Literature search from ms 29/4/2010

Fine-Goulden, M. R., S. Manna, et al. (2009). "Cor pulmonale due to congenital central hypoventilation syndrome presenting in adolescence." Pediatric Critical Care Medicine 10(4): e41-2.

OBJECTIVE: To report the first case of congenital central hypoventilation syndrome (CCHS) presenting with severe cor pulmonale in an adolescent. METHODS AND DESIGN: Case report and literature review. Our Institutional Review Board waived the need for consent. SETTING: Pediatric intensive care unit in a tertiary care children's hospital. PATIENT: A 12-year-old girl who developed profound hypoxia following routine dental extraction under intravenous opiate sedation and became progressively obtunded due to marked hypoventilation without hypoxic arousal, requiring mechanical ventilation. She had evidence of severe right heart failure, but no cardiac, pulmonary, neurologic, or neuromuscular cause was identified. The diagnosis of CCHS was suspected and subsequently confirmed by blood polymerase chain reaction analysis that revealed a heterozygous polyalanine expansion mutation of the PHOX2B gene (five polyalanine repeats). CONCLUSIONS: This report describes the unusual presentation of severe cor pulmonale in an adolescent with so-called "late-onset" CCHS. CCHS was previously thought to be a disease affecting only neonates, but the late-onset phenotype has now been well described in adults. It should be considered in any child presenting with unexplained right heart failure without an identifiable cause, particularly if central sleep apnea is present, because early initiation of ventilatory support can prevent cardiac and neurologic sequelae and improve outcome.

Fischer, P. W. F., M. Vigneault, et al. (2009). "Sodium food sources in the Canadian diet." Applied Physiology, Nutrition, & Metabolism = Physiologie Appliquee, Nutrition et Metabolisme 34(5): 884-92.

The purpose of this study is to provide information on the current sources of dietary sodium in the Canadian food supply to provide a baseline to measure against the effectiveness of strategies to reduce salt consumption. Such strategies are being developed by a Health Canada-led multistakeholder Working Group. Data from the 2004 Canadian Community Health Survey (CCHS) 2.2, Nutrition, were used to determine the leading food group contributors of sodium in the diet. The total sample size was more than 35,000 respondents. The results from this study were reported for 4 age and sex groups, namely, youths aged 1 to 8 years, youths aged 9 to 18 years, males aged 19 years and older, and females aged 19 years and older. Average daily intakes of sodium for these groups were 2388 mg, 3412 mg, 3587 mg, and 2684 mg, respectively. In all cases these intakes exceeded the tolerable upper intake level (UL) established by the Institute of Medicine, as well as targets set by the governments of the United Kingdom and the United States and the World Health Organization. The contribution of sodium to the food supply by the top 40 food groups is presented for each of the age and sex groups. The key food group contributors of sodium are breads (13.88%), processed meats (8.90%), and pasta dishes (5.67%). Although breads are found to be major contributors of sodium, this is mainly because of the large consumption, rather than a high concentration of sodium. Higher-sodium foods, such as processed meats, are eaten in smaller quantities but, because of their sodium density, contribute significant amounts of sodium to the diet of Canadians. Some very high sodium foods, such as frozen dinners, are eaten by only a small proportion of the population, but for those consuming these, the sodium could contribute a significant proportion of the UL just from a single meal.

Fisher, W. L. (1991). "CCHS and home care." Home Healthcare Nurse 9(5): 41-4.

Caring for a child with CCHS at home can be a challenge to home care nurses. Family support and advocacy are imperative.

Fishman, L. S., J. H. Samson, et al. (1965). "Primary Alveolar Hypoventilation Syndrome (Ondine's Curse)." American Journal of Diseases of Children 110: 155-61.

Fitze, G., I. R. Konig, et al. (2008). "Compound effect of PHOX2B and RET gene variants in congenital central hypoventilation syndrome combined with Hirschsprung disease." AMERICAN JOURNAL OF MEDICAL GENETICS Part A. 146A(11): 1486-9.

Fitze, G., E. Paditz, et al. (2003). "Association of germline mutations and polymorphisms of the RET proto-oncogene with idiopathic congenital central hypoventilation syndrome in 33 patients." JOURNAL OF MEDICAL GENETICS 40(2): E10.

