'No thanks'-reasons why pregnant women declined an offer of cystic fibrosis carrier screening.

The objective of this study was to assess attitudes and opinions of women declining the offer of cystic fibrosis (CF) carrier screening through a population-based programme in Victoria, Australia. Between December 2009 and May 2011, women declining an offer of CF carrier screening were invited to participate in a questionnaire-based study. Recruitment was at two private obstetric ultrasound clinics and two private obstetric practices in Melbourne. Of the participants (n = 54), the majority were well educated (76%), aged 30-34 years (54%), with a household income of >AUD$100,000 (76%). Compared to those who accepted screening (reported in a previous study) (Ioannou et al., Public Health Genomics 13:449-56, 2010), knowledge levels were significantly lower in participants declining screening (t = 3.32, p < 0.01). The main reasons for declining screening were having no family history of CF (58%) and not considering a termination of pregnancy for CF (53%). Providers and consumers should be informed that most children born with autosomal-recessive conditions such as CF have no family history of the condition.

Improved quality of life over one year is associated with improved adherence in patients with schizophrenia.

AIM: Quality of life (QoL) is increasingly considered an important outcome in health research. We wished to explore the determinants of change in QoL in patients with schizophrenia over the course of a one-year RCT. METHODS: Predictors of change in observer-rated QoL (Quality of Life Scale: QLS) were assessed in 363 patients with schizophrenia during the CUtLASS clinical trial. RESULTS: Change in QLS score over the course of a year correlated with change in psychotic and depressive symptoms and treatment adherence. Linear regression showed that improvement in QoL was predicted by reduction in negative and depressive symptoms and improvement in adherence rating. These three change scores together explained 38% of the variance in QLS change. Exploration of the direction of any possible causal effect, using TETRAD, indicated that improved adherence leads to improved QoL, and that change in depression also leads to QoL change. The relationship between QoL and negative symptoms suggests that greater social activity (reflected as better QoL scores) improves negative symptoms. Such a direct relationship between treatment adherence and QoL has not been reported before. CONCLUSION: Improving adherence to medication would appear to be a key approach to improving measured quality of life in people with schizophrenia.

Evaluation of a multi-disease carrier screening programme in Ashkenazi Jewish high schools.

A screening programme for Tay Sachs disease (TSD) carrier status was introduced in high schools in Victoria, Australia in 1997, and was expanded to screen for six other genetic conditions common in the Ashkenazi Jewish population in 2008. The aim of this study was to evaluate the current programme and compare it with an evaluation of the programme when screening was offered for TSD alone. All students from Jewish high schools in Melbourne who offered the programme in 2009 were invited to participate in the study. A purpose-designed questionnaire explored the following domains: knowledge (disease and genetics), reasons for screening, anxiety, and predicted negative feelings if found to be a carrier. Two hundred and seventy-three students were offered screening, and 272 (99.6%) completed the questionnaire. Only two students chose not to have screening. Two hundred and seventy-one students were in the penultimate year of high school (99.6%) and 222 were of Ashkenazi Jewish descent (82.5%). The main reasons for choosing screening were the desire to know carrier status and convenience. Knowledge level decreased and negative feelings increased in the current cohort compared to that when screening was offered for TSD alone. We conclude that the current programme is efficient, although increasing the number of conditions resulted in a decrease in knowledge and increase in predicted negative feelings if found to be a carrier of one of the conditions. This has implications for multi-disease screening programmes that will increase in frequency as more conditions can be screened for and costs diminish.

Hypoalbuminemia and lymphocytopenia in patients with decompensated biventricular failure.

