The impact of embedment of the side arms of 52 mg levonorgestrel-intrauterine device on bleeding and pain: A prospective cohort study.

PURPOSE: The purpose of this study was to analyse the impact of embedment of side arms of the levonorgestrel 52 mg intrauterine device (LNG-IUD) in the myometrium (assessed by three-dimensional transvaginal ultrasound (3D-TVUS)) on uterine bleeding and pain. MATERIALS AND METHODS: We performed a prospective cohort study in a large Dutch teaching hospital between February 2015 and December 2016. Participants over 18 years of age who selected a LNG-IUD for contraception or because of heavy menstrual bleeding were eligible for inclusion. Six weeks after insertion, a 3D-TVUS was performed to diagnose embedment of the side arms. At that moment participants filled in questionnaires about their bleeding pattern and pelvic pain. Menstruation patterns 'no bleeding', 'regular menstruation', 'sometimes a day of spotting (maximum once a week)' were classified as favourable bleeding pattern. Menstruation patterns 'heavy menstrual bleeding', 'several days a week bleeding days', 'several days a week spotting days', 'continuously spotting', and 'completely irregular cycle' were classified as unfavourable bleeding pattern. Univariate and multivariate logistic regression analysis was used to calculate odds ratios (OR) and 95 %-confidence intervals (CI). The multivariate analysis included endometrial thickness, reason for insertion and parity. The analysis of pelvic pain additionally included previous insertion. RESULTS: A total of 220 participants were evaluated for the study of whom 176 returned the questionnaires. Embedment of the side arms was observed in 43 of the 176 responding participants (24.4 %). Favourable bleeding pattern was reported by 25/43 (58.1 %) participants with embedment and 53/133 (39.8 %) participants without embedment (ORadj 1.8, 95 % CI 0.9-3.9). Pelvic pain was reported by 4/43 (9.3 %) participants with embedment and 24/133 (18.1 %) participants without embedment (ORadj 0.3; CI 0.1-1.2). CONCLUSIONS: The present study suggests that embedment of the side arms of the LNG-IUD in the myometrium assessed by 3D-TVUS is not associated with a unfavourable bleeding pattern nor pelvic pain six weeks after insertion. From this point of view, we do not recommend to perform standard 3D-TVUS for the purpose of excluding or demonstrating embedment.

Preventive treatment for migraine in primary care, a population-based study in the Netherlands.

BACKGROUND: Preventive treatment of migraine contributes to reducing the impact of migraine but its extent of use in routine care is unknown. OBJECTIVE: The objective of this article is to assess current use, previous use, duration and course of preventive treatment of migraine in Dutch general practice. METHODS: We conducted a retrospective cohort study, for the period between 1997 and 2007, in the Interdisciplinary Processing of Clinical Information (IPCI) database, a GP research database in the Netherlands (source population of more than half a million subjects). All prevalent and incident migraine patients ( N = 7367) were included. RESULTS: About 13% of all migraine patients currently use preventive therapy and almost half of migraine patients have prior use. Of those starting with preventive treatment, 56% (95% CI: 54.3-64.7) still used it after nine months. There was a long delay between migraine diagnosis and preventive treatment start. Forty-four percent (95% CI 43.0-45.7) started preventive therapy in the study period. CONCLUSION: This large primary-care database study shows that a limited number of patients are current users of preventive treatment, but many patients have prior use. After diagnosis there is often an extended time before preventive treatment is applied. Also there is often only one attempt. The continuation in time seems appropriate. Preventive therapy in migraine still deserves focus.

Recall bias in pain scores evaluating abdominal wall and groin pain surgery.

