41 research outputs found
Systematic monitoring of needs for care and global outcomes in patients with severe mental illness
<p>Abstract</p> <p>Background</p> <p>It was hypothesised that the introduction of tools that allow clinicians to assess patients' needs and to negotiate treatment (Cumulative Needs for Care Monitor; CNCM), would be associated with global outcome improvements in patients diagnosed with severe mental illness.</p> <p>Methods</p> <p>The CNCM was introduced in one region in South Limburg (the Netherlands) in 1998 (REGION-1998) and in the rest of South Limburg in 2004 (REGION-2004). By comparing these two regions, changes after the introduction of the CNCM could be assessed (between-region comparison). In addition, a pre-post within-patient comparison was conducted in both regions.</p> <p>Results</p> <p>The within-patient comparison revealed that global outcomes of psychopathology and impairment improved in the first 3-5 years after the introduction of the CNCM. The between-region comparison revealed an improvement in global psychopathology but not in global impairment in REGION-2004 after 2004, while there was no such improvement in REGION-1998.</p> <p>Conclusion</p> <p>Systematic clinical monitoring of individual severe mental illness patients, in combination with provision of feedback, is associated with global improvement in psychopathology. More research is needed to determine the degree to which this association reflects a causal effect.</p
Preclinical characterization and target validation of the antimalarial pantothenamide MMV693183.
Drug resistance and a dire lack of transmission-blocking antimalarials hamper malaria elimination. Here, we present the pantothenamide MMV693183 as a first-in-class acetyl-CoA synthetase (AcAS) inhibitor to enter preclinical development. Our studies demonstrate attractive drug-like properties and in vivo efficacy in a humanized mouse model of Plasmodium falciparum infection. The compound shows single digit nanomolar in vitro activity against P. falciparum and P. vivax clinical isolates, and potently blocks P. falciparum transmission to Anopheles mosquitoes. Genetic and biochemical studies identify AcAS as the target of the MMV693183-derived antimetabolite, CoA-MMV693183. Pharmacokinetic-pharmacodynamic modelling predict that a single 30âmg oral dose is sufficient to cure a malaria infection in humans. Toxicology studies in rats indicate aâ\u3eâ30-fold safety margin in relation to the predicted human efficacious exposure. In conclusion, MMV693183 represents a promising candidate for further (pre)clinical development with a novel mode of action for treatment of malaria and blocking transmission
Meeting Report: ESC Forum on Drug Eluting Stents European Heart House, Nice, 27-28 September 2007
A real-life observational study of the effectiveness of FACT in a Dutch mental health region
<p>Abstract</p> <p>Background</p> <p>ACT is an effective community treatment but causes discontinuity of care between acutely ill and currently stable patient groups. The Dutch variant of ACT, FACT, combines both intensive ACT treatment and care for patients requiring less intensive care at one time point yet likely to need ACT in the future. It may be hypothesised that this case mix is not beneficial for patients requiring intensive care, as other patient groups may "dilute" care provision. The effectiveness of FACT was compared with standard care, with a particular focus on possible moderating effects of patient characteristics within the case mix in FACT.</p> <p>Methods</p> <p>In 2002, three FACT teams were implemented in a Dutch region in which a cumulative routine outcome measurement system was in place. Patients receiving FACT were compared with patients receiving standard treatment, matched on "baseline" symptom severity and age, using propensity score matching. Outcome was the probability of being in symptomatic remission of psychotic symptoms.</p> <p>Results</p> <p>The probability of symptomatic remission was higher for SMI patients receiving FACT than for controls receiving standard treatment, but only when there was an unmet need for care with respect to psychotic symptoms (OR = 6.70, p = 0.002; 95% CI = 1.97 â 22.7).</p> <p>Conclusion</p> <p>Compared to standard care, FACT was more rather than less effective, but only when a need for care with respect to psychotic symptoms is present. This suggests that there is no adverse effect of using broader patient mixes in providing continuity of care for all patients with severe mental illness in a defined geographical area.</p
The cumulative needs for care monitor: a unique monitoring system in the south of the Netherlands
Into the dark serum proteome: personalized features of IgG1 and IgA1 repertoires in severe COVID-19 patients
Serum proteomics has matured and is now able to monitor hundreds of proteins quantitatively in large cohorts of patients. However, the fine characteristics of some of the most dominant proteins in serum, the immunoglobulins, are in these studies often ignored, due to their vast, and highly personalized, diversity in sequences. Here, we focus exclusively on these personalized features in the serum proteome and distinctively chose to study individual samples from a low diversity population: elderly donors infected by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). By using mass spectrometry-based methods, immunoglobulin IgG1 and IgA1 clonal repertoires were monitored quantitatively and longitudinally in more than 50 individual serum samples obtained from 17 Corona virus disease 2019 patients admitted to intensive care units. These clonal profiles were used to examine how each patient reacted to a severe SARS-CoV-2 infection. All 17 donors revealed unique polyclonal repertoires and substantial changes over time, with several new clones appearing following the infection, in a few cases leading to a few, very high, abundant clones dominating their repertoire. Several of these clones were de novo sequenced through combinations of top-down, middle-down, and bottom-up proteomics approaches. This revealed sequence features in line with sequences deposited in the SARS-CoV-specific antibody database. In other patients, the serological Ig profiles revealed the treatment with tocilizumab, that subsequently dominated their serological IgG1 repertoire. Tocilizumab clearance could be monitored, and a half-life of approximately 6 days was established. Overall, our longitudinal monitoring of IgG1 and IgA1 repertoires of individual donors reveals that antibody responses are highly personalized traits of each patient, affected by the disease and the chosen clinical treatment. The impact of these observations argues for a more personalized and longitudinal approach in patients' diagnostics, both in serum proteomics as well as in monitoring immune responses
Whole-epigenome analysis in multiple myeloma reveals DNA hypermethylation of B cell-specific enhancers
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Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures
Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 nonâcritically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (nâ=â257), ARB (nâ=â248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; nâ=â10), or no RAS inhibitor (control; nâ=â264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ supportâfree days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ supportâfree days among critically ill patients was 10 (â1 to 16) in the ACE inhibitor group (nâ=â231), 8 (â1 to 17) in the ARB group (nâ=â217), and 12 (0 to 17) in the control group (nâ=â231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ supportâfree days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570