Digital technology for early identification of exacerbations in people with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a life-limiting genetic condition affecting various organ systems including the gastrointestinal tract, endocrine system and especially the respiratory tract. Pulmonary exacerbations in CF result in increased symptoms, an acceleration in the rate of lung decline and an increased need for treatment. Early detection of infections or clinical worsening provides an opportunity for proactive treatment that may affect clinical outcomes. OBJECTIVES: To evaluate whether digital technology can effectively predict pulmonary exacerbations to allow earlier intervention and improved health outcomes without increasing the burden of treatment in people with CF. SEARCH METHODS: We used standard, extensive Cochrane search methods. We searched the Cochrane Cystic Fibrosis Trials Register and the reference lists of relevant articles and reviews on 13 October 2022. We searched Embase and the clinical trial registries on 3 January 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs in people with CF looking at whether digital technology can effectively predict pulmonary exacerbations to allow earlier intervention and improved health outcomes without increasing the burden of treatment.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. pulmonary exacerbations and 2. quality of life (QoL). Our secondary outcomes were 3. lung function, 4. hospitalisations, 5. intravenous (IV) antibiotics, 6. microbiology, 7. cost-effectiveness and 8. ADVERSE EVENTS: We used GRADE to assess certainty of evidence. MAIN RESULTS: We included three studies (415 participants) in people with CF aged 15 to 41 years over a 12-month period. One was a multicentre RCT, whilst two were single-centre RCTs.  The three studies were mostly similar in their risk of bias, having low or unclear risk of selection bias but a high risk of detection bias, due to the unblinded design of these studies. The studies used a variety of digital technologies to monitor symptoms such as a digital symptom diary either with or without home spirometry monitoring. As the trials only included adults and older children, we are not certain that the results would apply to younger children. One of our primary outcomes was to assess time to detection of pulmonary exacerbation and number of pulmonary exacerbations identified between the intervention and routine care groups. We were largely unable to pool results in a meta-analysis due to the variety of methodologies and ways of reporting data. Two studies noted a shorter time to detection of exacerbations in the intervention group and one of these also reported that the intervention group had a shorter time to first exacerbation (hazard ratio for time to first exacerbation 1.45, 95% confidence interval (CI) 1.09 to 1.93), whilst a further study reported a shorter time to detection of exacerbations in the intervention group requiring oral or IV antibiotics compared to the control group (median: 70 (interquartile range (IQR) 123) days with intervention versus 141 (IQR 140) days with control; P = 0.02). However, all three studies were concordant in finding no probable effect on spirometry in the intervention groups when compared with their routine care groups over a 12-month period.  We found that there is probably no difference between groups with regard to QoL scores across most domains except for Weight and Body Image, which favoured the usual care group. There is also probably no difference in the number of days of additional IV antibiotics needed or newly detected pathogens. No studies reported serious adverse events directly linked to the intervention and one study reported their smartphone application was generally well received. AUTHORS' CONCLUSIONS: Pulmonary exacerbations are universally accepted to be detrimental to progression of CF-related lung disease, therefore, it is intuitive that early detection and intervention would help to improve outcomes. Digital technology provides an opportunity to detect physiological and symptomatic changes to identify exacerbations early.  Our review found that digital technologies based on recording physiological change (spirometry) and symptoms probably allow earlier identification of exacerbations as a group. However, this may not reduce the number of exacerbations warranting IV antibiotics and there is probably no effect on lung function. This may be partly due to inconsistent definitions of pulmonary exacerbations and discrepancy in the management strategies for pulmonary exacerbations. Overall, the intervention may make little or no difference to QoL scores.  The adherence to and uptake of digital technologies, especially those which include physiological measurements, are not well sustained and the costs of these need to be balanced against the clinical efficacy.

Vitamin E supplementation in people with cystic fibrosis.