BACKGROUND: In patients hospitalized with decompensated biventricular failure having hypoalbuminemia and lymphocytopenia without underlying hepatic or renal disease, we addressed the presence of a protein-losing enteropathy (PLE). METHODS: We studied 78 patients having a dilated cardiomyopathy, who were hospitalized with congestive heart failure (CHF) and hypoalbuminemia of uncertain origin. In the first 19 patients, we investigated the presence of PLE using Tc-Dex scintigraphy together with serum albumin 2 to 4 weeks later when compensation had been restored. In the next 59 patients, presenting with reduced serum albumin and relative lymphocyte count at admission, these parameters were again monitored (2-4 weeks) later when symptoms and signs of CHF had resolved. RESULTS: PLE, documented by Tc-Dex(70) scintigraphy, was found in 10 of 19 patients and whose hypoalbuminemia (2.7 +/- 0.1 g/dL, mean +/- standard error of mean) were corrected (3.3 +/- 0.1 g/dL; P < 0.05) with the resolution of CHF, whereas in the 9 patients without a PLE, reduced baseline serum albumin (2.6 +/- 0.1 g/dL) failed to improve on follow-up (2.6 +/- 0.2 g/dL) in keeping with malnutrition. Relative lymphocyte count was reduced (14.6 +/- 1.5%) in patients with PLE but was normal (21.4 +/- 3.3%; P < 0.05) in those without PLE. Serum albumin and relative lymphocyte count were each reduced at admission (2.8 +/- 0.1 g/dL and 14.4 +/- 1.0%, respectively) in 59 patients and increased (P < 0.05) to normal values (3.5 +/- 0.1 g/dL and 24.9 +/- 1.0%) 2 to 4 weeks after they were compensated. CONCLUSIONS: Enteral losses of albumin and lymphocytes account for the reversible hypoalbuminemia and lymphocytopenia found in patients hospitalized with CHF having splanchnic congestion.

Population-based genetic screening for cystic fibrosis: attitudes and outcomes.

A population-based cystic fibrosis (CF) carrier screening program was introduced in Victoria, Australia in 2006, and was offered to couples planning a pregnancy or in early pregnancy for a fee. Individuals received pre-test advice from their doctor and through a brochure. Carriers identified received genetic counseling. The aim of this study was to assess the attitudes of people undertaking screening. Between January 2006 and June 2008 all carriers (n = 79) and a randomly selected cohort of non-carriers (n = 162) were invited to participate. A purpose-designed questionnaire explored the following domains: knowledge, recollection and meaning of carrier status, reasons for having screening, anxiety and communication of results to family members. Forty-seven carriers (62%) and 65 non-carriers (41%) returned the questionnaire. Most participants were female (97%) aged 35-39 (46%). The main reasons for choosing screening were the perception of CF as a severe condition and a doctor's recommendation. All carriers correctly recalled their carrier status and the risk of having a child with CF, while 3 non-carriers (4.7%) were unsure of their carrier status and 12 (22%) incorrectly recalled their residual risk. Carriers answered the knowledge questions correctly more often than non-carriers. There was no difference in anxiety between carriers and non-carriers. The majority of carriers informed relatives of their increased risk of being a carrier. We conclude that participants' attitude towards carrier screening for CF was generally very positive. Our model of screening could be applied on a larger scale.

Treatment of acne with oral isotretinoin in patients with cystic fibrosis.

BACKGROUND: Theoretical concerns about liver disease and vitamin A deficiency have limited the use of oral isotretinoin for troublesome acne in adolescents with cystic fibrosis. METHODS: Oral isotretinoin was administered to nine patients with cystic fibrosis who had troublesome acne unresponsive to antibiotics. All patients were followed for 1-4 years after cessation of treatment. RESULTS: Isotretinoin treatment cleared active acne lesions in all patients. It was well tolerated, and no patient had significant side effects. All nine patients were pleased or delighted with the improvement in their skin. CONCLUSIONS: Adolescents with cystic fibrosis and acne can be treated with oral isotretinoin. Oral isotretinoin should be considered for adolescents with cystic fibrosis who have acne associated with scarring, acne not clearing with topical and antibiotic treatment, acne associated with depression or severe cystic acne.

Problem behaviours and parenting in preschool children with cystic fibrosis.

