Hematopoietic stem cell transplantation for people with ß-thalassaemia.

BACKGROUND: Thalassaemia is an autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions, resulting in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In ß-thalassaemia there is an underproduction of ß-globin chains combined with excess of free α-globin chains. The excess free α-globin chains precipitate in red blood cells, leading to their increased destruction (haemolysis) and ineffective erythropoiesis. The conventional treatment is based on the correction of haemoglobin through regular red blood cell transfusions and treating the iron overload that develops subsequently with iron chelation therapy. Although, early detection and initiations of such supportive treatment has improved the quality of life for people with transfusion-dependent thalassaemia, allogeneic hematopoietic stem cell transplantation is the only widely available therapy with a curative potential. Gene therapy for ß-thalassaemia has recently received conditional authorisation for marketing in Europe, and may soon become widely available as another alternative therapy with curative potential for people with transfusion-dependent thalassaemia. This is an update of a previously published Cochrane Review. OBJECTIVES: To evaluate the effectiveness and safety of different types of hematopoietic stem cell transplantation, in people with transfusion-dependent ß-thalassaemia. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. Date of the most recent search: 07 April 2021. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen). DATA COLLECTION AND ANALYSIS: Two review authors independently screened trials and had planned to extract data and assess risk of bias using standard Cochrane methodologies and assess the quality using GRADE approach, but no trials were identified for inclusion in the current review. MAIN RESULTS: No relevant trials were retrieved after a comprehensive search of the literature. AUTHORS' CONCLUSIONS: We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of hematopoietic stem cell transplantation in people with transfusion-dependent ß-thalassaemia. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials.

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.

Percutaneous transluminal angioplasty for treatment of chronic cerebrospinal venous insufficiency (CCSVI) in people with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a leading cause of neurological disability in young adults. The most widely accepted hypothesis regarding its pathogenesis is that it is an immune-mediated disease. It has been hypothesised that intraluminal defects, compression, or hypoplasia in the internal jugular or azygos veins may be important factors in the pathogenesis of MS. This condition has been named 'chronic cerebrospinal venous insufficiency' (CCSVI). It has been suggested that these intraluminal defects restrict the normal blood flow from the brain and spinal cord, causing the deposition of iron in the brain and the eventual triggering of an auto-immune response. The proposed treatment for CCSVI is venous percutaneous transluminal angioplasty (PTA), which is claimed to improve the blood flow in the brain thereby alleviating some of the symptoms of MS. This is an update of a review first published in 2012. OBJECTIVES: To assess the benefit and safety of venous PTA in people with MS and CCSVI. SEARCH METHODS: We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group's Specialised Register up to 30 August 2018, CENTRAL (in the Cochrane Library 2018, issue 8), MEDLINE up to 30 August 2018, Embase up to 30 August 2018, metaRegister of Controlled Trials, ClinicalTrials.gov., the Australian New Zealand Clinical Trials Registry, and the World Health Organization (WHO) International Clinical Trials Registry platform. We examined the bibliographies of the included and excluded studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which PTA and sham interventions were compared in adults with MS and CCSVI. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility and risk of bias, and extracted data. We reported results as risk ratios (RR) with 95% confidence intervals (CI). We performed statistical analyses using the random-effects model; and we assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included three RCTs (238 participants) in this update. One hundred and thirty-four participants were randomised to PTA and 104 to sham treatment. We attributed low risk of bias to two (67%) studies for sequence generation and two (67%) studies for performance bias. All studies were at a low risk of detection bias, attrition bias, reporting bias and other potential sources of bias.There was moderate-quality evidence to suggest that venous PTA did not increase the proportion of patients who had operative or post-operative serious adverse events compared with the sham procedure (RR 3.33, 95% CI 0.36 to 30.44; 3 studies, 238 participants); nor did it increase the proportion of patients who improved on a functional composite measure including walking control, balance, manual dexterity, postvoid residual urine volume, and visual acuity over 12-month follow-up (RR 0.84, 95% CI 0.55 to 1.30; 1 study, 110 participants); nor did it reduce the proportion of patients who experienced new relapses at six- or 12-month follow-up (RR 0.87, 95% CI 0.51 to 1.49; 3 studies, 235 participants). There was no effect of venous PTA on disability worsening measured by the Expanded Disability Status Scale, which was reported at follow-up intervals of six months (one study), 11 months (one study) and 12 months (one study). Quality of life was reported in two studies with no difference between treatment groups. Moderate or severe pain during or post venography was reported in both PTA and sham-procedure participants in all included studies. Venous PTA was not effective in restoring blood flow assessed at one-month (one study) or 12-month follow-up (one study). AUTHORS' CONCLUSIONS: This systematic review identified moderate-quality evidence that, compared with sham procedure, venous PTA intervention did not provide benefit on patient-centred outcomes (disability, physical or cognitive functions, relapses, quality of life) in people with MS. Venous PTA has proven to be a safe technique but in view of the available evidence of its ineffectiveness, this intervention cannot be recommended in people with MS. All ongoing trials were withdrawn or terminated and hence this updated review is conclusive. No further randomised clinical studies are needed.

