Randomised controlled trial of perinatal vitamin D supplementation to prevent early-onset acute respiratory infections among Australian First Nations children: the 'D-Kids' study protocol.

INTRODUCTION: Globally, acute respiratory infections (ARIs) are a leading cause of childhood morbidity and mortality. While ARI-related mortality is low in Australia, First Nations infants are hospitalised with ARIs up to nine times more often than their non-First Nations counterparts. The gap is widest in the Northern Territory (NT) where rates of both acute and chronic respiratory infection are among the highest reported in the world. Vitamin D deficiency is common among NT First Nations neonates and associated with an increased risk of ARI hospitalisation. We hypothesise that perinatal vitamin D supplementation will reduce the risk of ARI in the first year of life. METHODS AND ANALYSIS: 'D-Kids' is a parallel (1:1), double-blind (allocation concealed), randomised placebo-controlled trial conducted among NT First Nations mother-infant pairs. Pregnant women and their babies (n=314) receive either vitamin D or placebo. Women receive 14 000 IU/week or placebo from 28 to 34 weeks gestation until birth and babies receive 4200 IU/week or placebo from birth until age 4 months. The primary outcome is the incidence of ARI episodes receiving medical attention in the first year of life. Secondary outcomes include circulating vitamin D level and nasal pathogen prevalence. Tertiary outcomes include infant immune cell phenotypes and challenge responses. Blood, nasal swabs, breast milk and saliva are collected longitudinally across four study visits: enrolment, birth, infant age 4 and 12 months. The sample size provides 90% power to detect a 27.5% relative reduction in new ARI episodes between groups. ETHICS AND DISSEMINATION: This trial is approved by the NT Human Research Ethics Committee (2018-3160). Study outcomes will be disseminated to participant families, communities, local policy-makers, the broader research and clinical community via written and oral reports, education workshops, peer-reviewed journals, national and international conferences. TRIAL REGISTRATION NUMBER: ACTRN12618001174279.

Listening to First Nations women's voices, hearing requests for continuity of carer, trusted knowledge and family involvement: A qualitative study in urban Darwin.

PROBLEM: Australian First Nations women are more likely to commence care later in pregnancy and underutilise maternal health services than non-First Nations women. BACKGROUND: Disrespectful maternity care is a major barrier to care-seeking in pregnancy, often resulting in later commencement and underutilisation of care. AIM: We aimed to identify barriers and enablers to pregnancy-related care-seeking for Australian First Nations women living in the Darwin region through yarning about their experiences of pregnancy care. METHODS: Ten Australian First Nations women shared stories about their pregnancy care journeys. Yarns took place at a time and location determined by the women, with recruitment continuing until saturation was reached. FINDINGS: Emerging themes included a desire for continuity of carer, particularly with midwives; access to trustworthy information, enabling informed decision-making; and a need to have family involved in all aspects of care. No specific barriers were identified within this cohort DISCUSSION: Universal access to continuity of carer models would provide women with the relational care they are asking for as well as address other identified needs, such as a desire for information relevant to their pregnancy; and space for partners/family members to be involved. The themes that emerged provide a picture of what a positive, respectful pregnancy care experience could be for First Nations women within the Darwin Region, thus enabling care-seeking in pregnancy. CONCLUSION: Although the public sector and Aboriginal Controlled Community Health Organisations currently provide continuity of carer models, robust systems ensuring these models are made available to all women are lacking.

Vitamin K supplementation for cystic fibrosis.