Fitzgerald, D., G. M. Davis, et al. (1996). "Diaphragmatic pacemaker failure in congenital central hypoventilation syndrome: a tale of two twiddlers." PEDIATRIC PULMONOLOGY 22(5): 319-21.

Two patients with congenital central hypoventilation syndrome (CCHS) experienced phrenic nerve pacer failure due to deliberate manipulation of the internal receiver implant ("twiddling"). The patients, aged 7 and 12 years, presented with repeated episodes of pacer failure associated with local pain over a period of 18 months. They had progressively coiled the pacing wires to the point of breakage, which only became apparent at surgery. The breaks were not recognized radiologically, although in retrospect progressive twisting of the wires was evident on serial chest radiographs. Both patients required replacement of the internal receivers under general anesthesia. We recommend that the chest radiograph that is undertaken to investigate the cause of pacer dysfunction include the internal receiver. A plain chest radiograph that demonstrates progressive coiling of the subcutaneous pacing wire should raise suspicion of pacer wire breakage regardless of the patient's age.
Flageole, H. (2003). "Central hypoventilation and diaphragmatic eventration: diagnosis and management." SEMINARS IN PEDIATRIC SURGERY 12(1): 38-45.

Congenital central alveolar hypoventilation syndrome (CCAHS) is a disorder of ventilatory control that occurs without neuromuscular blockade or pulmonary disease. It is characterized by a lack of response to habitual respiratory stimulants, especially hypercapnia. In this article, the management of this syndrome by diaphragmatic pacing is discussed. Paralysis of the phrenic nerve in small children usually results from injury during birth or during a cardiothoracic operation and results in eventration of the hemidiaphragm. Alternatively, eventration of the diaphragm may be a congenital condition. In both cases it may lead to respiratory distress in the newborn. In this article, we review the diagnosis of these conditions and their management, focusing on the surgical indications. We also discuss outcome. Copyright 2003, Elsevier Science (USA)

Flageole, H., V. R. Adolph, et al. (1995). "Diaphragmatic pacing in children with congenital central alveolar hypoventilation syndrome." SURGERY 118(1): 25-8.

BACKGROUND: The purposes of this study were to study congenital central alveolar hypoventilation syndrome (CCAHS), to report the experience at our institution with this disorder, and to describe the surgical technique of diaphragmatic pacing. Three patients are in our diaphragmatic pacing program. They all have CCAHS, documented by means of lack of respiratory drive to hypercapnia and normal peripheral nerve and muscle studies. Two patients have associated Hirschsprung's disease. METHODS: The ages of patients at insertion of bilateral phrenic nerve pacemakers were 1, 2, and 5 years. A bilateral axillary thoracotomy in the third interspace was used in two patients, and anterior thoracotomy was used in one for insertion of electrodes on the phrenic nerves. Counterincisions in both flanks were used in all patients for insertion of the receivers in subcutaneous pockets. RESULTS: In all patients pacing was commenced within 1 week of the surgical procedure, because no primary pacemaker failures occurred. One patient has experienced no failure of the equipment and no infectious complications at 4 years. A second patient has had the pacemakers for 6 months without complications. The third patient underwent placement of bilateral pacemakers in 1984. In this patient a 10-year experience has resulted in subcutaneous implant failure on two separate occasions; also the presence of a staphylococcal empyema necessitated the temporary removal of one phrenic nerve electrode for 6 months, with successful reinsertion. All patients now receive mechanical assisted ventilation when sleeping and phrenic nerve pacing when awake. CONCLUSIONS: Pediatric surgeons should be aware of CCAHS because it may be treated with surgically implanted electrodes that allow for pacing of the diaphragm. The technique has an acceptable complication rate, and it can greatly decrease the impact of the disease on the lifestyle and activity of the patient. CCAHS also may be associated with Hirschsprung's disease.

Flanagan, W., C. N. McIntosh, et al. (2006). "Deriving utility scores for co-morbid conditions: a test of the multiplicative model for combining individual condition scores." Population Health Metrics 4: 13.

