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1.
Eur J Gastroenterol Hepatol ; 35(4): 384-393, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36827533

ABSTRACT

GOALS: Assess outcomes in patients with an index presentation of spontaneous bacterial peritonitis (SBP) over a 13-year period. BACKGROUND: SBP, a bacterial infection of ascites, has a poor prognosis. STUDY: Retrospective cohort study assessing mortality (standardised to 32 months) and prognostic factors in patients with SBP during two periods: period 1 (June 2006-November 2012) and period 2 (December 2012-May 2019). RESULTS: The study included 178 patients who were followed up for 11.6 (29.2) months. Mortality was high, with 12-, 24- and 32-month survival being 32%, 26% and 24%, respectively. Inpatient mortality was 36% with mortality in those surviving hospitalisation being 62%. Serum creatinine at the time of SBP diagnosis was an independent predictor of mortality at 32 months [hazard ratio (HR) 1.002, P = 0.023] and inpatient mortality (HR 1.003, P = 0.035). Positive ascitic fluid culture and ascitic fluid neutrophil count were independent predictors of 32-month (HR 1.679, P = 0.008) and inpatient mortality (HR 1.0001, P = 0.005), respectively. Patients in period 2 had lower ascitic fluid albumin (5.9 ± 3.3 g/L vs. 10.8 ± 5.4 g/L, P < 0.001), higher ascitic fluid neutrophil count (815.0 cells/mm3 vs. 345.0 cells/mm3, P < 0.001) and higher rates of hepatorenal syndrome-acute kidney injury (58 vs. 35%, P = 0.002). Mortality at 32 months and mortality in those surviving hospitalisation were similar at 78 vs. 73%, P = 0.392 and 66 vs. 58%, P = 0.355, for periods 1 and 2, respectively. CONCLUSIONS: Despite more advanced initial presentations, mortality rates have remained similar over the last 13 years. Serum creatinine at the time of SBP diagnosis is an independent predictor of mortality.


Subject(s)
Bacterial Infections , Peritonitis , Humans , Liver Cirrhosis/diagnosis , Retrospective Studies , Creatinine , Ascitic Fluid/microbiology , Ascites , Bacterial Infections/diagnosis , Peritonitis/microbiology , Hospitalization
2.
J Psychopharmacol ; 35(5): 501-511, 2021 05.
Article in English | MEDLINE | ID: mdl-33345689

ABSTRACT

RATIONALE: Novel, evidence-based treatments are required for treatment-resistant post-traumatic stress disorder (PTSD). 3,4-Methylenedioxymethamphetamine (MDMA) has beneficially augmented psychotherapy in several small clinical trials. OBJECTIVE: To review the use of MDMA-assisted psychotherapy in treatment-resistant PTSD. METHODS: Systematic searches of four databases were conducted from inception to February 2020. A meta-analysis was performed on trials which were double-blinded, randomised, and compared MDMA-assisted psychotherapy to psychotherapy and placebo. The primary outcomes were the differences in Clinician Administered PTSD Scale (CAPS-IV) score and Beck's Depression Inventory (BDI). Secondary outcome measures included neurocognitive and physical adverse effects, at the time, and within 7 days of intervention. RESULTS: Four randomised controlled trials (RCTs) met inclusion criteria. When compared to active placebo, intervention groups taking 75 mg (MD -46.90; 95% (confidence intervals) CI -58.78, -35.02), 125 mg (MD -20.98; 95% CI -34.35, -7.61) but not 100 mg (MD -12.90; 95% CI -36.09, 10.29) of MDMA with psychotherapy, had significant decreases in CAPS-IV scores, as did the inactive placebo arm (MD -33.20; 95% CI -40.53, -25.87). A significant decrease in BDI when compared to active placebo (MD -10.80; 95% CI -20.39, -1.21) was only observed at 75 mg. Compared to placebo, participants reported significantly more episodes of low mood, nausea and jaw-clenching during sessions and lack of appetite after 7 days. CONCLUSION: These results demonstrate potential therapeutic benefit with minimal physical and neurocognitive risk for the use of MDMA-assisted psychotherapy in TR-PTSD, despite little effect on Beck's Depression Inventory. Better powered RCTs are required to investigate further. INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS: CRD42019109132 available online at www.crd.york.ac.uk/prospero.


Subject(s)
N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage , Psychotherapy/methods , Stress Disorders, Post-Traumatic/therapy , Combined Modality Therapy , Hallucinogens/administration & dosage , Hallucinogens/adverse effects , Humans , N-Methyl-3,4-methylenedioxyamphetamine/adverse effects , Psychiatric Status Rating Scales , Randomized Controlled Trials as Topic , Stress Disorders, Post-Traumatic/physiopathology , Treatment Outcome
3.
Cereb Cortex ; 30(6): 3573-3589, 2020 05 18.
Article in English | MEDLINE | ID: mdl-32083297

ABSTRACT

Choosing actions that result in advantageous outcomes is a fundamental function of nervous systems. All computational decision-making models contain a mechanism that controls the variability of (or confidence in) action selection, but its neural implementation is unclear-especially in humans. We investigated this mechanism using two influential decision-making frameworks: active inference (AI) and reinforcement learning (RL). In AI, the precision (inverse variance) of beliefs about policies controls action selection variability-similar to decision 'noise' parameters in RL-and is thought to be encoded by striatal dopamine signaling. We tested this hypothesis by administering a 'go/no-go' task to 75 healthy participants, and measuring striatal dopamine 2/3 receptor (D2/3R) availability in a subset (n = 25) using [11C]-(+)-PHNO positron emission tomography. In behavioral model comparison, RL performed best across the whole group but AI performed best in participants performing above chance levels. Limbic striatal D2/3R availability had linear relationships with AI policy precision (P = 0.029) as well as with RL irreducible decision 'noise' (P = 0.020), and this relationship with D2/3R availability was confirmed with a 'decision stochasticity' factor that aggregated across both models (P = 0.0006). These findings are consistent with occupancy of inhibitory striatal D2/3Rs decreasing the variability of action selection in humans.


Subject(s)
Decision Making/physiology , Learning/physiology , Neostriatum/metabolism , Receptors, Dopamine D2/metabolism , Receptors, Dopamine D3/metabolism , Reinforcement, Psychology , Adult , Bayes Theorem , Choice Behavior/physiology , Dopamine Agonists , Female , Humans , Male , Neostriatum/diagnostic imaging , Oxazines , Positron-Emission Tomography , Young Adult
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