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Postoperative antibiotic strategies in acute complicated appendicitis: a systematic review
Get PDFAcute appendicitis is a common surgical emergency, with complicated cases carrying an increased risk of infections and morbidity. Whilst preoperative antibiotics help reduce infections, the optimal postoperative regimen remains undefined. Variability exists in antibiotic choice, route and duration. This review aimed to examine recent evidence on postoperative antibiotic stewardship for complicated appendicitis to guide optimal treatment strategies. A systematic review was conducted in accordance with PRISMA guidelines and registered in the PROSPERO registry. A search on PubMed and Cochrane library databases identified studies on postoperative antibiotic use in appendicectomy. Two independent reviewers screened studies, including RCTs, cohort studies and observational studies. Data extraction covered study characteristics, interventions and outcomes. Risk of bias was assessed using RoB 2 and ROBINS-I, with GRADE used to evaluate evidence certainty. This review included 11 studies with 8361 participants. Shorter intravenous antibiotic courses (2–6 days) were found to be non-inferior to longer regimens in preventing infections and reducing hospital stays. Risk factors for prolonged antibiotic use included disease severity and surgical complexity. In selected patients, oral antibiotics were shown to be equally effective. Shorter intravenous antibiotic courses and early transition to oral antibiotics effectively managed complicated appendicitis, reducing hospital stays and healthcare costs without increasing complications. Individualised treatment decisions based on patient risk factors and intraoperative findings are essential. Tailoring antibiotic regimens to individual patient characteristics remains crucial. These findings support antibiotic stewardship efforts and highlight the need for further research, particularly in high-risk population
Current and novel approaches for critical care management of aneurysmal subarachnoid hemorrhage in critical care
No full textPurpose of the review
This review highlights recent advancements and evidence-based approaches in the critical care management of aneurysmal subarachnoid hemorrhage (aSAH), focusing on developments from the past 18 months. It addresses key challenges [rebleeding prevention, delayed cerebral ischemia (DCI), hydrocephalus, transfusion strategies, and temperature management], emphasizing multidisciplinary care and personalized treatment.
Recent findings
Recent studies underscore the importance of systolic blood pressure control (<160 mmHg) to reduce rebleeding risk before aneurysm securing. Novel prognostic tools, including the modified 5-item frailty index and quantitative imaging software, show promise in improving outcome prediction. Prophylactic lumbar drainage may reduce DCI and improve neurological outcomes, while milrinone and computed tomography perfusion-guided therapies are being explored for vasospasm management. Transfusion strategies suggest a hemoglobin threshold of 9 g/dl may optimize outcomes. Temperature management remains contentious, but consensus recommends maintaining normothermia (36.0–37.5 °C) with continuous monitoring.
Summary
Advances in aSAH care emphasize precision medicine, leveraging technology [e.g. Artificial intelligence (AI), quantitative imaging], and multidisciplinary collaboration. Key unresolved questions warrant multicenter trials to validate optimal blood pressure, transfusion, and temperature targets alongside emerging therapies for DCI
Fragility Fracture Network Position on Unrestricted Weight-Bearing After Hip Fracture Surgery
Get PDFObjectives
This position paper from the Fragility Fracture Network (FFN) responds to the observed global variation in weight-bearing prescriptions after hip fracture surgery in older adults.
Methods
The paper summarises current guidelines and evidence regarding unrestricted weight-bearing after hip fracture surgery.
Results
The synthesis of available evidence supports the endorsement of unrestricted weight-bearing after surgery to enhance patient outcomes.
Conclusion
The FFN endorses unrestricted weight-bearing and recommends healthcare professionals, institutions, and policymakers re-evaluate practices favouring limited or non-weight-bearing prescriptions and establish a standardised system for monitoring and auditing, with clear justification and documentation of any restrictions
Progress on the Global Research Agenda for Antimicrobial Resistance in Human Health in Pakistan: Findings and Implications
Get PDFBackground and Objective: Antimicrobial resistance (AMR) poses a formidable challenge to global public health, with low- and middle-income countries (LMICs) including Pakistan being particularly vulnerable. This study assesses the progress made in Pakistan following the Global Research Agenda for AMR, which builds on the key activities and goals of its national action plan to reduce AMR. The intention is to identify key gaps, achievements, and future areas of focus to help reduce rising AMR rates in Pakistan.
Methods: Utilizing a systematic-narrative hybrid literature review methodology approach, recent research publication and policy initiatives related to AMR, including those published on the internet, were examined and documented.
Findings: The findings from 349 published studies were divided into the 40 research priority areas. This included 23 papers (9.95%) specifically related to prevention and 55 (22.9%) to diagnosis, 64 (26.7%) for treatment and care of patients with infectious diseases, 59 (24.5%) for cross-cutting, and 44 (18.33%) for drug-resistant tuberculosis (TB). Currently, research on AMR in Pakistan is primarily concentrated in major urban centers across a limited number of cities. This needs addressing going forward. To effectively combat AMR in Pakistan, prioritizing prevention is crucial to curb disease spread and reduce reliance on prophylactic treatments, especially inappropriate prescribing and dispensing of antimicrobials. Enhancing diagnostic facilities, strengthening antimicrobial surveillance systems and promoting appropriate management of patients with infectious diseases, supported by robust antimicrobial stewardship programs, can also help enhance judicious antibiotic use in Pakistan and reduce AMR going forward.
