Opioids are frequently prescribed for the management of patients with chronic non-cancer pain (CNCP). Previous meta-analyses of efficacy and harms have combined treatment effects across all opioids; ...however, specific opioids, pharmacokinetic properties (ie, long acting vs short acting), or the type of formulation (ie, immediate vs extended release) may be a source of heterogeneity for pooled effects.
We will conduct a network meta-analysis (NMA) of randomized controlled trials evaluating opioids for CNCP. We will acquire eligible studies through systematic searches of EMBASE, MEDLINE, CINAHL, AMED, PsycINFO, and the Cochrane Central Registry of Controlled Trials (CENTRAL). Eligible studies will have randomly allocated adult CNCP patients to an oral or transdermal opioid versus another type of opioid (or formulation) or placebo, and follow patients for ≥ 4 weeks. We will collect outcome data for pain intensity, physical function, nausea, vomiting, and constipation. Pairs of reviewers will, independently and in duplicate, abstract data from eligible trials and assess risk of bias using a modified Cochrane tool. We will assess coherence of our networks through both a global test, and by comparing direct and indirect evidence for each comparison with node-splitting.
Using a frequentist approach, we will conduct random effects multiple treatment meta-analysis to establish treatment effects of individual opioids for each outcome. The certainty of evidence for pooled treatment effects will be assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. We will categorize interventions from most to least effective based on the effect estimates obtained from NMAs and their associated certainty of evidence, as follows: superior to both placebo and alternatives; superior to placebo, but inferior to alternatives; and no better than placebo.
This NMA will determine the relative effectiveness and adverse effects of individual opioids among patients with CNCP. Our results will help inform the appropriateness of assuming similar beneficial and adverse effects of varying opioid formulations.
This systematic review is registered with Prospective Register of Systematic Reviews, an international prospective register of systematic reviews (registration no.: CRD42018110331), available at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=110331.
There is a strong association between domestic violence victimization and HIV infection. This may lead to poor health outcomes including mental health disorders and reduced access to care. A ...standardized domestic violence screening interview was incorporated into ongoing care in the large and diverse population living with HIV in Southern Alberta, Canada. Results from May through December 2009 are reported, including the prevalence and outcomes of abuse. Thirty-four percent of 853 patients screened reported abuse. Of these, 16% reported abuse in their current relationship, 58% in a previous relationship, and 57% reported a history of childhood abuse. High-risk groups for abuse included females (43%), gay/bisexual males (35%), and Aboriginals (61%). We found an association between a history of domestic violence and delayed access to care (p < 0.05), missed appointments (p < 0.001), and an increased use of clinic resources such as social work (p < 0.0001) and psychiatry (p < 0.001). Mental health conditions prior to HIV diagnosis, including depression (p < 0.0001), suicidal ideation (p < 0.0001), and anxiety disorder (p < 0.0001) were associated with abuse at any time, while a history of adjustment disorder was associated with childhood abuse (p < 0.05). A simple domestic violence screening tool was helpful for identifying patients experiencing abuse in our diverse HIV-infected population. This high prevalence of domestic violence among our HIV patients was associated with poor outcomes and an increased use of medical resources. HIV caregivers should be aware of domestic violence in order to optimize care and refer patients to appropriate support professionals as needed.
Preexposure prophylaxis for HIV infection Siemieniuk, Reed A; Bogoch, Isaac I
The New England journal of medicine,
2015-Apr-30, Letnik:
372, Številka:
18
Journal Article
Highlights • Patients routinely present for HIV post-exposure prophylaxis (PEP); however there are many non-HIV-related needs that must be addressed in clinic. • 4.8% of patients presenting for PEP ...have a sexually transmitted infection. • 2.4% of patients presenting for PEP have chronic hepatitis C. • Over 20% of patients presenting for PEP do not have evidence of hepatitis B surface antibodies. • Many patients presenting for PEP have concomitant infections of public health importance. These clinics are an opportunity for health promotion and preventative medicine.
To explore the impact of applying the Grading of Recommendations and Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of the evidence in a published network ...meta-analysis (NMA) of antidepressant therapies.
