Haemodialysis and peritoneal dialysis patients admitted to intensive care units.

Hutchison and colleagues report a 10-year experience of dialysis patients admitted to intensive care units (ICUs) in the UK excluding Scotland. Their study is the largest published so far and raises issues of interest to both ICU physicians and nephrologists. Overall, the dialysis patients, although sicker on admission and having pre-existing co-morbidities, do as well as other ICU patients. Their clinical progress after leaving the ICU, however, is less good than for other ICU patients, raising the possibility that the patients might be leaving too early, or perhaps that dialysis patients should be discharged to a high-dependency unit rather than go direct to a renal ward. All in all, the paper by Hutchison and colleagues provides a useful foundation for planning the critical care management of dialysis patients in the UK and elsewhere

Deep unsupervised clustering with Gaussian mixture variational autoencoders

We study a variant of the variational autoencoder model with a Gaussian mixture as a prior distribution, with the goal of performing unsupervised clustering through deep generative models. We observe that the standard variational approach in these models is unsuited for unsupervised clustering, and mitigate this problem by leveraging a principled information-theoretic regularisation term known as consistency violation. Adding this term to the standard variational optimisation objective yields networks with both meaningful internal representations and well-defined clusters. We demonstrate the performance of this scheme on synthetic data, MNIST and SVHN, showing that the obtained clusters are distinct, interpretable and result in achieving higher performance on unsupervised clustering classification than previous approaches

Hemodynamic optimization in severe trauma: a systematic review and meta-analysis.

OBJECTIVE: Severe trauma can be associated with significant hemorrhagic shock and impaired organ perfusion. We hypothesized that goal-directed therapy would confer morbidity and mortality benefits in major trauma. METHODS: The MedLine, Embase and Cochrane Controlled Clinical Trials Register databases were systematically searched for randomized, controlled trials of goal-directed therapy in severe trauma patients. Mortality was the primary outcome of this review. Secondary outcomes included complication rates, length of hospital and intensive care unit stay, and the volume of fluid and blood administered. Meta-analysis was performed using RevMan software, and the data presented are as odds ratios for dichotomous outcomes and as mean differences (MDs) and standard MDs for continuous outcomes. RESULTS: Four randomized, controlled trials including 419 patients were analyzed. Mortality risk was significantly reduced in goal-directed therapy-treated patients, compared to the control group(OR=0.56, 95%CI: 0.34-0.92). Intensive care (MD: 3.7 days 95%CI: 1.06-6.5)and hospital length of stay (MD: 3.5 days,95%CI: 2.75-4.25) were significantly shorter in the protocol group patients.There were no differences in reported total fluid volume or blood transfusions administered. Heterogeneity in reporting among the studies prevented quantitative analysis of complications. CONCLUSION: Following severe trauma, early goal-directed therapy was associated with lower mortality and shorter durations of intensive care unit and hospital stays. The findings of this analysis should be interpreted with caution due to the presence of significant heterogeneity and the small number of th

Long- term outcome of paediatric patients with ANCA vasculitis

Background: Primary systemic vasculitis presenting in childhood is an uncommon but serious condition. As these patients transfer to adult clinics for continuing care, defining long term outcomes with emphasis on disease and treatment-related morbidity and mortality is important. The aim of this study is to describe the long-term clinical course of paediatric patients with ANCA vasculitis.Methods: The adult patients in our vasculitis clinics who had presented in childhood, with a follow up time of greater than 10 years were included. We also reviewed the literature for articles describing the clinical outcome of paediatric patients with ANCA vasculitis.Results: We describe the clinical course of 8 adults who presented in childhood with ANCA vasculitis. 7 patients had Wegener's granulomatosis and 1 had microscopic polyangiitis. The median age at presentation was 11.5 years, and follow up time ranged form 11 to 30 years. Induction therapy for all patients was steroids and/or cyclophosphamide. Maintenance therapy was with azathioprine or mycophenolate mofetil. Biological agents were used in 3 patients for relapsed disease in adulthood only. Seven patients achieved complete remission. All patients experienced disease relapse, with a median of 4 episodes. Kidney function was generally well preserved, with median eGFR 76 ml/min. Only one patient developed end-stage renal failure and one patient died after 25 years of disease. Treatment-related morbidity rates were high; 7 suffered from infections, 4 were infertile, 2 had skeletal complications, and 1 developed malignancy.Conclusion: Close long-term follow up of paediatric patients with ANCA vasculitis is imperative, as this patient cohort is likely to live long enough to develop significant treatment and disease-related morbidities. Prospective cohort studies with novel therapies including paediatric patients are crucial to help us determine the best approach to managing this complex group of patients. In addition, although not yet observed in our series, late cardiovascular morbidity remains a major longer-term potential concern for adult survivors of paediatric vasculitis