Conclusion and Interpretation: There are ongoing concerns regarding current research activities in Pakistan to reduce AMR. The pathway forward in Pakistan includes leveraging global partnerships to share knowledge, resources, and strategies to enhance the use of Access antibiotics as well as reduce AMR to reach agreed United Nations’ goals
Potential ways to improve the supply and use of quality-assured antibiotics across sectors in developing countries to reduce antimicrobial resistance
Get PDFLow/High Multi‐Frequency Stimulation of the Subthalamic Nucleus Improves Verbal Fluency Maintaining Motor Control in Parkinson's Disease
Get PDFBackground
High frequency deep brain stimulation of the subthalamic nucleus (STN‐DBS) is a well‐established therapy for Parkinson's disease (PD) motor symptoms, however, its effect on non‐motor symptoms is controversial. Low frequency DBS can improve cognition, but its effects on motor functions are detrimental.
Objective
Our goal was to evaluate the effect on verbal fluency (VF) of dual frequency STN‐DBS combining high and low frequency (130 + 10 Hz) as compared to 130 Hz or 10 Hz alone and to OFF stimulation. The effect on motor symptoms, working memory, and subjective feelings was also assessed.
Methods
We used a randomized order of experimental conditions with a double‐blind design to assess the effects of 130 Hz, 10 Hz, and 130 + 10 Hz stimulation as compared to OFF stimulation in 18 PD patients with STN‐DBS. In each condition, participants completed: phonemic and action VF, N‐back task, and visual analogue scales for fatigue and stress level. Motor functions and gait velocity were also assessed.
Friedman analysis of variance were conducted to determine whether change scores from baseline OFF stimulation, in our primary (VF) and secondary outcomes measures (motor functions, N‐back task, subjective feelings) were different in the three stimulation conditions.
Results
VF improved more in the 130 + 10 Hz condition than 130 Hz condition (P = 0.006); there was no difference between 130 + 10 Hz and 10 Hz (P = 0.2) and between 130HZ and 10 Hz (P = 0.6). There was a significant difference among the stimulation conditions for the motor score (χ2(2) = 11.1, P = 0.004), it being worse at 10 Hz than 130 Hz (P = 0.002) and 130 + 10 Hz (P = 0.01).
Conclusions
Dual frequency STN‐DBS improves phonemic VF while maintaining a beneficial effect on motor signs of PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
The 2025 British Society for Rheumatology management recommendations for ANCA-associated vasculitis
Get PDFANCA-associated vasculitis (AAV) is comprised of three specific conditions: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Since the publication of the last British Society for Rheumatology (BSR) and British Health Professionals in Rheumatology (BHPR) guideline for the management of adults with AAV in 2014, a plethora of randomized controlled trials, additional research and recommendations have provided novel insights into how the management of AAV can be optimized, thus improving patient quality of life. The BSR AAV Working Group (WG) reviewed published guidelines, undertook a systematic literature review and utilized expertise from specialist vasculitis centres across the UK and patient representatives to formulate a list of 26 recommendations with corresponding strength of agreement (SOA) scores. Recommendations were updated from the published 2014 BSR and BHPR guideline. The 26 recommendations encompassed five key domains: 1. Treatment for GPA and MPA; 2. Management of subglottic stenosis and ear, nose and throat (ENT) manifestations of AAV; 3. Management and treatment for EGPA; 4. Service specifications; 5. Patient education and support. These recommendations provide an update on care delivery of AAV based on current evidence and specialist opinion. In addition, we have provided research and audit recommendations to support equitable access to care and improve health outcomes. The lay summary that accompanies this abstract can be found in Supplementary Data S1, available at Rheumatology online
Liposomal amphotericin B prophylaxis in paediatrics: a systematic review
Get PDFBackground
Liposomal amphotericin B (LAmB) is widely used for prophylaxis in paediatric patients at high risk of invasive fungal diseases (IFD) but its use is off-label and there is significant variability in dosage and frequency. This systematic review was conducted to evaluate the published data on prophylactic LAmB use in the paediatric population and to present the reported proportions of breakthrough IFD and the associated toxicity profile.
Methods
EMBASE, Medline, Web of Science and the Cochrane Database were systematically searched for primary research reporting on the use of LAmB as prophylaxis for IFD in the paediatric population up to 7 December 2023, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Results
Twenty studies, comprising three clinical trials, 12 cohort studies, two point-prevalence surveys and three pharmacokinetic (PK) studies, with 2015 patients were included. A total of 717 cases presented individual patient data. Breakthrough IFD occurred in 7.2% (49/676). The most recognized side effects were hypokalaemia in 23.2% (125/538) and derangement of liver function tests in 15.0% (49/327). Discontinuation due to toxicity occurred in 6.0% (30/503) of patients. Of the four studies reporting PK data, two examined serum levels of LAmB, one analysed CSF levels and the remaining study peritoneal levels.