BACKGROUND: Malabsorption and deficiency of fat-soluble vitamins K may occur in cystic fibrosis, a genetic disorder affecting multiple organs. Vitamin K is known to play an important role in both blood coagulation and bone formation, hence the role of supplementation of vitamin K in this category needs to be reviewed. This is an updated version of the review. OBJECTIVES: To assess the effects of vitamin K supplementation in people with cystic fibrosis and to investigate the hypotheses that vitamin K will decrease deficiency-related coagulopathy, increase bone mineral density, decrease risk of fractures and improve quality of life in people with CF. Also to determine the optimal dose and route of administration of vitamin K for people with CF (for both routine and therapeutic use). SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 12 August 2019. SELECTION CRITERIA: Randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in patients with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two authors independently screened papers, extracted trial details and assessed their risk of bias. The quality of the evidence was assessed using the GRADE criteria. MAIN RESULTS: Three trials (total 70 participants, aged 8 to 46 years) assessed as having a moderate risk of bias were included. One trial compared vitamin K to placebo, a second to no supplementation and the third compared two doses of vitamin K. No trial in either comparison reported our primary outcomes of coagulation and quality of life or the secondary outcomes of nutritional parameters and adverse events. Vitamin K versus control Two trials compared vitamin K to control, but data were not available for analysis. One 12-month trial (n = 38) compared 10 mg vitamin K daily or placebo in a parallel design and one trial (n = 18) was of cross-over design with no washout period and compared 5 mg vitamin K/week for four-weeks to no supplementation for four-weeks. Only the 12-month trial reported on the primary outcome of bone formation; we are very uncertain whether vitamin K supplementation has any effect on bone mineral density at the femoral hip or lumbar spine (very low-quality evidence). Both trials reported an increase in serum vitamin K levels and a decrease in undercarboxylated osteocalcin levels. The cross-over trial also reported that levels of proteins induced by vitamin K absence (PIVKA) showed a decrease and a return to normal following supplementation, but due to the very low-quality evidence we are not certain that this is due to the intervention. High-dose versus low-dose vitamin K One parallel trial (n = 14) compared 1 mg vitamin K/day to 5 mg vitamin K/day for four weeks. The trial did report that there did not appear to be any difference in serum undercarboxylated osteocalcin or vitamin K levels (very low-quality evidence). While the trial reported that serum vitamin K levels improved with supplementation, there was no difference between the high-dose and low-dose groups. AUTHORS' CONCLUSIONS: There is very low-quality evidence of any effect of vitamin K in people with cystic fibrosis. While there is no evidence of harm, until better evidence is available the ongoing recommendations by national CF guidelines should be followed.

Antimicrobial susceptibility and impact of macrolide antibiotics on Moraxella catarrhalis in the upper and lower airways of children with chronic endobronchial suppuration.

INTRODUCTION: Moraxella catarrhalis is an important but insufficiently studied respiratory pathogen. AIM: To determine antibiotic susceptibility and impact of recent antibiotics on M. catarrhalis from children with chronic endobronchial suppuration. METHODOLOGY: We cultured nasopharyngeal (NP) swabs and bronchoalveolar lavage (BAL) fluids collected from children who were prospectively enrolled in studies of chronic cough and had flexible bronchoscopy performed. Recent ß-lactam or macrolide antibiotic use was recorded. M. catarrhalis isolates stored at -80 °C were re-cultured and susceptibility determined to a range of antibiotics including the macrolide antibiotic erythromycin. RESULTS: Data from concurrently collected NP and BAL specimens were available from 547 children (median age 2.4 years) enrolled from 2007 to 2016. M. catarrhalis NP carriage was detected in 149 (27  %) children and lower airway infection (≥104 c.f.u. ml-1 BAL) in 67 (12  %) children. In total, 91  % of 222 M. catarrhalis isolates were ß-lactamase producers, and non-susceptibility was high to benzylpenicillin (98 %), cefaclor (39 %) and cotrimoxazole (38 %). Overall, >97  % isolates were susceptible to cefuroxime, chloramphenicol, erythromycin and tetracycline; three isolates were erythromycin-resistant (MIC >0.5 mg l-1). Recent macrolide antibiotics (n=152 children, 28 %) were associated with significantly reduced M. catarrhalis carriage and lower airway infection episodes compared to children who did not receive macrolides; odds ratios 0.19 (95  % CI 0.10-0.35) and 0.15 (0.04-0.41), respectively. CONCLUSION: Despite the frequent use of macrolides, few macrolide-resistant isolates were detected. This suggests a fitness cost associated with macrolide resistance in M. catarrhalis. Macrolide antibiotics remain an effective choice for treating M. catarrhalis lower airway infection in children with chronic endobronchial suppuration.

Paediatric and adult bronchiectasis: Monitoring, cross-infection, role of multidisciplinary teams and self-management plans.

Bronchiectasis is a chronic lung disease associated with structurally abnormal bronchi, clinically manifested by a persistent wet/productive cough, airway infections and recurrent exacerbations. Early identification and treatment of acute exacerbations is an integral part of monitoring and annual review, in both adults and children, to minimize further damage due to infection and inflammation. Common modalities used to monitor disease progression include clinical signs and symptoms, frequency of exacerbations and/or number of hospital admissions, lung function (forced expiratory volume in 1 s (FEV1 )% predicted), imaging (radiological severity of disease) and sputum microbiology (chronic infection with Pseudomonas aeruginosa). There is good evidence that these monitoring tools can be used to accurately assess severity of disease and predict prognosis in terms of mortality and future hospitalization. Other tools that are currently used in research settings such as health-related quality of life (QoL) questionnaires, magnetic resonance imaging and lung clearance index can be burdensome and require additional expertise or resource, which limits their use in clinical practice. Studies have demonstrated that cross-infection, especially with P. aeruginosa between patients with bronchiectasis is possible but infrequent. This should not limit participation of patients in group activities such as pulmonary rehabilitation, and simple infection control measures should be carried out to limit the risk of cross-transmission. A multidisciplinary approach to care which includes respiratory physicians, chest physiotherapists, nurse specialists and other allied health professionals are vital in providing holistic care. Patient education and personalized self-management plans are also important despite limited evidence it improves QoL or frequency of exacerbations.