Vitamin D for the management of multiple sclerosis.

BACKGROUND: This review is an update of a previously published review, "Vitamin D for the management of multiple sclerosis" (published in the Cochrane Library; 2010, Issue 12). Multiple sclerosis (MS) is characterised by inflammation, demyelination, axonal or neuronal loss, and astrocytic gliosis in the central nervous system (CNS), which can result in varying levels of disability. Some studies have provided evidence showing an association of MS with low levels of vitamin D and benefit derived from its supplementation. OBJECTIVES: To evaluate the benefit and safety of vitamin D supplementation for reducing disease activity in people with MS. SEARCH METHODS: We searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Specialized Register up to 2 October 2017 through contact with the Information Specialist with search terms relevant to this review. We included references identified from comprehensive electronic database searches and from handsearches of relevant journals and abstract books from conferences. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that compared vitamin D versus placebo, routine care, or low doses of vitamin D in patients with MS. Vitamin D was administered as monotherapy or in combination with calcium. Concomitant interventions were allowed if they were used equally in all trial intervention groups. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the methodological quality of studies, while another review author sorted any disagreements. We expressed treatment effects as mean differences (MDs) for continuous outcomes (Expanded Disability Status Scale and number of magnetic resonance imaging (MRI) gadolinium-enhancing T1 lesions), as standardised MDs for health-related quality of life, as rate differences for annualised relapse rates, and as risk differences (RDs) for serious adverse events and minor adverse events, together with 95% confidence intervals (CIs). MAIN RESULTS: We identified 12 RCTs enrolling 933 participants with MS; 464 were randomised to the vitamin D group, and 469 to the comparator group. Eleven trials tested vitamin D3, and one trial tested vitamin D2. Vitamin D3 had no effect on the annualised relapse rate at 52 weeks' follow-up (rate difference -0.05, 95% CI -0.17 to 0.07; I² = 38%; five trials; 417 participants; very low-quality evidence according to the GRADE instrument); on the Expanded Disability Status Scale at 52 weeks' follow-up (MD -0.25, 95% CI -0.61 to 0.10; I² = 35%; five trials; 221 participants; very low-quality evidence according to GRADE); and on MRI gadolinium-enhancing T1 lesions at 52 weeks' follow-up (MD 0.02, 95% CI -0.45 to 0.48; I² = 12%; two trials; 256 participants; very low-quality evidence according to GRADE). Vitamin D3 did not increase the risk of serious adverse effects within a range of 26 to 52 weeks' follow-up (RD 0.01, 95% CI -0.03 to 0.04; I² = 35%; eight trials; 621 participants; low-quality evidence according to GRADE) or minor adverse effects within a range of 26 to 96 weeks' follow-up (RD 0.02, 95% CI -0.02 to 0.06; I² = 20%; eight trials; 701 participants; low-quality evidence according to GRADE). Three studies reported health-related quality of life (HRQOL) using different HRQOL scales. One study reported that vitamin D improved ratings on the psychological and social components of the HRQOL scale but had no effects on the physical components. The other two studies found no effect of vitamin D on HRQOL. Two studies reported fatigue using different scales. One study (158 participants) reported that vitamin D3 reduced fatigue compared with placebo at 26 weeks' follow-up. The other study (71 participants) found no effect on fatigue at 96 weeks' follow-up. Seven studies reported on cytokine levels, four on T-lymphocyte proliferation, and one on matrix metalloproteinase levels, with no consistent pattern of change in these immunological outcomes. The randomised trials included in this review provided no data on time to first treated relapse, number of participants requiring hospitalisation owing to progression of the disease, proportion of participants who remained relapse-free, cognitive function, or psychological symptoms. AUTHORS' CONCLUSIONS: To date, very low-quality evidence suggests no benefit of vitamin D for patient-important outcomes among people with MS. Vitamin D appears to have no effect on recurrence of relapse, worsening of disability measured by the Expanded Disability Status Scale (EDSS), and MRI lesions. Effects on health-related quality of life and fatigue are unclear. Vitamin D3 at the doses and treatment durations used in the included trials appears to be safe, although available data are limited. Seven ongoing studies will likely provide further evidence that can be included in a future update of this review.

