Neonatal sepsis: a systematic review of core outcomes from randomised clinical trials

Background The lack of a consensus definition of neonatal sepsis and a core outcome set (COS) proves a substantial impediment to research that influences policy and practice relevant to key stakeholders, patients and parents. Methods A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In the included studies, the described outcomes were extracted in accordance with the provisions of the Core Outcome Measures in Effectiveness Trials (COMET) handbook and registered. Results Among 884 abstracts identified, 90 randomised controlled trials (RCTs) were included in this review. Only 30 manuscripts explicitly stated the primary and/or secondary outcomes. A total of 88 distinct outcomes were recorded across all 90 studies included. These were then assigned to seven different domains in line with the taxonomy for classification proposed by the COMET initiative. The most frequently reported outcome was survival with 74% (n = 67) of the studies reporting an outcome within this domain. Conclusions This systematic review constitutes one of the initial phases in the protocol for developing a COS in neonatal sepsis. The paucity of standardised outcome reporting in neonatal sepsis hinders comparison and synthesis of data. The final phase will involve a Delphi Survey to generate a COS in neonatal sepsis by consensus recommendation. Impact This systematic review identified a wide variation of outcomes reported among published RCTs on the management of neonatal sepsis. The paucity of standardised outcome reporting hinders comparison and synthesis of data and future meta-analyses with conclusive recommendations on the management of neonatal sepsis are unlikely. The final phase will involve a Delphi Survey to determine a COS by consensus recommendation with input from all relevant stakeholders.

Practical Consensus Recommendations for Optimizing Risk versus Benefit of Chemotherapy in Patients with HR Positive Her2 Negative Early Breast Cancer in India

Breast cancer is a public health challenge globally as well as in India. Improving outcome and cure requires appropriate biomarker testing to assign risk and plan treatment. Because it is documented that significant ethnic and geographical variations in biological and genetic features exist worldwide, such biomarkers need to be validated and approved by authorities in the region where these are intended to be used. The use of western guidelines, appropriate for the Caucasian population, can lead to inappropriate overtreatment or undertreatment in Asia and India. A virtual meeting of domain experts discussed the published literature, real-world practical experience, and results of opinion poll involving 185 oncologists treating breast cancer across 58 cities of India. They arrived at a practical consensus recommendation statement to guide community oncologists in the management of hormone positive (HR-positive) Her2-negative early breast cancer (EBC). India has a majority (about 50%) of breast cancer patients who are diagnosed in the premenopausal stage (less than 50 years of age). The only currently available predictive test for HR-positive Her2-negative EBC that has been validated in Indian patients is CanAssist Breast. If this test gives a score indicative of low risk (< 15.5), adjuvant chemotherapy will not increase the chance of metastasis-free survival and should not be given. This is applicable even during the ongoing COVID-19 pandemic.

The ESTMJS (European Society of Temporomandibular Joint Surgeons) Consensus and Evidence-Based Recommendations on Management of Condylar Dislocation

Although condylar dislocation is not uncommon, terminology, diagnostics, and treatment concepts vary considerably worldwide. This study aims to present a consensus recommendation based on systematically reviewed literature and approved by the European Society of TMJ Surgeons (ESTMJS). Based on the template of the evidence-based German guideline (register # 007-063) the ESTMJS members voted on 30 draft recommendations regarding terminology, diagnostics, and treatment initially via a blinded modified Delphi procedure. After unblinding, a discussion and voting followed, using a structured consensus process in 2019. An independent moderator documented and evaluated voting results and alterations from the original draft. Although the results of the preliminary voting were very heterogenous and differed significantly from the German S3 guideline (p < 0.0005), a strong consensus was achieved in the final voting on terminology, diagnostics, and treatment. In this voting, multiple alterations, including adding and discarding recommendations, led to 24 final recommendations on assessment and management of TMJ dislocation. To our knowledge, the ESTMJS condylar dislocation recommendations are the first both evidence and consensus-based international recommendations in the field of TMJ surgery. We recommend they form the basis for clinical practice guidelines for the management of dislocations of the mandibular condyle.

Colorectal cancer during pregnancy or postpartum: Case series and literature review

Background Colorectal cancer in young adults is on the rise. This rise combined with delayed childbearing increases the likelihood of colorectal cancer diagnosed during pregnancy or in the postpartum period. Methods Electronic health records were used to identify individuals with colorectal cancer in pregnancy or the postpartum period from 1 August 2007 to 1 August 2019. Results Forty-two cases were identified. Median age at diagnosis was 33 years. Most (93%) were diagnosed in an advanced stage (III or IV) and had left-sided colorectal cancer tumors (81%). Molecular analysis was completed in 18 (43%) women with microsatellite status available in 40 (95%). The findings were similar to historical controls. Sixty percent were diagnosed in the postpartum period. Common presenting symptoms were rectal bleeding and abdominal pain. Conclusion Currently there is no consensus recommendation regarding how to manage colorectal cancer during pregnancy. Given the overlapping symptoms with pregnancy, patients often present with advanced disease. We encourage all health care professionals caring for pregnant women to fully evaluate women with persistent gastrointestinal symptoms to rule out colorectal cancer.