BACKGROUND: People with cystic fibrosis are at an increased risk of fat-soluble vitamin deficiency, including vitamin E. Vitamin E deficiency can cause a host of conditions such as haemolytic anaemia, cerebellar ataxia and cognitive difficulties. Vitamin E supplementation is widely recommended for people with cystic fibrosis and aims to ameliorate this deficiency. This is an updated version of the review. OBJECTIVES: To determine the effects of any level of vitamin E supplementation on the frequency of vitamin E deficiency disorders in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Group's Cystic Fibrosis Trials Register and also searched international online trial registries for any ongoing clinical trials that were not identified during our register search. Date of last search of the Register: 11 August 2020. Date of last search of international online trial registries: 20 July 2020. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing any preparation of vitamin E supplementation to placebo or no supplement, regardless of dosage or duration. DATA COLLECTION AND ANALYSIS: Two authors extracted outcome data from each study (published information) and assessed the risk of bias of each included study. They assessed the quality of the evidence using GRADE. MAIN RESULTS: Four studies with a total of 141 participants were included in the review, two of these were in children (aged six months to 14.5 years), and two did not specify participants' age. All studies used different formulations and doses of vitamin E for various durations of treatment (10 days to six months). Two studies compared the supplementation of fat-soluble as well as water-soluble formulations to no supplementation in different arms of the same study. A third study compared a water-soluble formulation to a placebo; and in the fourth study a fat-soluble formulation of vitamin E was assessed against placebo. There was limited detail about randomisation and blinding in the included studies which compromises the quality of the evidence base for the review. The heterogeneous mix of the formulations with differing biovailabilities among these studies also limits the generalisability of the data to the wider cystic fibrosis population. None of the studies in either comparison report the review's primary outcomes of vitamin E total lipid ratio or the incidence of vitamin E-specific deficiency disorders, or the secondary outcomes lung function or quality of life. Water-soluble vitamin E Water-soluble vitamin E may improve serum vitamin E levels compared with control at six months, one study (45 participants), mean difference (MD) 19.74 umol/L (95% confidence interval (CI) 13.48 to 26.00) (low-quality evidence). Similar results were also seen at one month, two studies (32 participants), MD 17.66 umol/L (95% CI 10.59 to 24.74) and at three months, one study (45 participants), MD 11.61 umol/L (95% CI 4.77 to 18.45). Only one study (45 participants) reported weight (secondary outcome of growth and nutritional status) at one and six months, but showed no difference between treatment and control at either time point. Fat-soluble vitamin E Two studies (36 participants) reported higher levels of serum vitamin E at one month with fat-soluble vitamin E compared with control, MD 13.59 umol/L (95% CI 9.52 to 17.66); however, at three months one study (36 participants) showed no difference between treatment and control. No studies in this comparison reported on growth or nutritional status. AUTHORS' CONCLUSIONS: Vitamin E supplementation may lead to an improvement in vitamin E levels in people with cystic fibrosis, although evidence we assessed was low quality. No data on other outcomes of interest were available to allow conclusions about any other benefits of this therapy. In future, larger studies are needed, especially in people already being treated with enteric-coated pancreatic enzymes and supplemented with vitamin E, to look at more specific outcome measures such as vitamin E status, lung function and nutritional status. Future studies could also look at the optimal dose of vitamin E required to achieve maximal clinical effectiveness.

Vitamin E supplementation in people with cystic fibrosis.