Clinical review: Goal-directed therapy - what is the evidence in surgical patients? The effect on different risk groups

Patients with limited cardiac reserve are less likely to survive and develop more complications following major surgery. By augmenting oxygen delivery index (DO2I) with a combination of intravenous fl uids and inotropes (goaldirected therapy (GDT)), postoperative mortality and morbidity of high-risk patients may be reduced. However, although most studies suggest that GDT may improve outcome in high-risk surgical patients, it is still not widely practiced. We set out to test the hypothesis that GDT results in greatest benefi t in terms of mortality and morbidity in patients with the highest risk of mortality and have undertaken a systematic review of the current literature to see if this is correct. We performed a systematic search of Medline, Embase and CENTRAL databases for randomized controlled trials (RCTs) and reviews of GDT in surgical patients. To minimize heterogeneity we excluded studies involving cardiac, trauma, and paediatric surgery. Extremely high risk, high risk and intermediate risks of mortality were defi ned as >20%, 5 to 20% and <5% mortality rates in the control arms of the trials, respectively. Metaanalyses were performed and Forest plots drawn using RevMan software. Data are presented as odd ratios (OR; 95% confi dence intervals (CI), and P-values). A total of 32 RCTs including 2,808 patients were reviewed. All studies reported mortality. Five studies (including 300 patients) were excluded from assessment of complication rates as the number of patients with complications was not reported. The mortality benefi t of GDT was confi ned to the extremely high-risk group (OR = 0.20, 95% CI 0.09 to 0.41; P < 0.0001). Complication rates were reduced in all subgroups (OR = 0.45, 95% CI 0.34 to 0.60; P < 0.00001). The morbidity benefi t was greatest amongst patients in the extremely high-risk subgroup (OR = 0.27, 95% CI 0.15 to 0.51; P < 0.0001), followed by the intermediate risk subgroup (OR = 0.43, 95% CI 0.27 to 0.67; P = 0.0002), and the high-risk subgroup (OR 0.56, 95% CI 0.36 to 0.89; P = 0.01). Despite heterogeneity in trial quality and design, we found GDT to be beneficial in all high-risk patients undergoing major surgery. The mortality benefit of GDT was confined to the subgroup of patients at extremely high risk of death. The reduction of complication rates was seen across all subgroups of GDT patients

FIGO postpartum intrauterine device initiative: Complication rates across six countries.

OBJECTIVE: To record and analyze complication rates following postpartum intrauterine device (PPIUD) insertion in 48 hospitals in six countries: Sri Lanka, India, Nepal, Bangladesh, Tanzania, and Kenya. METHODS: Healthcare providers were trained in counselling and insertion of PPIUD via a training-the-trainer model. Data were collected on methodology, timing, cadre of staff providing care, and number of insertions. Data on complications were collected at 6-week follow-up. Statistical analysis was performed to elucidate factors associated with increased expulsion and absence of threads. RESULTS: From May 2014 to September 2017, 36 766 PPIUDs were inserted: 53% vaginal and 47% at cesarean delivery; 74% were inserted by doctors. Follow-up was attended by 52%. Expulsion and removal rates were 2.5% and 3.6%, respectively. Threads were not visible in 29%. Expulsion was less likely after cesarean insertion (aOR 0.33; 95% CI, 0.26-0.41), following vaginal insertion at between 10 minutes and 48 hours (aOR 0.59; 95% CI, 0.42-0.83), and when insertion was performed by a nurse (aOR 0.33; 95% CI, 0.22-0.50). CONCLUSION: PPIUD has low complication rates and can be safely inserted by a variety of trained health staff. Given the immediate benefit of the one-stop approach, governments should urgently consider adopting this model

Factors influencing the likelihood of acceptance of postpartum intrauterine devices across four countries: India, Nepal, Sri Lanka, and Tanzania.