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.

Hematopoietic stem cell transplantation for people with ß-thalassaemia major.

BACKGROUND: Thalassemia is an inherited autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions. This results in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In ß-thalassaemia major there is an underproduction of ß-globin chains combined with excess of free α-globin chains. The excess free α-globin chains precipitate in red blood cells, leading to their destruction (haemolysis) and ineffective erythropoiesis. The conventional approach to treatment is based on the correction of haemoglobin status through regular blood transfusions and iron chelation therapy for iron overload. Although conventional treatment has the capacity to improve the quality of life of people with ß-thalassaemia major, allogeneic hematopoietic stem cell transplantation is the only currently available procedure which has the curative potential. This is an update of a previously published Cochrane Review. OBJECTIVES: To evaluate the effectiveness and safety of different types of allogeneic hematopoietic stem cell transplantation, in people with severe transfusion-dependant ß-thalassaemia major, ß-thalassaemia intermedia or ß0/+- thalassaemia variants requiring chronic blood transfusion. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies 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: 18 August 2016. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing allogeneic hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen). DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies and had planned to extract data and assess risk of bias using standard Cochrane methodologies but no studies were identified for inclusion. MAIN RESULTS: No relevant studies were retrieved after a comprehensive search of the literature. AUTHORS' CONCLUSIONS: We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of allogeneic stem cell transplantation in people with severe transfusion-dependant ß-thalassaemia major or ß0/+- thalassaemia variants requiring chronic blood transfusion. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials.

Neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis.

BACKGROUND: Cystic fibrosis is the most common, life-threatening, recessively inherited disease of Caucasian populations. It is a multisystem disorder caused by a mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator protein which is important in producing sweat, digestive juices and mucus.The impaired or absent function of this protein results in the production of viscous mucus within the lungs and an environment that is susceptible to chronic airway obstruction and pulmonary colonization by a range of pathogenic bacteria. Morbidity and mortality of cystic fibrosis is related to chronic pulmonary sepsis and its complications by these bacteria.Influenza can worsen the course of the disease in cystic fibrosis by increasing the risk of pneumonia and secondary respiratory complications. Antiviral agents form an important part of influenza management and include the neuraminidase inhibitors zanamivir and oseltamivir. These inhibitors can limit the infection and prevent the spread of the virus. OBJECTIVES: To assess the effects of neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis. 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.Most recent search: 02 November 2015. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing neuraminidase inhibitors with placebo or other antiviral drugs. DATA COLLECTION AND ANALYSIS: Two review authors had planned to independently screen studies, extract data and assess risk of bias using standard Cochrane methodologies. No studies were identified for inclusion. MAIN RESULTS: No relevant studies were retrieved after a comprehensive search of the literature. AUTHORS' CONCLUSIONS: We were unable to identify any randomised controlled studies or quasi-randomised controlled studies on the efficacy of neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis. The absence of high level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately powered, randomised controlled clinical studies.