BACKGROUND: People with cystic fibrosis are at an increased risk of fat-soluble vitamin deficiency including vitamin E. Vitamin E deficiency can cause a host of conditions such as haemolytic anaemia, cerebellar ataxia and cognitive difficulties. Vitamin E supplementation is widely recommended in cystic fibrosis and aims to ameliorate this deficiency. This is an updated version of the review. OBJECTIVES: To determine the effects of any level of vitamin E supplementation on the frequency of vitamin E deficiency disorders in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Group's Cystic Fibrosis Trials Register and also searched international trial registers for any ongoing clinical trials that were not identified during our register search.Date of last search of the Register: 10 October 2016. Date of last search of international trial registers: 15 February 2017. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing any preparation of vitamin E supplementation to placebo or no supplement, regardless of dosage or duration. DATA COLLECTION AND ANALYSIS: Two authors extracted outcome data from each study (published information) and assessed the risk of bias of each included study. MAIN RESULTS: Four studies with a total of 141 participants were included in the review, two of these were in children (aged six months to 14.5 years), and the other two did not specify participants' age. All studies used different formulations and doses of vitamin E for various durations of treatment (10 days to six months). Two studies compared the supplementation of fat-soluble as well as water-soluble formulations to no supplementation in different arms of the same study. A third study compared a water-soluble formulation to a placebo; and in the fourth study a fat-soluble formulation of vitamin E was assessed against placebo.At one month, three months and six months, water-soluble vitamin E significantly improved serum vitamin E levels compared with control: at one month, two studies, mean difference 17.66 (95% confidence interval 10.59 to 24.74); at three months, one study, mean difference 11.61 (95% confidence interval 4.77 to 18.45); and at six months, one study, mean difference 19.74 (95% confidence interval 13.48 to 26.00). At one month fat-soluble vitamin E significantly improved serum vitamin E levels compared with control: one month, two studies, mean difference 13.59 (95% CI 9.52 to 17.66). The findings at three months were imprecise; one study; mean difference 6.40 (95% confidence interval -1.45 to 14.25).None of the studies report the review's primary outcomes of vitamin E total lipid ratio or the incidence of vitamin E-specific deficiency disorders, or the secondary outcomes lung function or quality of life. Only one study, comparing water-soluble vitamin E with placebo, reported the secondary outcome of growth and nutritional status (weight), but the results are uncertain due to imprecision around the effect estimate.There was limited detail about randomisation and blinding in the included studies which compromises the quality of the evidence base for the review. The heterogeneous mix of the formulations with differing biovailabilities among these studies also limits the generalisability of the data to the wider cystic fibrosis population. AUTHORS' CONCLUSIONS: Vitamin E supplementation led to an improvement in vitamin E levels in people with cystic fibrosis, although the studies may have been at risk of bias. No data on other outcomes of interest were available to allow conclusions about any other benefits of this therapy.In future, larger studies are needed, especially in people already being treated with enteric-coated pancreatic enzymes and supplemented with vitamin E, to look at more specific outcome measures such as vitamin E status, lung function and nutritional status. Future studies could also look at the optimal dose of vitamin E required to achieve maximal clinical effectiveness.

Fifteen-minute consultation: approach to management of respiratory problems in children with neurodisability.

Children with neurodisability have an increased prevalence of respiratory symptoms and morbidity. Several underlying physiological impairments and coexistent problems, like aspiration, make these children vulnerable to respiratory difficulties. The management of these respiratory problems is aimed at improving the quality of life, reducing the risk of exacerbations and further lung damage. This is based on identifying and, where possible, modifying physiological impairments, managing any exacerbating factors and proactive treatment of any complications. Even though increased life expectancy is now possible, an ever-increasing dependence on technology can interfere with quality of life and decisions to escalate to these treatments should be individualised.

Vitamin E supplementation in people with cystic fibrosis.

BACKGROUND: People with cystic fibrosis are at an increased risk of fat-soluble vitamin deficiency including vitamin E. Vitamin E deficiency can cause a host of conditions such as haemolytic anaemia, cerebellar ataxia and cognitive difficulties. Vitamin E supplementation is widely recommended in cystic fibrosis and aims to ameliorate this deficiency. OBJECTIVES: To determine the effects of any level of vitamin E supplementation on the frequency of vitamin E deficiency disorders in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Group's Cystic Fibrosis Trials Register and also searched international trial registers for any ongoing clinical trials that were not identified during our register search.Date of last search of the Register: 10 February 2014. Date of last search of international trial registers: 30 August 2014. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing any preparation of vitamin E supplementation to placebo or no supplement, regardless of dosage or duration. DATA COLLECTION AND ANALYSIS: Two authors extracted outcome data from each study (published information) and assessed the risk of bias of each included study. MAIN RESULTS: Four studies with a total of 141 participants were included in the review, two of these were in children (aged six months to 14.5 years), and the other two did not specify participants' age. All studies used different formulations and doses of vitamin E for various durations of treatment (10 days to six months). Two studies compared the supplementation of fat-soluble as well as water-soluble formulations to no supplementation in different arms of the same study. A third study compared a water-soluble formulation to a placebo; and in the fourth study a fat-soluble formulation of vitamin E was assessed against placebo.At one month, three months and six months, water-soluble vitamin E significantly improved serum vitamin E levels compared with control: at one month, two studies, mean difference 17.66 (95% confidence interval 10.59 to 24.74); at three months, one study, mean difference 11.61 (95% confidence interval 4.77 to 18.45); and at six months, one study, mean difference 19.74 (95% confidence interval 13.48 to 26.00). At one month fat-soluble vitamin E significantly improved serum vitamin E levels compared with control: one month, two studies, mean difference 13.59 (95% CI 9.52 to 17.66). The findings at three months were imprecise; one study; mean difference 6.40 (95% CI -1.45 to 14.25).None of the studies report the review's primary outcomes of vitamin E total lipid ratio or the incidence of vitamin E-specific deficiency disorders, or the secondary outcomes lung function or quality of life. Only one study, comparing water-soluble vitamin E with placebo, reported the secondary outcome of growth and nutritional status (weight), but the results are uncertain due to imprecision around the effect estimate.There was limited detail about randomisation and blinding in the included studies which compromises the quality of the evidence base for the review. The heterogeneous mix of the formulations with differing biovailabilities among these studies also limits the generalisability of the data to the wider cystic fibrosis population. AUTHORS' CONCLUSIONS: Vitamin E supplementation led to an improvement in vitamin E levels in people with cystic fibrosis, although the studies may have been at risk of bias. No data on other outcomes of interest were available to allow conclusions about any other benefits of this therapy.In future, larger studies are needed, especially in people already being treated with enteric-coated pancreatic enzymes and supplemented with vitamin E, to look at more specific outcome measures such as vitamin E status, lung function and nutritional status. Future studies could also look at the optimal dose of vitamin E required to achieve maximal clinical effectiveness.