We applied the GRADE approach to rate the certainty of the evidence for two outcomes, efficacy and acceptability, in each of the 66 paired comparisons within a previously published NMA assessing the relative efficacy and acceptability of 12 new-generation antidepressants.
For the outcome of efficacy, of the 25 comparisons in which the 95% CrI of OR excluded 1, 18 had certainty of evidence rated high or moderate. For the outcome of acceptability, of the 13 comparisons whose 95% CrI excluded 1, 10 had certainty of evidence rated high or moderate. Of the 11 comparisons involving sertraline, the antidepressants that the authors of the NMA suggested to be best, only 3 demonstrated it to be more effective and only 3 showed better tolerance, based on a 95% CrI excluding 1 and a high or moderate rating of certainty.
In this example, application of GRADE highlighted varying evidence certainty, led to more conservative conclusions, and potentially avoided unwarranted strong inferences based on low certainty evidence.
Background.
Seronegative human immunodeficiency virus (HIV) infections are exceedingly rare but might inform HIV-host physiology.
Methods.
We investigate the cause and consequences of a patient ...infected with HIV who did not mount a humoral response to HIV for 4 years.
Results.
The patient was confirmed HIV-uninfected by nucleic acid testing 4 months before rapidly progressing to acquired immune deficiency syndrome. The patient's humoral deficit was specific to HIV: he mounted robust humoral responses to all challenge vaccines including influenza A(H1N1)pdm09 and all T cell-dependent and -independent serotypes in the 23-valent pneumococcal polysaccharide vaccine. The virus had similar gp120 antigenicity to HIV-positive control serum as NL4-3 and YU2 prototype strains. Two human leukocyte antigen alleles associated with rapid progression were identified (B*08 and B*35), and a cytotoxic T-lymphocyte epitope site variant was noted: E277K. Viral decay (t
1/2 ≈ 39 weeks) suggested that relatively long-lived cells were the source of ongoing viremia. Human immunodeficiency virus viremia was not suppressed until after the patient developed a humoral immune response, despite therapeutic antiretroviral levels. No resistance was detected by virtual phenotyping of virus obtained from serum or from gastrointestinal biopsies despite considerable antiretroviral selection pressure.
Conclusions.
Ineffective antibody production may be associated with a subgroup of extremely rapid HIV progressors. Although antiretroviral therapy may be sufficient to slow propagation of infection, it appears to be ineffective for HIV viral clearance in the absence of a humoral response.
Objective
To develop an evidence‐based recommendation concerning the use of α‐blockers for uncomplicated ureteric stones based on an up‐to‐date Cochrane review, as the role of medical expulsive ...therapy for uncomplicated ureteric stones remains controversial in the light of new contradictory trial evidence.
Methods
We applied the Rapid Recommendations approach to guideline development, which represents an innovative approach by an international collaborative network of clinicians, researchers, methodologists and patient representatives seeking to rapidly respond to new, potentially practice‐changing evidence with recommendations developed according to standards for trustworthy guidelines.
Results
The panel suggests the use of α‐blockers in addition to standard care over standard care alone in patients with uncomplicated ureteric stones (weak recommendation based on low‐quality evidence). The panel judged that the net benefit of α‐blockers was small and that there was considerable uncertainty about patients’ values and preferences. This means that the panel expects that most patients would choose treatment with α‐blockers but that a substantial proportion would not. This recommendation applies to both patients in whom the presence of ureteric stones is confirmed by imaging, as well as patients in whom the diagnosis is made based on clinical grounds only.
Conclusion
The Rapid Recommendations panel suggests the use of α‐blockers for patients with ureteric stones. Shared decision‐making is emphasised in making the final choice between the treatment options.
