Lung function decline preceding chronic respiratory failure in spinal muscular atrophy: a national prospective cohort study.

BACKGROUND: Progressive lung function decline, resulting in respiratory failure, is an important complication of spinal muscular atrophy (SMA). The ability to predict the need for mechanical ventilation is important. We assessed longitudinal patterns of lung function prior to chronic respiratory failure in a national cohort of treatment-naïve children and adults with SMA, hypothesizing an accelerated decline prior to chronic respiratory failure. METHODS: We included treatment-naïve SMA patients participating in a prospective national cohort study if they required mechanical ventilation because of chronic respiratory failure and if lung function test results were available from the years prior to initiation of ventilation. We analyzed Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 s (FEV1), Peak Expiratory Flow (PEF) and Maximum Expiratory Pressure (PEmax). We studied the longitudinal course using linear mixed-effects models. We compared patients who electively started mechanical ventilation compared to patients who could not be weaned after acute respiratory failure. RESULTS: We analyzed 385 lung function tests from 38 patients with SMA types 1c-3a. At initiation of ventilation median age was 18.8 years (IQR: 13.2-30.1) and median standardized FVC, FEV1 and PEF were 28.8% (95% CI: 23.5; 34.2), 28.8% (95% CI: 24.0; 33.7) and 30.0% (95% CI: 23.4; 36.7), with an average annual decline of 1.75% (95% CI: 0.86; 2.66), 1.72% (95% CI: 1.04; 2.40) and 1.65% (95% CI: 0.71; 2.59), respectively. Our data did not support the hypothesis of an accelerated decline prior to initiation of mechanical ventilation. Median PEmax was 35.3 cmH2O (95% CI: 29.4; 41.2) at initiation of mechanical ventilation and relatively stable in the years preceding ventilation. Median FVC, FEV1, PEF and PEmax were lower in patients who electively started mechanical ventilation (p < 0.001). CONCLUSIONS: Patterns of lung function decline cannot predict impending respiratory failure: SMA is characterized by a gradual decline of lung function. We found no evidence for an accelerated deterioration. In addition, PEmax remains low and stable in the years preceding initiation of ventilation. Patients who electively started mechanical ventilation had more restrictive lung function at initiation of ventilation, compared to patients who could not be weaned after surgery or a respiratory tract infection.

Starting HMV at home: a reasonable option for many patients?

BACKGROUND AND OBJECTIVE: In the current study, we undertook a more detailed exploration of the reasons why patients undergoing HMV were screened out of a recently published study in order to better understand how applicable home initiation of HMV is under real life conditions. METHODS: All referred patients who had an indication for starting HMV were screened to participate in the Homerun study. In this trial 512 patients were screened out of the study. Those patients not enrolled in the trial were divided into the following 3 groups: (1) those not fulfilling the inclusion criteria; 2) those meeting the exclusion criteria and 3) those excluded on the basis of medical or organisation reasons. Each group was then further divided into those who would likely have been suitable for initiation of HMV at home in real world practice and those who were unsuitable. RESULTS: Based on inclusion criteria (group 1) 116 patients could not start HMV in real life, while this was 245 patients in the study. Based on the exclusion criteria (group 2) 11 patients could not start in real life while this was 79 in the study. One hundred and eighty-eight could not be enrolled in the study due to medical and organisational reasons ( group 3), while in real life this was only 95. CONCLUSION: This study indicates that more than 55% of patients who did not participate in the Homerun study could have started HMV at home in real life.

Home mechanical ventilation: the Dutch approach.

In the Netherlands we have an unique organisation of only 4 centres being responsible for all patients who need Home Mechanical ventilation(HMV). Nationwide criteria for referral and initiation of HMV are stated in our national guideline and recently a unique national learning management system (LMS) for all caregivers and professionals was developed. A nationwide multi-centric research program is running and every centre is participating. In this paper we provide information about the evolution of HMV in the Netherlands during the last 30 years, including details about the number of patients, different diagnose groups, residence and the type of ventilators.

[Initiating patients on home mechanical ventilation]. / Instellen van patiënten op chronische thuisbeademing.