Stigma from medication use: an under recognised burden of care.

Children with respiratory diseases take treatments for the self-management of symptoms and to maintain disease control. Often, these treatments need to be taken in social environments like school. Respiratory treatments can foster a feeling of difference and stigmatisation, which negatively impact on the quality of life and adherence to treatment. Such perceptions can lead to a less than optimal disease control, a vicious cycle leading to further social exclusion and stigma. This aspect of "burden of treatment" is poorly recognised by clinicians. Recognition of how treatments and clinical practice can contribute to stigma, can help address this burden of care. EDUCATIONAL AIMS: To understand the meaning of the term "stigma" within the context of respiratory health conditions and how medication or treatments can contribute to stigma in children and young people.To understand the potential impact of stigma on adherence, disease control and quality of life.To consider strategies to manage the stigma associated with health treatments across spheres of influence.

Chronic kidney disease in children following lung and heart-lung transplantation.

CKD is a major co-morbidity in pediatric lung transplant recipients. We report the prevalence of renal impairment post-lung transplant at a single center, using a modified, age-adjusted eGFR for the best approximation of true GFR, and investigated associations and possible predictors of decline in renal function post-transplant. Renal function was assessed by eGFR pre-transplant, three and 12 months post-transplant, and at last follow-up. Decline in renal function was analyzed as percentage fall in eGFR in two phases (0-3 and 3-12). Furthermore, we investigated impact of gender, age, pre-transplant diagnosis and renal function, transplant type, early post-transplant dialysis, and tacrolimus trough levels on decline in eGFR using multivariate analysis. Over a five-yr period, 30 transplants were performed. Mean eGFR pretransplant was 117 mL/min/1.73 m(2) (s.d. 35) with mean decline in eGFR during the first three months post-transplant of 33% (s.d. 31, p < 0.001). Thereafter, mean decline in eGFR was 8% (s.d. 18, p = 0.02). None of the factors assessed were significantly associated with decline in eGFR post-transplant. In conclusion, many children have decline in renal function following lung transplantation, particularly early post-transplant. Unlike in adults, we were unable to detect any predictors of renal impairment in pediatric lung transplant recipients.

Adherence issues in asthma.

In any chronic disease like asthma, the effectiveness of therapy depends on how good the treatment is and how well the patient takes it. Non-adherence maybe in form of omission of doses, incorrect medication, incorrect dosages or schedules, premature discontinuation of drugs, not following advice to avoid allergens and sub optimal inhalation technique. Unrecognized non-adherence decreases the effectiveness of asthma therapy. Non adherence can result in an increased rate of illness exacerbation, hospitalization, emergency department visits and asthma related deaths. One hundred sixty eight patients and their guardians on follow up in pediatric asthma clinic were administered a questionnaire regarding adherence to anti asthma therapy. Non adherence of different forms was seen in up to 68 percent of patients. The purpose of this communication is to report the frequency of non adherence in patients with asthma and suggest remedial measures.