Vitamin A and beta (ß)-carotene supplementation for cystic fibrosis.

BACKGROUND: People with cystic fibrosis (CF) and pancreatic insufficiency are at risk of a deficiency in fat-soluble vitamins, including vitamin A. Vitamin A deficiency predominantly causes eye and skin problems, while excessive levels of vitamin A can harm the respiratory and skeletal systems in children and interfere with the metabolism of other fat-soluble vitamins. Most CF centres administer vitamin A as supplements to reduce the frequency of vitamin A deficiency in people with CF and to improve clinical outcomes such as growth, although the recommended dose varies between different guidelines. Thus, a systematic review on vitamin A and vitamin A-like supplementation (carotenes or other retinoids) in people with CF would help guide clinical practice. This is an update of an earlier Cochrane Review. OBJECTIVES: To determine if supplementation with vitamin A, carotenes or other retinoid supplements in children and adults with CF reduces the frequency of vitamin A deficiency disorders, improves general and respiratory health and affects the frequency of vitamin A toxicity. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register compiled from electronic database searches and handsearching of journals and conference abstract books. Additionally we searched several ongoing trials registries, including ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform and the International Standard Randomised Controlled Trial Number Registry.Most recent database searches: 01 June 2018. SELECTION CRITERIA: All randomised or quasi-randomised controlled studies comparing all preparations of oral vitamin A, carotenes or retinoids (or in combination), used as a supplement compared to placebo at any dose, for at least three months, in people with CF (diagnosed by sweat tests or genetic testing) with and without pancreatic insufficiency. DATA COLLECTION AND ANALYSIS: Two authors individually assessed study quality and extracted data on outcome measures. The authors assessed the quality of the evidence using the GRADE system. Investigators were contacted to retrieve missing quantitative data. MAIN RESULTS: No studies of vitamin A or other retinoid supplementation were eligible for inclusion. However, one randomised study of beta (ß)-carotene supplementation involving 24 people with CF who were receiving pancreatic enzyme substitution was included. The study compared successive ß-carotene supplementation periods (high dose followed by low dose) compared to placebo. The results for the low-dose supplementation period should be interpreted with caution, due to the lack of a wash-out period after the high-dose supplementation.The included study did not report on two of the review's primary outcomes (vitamin A deficiency disorders and mortality); results for our third primary outcome of growth and nutritional status (reported as z score for height) showed no difference between supplementation and placebo, mean difference (MD) -0.23 (95% confidence interval (CI) -0.89 to 0.43) (low-quality evidence). With regards to secondary outcomes, supplementation with high-dose ß-carotene for three months led to significantly fewer days of systemic antibiotics required to treat pulmonary exacerbations, compared to controls, MD -15 days (95% CI -27.60 to -2.40); however, this was not maintained in the second three-month section of the study when the level of ß-carotene supplementation was reduced, MD -8 days (95% CI -18.80 to 2.80) (low-quality evidence). There were no statistically significant effects between groups in lung function (low-quality evidence) and no adverse events were observed (low-quality evidence). Supplementation affected levels of ß-carotene in plasma, but not vitamin A levels. The study did not report on quality of life or toxicity. AUTHORS' CONCLUSIONS: Since no randomised or quasi-randomised controlled studies on retinoid supplementation were identified, no conclusion on the supplementation of vitamin A in people with CF can be drawn. Additionally, due to methodological limitations in the included study, also reflected in the low-quality evidence judged following the specific evidence grading system (GRADE), no clear conclusions on ß-carotene supplementation can be drawn. Until further data are available, country- or region-specific guidelines regarding these practices should be followed.

Treating Cough Due to Non-CF and CF Bronchiectasis With Nonpharmacological Airway Clearance: CHEST Expert Panel Report.