PURPOSE: To determine whether levels of pre-operative pain as recalled by a patient in the post-operative phase are possibly overestimated or underestimated compared to prospectively scored pain levels. If so, a subsequent misclassification may induce recall bias that may lead to an erroneous effect outcome. METHODS: Data of seven retrospective cohort studies on surgery for chronic abdominal wall and groin pain using three different pain scores were systematically analyzed. First, it was assessed whether retrospectively acquired pre-operative pain levels, as scored by the patient in the post-operative phase, differed from prospectively obtained pre-operative pain scores. Second, it was determined if errors associated with retrospectively obtained pain scores potentially lead to a misclassification of treatment outcome. Third, a meta-analysis established whether recall misclassifications, if present, affected overall study conclusions. RESULTS: Pain data of 313 patients undergoing remedial surgery were evaluated. The overall prevalence of misclassification due to a recall error was 13.7%. Patients not benefitting from surgery ('failures') judged their pre-operative pain level as more severe than it actually was. In contrast, patients who were pain free after remedial surgery ('successes') underestimated pre-operative pain scores. Recall misclassifications were significantly more present in failures than in successful patients (odds ratio 2.4 [95% CI 1.2-4.8]). CONCLUSION: One in seven patients undergoing remedial groin surgery is misclassified on the basis of retrospectively obtained pre-operative pain scores (success instead of failure, or vice versa). Misclassifications are relatively more present in failures after surgery. Therefore, the effect size of a therapy erroneously depends on its success rate.

The association between uterine contraction frequency and fetal scalp pH in women with suspicious or pathological fetal heart rate tracings: A retrospective study.

OBJECTIVE: Current guidelines provide little supporting literature for the definition of uterine tachysystole during labour and no distinction is made for optimal contraction frequency depending on the clinical situation. We hypothesize that fetal hypoxia is frequently caused by uterine tachysystole and that high uterine contraction frequencies are especially harmful when fetal heart rate (FHR) abnormalities are present. We studied the association between contraction frequency and fetal scalp pH values in women with an indication for fetal blood sampling (FBS) based on FHR abnormalities. STUDY DESIGN: A retrospective study including 762 women was performed in a tertiary teaching hospital in the Netherlands from January 2015 until January 2020. Women with a singleton pregnancy with a gestational age ≥ 34+0 weeks were included when FBS was performed because of suspicious or pathological FHR tracings. Exclusion criteria were maternal age < 18 years, failed fetal scalp pH values, lack of thirty minute registration by tocodynamometry prior to FBS, poor quality of uterine monitoring, intrauterine resuscitation in the thirty minutes prior to FBS, maternal body mass index ≥ 30 kg/m2 and neonatal birth weight < 10th percentile. Uterine contractions in the thirty minutes prior to FBS were manually annotated by a researcher who was blinded to FBS values, FHR and other obstetrical data. Linear and logistic analysis were used to explore the association between uterine contraction frequency and FBS results. RESULTS: Low fetal scalp pH values were significantly associated with contraction frequency prior to FBS. Fetuses of women with four to five contractions per ten minutes prior to FBS were 2.4 times more likely to have hypoxia as compared to fetuses of women with two to three contractions per ten minutes (aOR 2.4, 95% CI 1.1-5.4). With increasing contraction frequency, the risk of fetal hypoxia further increased. CONCLUSIONS: Contraction frequency above four per ten minutes prior to FBS is significantly associated with fetal hypoxia in women with FHR abnormalities. We suggest to aim for a maximum contraction frequency of four per ten minutes in these women.

Intrauterine fundal anaesthesia during endometrial ablation in the office: A randomised double-blind, non-inferiority trial.