BACKGROUND: Problems with sleep, eating and adherence to therapy may adversely affect health outcomes in children with cystic fibrosis (CF). Data on the prevalence of such problems, associated parenting styles and caregiver mental health are limited. AIMS: To determine: (a) the prevalence of sleep, mealtime, therapy adherence and externalising and internalising behavioural problems in preschool children with CF; (b) the prevalence of caregiver mental health problems and poor sleep quality; and (c) associations between child behavioural problems and parenting styles. METHODS: This was a cross sectional survey of caregivers of children aged 6 months to 5 years attending CF outpatient clinics at Royal Children's Hospital (Melbourne), Monash Medical Centre (Melbourne) and Sydney Children's Hospital. Main outcome measures were child externalising and internalising behaviours, sleep, eating and adherence with therapy; the predictor was parenting styles (harsh, inconsistent, overprotective). RESULTS: 117 of 139 families participated. Problems were common with child sleep (small PROBLEM: 31.6%; moderate/large problem: 21.9%), eating (32.4%) and adherence with physiotherapy (50.4%). Compared to normative data, sleep and mealtime problems were more prevalent. Caregivers reported high rates of symptoms indicating depression (33.3%), anxiety (16.4%) and stress (34.2%). Harsh parenting was associated with internalising behaviours (adjusted OR 3.9, 95% CI 1.16 to 13.17, p = 0.03). CONCLUSIONS: Problems with sleeping, eating and physiotherapy adherence were common in preschool children with CF. Caregivers reported high rates of symptoms indicative of mental health problems. Harsh parenting was associated with internalising problems. An intervention targeting child problem behaviours and parental mental health would be appropriate for CF families.

Antibiotics for whooping cough (pertussis).

BACKGROUND: Whooping cough is a highly contagious disease. Infants are at highest risk of severe disease and death. Erythromycin for 14 days is currently recommended for treatment and contact prophylaxis, but is of uncertain benefit. OBJECTIVES: To study the benefits and risks of antibiotic treatment of and contact prophylaxis against whooping cough. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library Issue 1, 2007); MEDLINE (January 1966 to March 2007); EMBASE (January 1974 to March 2007). SELECTION CRITERIA: All randomised and quasi-randomised controlled trials of antibiotics for treatment of, and contact prophylaxis against, whooping cough. DATA COLLECTION AND ANALYSIS: Three to four review authors independently extracted data and assessed the quality of each trial. MAIN RESULTS: Thirteen trials with 2197 participants met the inclusion criteria: 11 trials investigated treatment regimens; 2 investigated prophylaxis regimens. The quality of the trials was variable.Short-term antibiotics (azithromycin for three to five days, or clarithromycin or erythromycin for seven days) were as effective as long-term (erythromycin for 10 to 14 days) in eradicating Bordetella pertussis (B. pertussis) from the nasopharynx (relative risk (RR) 1.02, 95% confidence interval (CI) 0.98 to 1.05), but had fewer side effects (RR 0.66, 95% CI 0.52 to 0.83). Trimethoprim/sulfamethoxazole for seven days was also effective. Nor were there differences in clinical outcomes or microbiological relapse between short and long-term antibiotics. Contact prophylaxis of contacts older than six months of age with antibiotics did not significantly improve clinical symptoms or the number of cases developing culture-positive B. pertussis. AUTHORS' CONCLUSIONS: Although antibiotics were effective in eliminating B. pertussis, they did not alter the subsequent clinical course of the illness. There is insufficient evidence to determine the benefit of prophylactic treatment of pertussis contacts.

Lung contusion from focal low-moderate chest trauma.

Apparently minor chest trauma may result in localized pulmonary contusion. Complications of the contusion, particularly infection, may be delayed. The association between the infection and initial injury may not be appreciated due to the time frame between the injury and clinical presentation. We report two cases of low-moderate impact pulmonary trauma resulting in focal pulmonary contusion, complicated by infection.

Markedly elevated neonatal immunoreactive trypsinogen levels in the absence of cystic fibrosis gene mutations is not an indication for further testing.