BACKGROUND: In bronchiectasis due to cystic fibrosis (CF) and other causes, airway clearance is one of the mainstays of management. We conducted a systematic review on airway clearance by using non-pharmacological methods as recommended by international guidelines to develop recommendations or suggestions to update the 2006 CHEST guideline on cough. METHODS: The systematic search for evidence examined the question, "Is there evidence of clinically important treatment effects for non-pharmacological therapies in cough treatment for patients with bronchiectasis?" Populations selected were all patients with bronchiectasis due to CF or non-CF bronchiectasis. The interventions explored were the non-pharmacological airway clearance therapies. The comparison populations included those receiving standard therapy and/or placebo. Clinically important outcomes that were explored were exacerbation rates, quality of life, hospitalizations, and mortality. RESULTS: In both CF and non-CF bronchiectasis, there were systematic reviews and overviews of systematic reviews identified. Despite these findings, there were no large randomized controlled trials that explored the impact of airway clearance on exacerbation rates, quality of life, hospitalizations, or mortality. CONCLUSIONS: Although the cough panel was not able to make recommendations, they have made consensus-based suggestions and provided direction for future studies to fill the gaps in knowledge.

Vitamin K supplementation for cystic fibrosis.

BACKGROUND: Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. This is an updated version of the review. OBJECTIVES: To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 30 January 2017. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). DATA COLLECTION AND ANALYSIS: Two authors independently screened papers, extracted trial details and assessed their risk of bias. MAIN RESULTS: Two trials (total of 32 participants) each lasting one month were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial in children (aged 8 to 18 years); and the other (with an older cohort) had a cross-over design comparing supplements to no treatment, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K. AUTHORS' CONCLUSIONS: Evidence from randomised controlled trials on the benefits of routine vitamin K supplementation for people with CF is currently weak and limited to two small trials of short duration. However, no harm was found and until further evidence is available, the present recommendations should be adhered to.

Vitamin K supplementation for cystic fibrosis.

BACKGROUND: Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. OBJECTIVES: To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 08 October 2014. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). DATA COLLECTION AND ANALYSIS: Two authors independently screened papers, extracted trial details and assessed their risk of bias. MAIN RESULTS: Two trials (total of 32 participants) each lasting one month were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial in children (aged 8 to 18 years); and the other (with an older cohort) had a cross-over design comparing supplements to no treatment, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K. AUTHORS' CONCLUSIONS: Evidence from randomised controlled trials on the benefits of routine vitamin K supplementation for people with CF is currently weak and limited to two small trials of short duration. However, no harm was found and until further evidence is available, the present recommendations should be adhered to.

Upper airway viruses and bacteria detection in clinical pneumonia in a population with high nasal colonisation do not relate to clinical signs.

Indigenous Australian children have high (up to 90%) rates of nasopharyngeal microbial colonisation and of hospitalisation for pneumonia. In Indigenous children hospitalised with pneumonia in Central Australia, we describe the nasopharyngeal detection of viruses and bacteria and assessed whether their presence related to signs of pneumonia (tachypnoea and/or chest in-drawing) on hospital admission and during subsequent days. Nasopharyngeal swabs (NPS) and data were prospectively collected from 145 children (median age = 23.5 months, interquartile range [IQR] 8.7-50) hospitalised with pneumonia at Alice Springs Hospital, Australia, between April 2001 and July 2002. The cohort was enrolled in a randomised controlled study using zinc and/or vitamin A supplementation. NPS were taken within 24 hours of hospitalisation and kept frozen at-80°C until analysed in 2014. Polymerase chain reaction (PCR) was used to detect Moraxella catarrhalis, Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, Chlamydophila pneumoniae, Mycoplasma pneumoniae, and 16 respiratory viruses. Uni- and multi-variate analyses were used to examine the relationships. One or more organisms were present in 137 (94.5%) NPS; 133 (91.7%) detected ≥ 1 bacterium, 34 (37.2%) for ≥ 1 virus and 50 (34.5%) were positive for both viruses and bacteria. C. pneumoniae (n = 3) and M. pneumoniae (n = 2) were rare. In multi-variate analyses, age < 12 months (odds ratio [OR] 6.6 [95% confidence interval {CI} 1.7-25.4]) and fever (OR 4.1 [95% CI 1.7-10.4]) were associated with tachypnoea and chest in-drawing. However the presence of bacteria and/or virus type was not associated with tachypnoea and/or chest in-drawing on admission or during recovery. In children with high nasopharyngeal microbial colonisation rates, the utility of NPS in determining the diagnosis of clinical pneumonia or duration of tachypnoea or in-drawing is likely limited. Larger cohort and case-control studies are required to confirm our findings.