BACKGROUND: The co-morbidity of health conditions is becoming a significant health issue, particularly as populations age, and presents important methodological challenges for population health research. For example, the calculation of summary measures of population health (SMPH) can be compromised if co-morbidity is not taken into account. One popular co-morbidity adjustment used in SMPH computations relies on a straightforward multiplicative combination of the severity weights for the individual conditions involved. While the convenience and simplicity of the multiplicative model are attractive, its appropriateness has yet to be formally tested. The primary objective of the current study was therefore to examine the empirical evidence in support of this approach. METHODS: The present study drew on information on the prevalence of chronic conditions and a utility-based measure of health-related quality of life (HRQoL), namely the Health Utilities Index Mark 3 (HUI3), available from Cycle 1.1 of the Canadian Community Health Survey (CCHS; 2000-01). Average HUI3 scores were computed for both single and co-morbid conditions, and were also purified by statistically removing the loss of functional health due to health problems other than the chronic conditions reported. The co-morbidity rule was specified as a multiplicative combination of the purified average observed HUI3 utility scores for the individual conditions involved, with the addition of a synergy coefficient s for capturing any interaction between the conditions not explained by the product of their utilities. The fit of the model to the purified average observed utilities for the co-morbid conditions was optimized using ordinary least squares regression to estimate s. Replicability of the results was assessed by applying the method to triple co-morbidities from the CCHS cycle 1.1 database, as well as to double and triple co-morbidities from cycle 2.1 of the CCHS (2003-04). RESULTS: Model fit was optimized at s = .99 (i.e., essentially a straightforward multiplicative model). These results were closely replicated with triple co-morbidities reported on CCHS 2000-01, as well as with double and triple co-morbidities reported on CCHS 2003-04. CONCLUSION: The findings support the simple multiplicative model for computing utilities for co-morbid conditions from the utilities for the individual conditions involved. Future work using a wider variety of conditions and data sources could serve to further evaluate and refine the approach.

Fleming, P. J., D. Cade, et al. (1980). "Congenital central hypoventilation and sleep state." PEDIATRICS 66(3): 425-8.

Congenital central hypoventilation (Ondine's curse) is described in an infant with persistant symptoms throughout the first nine months of life. Respiratory control was most severely affected in quiet sleep, although abnormalities were present in rapid eye movement (REM) sleep and while awake. Failure of metabolic control in quiet sleep led to profound hypoventilation. Behavioral or "behavioral-like" inputs in the awake state and REM sleep increased ventilation, but not to expected normal levels. The ventilatory response to inhaled 4% CO2 was markedly depressed in all states.

Flora, A., H. Lucchetti, et al. (2001). "Sp proteins and Phox2b regulate the expression of the human Phox2a gene." JOURNAL OF NEUROSCIENCE 21(18): 7037-45.

Phox2a is a vertebrate homeodomain transcription factor that is involved in the specification of the autonomic nervous system. We have isolated the 5' regulatory region of the human Phox2a gene and studied the transcriptional mechanisms underlying its expression. We first identified the minimal gene promoter by means of molecular and functional criteria and demonstrated that its activity relies on a degenerate TATA box and a canonical Sp1 site. We then concentrated on the region immediately upstream of the promoter and found that it stimulates transcription in a neurospecific manner because its deletion caused a substantial decline in reporter gene expression only in neuronal cells. This DNA region contains a putative binding site for homeodomain transcription factors, and its mutation severely affects the transcriptional activity of the entire 5' regulatory region, thus indicating that this site is necessary for the expression of Phox2a in this cellular context. The use of the electrophoretic mobility shift assay showed that Phox2b/PMX2b is capable of specifically interacting with this site, and cotransfection experiments demonstrated that it is capable of transactivating the human Phox2a promoter. Many data obtained from knock-out mice support the hypothesis that Phox2a acts downstream of Phox2b during the development of most of the autonomic nervous system. We have provided the first molecular evidence that Phox2b can regulate the expression of Phox2a by directly binding to its 5' regulatory region.

Fodstad, H. (1989). "Pacing of the diaphragm to control breathing in patients with paralysis of central nervous system origin." Stereotactic & Functional Neurosurgery 53(4): 209-22.

Thirty-five patients, 21 males and 14 females, aged 2-69 years (mean 25 years) with partial or total respiratory paralysis due to high cervical cord lesions, brain stem lesions, or central hypoventilation syndrome (sleep apnoea, 'Ondine's curse'), received phrenic nerve stimulators for pacing of the diaphragm. At a mean follow-up time of 46 months (range 2 months to 10 years) 15 patients are entirely independent of respirator and 8 quadriplegics ventilate with pacers at different daytime intervals and use mechanical ventilators during the night. Five patients have stopped pacing and 7 additional cases have died of causes unrelated to electrophrenic stimulation.

