Gerrit A van Essen

The PINE study of epidural steroids and local anaesthetics to prevent postherpetic neuralgia: a randomised controlled trial

BACKGROUND Postherpetic neuralgia is the most frequent complication of herpes zoster. Treatment of this neuropathic pain syndrome is difficult and often disappointing. We assessed the effectiveness of a single epidural injection of steroids and local anaesthetics for prevention of postherpetic neuralgia in older patients with herpes zoster. METHODS We randomly assigned 598 patients older than 50 years, with acute herpes zoster (rash <7 days) below dermatome C6, to receive either standard therapy (oral antivirals and analgesics) or standard therapy with one additional epidural injection of 80 mg methylprednisolone acetate and 10 mg bupivacaine. The primary endpoint was the proportion of patients with zoster-associated pain 1 month after inclusion. Analyses were by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN32866390. FINDINGS At 1 month, 137 (48%) patients in the epidural group reported pain compared with 164 (58%) in the control group (relative risk [RR] 0.83, 95% CI 0.71-0.97, p=0.02). After 3 months these values were 58 (21%) and 63 (24%) respectively (0.89, 0.65-1.21, p=0.47) and, at 6 months, 39 (15%) and 44 (17%; 0.85, 0.57-1.13, p=0.43). We detected no subgroups in which the relative risk for pain 1 month after inclusion substantially differed from the overall estimate. No patient had major adverse events related to epidural injection. INTERPRETATION A single epidural injection of steroids and local anaesthetics in the acute phase of herpes zoster has a modest effect in reducing zoster-associated pain for 1 month. This treatment is not effective for prevention of long-term postherpetic neuralgia.

Respiratory Syncytial Virus and Other Respiratory Viral Infections in Older Adults With Moderate to Severe Influenza-like Illness

Abstract Background. Few studies have prospectively assessed viral etiologies of acute respiratory infections in community-based elderly individuals. We assessed viral respiratory pathogens in individuals ≥65 years with influenza-like illness (ILI). Methods. Multiplex reverse-transcriptase polymerase chain reaction identified viral pathogens in nasal/throat swabs from 556 episodes of moderate-to-severe ILI, defined as ILI with pneumonia, hospitalization, or maximum daily influenza symptom severity score (ISS) >2. Cases were selected from a randomized trial of an adjuvanted vs nonadjuvanted influenza vaccine conducted in elderly adults from 15 countries. Results. Respiratory syncytial virus (RSV) was detected in 7.4% (41/556) moderate-to-severe ILI episodes in elderly adults. Most (39/41) were single infections. There was a significant association between country and RSV detection (P = .004). RSV prevalence was 7.1% (2/28) in ILI with pneumonia, 12.5% (8/64) in ILI with hospitalization, and 6.7% (32/480) in ILI with maximum ISS > 2. Any virus was detected in 320/556 (57.6%) ILI episodes: influenza A (104/556, 18.7%), rhinovirus/enterovirus (82/556, 14.7%), coronavirus and human metapneumovirus (each 32/556, 5.6%). Conclusions. This first global study providing data on RSV disease in ≥65 year-olds confirms that RSV is an important respiratory pathogen in the elderly. Preventative measures such as vaccination could decrease severe respiratory illnesses and complications in the elderly.

AS03-adjuvanted versus non-adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial

BACKGROUND We aimed to compare AS03-adjuvanted inactivated trivalent influenza vaccine (TIV) with non-adjuvanted TIV for seasonal influenza prevention in elderly people. METHODS We did a randomised trial in 15 countries worldwide during the 2008-09 (year 1) and 2009-10 (year 2) influenza seasons. Eligible participants aged at least 65 years who were not in hospital or bedridden and were without acute illness were randomly assigned (1:1) to receive either AS03-adjuvanted TIV or non-adjuvanted TIV. Randomisation was done in an internet-based system, with a blocking scheme and stratification by age (65-74 years and 75 years or older). Participants were scheduled to receive one vaccine in each year, and remained in the same group in years 1 and 2. Unmasked personnel prepared and gave the vaccines, but participants and individuals assessing any study endpoint were masked. The coprimary objectives were to assess the relative efficacy of the vaccines and lot-to-lot consistency of the AS03-adjuvanted TIV (to be reported elsewhere). For the first objective, the primary endpoint was relative efficacy of the vaccines for prevention of influenza A (excluding A H1N1 pdm09) or B, or both, that was confirmed by PCR analysis in year 1 (lower limit of two-sided 95% CI had to be greater than zero to establish superiority). From Nov 15, to April 30, in both years, participants were monitored by telephone or site contact and home visits every week or 2 weeks to identify cases of influenza-like illness. After onset of suspected cases, we obtained nasal and throat swabs to identify influenza RNA with real-time PCR. Efficacy analyses were done per protocol. This trial is registered with ClinicalTrials.gov, number NCT00753272. FINDINGS We enrolled 43 802 participants, of whom 21 893 were assigned to and received the AS03-adjuvanted TIV and 21 802 the non-adjuvanted TIV in year 1. In the year 1 efficacy cohort, fewer participants given AS03-adjuvanted than non-adjuvanted TIV were infected with influenza A or B, or both (274 [1·27%, 95% CI 1·12-1·43] of 21 573 vs 310 [1·44%, 1·29-1·61] of 21 482; relative efficacy 12·11%, 95% CI -3·40 to 25·29; superiority not established). Fewer participants in the year 1 efficacy cohort given AS03-adjuvanted TIV than non-adjuvanted TIV were infected with influenza A (224 [1·04%, 95% CI 0·91-1·18] vs 270 [1·26, 1·11-1·41]; relative efficacy 17·53%, 95% CI 1·55-30·92) and influenza A H3N2 (170 [0·79, 0·67-0·92] vs 205 [0·95, 0·83-1·09]; post-hoc analysis relative efficacy 22·0%, 95% CI 5·68-35·49). INTERPRETATION AS03-adjuvanted TIV has a higher efficacy for prevention of some subtypes of influenza than does a non-adjuvanted TIV. Future influenza vaccine studies in elderly people should be based on subtype or lineage-specific endpoints. FUNDING GlaxoSmithKline Biologicals SA.

Predicting postherpetic neuralgia in elderly primary care patients with herpes zoster: prospective prognostic study.

Abstract Postherpetic neuralgia (PHN) is the most frequent complication of herpes zoster (HZ) and difficult to treat. Timely identification of high‐risk HZ‐patients enables physicians to focus on PHN prevention. To assess which simple to measure factors are independent predictors of PHN, and whether psychosocial and serological/virological parameters have additional predictive value, a prospective cohort study in primary care was conducted. We included 598 elderly (>50 years) consecutive patients with acute HZ (rash <7 days) below sixth cervical dermatome. At baseline demographic, clinical (e.g., duration and severity of pain and rash), psychological (Pain Cognition List [PCL] and Spielberger’s Anxiety Inventory), serological (VZV‐antibodies) and virological (viremia presence) variables were measured. Blood tests were performed in a random subset of 218 patients. Primary outcome was significant pain (VAS >30 on 0–100 scale) after three months. The final prediction model obtained from multivariable logistic regression was (internally) validated using bootstrapping techniques, and adjusted for optimism. Forty‐six (7.7%) patients developed PHN. Independent predictors were age (odds ratio [OR] = 1.08 per year), acute pain severity (OR = 1.02 per unit), presence of severe rash (OR = 2.31), and rash duration before consultation (OR = 0.78 per day): area under receiver‐operating‐characteristic curve [ROC area] = 0.77 (95% CI: 0.71–0.82). Of the five PCL scores, only factor V (‘trust in healthcare’) was an additional predictor (OR = 1.01 per unit), though it increased the ROC area with only 0.01 to 0.78. The Spielberger’s anxiety scores and serological and virological variables were no additional predictors. Thus, four simple variables can help physicians to timely identify elderly HZ‐patients at risk of PHN.