Conclusions
Despite widespread use of prophylactic LAmB, this systematic review highlights the paucity of paediatric data supporting its use. The heterogeneity observed in populations, dosing regimens and study design prevents conclusions being reached on its efficacy or the superiority of one dosing regimen. Overall, there is a clear need for further high-quality robust clinical data and targeted PK studies
All-cause mortality and infection-related outcomes of hospital-initiated kangaroo care versus conventional neonatal care for low-birthweight infants: a systematic review and meta-analysis
Get PDFBackground
Kangaroo care has a well-established role in preterm infant stabilisation and in protecting low-birthweight newborns from mortality. Yet kangaroo care is far from fully embedded in conventional inpatient neonatal care practice. The evidence on infection outcomes of hospital-initiated kangaroo care is unclear. We aimed to evaluate the existing evidence to understand the role of hospital-initiated kangaroo care in preventing mortality, sepsis, and invasive infection in low-birthweight infants.
Methods
In this systematic review and meta-analysis, we searched Embase, MEDLINE, Cochrane Library, and Web of Science databases for literature published between Jan 1, 2013, and Feb 26, 2025. At least two authors independently undertook study selection, data extraction, and quality assessment. Reports of randomised controlled trials presenting data on at least one of our set primary outcomes (all-cause mortality and/or sepsis and/or invasive infection) comparing kangaroo care with conventional neonatal care in low-birthweight infants (<2500 g) were eligible for inclusion. The primary outcomes were all-cause mortality, sepsis, and invasive infection (composite of necrotising enterocolitis, pneumonia, meningitis, and other severe infections). Hypothermia and apnoea were assessed as adverse events. A random effects model was used to estimate the pooled overall effect sizes for each outcome, presented as odds ratios (OR [95% CI]), with between-study heterogeneity assessed by Cochran's Q test and sources of heterogeneity investigated using univariable random effects meta-regression analyses. This study is registered with PROSPERO, CRD42024501546.
Findings
We synthesised data from 29 studies, mainly from lower-middle income countries, including 17 513 low-birthweight infants. Most studies were moderate-to-high quality. 25 (86%) of 29 studies reporting all-cause mortality were included in the meta-analysis of hospital-initiated kangaroo care, which showed that hospital-initiated kangaroo care reduced all-cause mortality (pooled OR 0·77 [95% CI 0·67–0·89]; high-quality evidence, with I2=0%). 17 (59%) of 29 trials reported sepsis as an outcome, and the pooled results showed that kangaroo care reduced the odds of sepsis (OR 0·55 [95% CI 0·37–0·82]; moderate-quality evidence, with I2 =53%). Similarly, among the 11 (38%) of 29 studies reporting invasive infection, the pooled results showed that kangaroo care reduced the odds of invasive infection (OR 0·49 [95% CI 0·33–0·74]; moderate-quality evidence, with I2 =0%). Kangaroo care was associated with a significant reduction in the odds of sepsis-related or invasive infection-related mortality (OR 0·63 [95% CI 0·47–0·84], I2 =0%, high-quality evidence), hypothermia (0·28 [0·16–0·46], I2 =72%, moderate-quality evidence), and apnoea (0·46 [0·25–0·85], I2 =45%, moderate-quality evidence). Meta-regression showed that between-study heterogeneity was due to variation in level of kangaroo care offered as part of conventional neonatal care.
Interpretation
The joint protective effect of hospital-initiated kangaroo care against all-cause mortality and infection in low-birthweight infants reinforces its importance in routine neonatal care across settings, in line with WHO recommendations. The extent of the protective effects in low-birthweight infants through averted infections suggests that kangaroo care should be integrated into standard infection prevention and control practice globally.
Funding
European Society for Paediatric Infectious Diseases, the EU, and the Machaon Foundation
Astrocytic RNA editing regulates the host immune response to alpha-synuclein
Get PDFRNA editing is a posttranscriptional mechanism that targets changes in RNA transcripts to modulate innate immune responses. We report the role of astrocyte-specific, ADAR1-mediated RNA editing in neuroinflammation in Parkinson’s disease (PD). We generated human induced pluripotent stem cell–derived astrocytes, neurons and cocultures and exposed them to small soluble alpha-synuclein aggregates. Oligomeric alpha-synuclein triggered an inflammatory glial state associated with Toll-like receptor activation, viral responses, and cytokine secretion. This reactive state resulted in loss of neurosupportive functions and the induction of neuronal toxicity. Notably, interferon response pathways were activated leading to up-regulation and isoform switching of the RNA deaminase enzyme, ADAR1. ADAR1 mediates A-to-I RNA editing, and increases in RNA editing were observed in inflammatory pathways in cells, as well as in postmortem human PD brain. Aberrant, or dysregulated, ADAR1 responses and RNA editing may lead to sustained inflammatory reactive states in astrocytes triggered by alpha-synuclein aggregation, and this may drive the neuroinflammatory cascade in Parkinson’s
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