AIMS: To investigate the immunoreactive trypsinogen (IRT) values above the usual 99th centile laboratory cut-off and determine the value of offering further testing to those infants with a markedly elevated IRT but no cystic fibrosis transmembrane regulator (CFTR) gene mutation identified by the screening programme. METHODS: All babies born in Victoria, Australia, between 1991 and 2003, were screened by IRT followed by CF gene mutation analysis. RESULTS: Of the 806,520 babies born, 9268 with the highest IRT levels had CFTR mutation analysis. There were 123 DeltaF508 homozygotes and 703 heterozygotes (86 with CF, 617 carriers). A total of 8442 babies had no CFTR gene mutation, of whom 18 (0.21%) had CF. The total number of CF babies with IRT greater than the laboratory cut-off was 227 (2.4%). The IRT results of the CF patients were distributed normally, with the majority above the laboratory cut-off of newborn IRT results. There was no evidence of an excess of babies with CF in the very highest levels of IRT above the 99th centile. CONCLUSIONS: Only a small proportion of babies with a neonatal IRT >99th centile have CF. Additional CF testing for infants with an elevated IRT but no CFTR gene mutation has an extremely low yield, no matter how high the IRT result.

Antibiotics for whooping cough (pertussis).

BACKGROUND: Whooping cough is a highly contagious disease. Infants are the population at highest risk of severe disease and death. Erythromycin for 14 days is recommended for treatment and contact prophylaxis but this regime is considered inconvenient and prolonged. The value of contact prophylaxis is uncertain. OBJECTIVES: To study the benefits and risks of antibiotic treatment of and contact prophylaxis against whooping cough. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2004); MEDLINE (January 1966 to February 2004); EMBASE (January 1974 to August 2003); conference abstracts and reference lists of articles were searched. Study investigators and pharmaceutical companies were approached for additional information (published or unpublished studies). There were no constraints based on language or publication status. SELECTION CRITERIA: All randomised and quasi-randomised controlled trials of antibiotics for treatment of and contact prophylaxis against whooping cough were included in the systematic review. DATA COLLECTION AND ANALYSIS: At least three reviewers independently extracted data and assessed the quality of each trial. MAIN RESULTS: Twelve trials with 1,720 participants met the inclusion criteria. Ten trials investigated treatment regimens and two investigated prophylaxis regimens. The quality of the trials was variable. Results showed that short-term antibiotics (azithromycin for three days, clarithromycin for seven days, or erythromycin estolate for seven days) were equally effective with long-term antibiotic treatment (erythromycin estolate or erythromycin for 14 days) in the microbiological eradication of Bordetella pertussis (B. pertussis) from the nasopharynx. The relative risk (RR) was 1.02 (95% confidence interval (CI) 0.98 to 1.05). Side effects were fewer with short-term treatment (RR 0.66; 95% CI 0.52 to 0.83). There were no differences in clinical improvement or microbiological relapse between short and long-term treatment regimens. Contact prophylaxis (of contacts older than six months of age) with antibiotics did not significantly improve clinical symptoms or the number of cases that developed culture positive B. pertussis. AUTHORS' CONCLUSIONS: Antibiotics are effective in eliminating B. pertussis from patients with the disease, rendering them non-infectious, but do not alter the subsequent clinical course of the illness. Effective regimens include: three days of azithromycin, seven days of clarithromycin, seven or 14 days of erythromycin estolate, and 14 days of erythromycin ethylsuccinate. Considering microbiological clearance and side effects, three days of azithromycin or seven days of clarithromycin are the best regimens. Seven days of trimethoprim/sulfamethoxazole also appeared to be effective for the eradication of B. pertussis from the nasopharynx and may serve as an alternative antibiotic treatment for patients who cannot tolerate a macrolide. There is insufficient evidence to determine the benefit of prophylactic treatment of pertussis contacts.

Implementation of evidence based guidelines for paediatric asthma management in a teaching hospital.

