treatment during HZ episodes. Nevertheless, as far as the prevention of PHN is concerned, the first consultation for an HZ episode is most crucial because any pre-emptive therapy must be started as soon possible. In cases of HZO, however, immediate consultation with an ophthalmologist is usually not necessary.
This is the first study that analyses how GPs actually treat HZ patients and which determinants influence their decision to prescribe antiviral therapy. HZ treatment in The Netherlands only partly reflects the recommendations of international guidelines. Several factors may be responsible for this discrepancy. First, GPs might not be sufficiently aware of risk factors for complications of HZ. It is well known that increasing age contributes to the risk of PHN.17 Pain severity and the extent of the rash are however also proven risk factors with a relatively high positive predictive value for prolonged pain after HZ.23 Although the results of several studies suggested a greater risk of protracted pain in patients with HZO, this relationship has not been found consistently.23 Diseases that, because of their nature or associated therapy, are potentially immunity-attenuating enhance the risk of occurrence of HZ. However, these conditions (such as asthma/COPD and diabetes) are not established risk factors for PHN. Second, GPs might question the effectiveness of therapies on the prevention of complications. Although antiviral medication has some effect on pain in the acute stage and on the duration of the skin lesions, evidence for reducing the risk of PHN is controversial.24 Some studies have, however, shown that famciclovir and valaciclovir shorten the duration of PHN,25,26 while the effect on reducing the risk of eye disorders in cases of HZO is undisputed.27 Corticosteroids can alleviate some of the pain in the acute stage, but have not been shown to influence the occurrence or duration of PHN.24,28 A small placebo-controlled study showed that treatment with amitriptyline during the acute stage of HZ reduced the risk of PHN by half; however, further evidence is lacking.29 The efficacy of cutaneous (e.g. topical local anaesthetics) and percutaneous (e.g. sympathetic and epidural blocks) interventions on the prevention of PHN has not yet been established.30
In summary, Dutch GPs have quite a reserved attitude towards drug treatment of acute HZ. Even though many patients are at risk of suffering HZ complications, the majority does not receive antiviral medication. More information about the GPs' motives for their policy is necessary in order to implement an optimal treatment strategy for patients with acute HZ.
|
Declaration |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionDeclarationReferences |
|---|
Funding: this study was funded by The Netherlands Organisation for Scientific Research.
Ethical approval: the study was carried out according to Dutch legislation on privacy. The privacy regulation of the study was approved by the Dutch Data Protection Authority.
Conflicts of interest: none.
|
Acknowledgments |
|---|
The authors thank NPA Zuithoff, MSc, for his help with the data analysis.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionDeclarationReferences |
|---|
1 Donahue JG, Choo PW, Manson JE, Platt R. The incidence of herpes zoster. Arch Intern Med 1995; 155: 1605–1609.
2 Hope-Simpson RE, MRCS. The nature of herpes zoster: a long-term study and a new hypothesis. Proc Royal Soc Med 1965; 58: 9–20.
3 Alper BS, Lewis PR. Treatment of postherpetic neuralgia: a systematic review of the literature. J Fam Pract 2002; 5: 121–128.
4 Cobo M, Foulks GN, Liesegang T, Lass J, Sutphin J, Wilhelmus K et al. Observations on the natural history of herpes zoster ophthalmicus. Curr Eye Res 1987; 6: 195–199.[Web of Science][Medline]
5 Kost RG, Straus SE. Postherpetic neuralgia–pathogenesis, treatment, and prevention. N Engl J Med 1996; 335: 32–42.
6 Guidelines for the management of shingles. report of a working group of the British Society for the Study of Infection (BSSI). J Infect 1995; 30: 193–200.[CrossRef][Medline]
7 Balfour HHJ. Antiviral Drugs. N Engl J Med 1999; 340: 1255–1268.
8 Cohen JI, Brunell PA, Straus SE, Krause PR. Recent advances in varicella-zoster virus infection. Ann Intern Med 1999; 130: 922–932.
9 Gilden DH, Kleinschmidt-DeMasters BK, LaGuardia JJ, Mahalingam R, Cohrs RJ. Neurologic complications of the reactivation of varicella-zoster virus. N Engl J Med 2000; 342: 635–645.
