Meta-analysis of statins in chronic kidney disease: who benefits?

Background: Attempts to reduce the burden of vascular disease in advanced chronic kidney disease (CKD) by control of lipids have not been as successful as predicted. Aim: To determine the extent to which the effectiveness of statins varies by kidney class. Design: Meta-analysis. Methods: We selected randomized trials of statin vs. placebo that gave outcomes for CKD3 (eGFR 30–59 ml/min), CKD4 (eGFR 15–29 ml/min), CKD5 (eGFR < 15 ml/min)/5D(dialysis) and transplant patients separately. Data sources were the Cholesterol Triallists’ Treatment Collaboration and previously published meta-analyses. Main outcome measures were major cardiovascular events (MACE), cardiovascular death and all-cause mortality (ACM). Results: A total of 13 studies provided 19 386 participants with CKD3, 2565 with CKD4, 7051 with CKD5/5D and 2102 with a functioning renal transplant. Statins reduced MACE (pooled HR 0.72, 95% CI 0.67–0.78) and ACM (0.82, 0.73–0.91) in CKD3; probably reduced MACE (0.78, 0.62–0.99) in CKD4; and probably reduced cardiovascular death (0.62, 0.40–0.96) in renal transplants. There were no cardiovascular or ACM data in CKD4; there was no convincing evidence of benefit for any outcome in CKD5/5D; and no significant reduction in MACE or ACM in patients with a functioning transplant. Conclusions: Statins are indicated in CKD3, probably indicated in CKD4, not indicated in CKD5/5D and probably indicated in patients with a functioning transplant. Too few patients with CKD4 and renal transplants have been included in lipid lowering trials for confident conclusions to be drawn

The challenges of renal replacement therapy and renal palliative care in the elderly

Much of the increase in take on rate for dialysis in recent years is accounted for by older patients in whom a treatment as demanding as dialysis was previously thought to be contraindicated. The decision to dialyse the elderly often remains difficult, as recent data suggest that those with significant comorbidities are unlikely to survive more than 4-6 months longer on dialysis than they would have done if treated conservatively. It is also important to recognise that conservative treatment is not simply defined by the decision not to dialyse. Good conservative care comprises active disease management eg treatment of anaemia with erythropoietin stimulating agents and intravenous iron, and supportive care which may become increasingly complex eg pain relief with fentanyl and alfentanyl, towards the end of life. Those older patients who do decide to dialyse must contend with all the usual end of life issues facing older people, in addition to the option, denied to the rest of us, of dialysis withdrawal which effectively allows them to die at a time of their choosing

Osteogenic Sarcoma in an Adolescent With Cystic Fibrosis: Successful Treatment Despite Significant Obstacles

Introduction: We describe the case of a 16-year old male with cystic fiborosis (CF) who presented with an osteosarcoma of his right distal tibia.Case Report: Treatment consisted of neoadjuvant chemotherapy of cisplatin, doxorubicin and high dose methotrexate followed by distal tibial resection and free fibula flap reconstruction and consolidation chemotherapy. Treatment was complicated by a pulmonary exacerbation, where Pseudomonas aeruginosa (PsA) and Staphylococcus aureus were grown on sputum culture which was treated with a 2-week course of intravenous piptazobactam and tobramycin. Mycobacterium intracellulare and Mycobacterium abscessus were also cultured following commencement of chemotherapy and successfully treated with a 6-month course of oral azithromycin, ethambutol, and moxifloxacin along with a 1-month course of inhaled amikacin. Pulmonary function improved during his treatment from baseline FEV1 of 3.8 l (93.9%) to 4.15 l (102.3% predicted) whilst nutritional status remained stable.Discussion: The combination of CF and osteosarcoma is rare with only one previous case reported (1). Our case is instructive as the patient faced the challenge of chronic PsA and the first reported culturing and successful treatment of non-tuberculous mycobacterium (NTM) during chemotherapy. Fatal outcomes have been reported previously for CF patients during immunosuppression (2). In concordance with our findings, a recent report noted an improvement in respiratory function in a child treated for leukemia (3). The anti-inflammatory nature of some chemotherapy agents could be responsible for the observed clinical improvement in CF with low dose methotrexate having been shown to increase FEV1 in adolescents with advanced CF (4). Whilst doxorubicin could improve pulmonary outcomes through increased total cellular CFTR protein expression and CFTR associated chloride secretion (5). It is hypothesized that the improved pulmonary function in patients with CF who require chemotherapy could be due to increased production of Multi-Drug Resistance Proteins (MDR) and Multi-Drug Resistant Associated Proteins (MRP) that may complement the depleted CFTR protein (6).Concluding Remarks: We report the well-tolerated management of osteosarcoma in a patient with CF including the first reported identification and eradication of NTM during chemotherapy. The observed positive pulmonary outcome following chemotherapy highlights several potential cellular mechanisms that deserve to be explored