Introducing a pneumococcal vaccine to an existing influenza immunization program : vaccination rates and predictors of noncompliance

PURPOSE Influenza vaccination has been recommended for all elderly people in The Netherlands since 1996, with greater than 80% compliance. It is unknown, however, if the addition of another vaccine to this immunization program will affect compliance. SUBJECTS AND METHODS General practitioners offered a pneumococcal vaccine together with the yearly influenza vaccination to 3365 patients aged 65 years and older. A questionnaire was then mailed to a stratified sample (n = 972) of these patients. Factors associated with noncompliance with vaccination were assessed using polytomous logistic regression. RESULTS A total of 2529 patients (75%) received the pneumococcal vaccine and 2812 (84%) received the influenza vaccine. Predictors of noncompliance with the pneumococcal vaccine were perceived lack of recommendation by the general practitioner (odds ratio [OR] = 4.6; 95% confidence interval [CI], 2.6 to 8.3) and fear of local side effects (OR = 2.8; 95% CI, 1.6 to 4.6). Predictors of noncompliance with both vaccinations also included unwillingness to comply with the doctors advice (OR = 6.1; 95% CI, 2.4 to 15.4), the belief that vaccinations weaken ones natural defenses (OR = 2.7; 95% CI, 1.4 to 5.3) or that influenza is not dangerous (OR = 2.9; 95% CI, 1.5 to 5.4), and the fear of becoming sick from pneumococcal vaccination (OR = 2.9; 95% CI, 1.1 to 7.9). People who felt healthy, found it difficult to visit the doctors office, had private medical insurance, or were younger than 75 years of age also had a greater risk of not being vaccinated. CONCLUSION Introducing a pneumococcal vaccine to an existing influenza immunization program resulted in high pneumococcal and influenza vaccination rates. A wider diversity of patient characteristics and attitudes was present when neither vaccination was received.

Clinical Diagnosis of Herpes Zoster in Family Practice

PURPOSE Family physicians usually diagnose herpes zoster on clinical grounds only, possibly resulting in false-positive diagnoses and unnecessary treatment. We wanted to determine the positive predictive value of the physicians’ judgment in diagnosing herpes zoster and to assess the applicability of dried blood spot analysis for diagnosis of herpes zoster in family practice. METHODS Our study population consisted of 272 patients older than 50 years with herpes zoster (rash for less than 7 days). Dried blood spot samples were collected from all patients and sent by mail to the laboratory. Baseline measurements included clinical signs (localization, severity, and duration of rash) and symptoms (duration and severity of pain). Varicella-zoster virus antibodies were determined at baseline and 5 to 10 days later. Multivariate logistic regression was used to assess independent associations between clinical variables and serological confirmation of herpes zoster. RESULTS Dried blood spot analysis was possible in 260 patients (96%). In 236 the diagnosis of herpes zoster was confirmed serologically (positive predictive value of clinical judgment 90.8%; 95% confidence interval, 87.3%–94.3%). Independent clinical variables for serologically confirmed herpes zoster were severity and duration of rash at first examination. CONCLUSION Family physicians have good clinical judgment when diagnosing herpes zoster in older patients. Dried blood spot analysis is a logistically convenient method for serological investigation of patients in family practice, but it is rarely needed for diagnosing herpes zoster.

Influenza immunization of Dutch general practitioners: Vaccination rate and attitudes towards vaccination

With effect from the 2008/2009 season, yearly influenza immunization will be recommended to all Dutch general practitioners (GPs). For successful implementation of this recommendation, knowledge about the current vaccination rate and attitudes towards vaccination is necessary. In February 2008, a questionnaire was mailed to a random sample (n=730) of practicing GPs. Vaccination rate was determined and the factors associated with not being vaccinated were assessed using multivariate logistic regression. Reasons for being vaccinated or not were also recorded. Of the 730 questionnaires sent out, 698 (96%) were completed and returned. In total, 248 GPs (36%) had been immunized against influenza. Independent factors related to not being vaccinated were female gender and age <40 years. Having no medical indication for an influenza vaccination and the conviction that one is protected against influenza because of frequent professional exposure to the virus were the most frequently reported reasons for not being vaccinated. The most frequently reported motives for being vaccinated were personal protection against influenza and a lower risk of transmitting the virus to patients. Education of GPs about the effects of vaccination may be needed to ensure their compliance to the current recommendation of yearly influenza immunization.