10 Gnann JW Jr, Whitley RJ. Clinical practice. Herpes zoster. N Engl J Med 2002; 347: 340–346.
11 Johnson RW. Herpes zoster and postherpetic neuralgia. Optimal treatment. Drugs Aging 1997; 10: 80–94.[Web of Science][Medline]
12 Gross G, Schofer H, Wassilew S, Friese K, Timm A, Guthoff R et al. Herpes zoster guideline (1) of the German Dermatology Society (DDG). J Clin Virol 2003; 26: 277–289.[CrossRef][Web of Science][Medline]
13 Peyramond D, Chidiac C, Lucht F, Perronne C, Saimot AG, Soussy JC et al. Management of infections due to the varicella-zoster virus. 11th consensus conference on anti-infectious therapy of the French-speaking Society of Infectious Diseases (SPILF). Eur J Dermatol 1998; 8: 397–402.[Web of Science][Medline]
14 EBM Guidelines. www.ebm-guidelines.com 2004.
15 Bradley SF. Infections. In Jones R (ed.) Oxford Textbook of Primary Medical Care. Oxford: Oxford University Press; 2004, 1245.
16 Dworkin RH. Prevention of postherpetic neuralgia. Lancet 1999; 353: 1636–1637.[CrossRef][Web of Science][Medline]
17 Opstelten W, Mauritz JW, de Wit NJ, van Wijck AJ, Stalman WA, van Essen GA. Herpes zoster and postherpetic neuralgia: incidence and risk indicators using a general practice research database. Fam Pract 2002; 19: 471–475.
18 Westert GP, Schellevis FG, Bakker DHd, Groenewegen PP, Bensing JM, Zee Jvd. Monitoring health inequalities through General Practice: the Second Dutch Narional Survey of General Practice. Eur J Public Health 2005; 15: 59–65.
19 Joshi GP, Viscusi ER, Gan TJ, Minkowitz H, Cippolle M, Schuller R et al. Effective treatment of laparoscopic cholecystectomy pain with intravenous followed by oral COX-2 specific inhibitor. Anesth Analg 2004; 98: 336–342.
20 Database. ENC. www.Europe.eu.int/comm/euronet.
21 MIXOR. http://tigger.uic.edu/~hedeker/mix.html. 2004.
22 Opstelten W, van Wijck AJM, van Essen GA, Buskens E, Bak AAA, Kalkman CJ et al. The PINE study: rationale and design of a randomised comparison of epidural injection of local anaesthetics and steroids versus care-as-usual to prevent postherpetic neuralgia in the elderly [ISRCTN32866390]. BMC Anesthesiology 2004; 4.
23 Jung BF, Johnson RW, Griffin DRJ, Dworkin RH. Risk factors for postherpetic neuralgia in patients with herpes zoster. Neurology 2004; 62: 1545–1551.
24 Alper BS, Lewis PR. Does treatment of acute herpes zoster prevent or shorten postherpetic neuralgia? J Fam Pract 2000; 49: 255–264.[Web of Science][Medline]
25 Tyring S, Barbarash RA, Nahlik JE, Cunningham A, Marley J, Heng M et al. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Collaborative Famciclovir Herpes Zoster Study Group. Ann Intern Med 1995; 123: 89–96.
26 Beutner KR, Friedman DJ, Forszpaniak C, Andersen PL, Wood MJ. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother 1995; 39: 1546–1553.[Abstract]
27 Cobo LM, Foulks GN, Liesegang T, Lass J, Sutphin JE, Wilhelmus K et al. Oral acyclovir in the treatment of acute herpes zoster ophthalmicus. Ophthalmology 1986; 93: 763–770.[Web of Science][Medline]
28 Whitley RJ, Weiss H, Gnann JW Jr, Tyring S, Mertz GJ, Pappas PG et al. Acyclovir with and without prednisone for the treatment of herpes zoster. A randomized, placebo-controlled trial. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Ann Intern Med 1996; 125: 376–383.
29 Bowsher D. The effects of pre-emptive treatment of postherpetic neuralgia with amitriptyline: a randomized, double-blind, placebo-controlled trial. J Pain Symptom Manage 1997; 13: 327–331.[CrossRef][Web of Science][Medline]
30 Opstelten W, van Wijck AJ, Stolker RJ. Interventions to prevent postherpetic neuralgia: cutaneous and percutaneous techniques. Pain 2004; 107: 202–206.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Buurma, T. Schalekamp, A. C. Egberts, and P. A. De Smet Compliance with National Guidelines for the Management of Drug Drug Interactions in Dutch Community Pharmacies Ann. Pharmacother., December 1, 2007; 41(12): 2024 - 2031. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||