OBJECTIVE: To evaluate the effect of intrauterine fundal anaesthesia during outpatient endometrial ablation. STUDY DESIGN: A randomised, double-blinded non-inferiority trial was performed in one hospital and one independent treatment center in the Netherlands. A total of 96 women who were planned for a NovaSure® endometrial ablation under local anaesthesia between December 2015 and February 2018 were included in this trial. These women were randomised to paracervical anaesthesia combined with hysteroscopic fundal infiltration with anaesthestics or paracervical anaesthesia combined with hysteroscopic fundal infiltration with saline. The primary outcome was pain during ablation. To study non-inferiority of paracervical anaesthesia without fundal anaesthesia, we assessed the co-primary endpoints Faces Pain Score and Numeric Rating Score. Secondary outcomes included pain scores at other moments during and after the procedure, postoperative use of analgesics, satisfaction, side-effects and complications. The primary outcomes were tested with a non-inferiority margin (2.0 points on changes in pain), and the secondary outcomes were compared using conventional statistical methods. RESULTS: Paracervical anaesthesia without fundal anaesthesia did not establish non-inferiority to the combination of paracervical anaesthesia and fundal infiltration with anaesthetics when both primary outcome variables of pain were taken into account (Numeric Rating Scale 5.0 versus 3.9 (mean difference 1.2 (95% CI 0.1-2.2)) and Faces Pain Score 5.4 versus 4.8 (mean difference 0.6 (95% CI -0.3-1.5))). Secondary pain scores measured during the procedure were higher or similar in women receiving fundal infiltration with saline as compared to women who received fundal infiltration with anaesthetics. After the procedure, there were no differences in reported pain scores, satisfaction, and side-effects. In the group who received fundal infiltration with saline, more women were admitted to the hospital because of severe pain (3 versus 0 women) and endometritis (1 versus 0 women). CONCLUSION: This study did not confirm non-inferiority of paracervical anaesthesia without fundal anaesthesia to the combination of paracervical anaesthesia with fundal anaesthesia in the reduction of pain during endometrial ablation and therefore provides no reason to leave out fundal anaesthesia. We recommend to use fundal anaesthesia combined with paracervical anaesthesia to reduce pain during endometrial ablation in the office.

Estrogens and the risk of complex regional pain syndrome (CRPS).

OBJECTIVE: Since complex regional pain syndrome (CRPS) shows a clear female predominance, we investigated the association between the cumulative as well as current exposure to estrogens, and CRPS. METHODS: A population-based case-control study was conducted in the Integrated Primary Care Information (IPCI) project in the Netherlands. Cases were identified from electronic records (1996-2005) and included if they were confirmed during a visit (using International Association for the Study of Pain Criteria), or had been diagnosed by a specialist. Controls were matched to cases on gender, age, calendar time, and injury. Measures of cumulative endogenous estrogen exposure were obtained by questionnaire and included age of menarche and menopause, menstrual life, and cumulative months of pregnancy and breast-feeding. Current estrogen exposure at CRPS onset was retrieved from the electronic medical records and determined by current pregnancy or by the use of oral contraceptive (OC) drugs or hormonal replacement therapy (HRT). RESULTS: Hundred and forty-three female cases (1493 controls) were included in analyses on drug use and pregnancies, while cumulative endogenous estrogen exposure was studied in 53 cases (58 controls) for whom questionnaire data were available. There was no association between CRPS and either cumulative endogenous estrogen exposure, OC, or HRT use. CRPS onset was increased during the first 6 months after pregnancy (OR: 5.6, 95%CI: 1.0-32.4), although based on small numbers. DISCUSSION: We did not find an association between CRPS onset and cumulative endogenous estrogen exposure or current OC or HRT use, but more powered studies are needed to exclude potential minor associations.

Referral and treatment patterns for complex regional pain syndrome in the Netherlands.

BACKGROUND: Patients with complex regional pain syndrome (CRPS) are seen and treated by a variety of physicians. The present study aims to describe referral and treatment patterns for CRPS patients in the Netherlands. METHODS: Patients, who were selected (1996-2005) from an electronic general practice (GP) database (Integrated Primary Care Information Project), were invited for study participation, involving diagnosis verification (International Association for the Study of Pain criteria) and assessment of referrals and treatment through information retrieved from GP journals, patients' questionnaires, pharmacy dispensing lists and specialist letters if available. RESULTS: One hundred and two patients were included. Sixty-one percent had presented first at the GP, while 80% subsequently consulted one or more medical specialists, most frequently an anesthetist (55% of the cases) or a specialist in rehabilitation medicine (41%). Over 90% of the patients received oral or topical pharmacotherapy, 45% received intravenous therapy, 89% received non-invasive therapy (i.e. physiotherapy) and 18% received nerve blocks. Analgesics and free radical scavengers were administered early during CRPS, while vasodilating drugs and drugs against neuropathic pain (antidepressants and anti-epileptics) were administered later on. Pharmacotherapy was usually initiated by a medical specialist. CONCLUSION: The Dutch treatment guidelines, issued in 2006, recommend free radical scavenger prescription (plus physiotherapy) as the initial treatment step for CRPS. Until 2005 only half of the patients received a scavenger within 3 months after disease onset, and the majority presents first at the GP, in particular GPs may be encouraged to initiate treatment with scavengers, while waiting for the results of further specialist consultation.