AIMS: To evaluate a systematic approach to the development and implementation of evidence based asthma management guidelines. METHODS: Comparative study of children (2-18 years) with acute asthma; a control cohort (cohort 1) was recruited before implementation of the guidelines and two cohorts were recruited after implementation (cohorts 2 and 3). RESULTS: There was no difference in the proportion of patients who reattended in the six months following initial presentation for cohort 1 (21.5%), cohort 2 (27.8%), or cohort 3 (25.4%) and no difference in readmission rates (11.4%, 11.3%, 11.0% respectively). There was no difference in measures of asthma morbidity between the cohorts at 3 and 6 months across three domains: interval symptoms, exercise limitation, and bronchodilator use. Of those who did not have a management plan before presentation, one was provided to 46.9% of cohort 1, 74.8% of cohort 2, and 81.1% of cohort 3. There was no difference comparing cohort 2 or cohort 3 with cohort 1 regarding quality of life for either the subjects or their parents. CONCLUSIONS: Implementation of our evidence based guidelines was associated with the improved provision of asthma management plans, but there was no effect on reattendance or readmission to hospital, asthma morbidity, or quality of life. Future efforts to improve asthma management should target specific components of asthma care.

Genetic counselling after carrier detection by newborn screening when one parent carries DeltaF508 and the other R117H.

Newborn screening (NBS) for cystic fibrosis (CF) has been carried out in Victoria, Australia since 1989. The primary screen is immunoreactive trypsinogen (IRT) followed by DeltaF508 mutation analysis. As part of this process, carrier babies are detected and their parents are routinely offered carrier testing as part of their follow up. The DeltaF508 parent is identified and the other parent has an extended mutation analysis performed in case they are also a carrier. One of the mutations in the extended analysis is R117H which is associated with a broad phenotypic range, from CF with suppurative lung disease, to no clinical disease. We present four healthy DeltaF508 carrier babies identified by our NBS service with both parents identified as carriers, one DeltaF508 and the other R117H. Owing to the variable phenotype associated with R117H we have developed an approach to this difficult genetic counselling situation. Centres offering or considering NBS for CF will need an approach to this problem.

A morphologic, biochemical, and biomechanical assessment of short-term effects of osteochondral autograft plug transfer in an animal model.

PURPOSE: The objective of this study was to assess the short-term changes that occur after an osteochondral autograft plug transfer from the femoral trochlea to the medial femoral condyle in a goat model. TYPE OF STUDY: Articular cartilage repair animal study. METHODS: Six adult male goats were used in this study. Two 4.5-mm osteochondral plugs were transferred from the superolateral femoral trochlea to 2 recipient sites in the central portion of the medial femoral condyle for a survival period of 12 weeks. Postmortem, the global effects of the procedure were assessed by gross morphologic inspection and by analyzing the synovial DNA for inflammatory response. The recipient sites were also evaluated histologically and biomechanically. Metabolic activity was determined by (35)SO(4) uptake, and viability was assessed using a live/dead stain and by confocal laser microscopy. RESULTS: There was no evidence of significant gross morphologic or histologic changes in the operative knee as a result of the osteochondral donor or recipient sites. The patella, tibial plateau, and medial meniscus did not show any increased degenerative changes as a result of articulating against the donor or recipient sites of the osteochondral autografts. Analysis of synovial DNA revealed no inflammatory response. Biomechanically, 6- to 7-fold greater stiffness was noted in the cartilage of the transferred plugs compared with the control medial femoral condyle. Furthermore, on histologic examination, the healing subchondral bone interface at the recipient site had increased density. Glycosaminoglycan synthesis as determined by (35)SO(4) uptake was upregulated in the transplanted cartilage plug relative to the contralateral control, showing a repair response at the site of implantation. And finally, confocal microscopy showed 95% viability of the transferred plugs in the medial femoral condyle region. CONCLUSIONS: Our findings demonstrate the ability to successfully transfer an osteochondral autograft plug with maintenance of chondrocyte cellular viability. The transferred cartilage is stiffer than the control medial femoral condyle cartilage, and there is concern regarding the increased trabecular mass in the healing subchondral plate, but these do not result in increased degenerative changes of the opposing articular surfaces in the short term.