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.

Hematopoietic stem cell transplantation for people with ß-thalassaemia major.

BACKGROUND: Thalassemia is an inherited blood disorder, caused by mutations in regulatory genes and transmitted as an autosomal recessive disorder, which results in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In ß-thalassaemia major there is an underproduction of ß-globin chains combined with excess of free α-globin chains. The excess free α-globin chains damage the red blood cell membranes, leading to their destruction and a phenomenon termed ineffective erythropoiesis. The conventional approach to treatment is based on the correction of haemoglobin status through regular blood transfusions and iron chelation therapy for iron overload. Although conventional treatment has the capacity to improve the quality of life of people with ß-thalassaemia major, allogeneic hematopoietic stem cell transplantation is the only currently available procedure which has the potential to definitively cure the disease. OBJECTIVES: To evaluate the effectiveness and safety of different types of allogeneic hematopoietic stem cell transplantation, in people with severe transfusion-dependant ß-thalassaemia major, ß-thalassaemia intermedia or ß0/+- thalassaemia variants requiring chronic blood transfusion. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies 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: 11 November 2013. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing allogeneic hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen). DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies and had planned to extract data and assess risk of bias using standard Cochrane Collaboration methodologies but no studies were identified for inclusion. MAIN RESULTS: No relevant studies were retrieved after a comprehensive search of the literature. AUTHORS' CONCLUSIONS: We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of allogeneic stem cell transplantation in people with severe transfusion-dependant ß-thalassaemia major or ß0/+- thalassaemia variants requiring chronic blood transfusion. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials.

Neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis.

BACKGROUND: Cystic fibrosis is the most common, life-threatening, recessively inherited disease of Caucasian populations. It is a multisystem disorder caused by a mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator protein which is important in producing sweat, digestive juices and mucus.The impaired or absent function of this protein results in the production of viscous mucus within the lungs and an environment that is susceptible to chronic airway obstruction and pulmonary colonization by a range of pathogenic bacteria. Morbidity and mortality of cystic fibrosis is related to chronic pulmonary sepsis and its complications by these bacteria.Influenza can worsen the course of the disease in cystic fibrosis by increasing the risk of pneumonia and secondary respiratory complications. Antiviral agents form an important part of influenza management and include the neuraminidase inhibitors zanamivir and oseltamivir. These inhibitors can limit the infection and prevent the spread of the virus. OBJECTIVES: To assess the effects of neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis. 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.Most recent search: 08 July 2013. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing neuraminidase inhibitors with placebo or other antiviral drugs. DATA COLLECTION AND ANALYSIS: Two review authors had planned to independently screen studies, extract data and assess risk of bias using standard Cochrane Collaboration methodologies. No studies were identified for inclusion. MAIN RESULTS: No relevant studies were retrieved after a comprehensive search of the literature. AUTHORS' CONCLUSIONS: We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the efficacy of neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis. The absence of high level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately powered, randomised controlled clinical trials.

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.

Percutaneous transluminal angioplasty for treatment of chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis patients.