Prevalence and treatment of hypertensive patients with multiple concomitant cardiovascular risk factors in The Netherlands and Italy.

The Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA) trial demonstrated the benefits of combined antihypertensive/lipid-lowering treatment over antihypertensive treatment alone in hypertensive patients with > or =3 additional cardiovascular (CV) risk factors. We assessed the prevalence and treatment of patients with hypertension and > or =3 additional CV risk factors in The Netherlands and Italy in a retrospective cohort study using the Integrated Primary Care Information (IPCI) database in The Netherlands and the Health Search/Thales Database (HSD) in Italy. Patients aged > or =16 years, with 1 year of valid database history, diagnosed and/or treated for hypertension (>140/90 mmHg) during 2000-2002 were included in the study. The IPCI and HSD populations consisted of approximately 175000 and approximately 325000 patients, respectively. The prevalence of hypertension increased from 20.3 to 22.3% in the IPCI, and from 19.0 to 21.8% in the HSD during 2000-2002. The prevalence of > or =3 concomitant risk factors among hypertensive patients increased from 31.2 and 31.1% in 2000 to 34.2 and 39.3% in 2002 in the IPCI and HSD, respectively. From 2000 to 2002, among hypertensive patients with > or =3 CV risk factors and no prior symptomatic CV disease (CVD) approximately 54-57% in the IPCI and 80-83% in the HSD received antihypertensive treatment. In these patients, the use of combined antihypertensive and lipid-lowering treatment increased from 14.2 to 17.6% in the IPCI and from 15.5 to 17.4% in the HSD from 2000 to 2002. This study shows that primary prevention of CVD in hypertensive patients in The Netherlands and Italy could be improved.

Patient-reported outcome measurement compared with professional judgment of cosmetic results after breast-conserving therapy.

Background: In the present study, we set out to compare patient-reported outcomes with professional judgment about cosmesis after breast-conserving therapy (bct) and to evaluate which items (position of the nipple, color, scar, size, shape, and firmness) correlate best with subjective outcome. Methods: Dutch patients treated with bct between 2008 and 2009 were analyzed. Exclusion criteria were prior amputation or bct of the contralateral breast, metastatic disease, local recurrence, or any prior cosmetic breast surgery. Structured questionnaires and standardized six-view photographs were obtained with a minimum of 3 years' follow-up. Cosmetic outcome was judged by the patients and, based on photographs, by 5 different medical professionals using 3 different scoring systems: the Harvard scale, the Sneeuw questionnaire, and a numeric rating scale. Agreement was scored using the intraclass correlation coefficient (icc). The association between items of the Sneeuw questionnaire and a fair-poor Harvard score was estimated using logistic regression analysis. Results: The study included 108 female patients (age: 40-91 years). Based on the Harvard scale, agreement on cosmetic outcome between the professionals was good (icc: 0.78). In contrast, agreement between professionals as a group compared with the patients was found to be fair to moderate (icc range: 0.38-0.50). The items "size" and "shape" were identified as the strongest determinants of cosmetic outcome. Conclusions: Cosmetic outcome was scored differently by patients and professionals. Agreement was greater between the professionals than between the patients and the professionals as a group. In general, size and shape were the most prominent items on which cosmetic outcome was judged by patients and professionals alike.