More and more patients with chronic respiratory insufficiency are eligible for home mechanical ventilation. As a result, medical doctors are increasingly confronted with said patients. The treatment goal of this supporting therapy is to improve quality of life and possibly life extension. Centres for home mechanical ventilation decide on the indication, whereas the clinical setup of the ventilator takes place in a hospital setting. Staff in the Dutch Gelderse Vallei hospital have been initiating - both non-invasive and invasive - home mechanical ventilation for various patient groups for the last 4 years. This is a labour-intensive process during which numerous issues can occur. Experience and expertise is necessary for a successful process. A multidisciplinary approach and accessible consultation between stakeholders is of great importance when setting up home mechanical ventilation for these patients.

Treatment of respiratory impairment in patients with motor neuron disease in the Netherlands: patient preference and timing of referral.

BACKGROUND AND PURPOSE: We assessed the first evaluation at a large ventilation clinic in the Netherlands to: (i) determine what proportion of patients with motor neuron disease would benefit from earlier referral; and (ii) examine the patient preferences regarding ventilatory support. METHODS: Observational study at a single centre with a catchment area of 7.6 million inhabitants. Data on disease status, the referral process and patients' preferences regarding ventilatory support were collected during the first home ventilation services (HVS) assessment and analysed for correlation with the presence of daytime hypercapnia and suspected nocturnal hypoventilation. The latter conditions require immediate (within 48 h) or subacute (within 3 weeks) initiation of ventilatory support. RESULTS: Vital capacity (in percentage of predicted value, VC%pred) was assessed by referring physicians in 84% of the 217 referred patients; the mean VC%pred was 69% (SD 16). One-hundred and ninety-one patients attended the first HVS assessment without ventilatory support, at a median of 21 days following referral: 18% had respiratory failure (daytime hypercapnia), 19% had normocapnia but were suspected of nocturnal hypoventilation, and 63% had normocapnia without symptoms. Following the HVS assessment, 25 patients (13%) declined home mechanical ventilation; this occurred more often in patients with (14/70) compared with patients without respiratory impairment (11/121; P < 0.05). CONCLUSION: A meaningful proportion of patients who desire ventilatory support are referred to a ventilation clinic after already developing respiratory failure. Future studies could examine means, including more sensitive respiratory measures, to detect those patients who could benefit from earlier referral.

The incidence of neonatal herpes in The Netherlands.

BACKGROUND: In The Netherlands the incidence of neonatal herpes was 2.0-2.9 per 100,000 live births during the period 1981-1998. The low incidence warranted a rather conservative prevention policy. OBJECTIVES: To monitor for potential changes in the incidence of neonatal herpes in The Netherlands between 1999 and 2005, which may affect the prevention policy. STUDY DESIGN: Questionnaires were sent to all virological laboratories, the gynaecological and paediatric departments of every university hospital and half the number of the general hospitals in The Netherlands. The questionnaires pertained to the incidence of proven cases of neonatal herpes, the numbers of caesarean sections performed for the prevention of neonatal herpes and the numbers of pregnant women with genital herpes. RESULTS: In the period 1999-2005 33 cases of neonatal herpes were reported, yielding an incidence of 3.2 cases per 100,000 live births per year. The estimated annual numbers of pregnant women with genital herpes ranged from 200 to 240. Approximately 9 caesarean sections were performed annually to prevent neonatal herpes. CONCLUSIONS: In The Netherlands neonatal herpes is still a rare condition. From the findings of this study it is concluded that it is not necessary to revise the Dutch guidelines for the prevention of neonatal herpes simplex infection.

[Incidence of herpes neonatorum in Netherlands]. / De incidentie van herpes neonatorum in Nederland.

OBJECTIVE: Investigation of the incidence of neonatal herpes in the Netherlands between 1992 and 1998. DESIGN: Inventory questionnaire survey. METHODS: All virological laboratories in the Netherlands were sent a questionnaire on the number of culture proven cases of neonatal herpes recorded between 1992 and 1998 and on the type of herpes simplex virus (HSV-1 or HSV-2). The gynaecological and paediatric departments of all university hospitals and of half of the general hospitals were sent questionnaires as well. Gynaecologists were asked how often caesarean section was performed in order to prevent neonatal herpes and how frequently pregnant women were seen with genital herpes. Paediatricians were asked how often they observed neonatal herpes, the type of HSV and the possible transmission route. Based on these data the figures for the whole of the Netherlands were estimated. RESULTS: The incidence of neonatal herpes in the Netherlands in the period 1992 to 1998 was 2.4 per 100,000 neonates. HSV-1 was the cause of neonatal herpes in 73%, HSV-2 in 9%, and in 18% of the cases the type of infection was not recorded. The number of pregnant women with genital herpes had increased, but, in agreement with a consensus statement, the gynaecologists hardly performed caesarean sections any more to prevent neonatal herpes (2 per year). CONCLUSIONS: The incidence of neonatal herpes in the Netherlands had not increased. There was no predominant role of HSV type 2 causing neonatal herpes.