Fodstad, H., B. Ljunggren, et al. (1990). "Ondine's curse with Hirschsprung's disease." BRITISH JOURNAL OF NEUROSURGERY 4(2): 87-93.

Hirschsprung's disease can be associated with other congenital abnormalities, some of which are neural in origin. A rare association is with congenital failure of automatic control of respiration--central hypoventilation syndrome, sleep apnoea or Ondine's curse. Patients with this combination tend to have a short life expectancy. Diaphragmatic pacing by electrophrenic stimulation has proven useful in management of patients with central hypoventilation. Three children, two females and one male, with this combination are described. The male child, who had total intestinal aganglionosis, died at the age of one month despite an ileostomy and nocturnal mechanical ventilation. The two females had aganglionosis more typical of Hirschsprung's disease, one requiring colostomy. At the ages of 2 and 6 years, respectively, phrenic nerve stimulators were implanted. Both girls remain independent of nocturnal, mechanical ventilation two and three years after commencement of diaphragm pacing. In patients with Ondine's curse and Hirschsprung's disease in whom the aganglionosis can be effectively managed, diaphragm pacing may lead to independence from mechanical ventilation and prolongation of life of an acceptable quality.

Folgering, H., F. Kuyper, et al. (1979). "Primary alveolar hypoventilation (Ondine's curse syndrome) in an infant without external arcuate nucleus. Case report." Bulletin Europeen de Physiopathologie Respiratoire 15(4): 659-65.

A five month old boy suffered from primary alveolar hypoventilation, with attacks of apnea during sleep (Ondine's curse syndrome). The ventilation did not increase when PACO2 was increased. However, it decreased during hyperoxia. This indicates a strong peripheral chemoreceptor drive and a dysfunction of the central chemoreception. The infant died from circulatory failure following an aspiration pneumonia. Autopsy revealed the absence of the external arcuate nucleus, which may be involved in the central chemocreception.

Fontana, G. A., F. Lavorini, et al. (2004). "Cough in children with congenital central hypoventilation syndrome." Pulmonary Pharmacology & Therapeutics 17(6): 425-9.

Congenital central hypoventilation syndrome (CCHS) is defined as failure of the chemical (autonomic) control of breathing causing alveolar hypoventilation in the absence of pulmonary, cardiac, neuromuscular or patent brainstem lesions. Hypoventilation is predominant in non-rapid-eye-movement sleep, during which breathing is primarily under chemical control. Failure of the central integration of chemosensory inputs is proposed as the putative defect. A genetic basis for CCHS is supported by lines of evidence. In some diseases of the central nervous system there is more or less complete depression of the cough reflex, whereas spontaneous ventilation is generally preserved. Little is known regarding cough in CCHS patients. Parents consistently report that their children cough 'normally' during airway infections; in contrast, experimental lines of evidence suggest that CCHS children lack a cough response following inhalation of a tussigenic agent. Although several factors may account for the discrepancy, the possibility of a weakened or even absent cough reflex remains to be fully ascertained. Conceivably, a defective cough reflex, in conjunction with the well established lack of perception of respiratory discomfort, might result in an increased risk of potentially serious respiratory complications in CCHS patients. [References: 52]

Forbes, D. A., D. Debra, et al. (2006). "Rural and urban canadians with dementia: use of health care services." Canadian Journal on Aging 25(3): 321-30.

The purpose of this research was to examine the characteristics of older Canadians with dementia (compared to those without dementia), their use of health care services, and the impact of place (rural/urban) on use of services. Andersen and Newman's Behavioural Model of Health Services Use (1973) guided the study. A cross-sectional design used data from the Canadian Community Health Survey (CCHS) Cycle 1.1 (N(1/4)49,995 older Canadians; those with dementia(1/4)313). Results indicated that among Canadian females between the ages of 50 and 64, those with dementia were more likely than those without dementia to live in rural areas. Among females 80 years of age and over, those with dementia had higher levels of education and income than those without dementia. In addition, a higher proportion of white than of visible minority Canadians was afflicted with dementia. The results further suggest that Canadians with dementia primarily required support services and that they were more likely than persons without dementia to report that their health care needs were unmet. It is recommended that publicly funded national home care programs be expanded to ensure that the supportive services needed by this population are available.