Adherence to gastroprotection and the risk of NSAID-related upper gastrointestinal ulcers and haemorrhage.

BACKGROUND: Upper gastrointestinal (UGI) complications are a well-recognized risk of NSAID treatment, requiring preventive measures in high-risk patients. Adherence to gastroprotective agents (GPAs) in NSAID users has been suggested to be suboptimal. AIM: To investigate the association between adherence to GPAs (proton pump inhibitors or H(2)-receptor antagonists) and the risk of NSAID-related UGI ulcers or haemorrhage in high-risk patients. METHODS: A population-based nested case-control study was conducted within a cohort of new NSAID users with at least one risk factor for a NSAID-related UGI complication, identified in the Dutch IPCI database during 1996-2005. Adherence to GPAs was calculated as the proportion of NSAID treatment days covered (PDC) by a GPA prescription. Multivariate conditional logistic regression analysis was used to calculate odds ratios with 95% confidence intervals (95% CI). RESULTS: Fifteen percent of the non-selective NSAID users received GPAs. The risk of a NSAID-related UGI complication among NSAID users increased 16% for every 10% decrease in adherence. Compared to patients with a PDC of >80%, patients with PDCs of 20-80% and <20% had a 2.5-fold (95% CI: 1.0-6.7) respectively 4.0-fold (95% CI: 1.2-13.0) increased risk. CONCLUSION: There is a strong inverse relationship between adherence to GPAs and the risk of UGI complications in high-risk NSAID users.

[Increased risk of gastrointestinal bleeding or ulcers when using spironolactone: a case-control study]. / Toegenomen kans op gastro-intestinale bloedingen of ulcera bij gebruik van spironolacton: patiënt-controlestudie.

OBJECTIVE: To study the association between the use of spironolactone and the risk of upper gastrointestinal bleeding or ulcers. DESIGN: Case-control study. METHOD: The study used the computerized 'integrated primary care information' (IPCI) database in the Netherlands. All persons, 18 years or older during the study period from January 1st 1996 through September 30th 2003 with at least one year of valid case history were included. Patients with a medical history of alcoholism or gastrointestinal cancer were excluded. For each case of gastroduodenal ulcer or upper gastrointestinal bleeding, 10 controls were sampled from the same database, matched on age (year of birth), gender and index date. The association between the use ofspironolactone, calculated from the number of general practitioners' prescriptions, and the occurrence of an upper gastrointestinal event (upper gastrointestinal bleeding or ulcers) was analysed by means of a conditional logistic regression analysis. RESULTS: Within the source population of 306,645 patients, 523 cases with gastric or duodenal ulcers or upper gastrointestinal bleeding were identified and matched with 5,230 controls. Current use of spironolactone was associated with a 2.7-fold (adjusted odds ratio (OR); 95% CI: 1.2-6.0) increased risk of gastrointestinal events. This risk was higher in patients on high dosages and was the highest in patients using spironolactone in combination with an ulcerogenic drug (NSAIDs, platelet aggregation inhibitors, corticosteroids or vitamin K antagonist) (adjusted OR: 7.3; 95% CI: 2.9-18.7). CONCLUSION: The risk of upper gastrointestinal bleeding or ulcer was increased 2.7 times when spironolactone was used.

Persistence and adherence to proton pump inhibitors in daily clinical practice.