Homocysteine metabolism and effects of folic acid supplementation in patients affected with spina bifida.

Folic acid supplementation around conception decreases the risk of having offspring with a neural tube defect. However, the aetiology is often still unknown. This study investigated whether spina bifida patients have lower blood folate and higher fasting and post-methionine-load plasma total homocysteine (tHcy) concentrations than control patients. Moreover, the effects of supplementation with 500 microg folic acid/d on folate and tHcy concentrations were determined. Spina bifida patients (n = 12) and disabled control patients (n = 15) received 4 weeks of placebo treatment followed by 4 weeks of intervention with 500 microg folic acid/d. Blood was collected at the start and after 4 and 8 weeks. A methionine-loading test was performed at the start and the end of the study. At baseline, no significant differences occurred between spina bifida and control patients. Folic acid supplementation significantly increased plasma and red blood cell folate concentrations in both groups. Folic acid decreased fasting tHcy concentrations in control patients by 1.6+/-0.5 micromol/l (p<0.01) and in spina bifida patients by 2.2 +/- 1.3 micromol/l (p = 0.10). This study does not show a derangement in homocysteine metabolism in spina bifida compared to control patients. Moreover, folic acid supplementation seems at least as effective in spina bifida patients as in controls.

[Preconception counseling in family practice; a survey of 100 family physicians]. / Preconceptionele advisering in de huisartspraktijk; een enquête onder 100 huisartsen.

OBJECTIVE: To assess the awareness, opinions on desirability and preconditions such as special knowledge with regard to the concept of preconceptional health counselling among general practitioners. DESIGN: Descriptive. SETTING: General practices in the Groot Gelre district of the Dutch General Practitioners Society. METHOD: A representative sample of 100 general practitioners were asked by phone for permission to send a questionnaire; 89 out of the 94 general practitioners who were sent a questionnaire replied (response: 89%). RESULTS: Almost all general practitioners (88%) knew about the concept of preconceptional health counselling and most of them already gave some kind of preconceptional advice. 93% considered preconceptional health counselling part of their job responsibility and 91% were prepared to give more preconceptional health care in the future. 53% of all general practitioners, however, indicated that they lacked sufficient knowledge to give adequate advice. The advantages of preconceptional health care were considered to outweigh possible disadvantages such as medicalization of pregnancy. CONCLUSION: The general practitioners knew about preconceptional health care and considered it part of their job. Many already provided preconceptional health care, although not in a structured way. General practitioners appeared to lack time and appropriate knowledge, which indicates a need for postgraduate training.

PIP: In April and May 1997, a total of 100 general practitioners (GPs) in the Groot Gelre district of the Dutch General Practitioners Society were surveyed by phone for permission to send a questionnaire. 89 of 94 GPs who were sent a questionnaire replied, yielding a response rate of 89%. 78 of 89 GPs (88%) knew about the concept of pre-pregnancy health (PH) counseling and most of them already gave some kind of preconceptional advice (98% about folic acid, 93% about smoking, 88% about alcohol, 94% about various other substances, and 73% about the prevention of infections--toxoplasmosis, rubella). 87% of GPs questioned the patients about hereditary/congenital diseases that the child might inherit, 76% about hereditary diseases in the family, and 62% about diabetes. Less frequently occurring hereditary diseases were much less often asked about, such as Huntington's disease (14%), cystic fibrosis (19%), and hemophilia (14%). If the woman expressed the desire to have a child, 25% of GPs took an expanded case history. If a GP indicated a risk factor with regard to a potential pregnancy, 75% of them identified the possible consequences and informed the patient about them. 93% considered PH counseling part of their job responsibility and 91% were prepared to provide more PH care in the future. 53% of all GPs, however, indicated that they lacked sufficient knowledge to give adequate advice. The advantages of PH care were considered to outweigh possible disadvantages, such as medicalization of pregnancy, according to 74% of GPs. GPs appeared to lack time and appropriate knowledge, which indicates a need for postgraduate training.