Singing as an adjunct therapy for children and adults with cystic fibrosis.

BACKGROUND: Cystic fibrosis is a genetically inherited, life-threatening condition that affects major organs. The management of cystic fibrosis involves a multi-faceted daily treatment regimen that includes airway clearance techniques, pancreatic enzymes and other medications. Previous studies have found that compliance with this intensive treatment is poor, especially among adolescents. Because of both the nature and consequences of the illness and the relentless demands of the treatment, many individuals with cystic fibrosis have a poor quality of life. Anecdotal reports suggest that singing may provide both appropriate exercise for the whole respiratory system and a means of emotional expression which may enhance quality of life. OBJECTIVES: To evaluate the effects of singing as an adjunct therapy to standard treatment on the quality of life, morbidity, respiratory muscle strength and pulmonary function of children and adults with cystic fibrosis. SEARCH METHODS: We searched the Group's Cystic Fibrosis Trials Register and the Cochrane Central Register of Controlled Trials. Date of latest search: 31 March 2014.We also searched major allied complementary data bases, and clinical trial registers. Additionally, we handsearched relevant conference proceedings and journals. Date of latest search: 24 May 2012. SELECTION CRITERIA: Randomised controlled trials in which singing (as an adjunct intervention) is compared with either a control intervention (for example, playing computer games or doing craft activities) or no singing in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against pre-determined criteria for inclusion. Only one eligible trial was available for analysis. MAIN RESULTS: Since only one small study was included, no meta-analysis could be performed. The included study was a parallel, randomised controlled trial undertaken at two paediatric hospitals in Australia. The study evaluated the effects of a singing program on the quality of life and respiratory muscle strength of hospitalised children with cystic fibrosis (mean age 11.6 years, 35% male). While the singing group received eight individual singing sessions, the control group participated in preferred recreational activities, such as playing computer games or watching movies. This study was limited by a small sample size (51 participants) and a high drop-out rate (21%). There were no significant differences between the groups at either post-intervention or follow up; although by the end of treatment there were some within-group statistically significant increases for both singing and control groups in some of the domains of the quality of life questionnaire Cystic Fibrosis Questionnaire-Revised (e.g. emotional, social and vitality domains). For the respiratory muscle strength indices, maximal expiratory pressure at follow up (six to eight weeks post-intervention) was higher in the singing group, mean difference 25.80 (95% confidence interval 5.94 to 45.66). There was no significant difference between groups for any of the other respiratory function parameters (maximal inspiratory pressure, spirometry) at either post-intervention or follow up. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine the effects of singing on quality of life or on the respiratory parameters in people with cystic fibrosis. However, there is growing interest in non-medical treatments for cystic fibrosis and researchers may wish to investigate the impact of this inexpensive therapy on respiratory function and psychosocial well-being further in the future.

Management and diagnosis of psychogenic cough, habit cough, and tic cough: a systematic review.

BACKGROUND: Several pharmacologic and nonpharmacologic therapeutic options have been used to treat cough that is not associated with a pulmonary or extrapulmonary etiology. METHODS: We conducted a systematic review to summarize the evidence supporting different cough management options in adults and children with psychogenic, tic, and habit cough. Medline, EMBASE, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched from the earliest inception of each database to September 2013. Content experts were contacted, and we searched bibliographies of included studies to identify additional references. RESULTS: A total of 18 uncontrolled studies were identified, enrolling 223 patients (46% male subjects, 96% children and adolescents). Psychogenic cough was the most common descriptive term used (90% of the studies). Most of the patients (95%) had no cough during sleep; barking or honking quality of cough was described in only eight studies. Hypnosis (three studies), suggestion therapy (four studies), and counseling and reassurance (seven studies) were the most commonly used interventions. Hypnosis was effective in resolving cough in 78% of the patients and improving it in another 5%. Suggestion therapy resolved cough successfully in 96% of the patients. The greatest majority of improvements noted with these forms of therapy occurred in the pediatric age group. The quality of evidence is low due to the lack of control groups, the retrospective nature of all the studies, heterogeneity of definitions and diagnostic criteria, and the high likelihood of reporting bias. CONCLUSIONS: Only low-quality evidence exists to support a particular strategy to define and treat psychogenic, habit, and tic cough. Patient values, preferences, and availability of potential therapies should guide treatment choice.

Vitamin A supplementation for cystic fibrosis.