BACKGROUND: Proton pump inhibitors are widely used, but little is known about the usage pattern in different indications. AIM: To analyse proton pump inhibitor usage patterns in the general population. METHODS: A cohort of 16 311 incident proton pump inhibitor users was identified in the Integrated Primary Care Information database, a Dutch general practice research database. Persistence and adherence were calculated by indication. Risk factors were identified by logistic regression analysis. RESULTS: One-year persistence was 31% in patients using proton pump inhibitors for gastro-oesophageal reflux. Persistence was higher in oesophagitis grade A/B (54%), grade C/D (73%) and Barrett's oesophagus (72%), compared to patients with only reflux symptoms (27%). Approximately 25% of patients with non-reflux dyspepsia or Helicobacter pylori-associated indications used proton pump inhibitors for more than 6 months. Half of all patients used proton pump inhibitors <80% of time indicating intermittent use, which was independent of indication. Exception were patients with Barrett's oesophagus, who were most adherent. CONCLUSIONS: A substantial proportion of patients with indications not requiring long-term treatment use proton pump inhibitors for an extended period. Half of the patients used proton pump inhibitors on-demand or intermittently. Such usage pattern is probably sufficient for most patients, but may be inadequate if proton pump inhibitors are used for serious diseases, such as severe oesophagitis or Barrett's oesophagus.

Urological complaints in relation to indinavir plasma concentrations in HIV-infected patients.

OBJECTIVE: To assess the relationship between indinavir-associated urological complaints and indinavir plasma concentrations. DESIGN: Case series, comparing indinavir plasma concentrations in cases with average concentrations in a control group. METHODS: Patients taking 800 mg indinavir three times a day (tid), who presented with overt urological complaints (renal colic, flank pain or haematuria) were selected for the study. Plasma indinavir concentrations were measured by means of a standardized high performance liquid chromatography (HPLC) method. Plasma samples taken at 1.5-8 h after the last indinavir ingestion were included for evaluation. Results were compared with the full pharmacokinetic curves of indinavir plasma concentrations from a control group of 14 patients taking 800 mg indinavir tid without urological complaints, and were expressed as concentration ratios. A ratio of 1 indicated a plasma concentration equalling the average concentration in the control population at the same point in time after the ingestion of indinavir. RESULTS: Seventeen patients (five women) were enrolled and the indinavir concentrations of 15 patients could be evaluated. Fourteen (93%) patients had a concentration above the mean of the controls, 12 (80%) patients had a concentration above the upper 95% confidence limit, and one (7%) patient had a concentration below the lower 95% confidence limit. The mean indinavir concentration in patients with urological complaints (ratio range 0.55-11.49) was significantly higher than the average concentration and the upper 95% confidence limit of the control group (P < 0.05). The results could not be explained by differences in weight, sex or drug interactions. Two patients had chronic active hepatitis B infection. In six patients with indinavir concentrations above the upper 95% limit, indinavir was reduced to 600 mg tid. Upon repeat measurement after the dose adjustment, their indinavir plasma concentrations fell within the 95% confidence interval around the mean of the control population. All six patients remained asymptomatic and had viral loads of less than 500 copies per ml after a follow-up of 5-16 months. CONCLUSIONS: Urological complications occurring during indinavir treatment were associated with elevated indinavir plasma concentrations in 80% of patients in this study. Indinavir plasma concentrations should be monitored upon presentation of urological complaints, on the basis of which dose reductions may be applied if brief interruption and increased hydration are ineffective.

Adherence to proton pump inhibitors or H2-receptor antagonists during the use of non-steroidal anti-inflammatory drugs.

BACKGROUND: The efficacy of proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) prescribed as prophylaxis for NSAID-related upper gastrointestinal (UGI) toxicity is dependent upon patient adherence. AIM: To describe patient adherence to prophylactically prescribed PPIs and H2RAs in the clinical setting. METHODS: We conducted a retrospective observational cohort study using the Integrated Primary Care Information Project database. The study population consisted of incident non-specific NSAID users prescribed a PPI or H2RA specifically as prophylaxis for NSAID-related UGI toxicity. Patients were classified as non-adherent if < 75% of days of NSAID use were covered by one of these agents, and as continuing users after discontinuation of NSAID use if they had a renewed prescription for these agents after their last NSAID prescription. RESULTS: The study cohort comprised 784 patients: 374 with H2RAs, 405 with PPIs, and 5 with both PPI and H2RA. Eighty-five percent of H2RA users and 7% of PPI users were prescribed these drugs at doses below the minimum recommended/effective dose for NSAID-associated gastroduodenal ulcer prophylaxis. Thirty-seven percent of patients were non-adherent. The lowest rate of non-adherence was associated with the first NSAID prescription (9%), increasing to 61% for patients with >/= 3 prescriptions. In a cohort of subjects who stopped their NSAID and were followed for up to 2 years (n = 711), there was significant persistent use of acid suppressive agents; 40% of patients had at least one additional prescription for the acid suppressive agent after stopping NSAIDs, and> 30% received enough drug to cover a period longer than 2 months after stopping their NSAID. CONCLUSIONS: The pattern of PPI and H2RA prescriptions, when prescribed as prophylactic strategy, does not correspond with the pattern of NSAID use. Physicians should consider the medical impact of non-adherence with dual therapies and the impact of prolonged use of GPAs on treatment cost.