BACKGROUND: Multiple sclerosis (MS) is a leading cause of neurological disability in young adults. The most widely accepted hypothesis regarding its pathogenesis is that it is an immune-mediated disease. It has been hypothesised more recently that chronic venous congestion may be an important factor in the pathogenesis of MS. This concept has been named 'chronic cerebrospinal venous insufficiency' (CCSVI) and is characterised by stenoses of either the internal jugular or azygos veins, or both. It is suggested that these stenoses restrict the normal blood flow from the brain, causing the deposition of iron in the brain and the eventual triggering of an auto-immune response. The proposed treatment for CCSVI is percutaneous transluminal angioplasty, also known as the 'liberation procedure', which is claimed to improve the blood flow in the brain thereby alleviating some of the symptoms of MS. OBJECTIVES: To assess the effects of percutaneous transluminal angioplasty for the treatment of CCSVI in people with MS. SEARCH METHODS: We searched the following databases up to June 2012: The Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register, CENTRAL in The Cochrane Library 2012, Issue 5, MEDLINE (from 1946), EMBASE (from 1974), and reference lists of articles. We also searched several online trials registries for ongoing trials. SELECTION CRITERIA: Randomised controlled trials assessing the effects of percutaneous transluminal angioplasty in adults with multiple sclerosis, that have been diagnosed to have CCSVI. DATA COLLECTION AND ANALYSIS: Our searches retrieved 159 references, six of which were to ongoing trials. Based on assessment of the title or abstract, or both, we excluded all of the studies, with the exception of one which was evaluated following examination of the full text report. However, this study also did not meet our inclusion criteria and was subsequently excluded. MAIN RESULTS: No randomised controlled trials met our inclusion criteria. AUTHORS' CONCLUSIONS: There is currently no high level evidence to support or refute the efficacy or safety of percutaneous transluminal angioplasty for treatment of CCSVI in people with MS. Clinical practice should be guided by evidence supported by well-designed randomised controlled trials: closure of some of the gaps in the evidence may be feasible at the time of completion of the six ongoing clinical trials.

Routine neonatal circumcision for the prevention of urinary tract infections in infancy.

BACKGROUND: Neonatal circumcision is a fairly common surgical procedure that may be carried out for medical reasons, one of them being prevention of urinary tract infections (UTI) in male infants. Circumcision could help in reducing the incidence of UTI by reducing periurethral bacterial colonization, which is accepted as a potential risk factor in UTI. Evidence is needed to inform the benefits or harm for the routine use of this intervention. OBJECTIVES: To assess the effectiveness and safety of routine neonatal circumcision for the prevention of UTIs in infancy. SEARCH METHODS: We searched the Cochrane Neonatal Review Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We completed this search 30 June 2011. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials. DATA COLLECTION AND ANALYSIS: Two review authors had planned to independently screen studies, extract data and assess risk of bias using standard Cochrane Collaboration methodologies. We did not identify any studies for inclusion in this review. MAIN RESULTS: We did not identify any relevant studies after a comprehensive search of the literature. AUTHORS' CONCLUSIONS: We were unable to identify any randomised controlled trials on the use of routine neonatal circumcision for prevention of UTI in male infants. Until further evidence becomes available, clinicians should continue to base their decisions on position statements and recommendations and in conjunction with the opinions of the children's parents.

Beta2-adrenoceptor agonists for dysmenorrhoea.

BACKGROUND: Dysmenorrhoea is a common gynaecological complaint that can affect as many as 50% of premenopausal women, 10% of whom suffer severely enough to be rendered incapacitated for one to three days during each menstrual cycle. Primary dysmenorrhoea is where women suffer from menstrual pain but lack any pathology in their pelvic anatomy. Beta2-adrenoceptor agonists have been used in the treatment of women with primary dysmenorrhoea but their effects are unclear. OBJECTIVES: To determine the effectiveness and safety of beta2-adrenoceptor agonists in the treatment of primary dysmenorrhoea. SEARCH METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register; CENTRAL (The Cochrane Library 2011, Issue 8); MEDLINE; EMBASE; PsycINFO and the EBM Reviews databases. The last search was on 22 August 2011. SELECTION CRITERIA: Randomised controlled trials comparing beta2-adrenoceptor agonists with placebo or no treatment, each other or any other conventional treatment in women of reproductive age with primary dysmenorrhoea. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted the data. MAIN RESULTS: Five trials involving 187 women with an age range of 15 to 40 years were included. Oral isoxsuprine was compared with placebo in two trials; terbutaline oral spray, ritodrine chloride and oral hydroxyphenyl-orciprenalin were compared with placebo in a further three trials. Clinical diversity in the studies in terms of the interventions being evaluated, assessments at different time points and the use of different assessment tools mitigated against pooling of outcome data across studies in order to provide a summary estimate of effect for any of the comparisons. Only one study, with unclear risk of bias, reported pain relief with a combination of isoxsuprine, acetaminophen and caffeine. None of the other studies reported any significant clinical difference in effectiveness between the intervention and placebo. Adverse effects were reported with all of these medications in up to a quarter of the total number of participants. They included nausea, vomiting, dizziness, quivering, tremor and palpitations. AUTHORS' CONCLUSIONS: The evidence presented in this review was based on a few relatively small-sized studies that were categorised to have unclear to high risk of bias, which does not allow confident decision-making at present about the use of beta2-adrenoceptor agonists for dysmenorrhoea. The benefits as reported in one study should be balanced against the wide array of unacceptable side effects documented with this class of medication. We have emphasised the lack of precision and limitations in the reported data where appropriate.

