A systematic review of reports of quality improvement for bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common morbidity of preterm infants, and its incidence has not responded to research and intervention efforts to the same degree as other major morbidities associated with prematurity. The complexity of neonatal respiratory care as well as persistent inter-institutional variability in BPD rates suggest that BPD may be amenable to quality improvement (QI) efforts. We present a systematic review of QI for BPD in preterm infants. We identified 22 reports from single centers and seven from collaborative efforts published over the past two decades. In almost all of the reports, respiratory QI interventions successfully reduced BPD or other key respiratory measures, particularly for infants with birth weight over 1000 g. Several themes and lessons from existing reports may help inform future efforts in both research and QI to impact the burden of BPD.

Hyperuricaemia, gout and allopurinol in the CKD Queensland registry.

INTRODUCTION: There is scant data on the role of hyperuricaemia, gout and allopurinol treatment in chronic kidney disease (CKD). Therefore, our aim is to investigate the possible associations between hyperuricaemia, gout, prescription of allopurinol and renal outcomes in patients with CKD. METHODS: The retrospective cohort study involved 1123 Royal Brisbane and Women's Hospital (RBWH) patients, enrolled in the CKD.QLD registry from May 2011 to August 2017. Patients were divided into two uric acid categories, with uric acid ≤ 0.36 mmol/L and > 0.36 mmol/L. Association of delta estimated glomerular filtration rate (eGFR) with gout, allopurinol treatment and hyperuricaemia were analysed. RESULTS: Patients with an entry urate > 0.36 mmol/L were older, had higher body mass index (BMI) and worse baseline kidney function. Proportion of patients with gout, hyperuricaemia and allopurinol treatment increased with advanced CKD stages. Age-adjusted analysis revealed a significant association between serum urate level and delta eGFR, with no significant association between gout, treatment with allopurinol and delta eGFR. Furthermore, neither gout nor the prescription of allopurinol had a significant effect on the time to renal death (composite end point of kidney replacement therapy or death). CONCLUSION: Hyperuricaemia seemed to be independently associated with faster CKD progression or renal death. This was not observed with gout or prescription of allopurinol. Furthermore, allopurinol was not associated with decreased incidence of cardiovascular events. These data suggest that hyperuricaemia is likely the effect and not the cause of CKD or CKD progression.

Sustained remission of systemic lupus erythematosus related calciphylaxis.

Calciphylaxis continues to present a clinical challenge for patient management. As in this case, it can be associated with connective tissue disease (CTD) such as systemic lupus erythematosus (SLE). Unlike previous reported cases, long-term remission has been attained. This provides some insight into methods of therapy as well as potential pathogenic models for this disease.

Cardiovascular disease in peritoneal dialysis patients.

Patients on peritoneal dialysis have a high level of morbidity and mortality associated with atherosclerotic cardiovascular disease and they also have an increased risk of sudden death. The atherosclerosis seen in peritoneal dialysis patients is associated with both traditional cardiovascular risk factors such as low levels of physical activity, hyperlipidemia, hypertension, diabetes and smoking as well as non-traditional risk factors such as elevated oxidative stress and inflammation. The atherosclerosis may be preceded by endothelial dysfunction and increased arterial stiffness. Measures of arterial stiffness such as aortic pulse wave velocity predict morbidity and mortality. Numerous studies have reported that the elevated levels of oxidative stress and inflammation in this population are associated with arterial stiffness and in turn with the development of cardiovascular disease. A number of studies have reported that peritoneal dialysis is associated with lower levels of oxidative stress and inflammation compared to haemodialysis. A small number of trials have extended this work to determine associations between oxidative stress and inflammation with vascular or myocardial structure and function with equivocal results. The decision to undergo either peritoneal or haemodialysis is based on many factors which include the differential damage the renal replacement therapy may have on the cardiovascular system. Current evidence suggests this may vary over time. Previous randomised controlled trials and many other observational studies have produced conflicting results as to which therapy may have a cardiovascular advantage. Some registry data suggests peritoneal dialysis is associated with a lower mortality than haemodialysis in the first one-two years but thereafter may be higher on peritoneal dialysis than haemodialysis. Other registry data do not support this. Further long-term studies assessing surrogate and hard endpoint cardiovascular outcomes in peritoneal dialysis are required.