ObjectiveTo investigate women’s values and preferences regarding antiretroviral therapy (ART) during pregnancy to inform a BMJ Rapid Recommendation.SettingPrimary studies reporting patient-reported ...outcomes relevant to decision-making regarding ART in any clinical and geographical setting.ParticipantsWomen living with HIV who are pregnant, postpartum or considering pregnancy.Outcome measuresQuantitative measurements and qualitative descriptions of values and preferences in relation to ART during pregnancy. We also included studies on women’s reported barriers and facilitators to adherence. We excluded studies correlating objective measures (eg, CD4 count) with adherence, or reporting only outcomes which are not expected to differ between ART alternatives (eg, access to services, knowledge about ART).ResultsWe included 15 qualitative studies reporting values and preferences about ART in the peripartum period; no study directly studied choice of ART therapy during pregnancy. Six themes emerged: a desire to reduce vertical transmission (nine studies), desire for child to be healthy (five studies), concern about side effects to the child (eight studies), desire for oneself to be healthy (five studies), distress about side effect to oneself (10 studies) and pill burden (two studies). None of the studies weighed the relative importance of these outcomes directly, but pill burden/medication complexity appears to be a lower priority for most women compared with other factors. Overall, the body of evidence was at low risk of bias, with minor limitations.ConclusionsWomen who are or may become pregnant and who are considering ART appear to place a high value on both their own and their children’s health. Evidence on the relative importance between these values when choosing between ART regimens is uncertain. There is variability in individual values and preferences among women. This highlights the importance of an individualised women-centred approach, such as shared decision-making when choosing between ART alternatives.Trial registration numberInternational Prospective Register of Systematic Reviews:CRD42017057157.
The optimal empiric antibiotic regimen for non–ventilator-associated hospital-acquired pneumonia (HAP) is uncertain.
To compare the effectiveness and safety of alternative empiric antibiotic regimens ...in HAP using a network meta-analysis.
Medline, EMBASE, Cochrane CENTRAL, Web of Science, and CINAHL from database inception to July 06, 2023.
RCTs.
Adults with clinical suspicion of HAP.
Any empiric antibiotic regimen vs. another, placebo, or no treatment.
Paired reviewers independently assessed risk of bias using a modified Cochrane tool for assessing risk of bias in randomized trials.
Paired reviewers independently extracted data on trial and patient characteristics, antibiotic regimens, and outcomes of interest. We conducted frequentist random-effects network meta-analyses for treatment failure and all-cause mortality and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach.
Thirty-nine RCTs proved eligible. Thirty RCTs involving 4807 participants found low certainty evidence that piperacillin-tazobactam (RR compared to all cephalosporins: 0.65; 95% CI: 0.42, 1.01) and carbapenems (RR compared to all cephalosporins: 0.77; 95% CI: 0.53, 1.11) might be among the most effective in reducing treatment failure. The findings were robust to the secondary analysis comparing piperacillin-tazobactam vs. antipseudomonal cephalosporins or antipseudomonal carbapenems vs. antipseudomonal cephalosporins. Eleven RCTs involving 2531 participants found low certainty evidence that ceftazidime and linezolid combination may not be convincingly different from cephalosporin alone in reducing all-cause mortality. Evidence on other antibiotic regimens is very uncertain. Data on other patient-important outcomes including adverse events was sparse, and we did not perform network or pairwise meta-analysis.
For empiric antibiotic therapy of adults with HAP, piperacillin-tazobactam might be among the most effective in reducing treatment failure. Empiric methicillin-resistant Staphylococcus aureus coverage may not exert additional benefit in reducing mortality.
PROSPERO (CRD 42022297224).
A strong inflammatory response to community-acquired pneumonia (CAP) is associated with excess morbidity and mortality. There is a growing interest in corticosteroids as an adjunctive treatment for ...patients hospitalized with CAP. We review recent randomized trials addressing the use of corticosteroids across the full range of CAP patients. Thirteen randomized controlled trials including 2005 patients have addressed the effect of short-term (single dose to 10 days) corticosteroid administration in patients with CAP. The results consistently show a shorter time to clinical stability and a shorter length of hospital stay on the order of 1 day. Some studies have also suggested a possible reduction in mortality. Adverse effects, primarily hyperglycemia and neuropsychiatric symptoms, are uncommon and neither serious nor prolonged. The results indicate a possibility that steroid administration should become a standard of care for patients with CAP.
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