It must be true … I read it in the tabloids

Background Previous attempts to improve the quality of health journalism have not led to more responsible reporting of health news. Method We reviewed the front pages of three daily tabloid and three daily broadsheet UK newspapers during a 1 month period in 2017 for medical headlines in which claims were made for diets, lifestyle behaviours or drug therapies that influence health. Results Front page medical headlines were carried by the Daily Express (11), Daily Mail (two), Daily Mirror (one) and Daily Telegraph (one). Neither the Guardian nor the Independent carried medical stories on their front pages during the period of study. Eleven headlines suggested benefits and three suggested harm. One headline accurately reflected its source material, but in this instance the source material was of doubtful clinical relevance. The remaining 13 headlines either exaggerated benefit (seven), exaggerated harm (two) or made false claims (four). Conclusions The cumulative effect of everyday misreporting of medical stories in UK newspapers may not only serve to confuse the public but also have serious consequences for public health

Relation between coronary risk and coronary mortality in women of the Renfrew and Paisley survey: comparison with men

Most epidemiological and intervention studies in patients with coronary artery disease have focused on men, the assumption being that such data can be extrapolated to women. However, there is little evidence to support this belief. We have completed a fifteen-year follow-up of 15 399 adults, including 8262 women, who lived in Renfrew and Paisley and were aged 45-64 years when screened between 1972 and 1976. We identified 490 deaths from coronary heart disease (CHD) in women and 878 in men. Women were more likely to have high cholesterol, to be obese, and to come from lower social classes than men, but they smoked less and had similar blood pressures. The relative risk--top to bottom quintile (95% Cl)--of cholesterol for coronary death after adjustment for all other risk markers was slightly greater in women (1[middle dot]77 [1[middle dot]45, 2[middle dot]16]) than in men (1[middle dot]56 [1[middle dot]32, 1[middle dot]85]), but absolute and attributable risk were lower. Thus, women in the top quintile for cholesterol had lower coronary mortality (6[middle dot]1 deaths per thousand patient years) than men in the bottom quintile (6[middle dot]8 deaths per thousand patient years). Moreover, it was estimated that there would have been only 103 (21 %) fewer CH D deaths in women, yet 211 (24%) fewer in men, if mortality had been the same for women and men in the lowest quintiles of cholesterol. Trends showing similar relative risks in these women, but lower absolute and attributable risks than in men, were present for smoking, diastolic blood pressure, and social class. There was no relation between obesity and coronary death after adjustment for other risks. Our results suggest that some other factors protect women against CHD. The potential for women to reduce their risk of CH D by changes in lifestyle may be less than for men.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30146/1/0000523.pd

Distinct physiological and behavioural functions for parental alleles of imprinted Grb10

Imprinted genes, defined by their preferential expression of a single parental allele, represent a subset of the mammalian genome and often have key roles in embryonic development1, but also postnatal functions including energy homeostasis2 and behaviour3, 4. When the two parental alleles are unequally represented within a social group (when there is sex bias in dispersal and/or variance in reproductive success)5, 6, imprinted genes may evolve to modulate social behaviour, although so far no such instance is known. Predominantly expressed from the maternal allele during embryogenesis, Grb10 encodes an intracellular adaptor protein that can interact with several receptor tyrosine kinases and downstream signalling molecules7. Here we demonstrate that within the brain Grb10 is expressed from the paternal allele from fetal life into adulthood and that ablation of this expression engenders increased social dominance specifically among other aspects of social behaviour, a finding supported by the observed increase in allogrooming by paternal Grb10-deficient animals. Grb10 is, therefore, the first example of an imprinted gene that regulates social behaviour. It is also currently alone in exhibiting imprinted expression from each of the parental alleles in a tissue-specific manner, as loss of the peripherally expressed maternal allele leads to significant fetal and placental overgrowth. Thus Grb10 is, so far, a unique imprinted gene, able to influence distinct physiological processes, fetal growth and adult behaviour, owing to actions of the two parental alleles in different tissues

Observations of red-giant variable stars by Aboriginal Australians

Aboriginal Australians carefully observe the properties and positions of stars, including both overt and subtle changes in their brightness, for subsistence and social application. These observations are encoded in oral tradition. I examine two Aboriginal oral traditions from South Australia that describe the periodic changing brightness in three pulsating, red-giant variable stars: Betelgeuse (Alpha Orionis), Aldebaran (Alpha Tauri), and Antares (Alpha Scorpii). The Australian Aboriginal accounts stand as the only known descriptions of pulsating variable stars in any Indigenous oral tradition in the world. Researchers examining these oral traditions over the last century, including anthropologists and astronomers, missed the description of these stars as being variable in nature as the ethnographic record contained several misidentifications of stars and celestial objects. Arguably, ethnographers working on Indigenous Knowledge Systems should have academic training in both the natural and social sciences.Comment: The Australian Journal of Anthropology (2018