Opioid safety recommendations in adult palliative medicine: a North American Delphi expert consensus

ObjectivesDespite the escalating public health emergency related to opioid-related deaths in Canada and the USA, opioids are essential for palliative care (PC) symptom management.Opioid safety is the prevention, identification and management of opioid-related harms. The Delphi technique was used to develop expert consensus recommendations about how to promote opioid safety in adults receiving PC in Canada and the USA.MethodsThrough a Delphi process comprised of two rounds, USA and Canadian panellists in PC, addiction and pain medicine developed expert consensus recommendations. Elected Canadian Society of Palliative Care Physicians (CSPCP) board members then rated how important it is for PC physicians to be aware of each consensus recommendation.They also identified high-priority research areas from the topics that did not achieve consensus in Round 2.ResultsThe panellists (Round 1, n=23; Round 2, n=22) developed a total of 130 recommendations from the two rounds about the following six opioid-safety related domains: (1) General principles; (2) Measures for healthcare institution and PC training and clinical programmes; (3) Patient and caregiver assessments; (4) Prescribing practices; (5) Monitoring; and (6) Patients and caregiver education. Fifty-nine topics did not achieve consensus and were deemed potential areas of research. From these results, CSPCP identified 43 high-priority recommendations and 8 high-priority research areas.ConclusionsUrgent guidance about opioid safety is needed to address the opioid crisis. These consensus recommendations can promote safer opioid use, while recognising the importance of these medications for PC symptom management.

Patient with Lobular Carcinoma of the Breast and Activating AKT1 E17K Variant

<p><strong>Objective</strong>. To present the characteristics of the AKT1E117K gene variant and a description of the clinical application in a patient with metastatic breast cancer.</p><p><strong>Results</strong>. 63 y/o woman with Stage IV Invasive lobular carcinoma at diagnosis was treated with Palbociclib and aromatase inhibitors (AI). At progression, tissue was sent for comprehensive genomic profiling to Foundation Medicine (FM) which revealed AKT1E17K mutation. In lieu of available clinical data within the patient’s tumor type (HR+ HER2- breast cancer), extrapolated data from the Flatiron Health-FM (FH-FMI) Clinico-genomic Database (CGDB) was dis- cussed at our Molecular Tumor Board (MTB). After multidisciplinary discussion, the consensus recommendation was to start treatment with the combination of mTOR inhibitor everolimus, and AI, exemestane. Patient tolerated treatment without major side effects. By the second clinical visit the patient’s breast showed signs of improvement. PET/CT showed diminished left axillary uptake, decreased right paratracheal lymph node PET avidity, and stable bone disease consistent with a partial response. The most recent office visit in January 2021, breast exam revealed a normal-appearing skin with only faint erythema. All other skin lesions have resolved. Although, the role of AKT1 variant described here is not well defined and therapeutic significance of M-Tor inhibitors not established in metastatic breast cancers, comprehensive approach to this case unraveled new and successful therapeutic option in this patient. Conclusion. This demonstrates that applying available Precision Medicine tools like MTB and real world data sets from patient populations with similar clinical and genomic profiles may provide more options for treatment.</p>

Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation

Purpose By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). Methods We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. Results We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. Conclusion The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS.

Distinct Approaches in Managing Adult and Pediatric Trigger Finger

Background: Trigger finger is the most common disease that causing pain in the adult population. Trigger finger may occur at any finger, which usually occurs in the thumb and ring finger. A1 pulley sheath or metacarpal-phalangeal joint. There is a different recommendation toward treatment options for trigger fingers in adults and pediatrics. Method: This paper is done by reviewing and searching journals with “trigger finger”, “treatment”, “pediatric trigger finger”, and “adult trigger finger” on the search engines. The authors found 45 journals that were suitable for our references. Outcome: Trigger finger treatments vary as there are many acceptable treatment options. There is a different choice of therapy that should be considered in adult and pediatric trigger fingers. This should be considered to get better treatment outcomes. Cost analysis is also important to choose the most cost-effective treatment for trigger finger patients. Conclusion: There is no exact consensus recommendation for choosing the exact treatment. pediatric trigger finger is caused by a multifactorial aspect resulting in unpredictable conservative treatment outcomes unlike in adults. The majority of trigger fingers in pediatrics will need surgical procedures while some cases of adult trigger fingers may resolve naturally. Further large studies are needed to develop a treatment algorithm in these two age groups that trigger fingers. Keywords: adult trigger finger, trigger finger, pediatric trigger finger, treatment.