The incidence of sudden cardiac death in the general population.

BACKGROUND AND OBJECTIVES: To determine the incidence of sudden cardiac death in a general (Dutch) population. METHODS: Cohort study in the Integrated Primary Care Information (IPCI) project, a database with all medical data from 150 general practices in The Netherlands. The study population comprised 249,126 subjects with a mean follow-up of 2.54 years. RESULTS: In this period 4,892 deaths were identified, 582 of which were classified as (probable) sudden cardiac death. The overall incidence of sudden cardiac death in this population was 0.92 cases per 1,000 person-years (95%CI: 0.85-0.99). The risk was 2.3-fold higher in men than in women, and increased with age. The incidence of sudden cardiac death peaked in October and was lowest in August. CONCLUSIONS: The incidence of sudden cardiac death in the general Dutch population was almost 1 per 1,000 person-years per year during the period 1 January, 1995 to 1 April, 2001. Most of the cases occurred at home.

Annual revaccination against influenza and mortality risk in community-dwelling elderly persons.

CONTEXT: Although large-scale observational studies have demonstrated the effectiveness of influenza vaccination, no large studies have systematically addressed the clinical benefit of annual revaccinations. OBJECTIVE: To investigate the effect of annual influenza revaccination on mortality in community-dwelling elderly persons. DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort study using the computerized Integrated Primary Care Information (IPCI) database in the Netherlands including community-dwelling individuals aged 65 years or older from 1996 through 2002. For each year, we computed the individual cumulative exposure to influenza vaccination since study start. MAIN OUTCOME MEASURE: Association between the number of consecutive influenza vaccinations and all-cause mortality vs no vaccination after adjusting for age, sex, chronic respiratory and cardiovascular disease, hypertension, diabetes mellitus, renal failure, and cancer. RESULTS: The study population included 26,071 individuals, of whom 3485 died during follow-up. Overall, a first vaccination was associated with a nonsignificant annual reduction of mortality risk of 10% (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.78-1.03) while revaccination was associated with a reduced mortality risk of 24% (HR, 0.76; 95% CI, 0.70-0.83). Compared with a first vaccination, revaccination was associated with a reduced annual mortality risk of 15% (HR, 0.85; 95% CI, 0.75-0.96). During the epidemic periods this reduction was 28% (HR, 0.72; 95% CI, 0.53-0.96). Similar estimates were obtained for persons with and without chronic comorbidity and those aged 70 years or older at baseline. Overall, influenza vaccination is estimated to prevent 1 death for every 302 vaccinees at a vaccination coverage that varied between 64% and 74%. CONCLUSION: Annual influenza vaccination is associated with a reduction in all-cause mortality risk in a population of community-dwelling elderly persons, particularly in older individuals.

[Highly active antiretroviral therapy (HAART) in HIV-positive pregnant women in the Netherlands, 1997-2003: safe, effective and with few side effects]. / Krachtige antiretrovirale therapie (HAART) bij HIV-positieve zwangeren in Nederland, 1997-2003: veilig, effectief en met weinig bijwerkingen.