Foster, P. P., J. H. Williams, et al. (2010). "Recruitment of rural physicians in a diabetes internet intervention study: overcoming challenges and barriers." JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION 102(2): 101-7.

PURPOSE: This paper highlights a descriptive study of the challenges and lessons learned in the recruitment of rural primary care physicians into a randomized clinical trial using an Internet-based approach. METHODS: A multidisciplinary/multi-institutional research team used a multilayered recruitment approach, including generalized mailings and personalized strategies such as personal office visits, letters, and faxes to specific contacts. Continuous assessment of recruitment strategies was used throughout study in order to readjust strategies that were not successful. RESULTS: We recruited 205 primary care physicians from 11 states. The 205 lead physicians who enrolled in the study were randomized, and the overall recruitment yield was 1.8% (205/11231). In addition, 8 physicians from the same practices participated and 12 nonphysicians participated. The earlier participants logged on to the study Web site, the greater yield of participation. Most of the study participants had logged on within 10 weeks of the study. CONCLUSION: Despite successful recruitment, the 2 major challenges in recruitment in this study included defining a standardized definition of rurality and the high cost of chart abstractions. Because many of the patients of study recruits were African American, the potential implications of this study on the field of health disparities in diabetes are important.

Medical Subject Headings (MeSH) Diabetes Mellitus [*therapy]; Education, Medical, Continuing [organization & administration]; Guidelines as Topic; Internet; *Patient Selection; *Physician's Practice Patterns [standards]; Primary Health Care [standards]; Program Development; *Rural Health; Rural Population; United States

Frikke-Schmidt, R., B. G. Nordestgaard, et al. (2008). "Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease." JAMA 299(21): 2524-32.

CONTEXT: Low levels of high-density lipoprotein (HDL) cholesterol are inversely related to cardiovascular risk. Whether this is a causal effect is unclear. OBJECTIVE: To determine whether genetically reduced HDL cholesterol due to heterozygosity for 4 loss-of-function mutations in ABCA1 cause increased risk of ischemic heart disease (IHD). DESIGN, SETTING, AND PARTICIPANTS: Three studies of white individuals from Copenhagen, Denmark, were used: the Copenhagen City Heart Study (CCHS), a 31-year prospective general population study (n = 9022; 28 heterozygotes); the Copenhagen General Population Study (CGPS), a cross-sectional general population study (n = 31,241; 76 heterozygotes); and the Copenhagen Ischemic Heart Disease Study (CIHDS), a case-control study (n = 16,623; 44 heterozygotes). End points in all 3 studies were recorded during the period of January 1, 1976, through July 9, 2007. MAIN OUTCOME MEASURES: Levels of HDL cholesterol in the general population, cellular cholesterol efflux, and the association between IHD and HDL cholesterol and genotype. RESULTS: Heterozygotes vs noncarriers for 4 ABCA1 mutations (P1065S, G1216V, N1800H, R2144X) had HDL cholesterol levels of 41 mg/dL (interquartile range, 31-50 mg/dL) vs 58 mg/dL (interquartile range, 46-73 mg/dL), corresponding to a reduction in HDL cholesterol of 17 mg/dL (P < .001). A 17-mg/dL lower HDL cholesterol level in the CCHS was associated with a multifactorially adjusted hazard ratio for IHD of 1.70 (95% confidence interval [CI], 1.57-1.85). However, for IHD in heterozygotes vs noncarriers, the multifactorially adjusted hazard ratio was 0.67 (95% CI, 0.28-1.61; 1741 IHD events) in the CCHS, the multifactorially adjusted odds ratio was 0.82 (95% CI, 0.34-1.96; 2427 IHD events) in the CGPS, and the multifactorially adjusted odds ratio was 0.86 (95% CI, 0.32-2.32; 2498 IHD cases) in the CIHDS. The corresponding odds ratio for IHD in heterozygotes vs noncarriers for the combined studies (n = 41,961; 6666 cases; 109 heterozygotes) was 0.93 (95% CI, 0.53-1.62). CONCLUSION: Lower plasma levels of HDL cholesterol due to heterozygosity for loss-of-function mutations in ABCA1 were not associated with an increased risk of IHD.
Fruhmann, G. (1972). "Hypersomnia with primary hypoventilation syndrome and following cor pulmonale (Ondine's curse syndrome)." Bulletin de Physio-Pathologie Respiratoire 8(5): 1173-9.