One health: perspectives on ethical issues and evidence from animal experiments.

Zoonoses constitute more than 60% of all known infectious diseases and 75% of emerging infectious diseases. Their impact is not monitored, prevented and treated in an integrated way. The efficacy of therapeutic interventions for zoonotic diseases is deemed to be comparable across species with scientifically valid results originating from a range of animal experiments. Ethical obligations limit the number of animals used in experiments as well as reduce repetition of studies. The evidence based on randomized controlled trails and systematic reviews for the effectiveness of health care interventions is often inconclusive. Subjecting human volunteers to risk in the absence of scientifically valid results from animal experiments is unethical. The One Health concept is a comparative, clinical approach directed towards zoonoses which present challenges to research workers and clinicians. Optimal health for all--One Health--should be underpinned by ethically conducted research in animals or humans and the results should be complementary to both.

Effects of 12 sessions of steam bath intervention on spirometry parameters among healthy adult volunteers.

OBJECTIVES: Steam bath is extensively used around the world. However, its physiological influence is not understood in detail. Objective of the current study is to examine the effects of 12 sessions of steam bath on spirometric parameters among healthy participants. METHODS: Forty healthy adult volunteers of both sex (14 male and 26 female) aged 26.38 ± 8 years participated in the study. A steam bath session (10-15 min) was given once a week for 12 weeks. The spirometric parameters [forced expiratory volume in the 1st second (FEV1, L), forced vital capacity (FVC, L), FEV1/FVC ratio (absolute value), maximal mid-expiratory flow (MMEF, L/s) and peak expiratory flow (PEF, L/s)] were measured by Helios 401 spirometer. RESULTS: Compared to baseline, post-intervention spirometric parameters showed significant (p<0.05) improvement in the FVC (82.40 ± 11.24 to 96.91 ± 18.76), FEV1 (86.13 ± 14.39 to 91.17 ± 12.48), FEV1/FVC ratio (86.96 ± 3.64 to 93.75 ± 4.80), MMEF 25-75% (86.96 ± 3.64 to 94.16 ± 11.57), peak expiratory flow rate (79.82 ± 14.90 to 92.18 ± 18.96). CONCLUSIONS: Taking steam bath improves the spirometric parameters of healthy adult participants. However, future randomized controlled trials with on a large scale have to done to validate our findings.

Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents.

BACKGROUND: Vomiting is a common manifestation of acute gastroenteritis in children and adolescents. When untreated it can be a hindrance to oral rehydration therapy, which is the cornerstone in the management of acute gastroenteritis. Evidence is needed concerning the safety and efficacy of antiemetic use for vomiting in acute gastroenteritis in children. OBJECTIVES: To assess the safety and effectiveness of antiemetics on gastroenteritis induced vomiting in children and adolescents. SEARCH STRATEGY: We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register comprising references identified from comprehensive electronic database searches and hand searches of relevant journals and abstract books of conferences.The search was re-run and is up to date as on 20 July 2010. SELECTION CRITERIA: Randomized controlled trials comparing antiemetics with placebo or no treatment, in children and adolescents under the age of 18, for vomiting due to gastroenteritis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: We included seven trials involving 1,020 participants. Mean time to cessation of vomiting in one study was 0.34 days less with dimenhydrinate suppository compared to placebo (P value = 0.036). Pooled data from three studies comparing oral ondansetron with placebo showed: a reduction in the immediate hospital admission rate (RR 0.40, NNT 17, 95% CI 10 to 100) but no difference between the hospitalization rates at 72 hours after discharge from the Emergency Department (ED); a reduction in IV rehydration rates both during the ED stay (RR 0.41, NNT 5, 95% CI 4 to 8), and in follow-up to 72 hours after discharge from the ED stay (worst-best scenario for ondansetron RR 0.57, NNT 6, 95% CI 4 to 13) and an increase in the proportion of patients with cessation of vomiting (RR 1.34, NNT 5, 95% CI 3 to 7)). No significant difference was noted in the revisit rates or adverse events, although diarrhea was reported as a side effect in four of the five ondansetron studies. In one study the proportion of patients with cessation of vomiting in 24 hours was (58%) with IV ondansetron, (17%) placebo and (33%) in the metoclopramide group (P value = 0.039). AUTHORS' CONCLUSIONS: Oral ondansetron increased the proportion of patients who had ceased vomiting and reduced the number needing intravenous rehydration and immediate hospital admission. Intravenous ondansetron and metoclopramide reduced the number of episodes of vomiting and hospital admission, and dimenhydrinate as a suppository reduced the duration of vomiting.