BACKGROUND: People with cystic fibrosis and pancreatic insufficiency are at risk of fat soluble vitamin deficiency as these vitamins (A, D, E and K) are co-absorbed with fat. Thus, some cystic fibrosis centres routinely administer these vitamins as supplements but the centres vary in their approach of addressing the possible development of deficiencies in these vitamins. Vitamin A deficiency causes predominantly eye and skin problems while supplementation of vitamin A to excessive levels may cause harm to the respiratory and skeletal systems in children. Thus a systematic review on vitamin A supplementation in people with cystic fibrosis would help guide clinical practice. OBJECTIVES: To determine if vitamin A supplementation in children and adults with cystic fibrosis:1. reduces the frequency of vitamin A deficiency disorders;2. improves general and respiratory health;3. increases the frequency of vitamin A toxicity. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 07 April 2014. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing all preparations of oral vitamin A used as a supplement compared to either no supplementation (or placebo) at any dose and for any duration, in children or adults with cystic fibrosis (defined by sweat tests or genetic testing) with and without pancreatic insufficiency. DATA COLLECTION AND ANALYSIS: No relevant studies for inclusion were identified in the search. MAIN RESULTS: No studies were included in this review. AUTHORS' CONCLUSIONS: As there were no randomised or quasi-randomised controlled trials identified, we cannot draw any conclusions on the benefits (or otherwise) of regular administration of vitamin A in people with cystic fibrosis. Until further data are available, country or region specific guidelines on the use of vitamin A in people with cystic fibrosis should be followed.

Vitamin D supplementation for cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a genetic disorder with multiorgan effects. In a subgroup with pancreatic insufficiency malabsorption of the fat soluble vitamins (A, D, E, K) may occur. Vitamin D is involved in calcium homeostasis and bone mineralisation and may have extraskeletal effects. This review examines the evidence for vitamin D supplementation in cystic fibrosis. OBJECTIVES: To assess the effects of vitamin D supplementation on the frequency of vitamin D deficiency, respiratory outcomes and vitamin D toxicity in the cystic fibrosis population. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 08 July 2013. SELECTION CRITERIA: Randomised and quasi-randomised controlled studies of vitamin D supplementation compared to placebo in the cystic fibrosis population regardless of exocrine pancreatic function. DATA COLLECTION AND ANALYSIS: Both authors independently assessed the risk of bias of each included study and extracted outcome data (from published study information) for assessment of bone mineralization, growth and nutritional status, frequency of vitamin D deficiency, respiratory status, quality of life and adverse events. MAIN RESULTS: Six studies (239 participants) are included, although only three studies provided data from 69 adults and children with cystic fibrosis for analysis. One study compared a single high dose of vitamin D (250,000 IU) to placebo at the time of hospital admission with a respiratory exacerbation in 30 pancreatic insufficient adults with cystic fibrosis. The second study compared supplemental 800 international units (IU) vitamin D and placebo for 12 months in 30 osteopenic pancreatic insufficient adults; both groups continued 900 IU vitamin D daily. The third study compared supplemental 1 g calcium alone, 1600 IU vitamin D alone, 1600 IU vitamin D and 1 g calcium and placebo in a double-blind randomised cross-over study; only nine children who completed both vitamin D and placebo groups after six-months supplementation and a three-month washout period are included; pancreatic sufficiency or disease status of participants are not defined. The studies are not directly comparable due to differences in supplementation, outcome reporting and possibly participant characteristics (e.g. severity of lung disease, growth and nutrition, pancreatic sufficiency).The only outcome for which we could combine data from more than two studies was 25-hydroxyvitamin D levels; patients receiving vitamin D supplementation had significantly higher levels, mean difference 7.24 ng/ml (95% confidence interval 5.01 to 9.46). However, ironically one study reported 1,25(OH)2D with levels significantly favouring the placebo group, mean difference -30.30 pmol/ml (95% confidence interval -59.89 to -0.71). Bone mineral density was measured in two studies; both described no significant change between groups. There were no adverse events in any study.The remaining three studies are published as abstracts only and did not provide data for analysis. These abstracts include: a report of pre-intervention data in a study comparing daily calcitriol (0.25 or 0.5 micrograms) with placebo in pancreatic insufficient children and young adults; an interim report of a double-blind randomised control study comparing 5000 IU vitamin D daily for 12 weeks during winter in 67 adult cystic fibrosis patients; and a comparison of the effect of three months of vitamin D supplementation (dose not specified) with placebo on bone mineral density in 42 children with cystic fibrosis and low bone mineral density.Risk of bias was highly variable between all studies. Only one study had a low risk of bias for the five main criteria (random sequence generation, allocation, blinding, attrition and reporting). The rest of the studies had unclear or high risks of bias. Two studies had a low risk of bias for blinding and another two studies for attrition bias. In the studies published as abstracts, assessment of the risks of bias was uncertain in many aspects. AUTHORS' CONCLUSIONS: In patients receiving vitamin D supplementation, 25-hydroxyvitamin D levels are significantly higher. However, there is no evidence of clinical benefit or harm in the limited number of small-sized published studies. Adherence to relevant cystic fibrosis guidelines on vitamin D supplementation should be considered until further evidence is available.