Anatomic and biomechanical analysis of the lower lumbar foraminal ligaments.

STUDY DESIGN: An anatomic cadaveric study to characterize the lumbar intraforaminal nerve root attachments. OBJECTIVES: To characterize the intraforaminal nerve root attachments and describe their anatomic relationships and biomechanical properties. SUMMARY OF BACKGROUND DATA: Observations during foraminotomies for lateral recess stenosis as well as lateral approaches for far lateral disc herniation have shown dense attachments between the nerve root and adjacent structures. Little or no information has appeared in the literature describing intraforaminal nerve root attachments. METHODS: Twelve fresh-frozen human cadaveric lumbar spines were used to study intraforaminal ligamentous structures. Four cadavers were cut into sagittal sections for qualitative description, and eight were used for biomechanical testing. Histologic analyses were performed on samples of the foraminal attachments to assure that they were not vascular or neural structures. Biomechanical testing of the nerve roots with ligamentous attachments was performed measuring load to failure along the anatomic axis of the root. RESULTS: The dissections showed four distinct bands extending radially from the nerve root sleeve. The most prominent nerve root attachment was to the facet capsule posteriorly. Other ligaments fanned out with attachments inferiorly and superiorly to the adjacent pedicles and anteriorly to the intervertebral disc. Biomechanical study of the L3, L4, and L5 nerve roots showed a significant increase in strength at failure with axial traction, progressing from L3 to L5. CONCLUSIONS: The results demonstrate that these foraminal ligaments are normal anatomic structures within the intervertebral foramen of the lumbar spine. In addition, they may play a role in limiting motion along the nerve root.

Bronchial granuloma - where's the foreign body?

Airway masses are uncommon in children. The majority of bronchial tumors are granulomata secondary to an inhaled foreign body. However, other rare diseases like primary bronchopulmonary tumors should always be considered in the evaluation of a bronchial granuloma in children. The differential diagnosis of bronchial granuloma is presented. We report a 7-year-old girl with a 3-year history of recurrent cough and fevers who was found to have a bronchial granuloma in the left upper lobe bronchus. The diagnosis of foreign body-related granuloma was eventually made after combined and repeated rigid and flexible bronchoscopy. This case highlights the need to search aggressively for a foreign body in the presence of an airway granuloma in children, even in the absence of a history of aspiration.

Sweat testing following newborn screening for cystic fibrosis.

Sweat testing remains the "gold standard" for the diagnosis of cystic fibrosis (CF) and is a critical component of newborn screening programs. We retrospectively reviewed sweat test results reported to a neonatal screening program for CF with respect to completeness of reported results and the values recorded for sweat chloride (Cl(-)) and sodium (Na(+)) concentrations and the Cl(-):Na(+) ratio in screened infants. Thirty-nine of 85 DeltaF508 homozygous (DeltaF508/DeltaF508) and 270 of 274 DeltaF508 heterozygous (DeltaF508/-) infants had sweat tests reported to the screening program. Of those, 30 and 213 sweat test reports, respectively, were complete, i.e., sweat weight, sweat chloride, and sodium were reported. Three centers accounted for 37 of 68 (54%) incomplete results, and 4 centers performed 4 or less post-screening sweat tests in the study period. There were 6 DeltaF508 heterozygous infants with sweat Cl(-) concentrations of 40-60 mmol/L and 4 had CF confirmed by additional genotyping (n = 2) or clinical and repeat sweat Cl results (n = 2). Forty-one percent of DeltaF508/-infants with sweat Cl(-) <40 mmol/L had Cl:Na >1. We conclude that the reporting of incomplete sweat tests is common following newborn screening for CF. Infants with sweat Cl(-) levels of 40-60 mmol/L require further investigation and review, but they almost certainly have CF. The Cl(-):Na(+) ratio does not appear useful in establishing a diagnosis of CF in infants.