OBJECTIVE: To assess the side effects, safety and efficacy of highly active antiretroviral therapy (HAART) in a cohort of HIV-infected pregnant women in the Netherlands. DESIGN: Retrospective. METHOD: Data were collected from the medical records of HIV-infected pregnant women who received HAART during pregnancy in the period 1 January 1997-1 June 2003 at 14 HIV-specialized centres in the Netherlands. The inclusion criteria were at least a triple drug regimen and birth at 20 or more weeks of gestation. Information was collected about patient characteristics, HAART prescribed, side effects, viral load response, mode of delivery and HIV-status of the neonate. RESULTS: A total of 267/413 women satisfied the inclusion criteria. Most women (n = 199) had not previously received anti-retroviral therapy and started HAART between weeks 21 and 28 of the pregnancy. The two most frequently used regimens contained nelfinavir (57%) or nevirapine (31%). Gastrointestinal side effects were more frequently observed in the nelfinavir group, while rash and hepatotoxicity were more frequently reported in the nevirapine group. Efficacy and pregnancy outcome were similar in both groups. Two infants (0.7%) were HIV-infected. CONCLUSION: HAART regimens containing nelfinavir or nevirapine in HIV-infected pregnant women were safe, effective and well tolerated.

[Lipodystrophy and 'buffalo hump' during treatment with HIV protease inhibitors]. / Lipodystrofie en 'buffalo hump' bij de behandeling met HIV-proteaseremmers.

In three patients, a 36-year-old HIV seropositive homosexual man and two women aged 35 and 59 years who had acquired HIV infection through heterosexual contact, signs of lipodystrophy developed after prolonged anti-HIV triple therapy. The observed syndrome is seen after prolonged use of HIV protease inhibitors: it is characterized by peripheral fat wasting, central fat accumulation, hyperlipidaemia and insulin resistance. Typically the subcutaneous fatty tissue disappears resulting in prominent zygomata, veins and muscles and thinning of extremities and buttocks. In addition to abdominal fat accumulation, there have been reports on the occurrence of a dorsocervical fat pad, the so-called buffalo hump. Lipodystrophy caused by protease inhibitors is a risk factor for cardiovascular disease. Recognition of the syndrome is essential for adequate follow-up and possible treatment.

[Treatment adherence amongst HIV-infected patients in Rotterdam: poorer prognosis independent of nationality in heterosexual infected patients, intravenous drug users, Negroid and Latin-American patients]. / Therapietrouw onder HIV-geïnfecteerden in Rotterdam: onafhankelijk van nationaliteit slechter bij heteroseksueel besmette patiënten, intraveneuzedruggebruikers, negroïde en Latijns-Amerikaanse patiënten.

OBJECTIVE: To assess adherence to antiretroviral therapy (ART) in Dutch and non-Dutch HIV-infected patients. DESIGN: Observational, cross-sectional study. METHODS: Consecutive HIV-infected patients taking ART and visiting the internal medicine outpatients' clinic at the Rotterdam Dijkzigt University Hospital between 1 February until 30 April 2001 were interviewed by a multilingual interviewer using a standard questionnaire. Classification of adherence was based on the interview data. Multivariate analysis was used to determine independent predictors of adherence. Nationality was defined as 'Dutch' if the person was born in the Netherlands, and otherwise as 'non-Dutch'. RESULTS: The 203 patients included in this study comprised 131 men and 69 women with an average age of 42 years. There were no data available on treatment adherence for 3 of the patients. Of the 81 Dutch patients, 60 (74%) adhered to the treatment compared with 68 (57%) of the 119 non-Dutch patients. However, after correction for sex, risk group, race and duration of treatment, there was no difference in treatment adherence between these two groups (OR: 0.6; 95% CI: 0.2-1.9). Failure to adhere to treatment was seen most frequently in the 109 heterosexually infected patients (OR: 2.6; 0.98-6.7), the 22 intravenous drug users (OR: 3.3; 1.04-10.1), as well as in the group of Negroid patients (OR: 3.5; 1.1-11.3) and Latin-American patients (OR: 8.5; 1.7-42.7).