Respiratory exacerbations in indigenous children from two countries with non-cystic fibrosis chronic suppurative lung disease/bronchiectasis.

BACKGROUND: Acute respiratory exacerbations (AREs) cause morbidity and lung function decline in children with chronic suppurative lung disease (CSLD) and bronchiectasis. In a prospective longitudinal cohort study, we determined the patterns of AREs and factors related to increased risks for AREs in children with CSLD/bronchiectasis. METHODS: Ninety-three indigenous children aged 0.5 to 8 years with CSLD/bronchiectasis in Australia (n = 57) and Alaska (n = 36) during 2004 to 2009 were followed for > 3 years. Standardized parent interviews, physical examinations, and medical record reviews were undertaken at enrollment and every 3 to 6 months thereafter. RESULTS: Ninety-three children experienced 280 AREs (median = 2, range = 0-11 per child) during the 3-year period; 91 (32%) were associated with pneumonia, and 43 (15%) resulted in hospitalization. Of the 93 children, 69 (74%) experienced more than two AREs over the 3-year period, and 28 (30%) had more than one ARE in each study year. The frequency of AREs declined significantly over each year of follow-up. Factors associated with recurrent (two or more) AREs included age < 3 years, ARE-related hospitalization in the first year of life, and pneumonia or hospitalization for ARE in the year preceding enrollment. Factors associated with hospitalizations for AREs in the first year of study included age < 3 years, female caregiver education, and regular use of bronchodilators. CONCLUSIONS: AREs are common in children with CSLD/bronchiectasis, but with clinical care and time AREs occur less frequently. All children with CSLD/bronchiectasis require comprehensive care; however, treatment strategies may differ for these patients based on their changing risks for AREs during each year of care.

Vitamin K supplementation for cystic fibrosis.

BACKGROUND: Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. OBJECTIVES: To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 11 October 2012. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). DATA COLLECTION AND ANALYSIS: Two authors independently screened papers, extracted trial details and assessed their risk of bias. MAIN RESULTS: Two trials (total of 32 participants) were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial; and the other had a cross-over design, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K. AUTHORS' CONCLUSIONS: Evidence from randomised controlled trials on the benefits of routine vitamin K supplementation for people with CF is currently weak and limited to two small trials of short duration. However, no harm was found and until further evidence is available, the present recommendations should be adhered to.

Vitamin A supplementation for cystic fibrosis.

BACKGROUND: People with cystic fibrosis and pancreatic insufficiency are at risk of fat soluble vitamin deficiency as these vitamins (A, D, E and K) are co-absorbed with fat. Thus, some cystic fibrosis centres routinely administer these vitamins as supplements but the centres vary in their approach of addressing the possible development of deficiencies in these vitamins. Vitamin A deficiency causes predominantly eye and skin problems while supplementation of vitamin A to excessive levels may cause harm to the respiratory and skeletal systems in children. Thus a systematic review on vitamin A supplementation in people with cystic fibrosis would help guide clinical practice. OBJECTIVES: To determine if vitamin A supplementation in children and adults with CF: 1. reduces the frequency of vitamin A deficiency disorders; 2. improves general and respiratory health; 3. increases the frequency of vitamin A toxicity. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 23 May 2012. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing all preparations of oral vitamin A used as a supplement compared to either no supplementation (or placebo) at any dose and for any duration, in children or adults with cystic fibrosis (defined by sweat tests or genetic testing) with and without pancreatic insufficiency. DATA COLLECTION AND ANALYSIS: No relevant studies for inclusion were identified in the search. MAIN RESULTS: No studies were included in this review. AUTHORS' CONCLUSIONS: As there were no randomised or quasi-randomised controlled trials identified, we cannot draw any conclusions on the benefits (or otherwise) of regular administration of vitamin A in people with cystic fibrosis. Until further data are available, country or region specific guidelines on the use of vitamin A in people with cystic fibrosis should be followed.