Do the affective properties of smoking-related cues influence attentional and approach biases in cigarette smokers?

Research indicates that drug-related cues elicit attention and approach biases in drug users. However, attentional biases are not unique to addiction (e.g., they are also found for emotional information). This study examined whether attentional and approach biases in cigarette smokers are mediated by the motivational salience of cues (relevance to drug-taking), rather than by their affective properties (subjective liking of the cues). Cues included pleasant and unpleasant smoking-related pictures. Attentional biases, approach tendencies and subjective evaluation of the cues were assessed on visual probe, stimulus-response compatibility and rating tasks, respectively. Compared with non-smokers, smokers showed a greater attentional bias for both pleasant and unpleasant smoking-related cues presented for 2000 ms, but not for 200 ms. Smokers showed a greater approach bias for unpleasant cues, although the groups did not differ significantly in approach bias for pleasant smoking-related cues. Smokers rated both pleasant and unpleasant smoking pictures more positively than did non-smokers. Results suggest that a bias to maintain attention on smoking-related cues in young adult smokers is primarily a function of drug-relevance, rather than affective properties, of the cues. In contrast, approach tendencies and pleasantness judgements were influenced by drug use, drug-relevance and the affective properties of the cues.

Difficult decisions in the intensive care unit: an illustrative case.

Difficult clinical decision-making is a common experience in intensive care units. There is often considerable pressure on time and decisions may have to be made in a stressful environment. Patients in the intensive care unit not infrequently present with extreme or rare manifestations of a disease process. Clinical evidence to guide management of such patients may be incomplete, non-existent, or its relevance to the problem at hand may be questionable. In this context, formal decision-making analytical tools are often impractical. Unconscious cognitive biases have been shown to play an important role in medical decision-making, particularly in these settings. While mostly these contribute to doctors making appropriate and timely decisions, occasionally they lead to errors. Despite 30 years of research into models of clinical reasoning, most doctors are unaware of how biases affect their thinking and are unfamiliar with techniques of detecting and neutralising bias in clinical practice. We present the case of a patient with Wegener's granulomatosis, which highlights many of the difficulties outlined above. We review the clinical evidence for our decisions at each stage and explain the rationale for our choices, highlighting the many situations for which high quality evidence was lacking. Examples of cognitive bias are identified and techniques of metacognition (thinking about thinking) that can be useful in limiting the effects of bias on complex decision-making are reviewed. The intensivist's evaluation of management alternatives has an important role in steering medical management towards optimal patient outcomes.

The recurrent neurotrophic buttock ulcer in the meningomyelocele paraplegic: a sensate flap solution.

A large percentage of meningomyelocele paraplegic patients have a distal zone of sensation-bearing skin on their thighs. This sensate skin can be used as a fasciocutaneous flap to resurface a recidivistic ulcer after excision. In this study, because the transposition distance was significant, the flap length-width ratio was greater than normal and, therefore, required a 3-week elevation delay. This also permitted appraisal of the sensate flap after the first stage. The wound-healing was excellent after both stages. This reconstructive procedure was completed in four patients, with an average follow-up period of 13 years. These patients remain chronic sitters in administrative jobs and have been pressure sore-free after flap repair.

Chronic inflammatory demyelinating polyradiculoneuropathy and severe peripheral oedema: a renal explanation.

Inflammatory demyelinating neuropathies have been associated with membranous and focal sclerosing glomerulonephritis. Here we describe a 58 year old man with a clinical history, physical examination and laboratory investigations consistent with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), who also had severe lower limb and sacral oedema resistant to medical therapy. Mild proteinuria was present and a renal biopsy showed features consistent with focal sclerosing glomerulonephritis (FSGN). The patient's weakness and oedema did not respond to i.v. immunoglobulin or plasmapheresis but responded to high dose oral prednisone. The oedema was not explained by immobility, hypoproteinaemia or local factors. The occurrence of the oedema in a person with CIDP and FSGN and its improvement with prednisone, together with improvement in CIDP and FSGN, suggests that it was immune mediated, possibly due to increased capillary permeability. The presence of renal disease in patients with inflammatory demyelinating neuropathies may be more common than currently realised.