Kawasaki disease.

Kawasaki disease (KD) is a common vasculitic disorder usually seen in children below 5 years of age. The disease can present with protean clinical manifestations which include high grade fever (for at least 5 days), rash, redness of the lips and a typical strawberry tongue, cervical lymph node enlargement (often unilateral), swelling over the hands/feet and, later a characteristic peripheral desquamation over the fingers and toes. These clinical features appear sequentially and the findings may change from day-to-day. Thus, all these features may not be seen together at any one point of time. The diagnosis rests on the recognition of this characteristic temporal sequence of clinical events, none of which are, by themselves, pathognomonic. Establishing a diagnosis of KD may be further complicated by the occurrence of several other, seemingly unrelated, clinical features. These include irritability, neck stiffness, sterile pyuria, pneumonitis, hydrops of the gallbladder and hepatitis among many others. There is no laboratory test that can help in confirming a diagnosis of KD. Left untreated, up to 20% of children with KD can develop coronary aneurysms with catastrophic long term sequelae. It is important to diagnose KD in the first 10 days of the illness so that appropriate therapy with intravenous immunoglobulin and aspirin can be Initiated. All paediatricians, and physicians looking after children, need to be aware of this condition which is now being increasingly recognized in India.

Hypocalcaemia following therapy of thyrotoxicosis in an infant.

UNLABELLED: A 2-mo-old infant born to a mother with Graves' disease and having symptoms of thyrotoxicosis was started on antithyroid drugs. Life-threatening hypocalcaemia requiring high-dose calcium infusions developed 1 mo after starting therapy. Serum alkaline phosphatase and paratharmone levels were elevated. This communication may serve to alert treating physicians about this rare complication in infants with thyrotoxicosis after initiation of antithyroid therapy. CONCLUSION: Severe hypocalcaemia may follow initiation of antithyroid therapy in infants with thyrotoxicosis.

Adherence issues in asthma.

In any chronic disease like asthma, the effectiveness of therapy depends on how good the treatment is and how well the patient takes it. Non-adherence maybe in form of omission of doses, incorrect medication, incorrect dosages or schedules, premature discontinuation of drugs, not following advice to avoid allergens and sub optimal inhalation technique. Unrecognized non-adherence decreases the effectiveness of asthma therapy. Non adherence can result in an increased rate of illness exacerbation, hospitalization, emergency department visits and asthma related deaths. One hundred sixty eight patients and their guardians on follow up in pediatric asthma clinic were administered a questionnaire regarding adherence to anti asthma therapy. Non adherence of different forms was seen in up to 68 percent of patients. The purpose of this communication is to report the frequency of non adherence in patients with asthma and suggest remedial measures.

Kawasaki disease.

Kawasaki disease (KD) is a common vasculitic disorder usually seen in children below 5 years of age. The disease can present with protean clinical manifestations which include high grade fever (for at least 5 days), rash, redness of the lips and a typical strawberry tongue, cervical lymph node enlargement (often unilateral), swelling over the hands/feet and, later a characteristic peripheral desquamation over the fingers and toes. These clinical features appear sequentially and the findings may change from day-to-day. Thus, all these features may not be seen together at any one point of time. The diagnosis rests on the recognition of this characteristic temporal sequence of clinical events, none of which are, by themselves, pathognomonic. Establishing a diagnosis of KD may be further complicated by the occurrence of several other, seemingly unrelated, clinical features. These include irritability, neck stiffness, sterile pyuria, pneumonitis, hydrops of the gallbladder and hepatitis among many others. There is no laboratory test that can help in confirming a diagnosis of KD. Left untreated, up to 20% of children with KD can develop coronary aneurysms with catastrophic long term sequelae. It is important to diagnose KD in the first 10 days of the illness so that appropriate therapy with intravenous immunoglobulin and aspirin can be Initiated. All paediatricians, and physicians looking after children, need to be aware of this condition which is now being increasingly recognized in India.