Vitamin D supplementation for cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a genetic disorder with multiorgan effects. In a subgroup with pancreatic insufficiency malabsorption of the fat soluble vitamins (A, D, E, K) may occur. Vitamin D is involved in calcium homeostasis and bone mineralisation and may have extraskeletal effects. This review examines the evidence for vitamin D supplementation in CF. OBJECTIVES: To assess the effects of vitamin D supplementation on the frequency of vitamin D deficiency, respiratory outcomes and vitamin D toxicity in the CF population. SEARCH METHODS: We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 15 February 2012. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of vitamin D supplementation compared to placebo in the CF population regardless of exocrine pancreatic function. DATA COLLECTION AND ANALYSIS: Both authors independently assessed the 'risk of bias' of each included trial and extracted outcome data (from published trial information) for assessment of bone mineralization, growth and nutritional status, frequency of vitamin D deficiency, respiratory status, quality of life and adverse events. MAIN RESULTS: Three studies are included, although only data from two were available (41 adults and children with CF). One of these studies compared supplemental 800 international units (IU) vitamin D and placebo for 12 months in 30 osteopenic pancreatic insufficient adults; both groups continued 900 IU vitamin D daily. The other (abstract only) compared supplemental 1g calcium alone, 1600 IU vitamin D alone, 1600 IU vitamin D and 1g calcium and placebo in a double-blind randomised cross-over trial; only 11 children (vitamin D and placebo groups) after six-months supplementation are included; inclusion criteria, pancreatic sufficiency or disease status of participants are not defined. There were no significant differences in primary or secondary outcomes in either study. The studies are not directly comparable due to differences in supplementation, outcome reporting and possibly participant characteristics (eg severity of lung disease, growth and nutrition, pancreatic sufficiency). There were no adverse events in either study. The third study (abstract only) compared daily calcitriol (0.25 or 0.5 micrograms) with placebo in pancreatic insufficient children and young adults, only pre-intervention data were available. AUTHORS' CONCLUSIONS: There is no evidence of benefit or harm in the limited number of small-sized published trials. Adherence to relevant CF guidelines on vitamin D should be considered until further evidence is available.

Identification of radiological alveolar pneumonia in children with high rates of hospitalized respiratory infections: comparison of WHO-defined and pediatric pulmonologist diagnosis in the clinical context.

BACKGROUND: A reliable standardized diagnosis of pneumonia in children has long been difficult to achieve. Clinical and radiological criteria have been developed by the World Health Organization (WHO), however, their generalizability to different populations is uncertain. We evaluated WHO defined chest radiograph (CXRs) confirmed alveolar pneumonia in the clinical context in Central Australian Aboriginal children, a high risk population, hospitalized with acute lower respiratory illness (ALRI). METHODS: CXRs in children (aged 1-60 months) hospitalized and treated with intravenous antibiotics for ALRI and enrolled in a randomized controlled trial (RCT) of Vitamin A/Zinc supplementation were matched with data collected during a population-based study of WHO-defined primary endpoint pneumonia (WHO-EPC). These CXRs were reread by a pediatric pulmonologist (PP) and classified as pneumonia-PP when alveolar changes were present. Sensitivities, specificities, positive and negative predictive values (PPV, NPV) for clinical presentations were compared between WHO-EPC and pneumonia-PP. RESULTS: Of the 147 episodes of hospitalized ALRI, WHO-EPC was significantly less commonly diagnosed in 40 (27.2%) compared to pneumonia-PP (difference 20.4%, 95% CI 9.6-31.2, P < 0.001). Clinical signs on admission were poor predictors for both pneumonia-PP and WHO-EPC; the sensitivities of clinical signs ranged from a high of 45% for tachypnea to 5% for fever + tachypnea + chest-indrawing. The PPV range was 40-20%, respectively. Higher PPVs were observed against the pediatric pulmonologist's diagnosis compared to WHO-EPC. CONCLUSIONS: WHO-EPC underestimates alveolar consolidation in a clinical context. Its use in clinical practice or in research designed to inform clinical management in this population should be avoided.

Vitamin K supplementation for cystic fibrosis.

BACKGROUND: Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. OBJECTIVES: To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 15 April 2010. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). DATA COLLECTION AND ANALYSIS: Two authors independently screened papers, extracted trial details and assessed their risk of bias. MAIN RESULTS: Two trials (total of 32 participants) were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial; and the other had a cross-over design, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K. AUTHORS' CONCLUSIONS: Evidence from randomised controlled trials on the benefits of routine vitamin K supplementation for people with CF is currently weak and limited to two small trials of short duration. However, no harm was found and until further evidence is available, the present recommendations should be adhered to.