OBJECTIVE: To examine the factors that positively influenced the likelihood of accepting provision of postpartum intrauterine devices (PPIUDs) across four countries: Sri Lanka, Nepal, Tanzania, and India. METHODS: Healthcare providers were trained across 24 facilities in counselling and insertion of PPIUDs as part of a large multicountry study. Women delivered were asked to take part in a 15-minute face-to-face structured interview conducted by in-country data collection officers prior to discharge. Univariate analysis was performed to investigate factors associated with acceptance. RESULTS: From January 2016 to November 2017, 6477 health providers were trained, 239 033 deliveries occurred, and 219 242 interviews were conducted. Of those interviewed, 68% were counselled on family planning and 56% on PPIUD, with 20% consenting to PPIUD. Multiple counselling sessions was the only factor resulting in higher consent rates (OR 1.30-1.39) across all countries. Odds ratios for women's age, parity, and cadre of provider counselling varied between countries. CONCLUSION: Consent for contraception, specifically PPIUD, is such a culturally specific topic and generalization across countries is not possible. When planning contraceptive policy changes, it is important to have an understanding of the sociocultural factors at play

P2X7 receptor and Sepsis-Induced Acute Kidney Injury

Acute kidney injury (AKI) is a common clinical problem within the intensive care unit. Sepsis is implicated in half the cases of AKI; in those patients requiring acute renal replacement therapy there is an associated mortality of 50%. However, other than maintenance of an adequate circulation, no specific therapy exists for septic AKI. This is in large part related to a poor understanding of the underlying pathophysiology.. I used a 72 hr clinically relevant, fluid-resuscitated rat model of sepsis and recovery to undertake a detailed temporal characterization of the pathophysiology of septic AKI and relevant biomarkers of kidney injury and dysfunction, and to assess the impact of targeted treatments. As with human studies, renal histology demonstrated minimal tissue injury or early inflammatory cell infiltration, however renal recovery was associated with a marked increase in renal macrophage infiltration. A panel of 8 renal biomarkers revealed that urine NGAL was the most sensitive marker, having risen by 3 hours’ post-insult and elevated for 24hrs. Renal blood flow was maintained over the first 24 hrs, however a fall in renal cortical oxygenation occurred despite similar renal oxygen delivery and utilization at 24 hrs. Though electron microscopy showed normal mitochondrial structure, I found an increased expression of mitochondrial uncoupling protein-2 (UCP-2); this may further uncouple mitochondrial respiration. Multiphoton imaging of live healthy kidney slices incubated in either sham or septic serum showed a rise in tubular reactive oxygen species (ROS) and falls in NADH and mitochondrial membrane potential in the septic serum group, findings that are consistent with uncoupling. Pre-incubation with the ROS scavenger, 4-OHTEMPO, prevented these effects. The NLRP3 inflammasome plays an important role in pro-inflammatory cytokine production. A NLRP3 inflammasome inhibitor, P2X7 antagonist, prevented LPS-induced IL-1β production by peripheral blood monocytes in vitro, however this was related in part to its diluent vehicle, dimethyl sulfoxide (DMSO). In the kidney, proximal tubular P2X7 and caspase-1 expression was seen both in vivo and ex vivo during sepsis. DMSO/P2X7 antagonist treatment after the onset of sepsis was associated with reduced renal IL-1β expression and improvements in tachycardia, stroke volume, albumin and lactate however effects on renal function were inconclusive. Further studies targeting the NLRP3 inflammasome in sepsis are warranted

The vaginal microbiome during pregnancy and the postpartum period in a European population

The composition and structure of the pregnancy vaginal microbiome may influence susceptibility to adverse pregnancy outcomes. Studies on the pregnant vaginal microbiome have largely been limited to Northern American populations. Using MiSeq sequencing of 16S rRNA gene amplicons, we characterised the vaginal microbiota of a mixed British cohort of women (n = 42) who experienced uncomplicated term delivery and who were sampled longitudinally throughout pregnancy (8–12, 20–22, 28–30 and 34–36 weeks gestation) and 6 weeks postpartum. We show that vaginal microbiome composition dramatically changes postpartum to become less Lactobacillus spp. dominant with increased alpha-diversity irrespective of the community structure during pregnancy and independent of ethnicity. While the pregnancy vaginal microbiome was characteristically dominated by Lactobacillus spp. and low alpha-diversity, unlike Northern American populations, a significant number of pregnant women this British population had a L. jensenii-dominated microbiome characterised by low alpha-diversity. L. jensenii was predominantly observed in women of Asian and Caucasian ethnicity whereas L. gasseri was absent in samples from Black women. This study reveals new insights into biogeographical and ethnic effects upon the pregnancy and postpartum vaginal microbiome and has important implications for future studies exploring relationships between the vaginal microbiome, host health and pregnancy outcomes