Microvascular complications in cystic fibrosis-related diabetes mellitus: a case report.

CONTEXT, The prevalence of cystic fibrosis-related diabetes mellitus is increasing and is associated with increased survival from cystic fibrosis. CASE REPORT, This study describes a case of the premature onset of disabling and widespread microvascular complications resulting from cystic fibrosis-related diabetes mellitus. Previously asymptomatic retinopathy was diagnosed on recognition of diabetic nephropathy. CONCLUSIONS, The treatment of pulmonary exacerbations has become more complex due to the nephrotoxic potential of intravenous aminoglycoside drugs which are frequently used to control chronic Pseudomonas infection in cystic fibrosis.

Efficient infection from cDNA clones of cucumber mosaic cucumovirus RNAs in a new plasmid vector.

Full-length cucumber mosaic cucumovirus (CMV) cDNAs were cloned into a new plasmid vector containing a modified plant virus promoter designed to transcribe the inserted sequence from its first nucleotide. cDNA copies of CMV strain Q (Q-CMV) genomic RNAs 1, 2 and 3 cloned into this vector were infectious when inoculated together, producing symptoms indistinguishable from those caused by wildtype Q-CMV infection. The infectivity of the clones could be substantially increased by excision of the viral insert together with the transcriptional promoter and terminator prior to inoculation. A diagnostic but silent mutation was introduced into the RNA 2 cDNA and found to be stably maintained in viral infection, allowing distinction of the recombinant virus from native contaminants. The infectious cDNA clones supported the replication of CMV satellite RNA when co-inoculated with biologically active Q-CMV satellite RNA transcripts. Using the infectious cDNAs described, it was found that a newly-identified overlapping gene (2b) encoded by Q-CMV RNA 2 was not essential for either systemic viral infection of Nicotiana glutinosa or replication of the satellite RNAs.

5-Aminolevulinate synthase in sideroblastic anemias: mRNA and enzyme activity levels in bone marrow cells.

To examine the role of 5-aminolevulinate synthase (ALAS) in the pathogenesis of sideroblastic anemias, levels of mRNAs for erythroid and housekeeping ALAS isozymes were examined, and total ALAS activity was assessed in bone marrow cells. In two patients with X-linked sideroblastic anemia the levels of mRNA for erythroid ALAS as well as for alpha and beta globin appear to be decreased while levels of mRNA for glycophorin A in both patients were the same as in normal individuals. However, amounts of housekeeping ALAS mRNA were increased two- to threefold in these patients. Total ALAS activity was also increased two- or threefold, perhaps reflecting increased transcription of the housekeeping gene in response to diminished cellular heme in erythroid cells and/or enhanced translation of the erythroid isoform in response to iron accumulation. In a third patient with X-linked sideroblastic anemia ALAS activity was low but increased to twice the normal value after pyridoxine administration, suggesting a structural defect of the enzyme. In a fourth patient, with isolated congenital, pyridoxine-responsive sideroblastic anemia, the erythroid ALAS mRNA was normal and a low enzyme activity was strikingly enhanced by pyridoxal-phosphate albeit to subnormal levels. In idiopathic acquired sideroblastic anemia, ALAS mRNA for both isozymes was normal and enzyme activity was slightly elevated. These observations thus reflect heterogeneous aberrations of erythroid heme synthesis in the various types of sideroblastic anemia and suggest that defects involving erythroid ALAS underlie at least some of them.

Renal complications of cytotoxic therapy.

The expanding use of cytotoxic drugs in cancer therapy has resulted in a confusing and increasingly frequent array of severe renal complications. This article reviews the nephrotoxicity and other renal and urological complications of commonly used drugs and the clinical setting in which they are prescribed. Emphasis is placed on the mechanisms, prevention and treatment of renal damage.