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.

Hematopoietic stem cell transplantation for people with ß-thalassaemia major.

BACKGROUND: Thalassemia is an inherited blood disorder, caused by mutations in regulatory genes and transmitted as an autosomal recessive disorder, which results in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In ß-thalassaemia major there is an underproduction of ß-globin chains combined with excess of free α-globin chains. The excess free α-globin chains damage the red blood cell membranes, leading to their destruction and a phenomenon termed ineffective erythropoiesis. The conventional approach to treatment is based on the correction of haemoglobin status through regular blood transfusions and iron chelation therapy for iron overload. Although conventional treatment has the capacity to improve the quality of life of people with ß-thalassaemia major, allogeneic hematopoietic stem cell transplantation is the only currently available procedure which has the potential to definitively cure the disease. OBJECTIVES: To evaluate the effectiveness and safety of different types of allogeneic hematopoietic stem cell transplantation, in people with severe transfusion-dependant ß-thalassaemia major, ß-thalassaemia intermedia or ß0/+- thalassaemia variants requiring chronic blood transfusion. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies 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: 27 May 2011. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing allogeneic hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen). DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies and had planned to extract data and assess risk of bias using standard Cochrane Collaboration methodologies but no studies were identified for inclusion. MAIN RESULTS: No relevant studies were retrieved after a comprehensive search of the literature. AUTHORS' CONCLUSIONS: We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of allogeneic stem cell transplantation in people with severe transfusion-dependant ß-thalassaemia major or ß0/+- thalassaemia variants requiring chronic blood transfusion. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials.

Neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis.

BACKGROUND: Cystic fibrosis is the most common, life-threatening, recessively inherited disease of Caucasian populations. It is a multisystem disorder caused by a mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator protein which is important in producing sweat, digestive juices and mucus.The impaired or absent function of this protein results in the production of viscous mucus within the lungs and an environment that is susceptible to chronic airway obstruction and pulmonary colonization by a range of pathogenic bacteria. Morbidity and mortality of cystic fibrosis is related to chronic pulmonary sepsis and its complications by these bacteria.Influenza can worsen the course of the disease in cystic fibrosis by increasing the risk of pneumonia and secondary respiratory complications. Antiviral agents form an important part of influenza management and include the neuraminidase inhibitors zanamivir and oseltamivir. These inhibitors can limit the infection and prevent the spread of the virus. OBJECTIVES: To assess the effects of neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis. SEARCH STRATEGY: 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.Most recent search: 12 August 2009. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing neuraminidase inhibitors with placebo or other antiviral drugs. DATA COLLECTION AND ANALYSIS: Two review authors had planned to independently screen studies, extract data and assess risk of bias using standard Cochrane Collaboration methodologies. No studies were identified for inclusion. MAIN RESULTS: No relevant studies were retrieved after a comprehensive search of the literature. AUTHORS' CONCLUSIONS: We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the efficacy of neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis. The absence of high level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately powered, randomised controlled clinical trials.