Determinants of non-compliance with herpes zoster vaccination in the community-dwelling elderly

As part of a series of studies on vaccine acceptance, we assessed determinants of compliance of the community-dwelling elderly with herpes zoster (HZ) vaccination in an existing influenza vaccination program. General practitioners (GPs) sent out a questionnaire to 1778 patients aged > or =65 years, and offered them free HZ vaccination simultaneously with the yearly influenza vaccination. In all, 690 patients (39%) were vaccinated against HZ; 1349 patients (76%) accepted influenza vaccination. Determinants of non-compliance with HZ vaccination were perceived lack of recommendation by the GP, unwillingness to comply with the doctors advice, perception of low risk of contracting HZ, perception of short pain duration of HZ, and the opinion that vaccinations weaken ones natural defenses. The same determinants were associated with non-compliance with both vaccinations, but objections in general towards vaccination, a high education and difficulties to visit GPs were also important. Uptake of HZ vaccination was rather low and more data on (cost-)effectiveness might encourage GPs to offer HZ vaccination to their patients.

Follow-up of mild alanine aminotransferase elevation identifies hidden hepatitis C in primary care

BACKGROUND Hepatitis C (HCV) and hepatitis B (HBV) virus infection can lead to serious complications if left untreated, but often remain undetected in primary care. Mild alanine aminotransferase (ALT) elevations (30-100 IU/l) are commonly found and could be associated with viral hepatitis; unfortunately, these findings frequently remain without follow-up. AIM To determine if and how mild ALT elevation can be used to identify hidden HCV and HBV infection in primary care. DESIGN AND SETTING Primary care patients referred for liver enzyme testing were selected by a large primary care Diagnostic Centre (Saltro). METHOD First, 750 anonymous samples were collected in three categories of ALT elevation (30-50 IU/l, 50-70 IU/l, and 70-100 IU/l) and tested for HCV and HBV. Second, the national prevalence of each ALT elevation was estimated by analysing all annual ALT tests performed at Saltro. RESULTS HCV prevalence was 1.6% and 1.2% in patients with an ALT of 50-70 IU/l and 70-100 IU/l respectively. In patients with an ALT of 30-50 IU/l, HCV prevalence was normal (≤0.1%). HBV prevalence was normal (≤0.4%) in all groups. The estimated number of ALT tests performed nationally each year in primary care was 1.1 million. An ALT of 30-50 IU/l was found in 21.1%, an ALT of 50-70 IU/l in 5.6%, and 2.6% had an ALT of 70-100 IU/l. CONCLUSION In primary care patients with an ALT level of 50-100 IU/l, HCV prevalence is tenfold the population prevalence, whereas HBV prevalence is not elevated. Therefore, diagnostic follow-up for HCV is indicated in these patients, even when other explanations for ALT elevation are present.

A support programme for primary care leads to substantial improvements in the effectiveness of a public hepatitis C campaign

INTRODUCTION Because of its lack of clinical signs, the detection of hepatitis C virus (HCV) infection in the Netherlands remains suboptimal. Therefore, the Dutch Health Council proposed an HCV campaign aimed to inform the general public and motivate people at risk to seek medical advice. Because knowledge and awareness of HCV infection is low among primary care workers, the implementation of a support programme for primary care complementary to a HCV campaign seems appropriate. OBJECTIVE To evaluate the added value of a support programme for primary care complementary to a public HCV campaign. METHODS We performed a non-randomized controlled intervention study. In two similar regions, a public HCV campaign was organized. In the intervention region, an additional support for primary care was provided by means of brochures, short courses and informative visits. RESULTS In the intervention region, the proportional increase in anti-HCV tests was 3.02 (57-172 tests). In the control region, this increase was 1.36 (86-118 tests). In the intervention region, the increase in positive anti-HCV tests was 1.7% (95% confidence interval (CI): -0.2% to -3.7%). In the control region, this number decreased by 0.9% (95% CI: -4.1% to 2.3%). CONCLUSIONS The addition of primary care practice support leads to considerable improvements in medical consciousness regarding HCV infection in primary care. Even though the positive effect on case finding cannot be indisputably demonstrated due to low prevalence, our results indicate such a positive effect. Therefore, future campaigns aimed at hepatitis C should invariably implement additional support for primary care to improve diagnostic uptake and optimize case finding.