Citations

Abstract At present, no research criteria exist for the diagnosis of prodromal behavioural variant frontotemporal dementia (bvFTD), though early detection is of high research importance. Thus, we sought to develop and validate a proposed set of research criteria for prodromal bvFTD, termed ‘mild behavioural and/or cognitive impairment in bvFTD’ (MBCI-FTD). Participants included 72 participants deemed to have prodromal bvFTD; this comprised 55 carriers of a pathogenic mutation known to cause frontotemporal lobar degeneration, and 17 individuals with autopsy-confirmed frontotemporal lobar degeneration. All had mild behavioural and/or cognitive changes, as judged by an evaluating clinician. Based on extensive clinical workup, the prodromal bvFTD group was divided into a Development Group (n = 22) and a Validation Group (n = 50). The Development Group was selected to be the subset of the prodromal bvFTD group for whom we had the strongest longitudinal evidence of conversion to bvFTD, and was used to develop the MBCI-FTD criteria. The Validation Group was the remainder of the prodromal bvFTD group and was used as a separate sample on which to validate the criteria. Familial non-carriers were included as healthy controls (n = 165). The frequencies of behavioural and neuropsychiatric features, neuropsychological deficits, and social cognitive dysfunction in the prodromal bvFTD Development Group and healthy controls were assessed. Based on sensitivity and specificity analyses, seven core features were identified: apathy without moderate-severe dysphoria, behavioural disinhibition, irritability/agitation, reduced empathy/sympathy, repetitive behaviours (simple and/or complex), joviality/gregariousness, and appetite changes/hyperorality. Supportive features include a neuropsychological profile of impaired executive function or naming with intact orientation and visuospatial skills, reduced insight for cognitive or behavioural changes, and poor social cognition. Three core features or two core features plus one supportive feature are required for the diagnosis of possible MBCI-FTD; probable MBCI-FTD requires imaging or biomarker evidence, or a pathogenic genetic mutation. The proposed MBCI-FTD criteria correctly classified 95% of the prodromal bvFTD Development Group, and 74% of the prodromal bvFTD Validation Group, with a false positive rate of <10% in healthy controls. Finally, the MBCI-FTD criteria were tested on a cohort of individuals with prodromal Alzheimer’s disease, and the false positive rate of diagnosis was 11–16%. Future research will need to refine the sensitivity and specificity of these criteria, and incorporate emerging biomarker evidence.

Background Erenumab (erenumab-aooe in the US) effectively reduces monthly migraine days in episodic and chronic migraine. This traditional outcome does not capture the intensity of headache pain on days with migraine. Methods This post hoc analysis of two pivotal randomized, placebo-controlled studies in patients with episodic migraine and chronic migraine examined the effect of erenumab 70 and 140 mg on migraine pain. Cumulative monthly migraine pain intensity is the sum of the peak pain intensity scores (0 = no migraine to 3 = migraine day with severe pain) on migraine days. Change from baseline in cumulative monthly migraine pain and average monthly pain intensity was assessed over months 4 to 6 for episodic migraine and month 3 for chronic migraine; change in average monthly pain intensity was assessed among monthly migraine days responders/non-responders. Results Efficacy analysis included 946 patients for the episodic migraine study and 656 patients for the chronic migraine study. Cumulative monthly migraine pain decreased significantly with erenumab versus placebo ( p < 0.001, for episodic migraine and chronic migraine). In addition, monthly average migraine pain intensity decreased significantly with erenumab versus placebo for episodic migraine ( p < 0.01); decreases were non-significant for chronic migraine. In comparison with placebo-treated patients, a greater proportion of erenumab-treated patients were pain intensity responders regardless of threshold used. Episodic migraine and chronic migraine patients with a ≥50% reduction in monthly migraine days (responders) had a greater reduction in monthly average pain intensity than non-responders. Conclusions Erenumab reduced cumulative monthly migraine pain in episodic migraine and chronic migraine patients and significantly reduced monthly average migraine pain in episodic migraine, demonstrating treatment benefit beyond reduction in migraine frequency. Clinical Trial Registration: ClinicalTrials.gov, NCT02456740; ClinicalTrials.gov, NCT02066415

Abstract Background Erenumab is a human anti‐calcitonin gene‐related peptide receptor monoclonal antibody approved for migraine prevention. We sought to further assess the temporal patterns of response to erenumab in patients with chronic migraine (CM), specifically the onset and sustainability of monthly migraine day (MMD) response. Methods This is a post hoc analysis of a 12‐week, randomized, double‐blind, placebo‐controlled study of erenumab for migraine prevention in patients with CM (≥15 headache days/month, including ≥8 migraine days/month). Onset and sustainability were assessed according to MMD reduction from baseline, with the following response categories: responders (≥50% reduction), partial responders (≥30% and <50%), or nonresponders (<30%). Results Among the erenumab 140 mg group ( n = 187), 54.0% (101/187) achieved a response at any month during the study with a median time to onset of monthly response of 1 month. This improvement was maintained in most patients with continued treatment. An initial response was achieved at Month 1 by 28.3% (53/187) of patients; 69.8% (37/53) of whom maintained a response at Months 2 and 3. Although many patients responded early, some patients required longer treatment to achieve a response; 79.4% (27/34) of initial partial responders and 21.0% (21/100) of initial nonresponders subsequently achieved a response. Similar findings were observed for the erenumab 70mg group ( n = 188). Conclusion A majority of erenumab‐treated patients with CM who achieved an initial response at Month 1 sustained this benefit. Many patients responded later with continued treatment. Our data support recommendations to assess outcomes after ≥3 months of preventive treatment with erenumab in CM.

PURPOSE This guideline updates recommendations of the ASCO guideline on chemotherapy and targeted therapy for patients with human epidermal growth factor receptor 2–negative metastatic breast cancer (MBC) that is either endocrine-pretreated or hormone receptor (HR)–negative. METHODS An Expert Panel conducted a targeted systematic literature review guided by a signals approach to identify new, potentially practice-changing data that might translate into revised guideline recommendations. RESULTS The Expert Panel reviewed abstracts from the literature review and retained 14 articles. RECOMMENDATIONS Patients with triple-negative, programmed cell death ligand-1–positive MBC may be offered the addition of immune checkpoint inhibitor to chemotherapy as first-line therapy. Patients with triple-negative, programmed cell death ligand-1–negative MBC should be offered single-agent chemotherapy rather than combination chemotherapy as first-line treatment, although combination regimens may be offered for life-threatening disease. Patients with triple-negative MBC who have received at least two prior therapies for MBC should be offered treatment with sacituzumab govitecan. Patients with triple-negative MBC with germline BRCA mutations previously treated with chemotherapy may be offered a poly (ADP-ribose) polymerase inhibitor rather than chemotherapy. Patients with HR-positive human epidermal growth factor receptor 2–negative MBC for whom chemotherapy is being considered should be offered single–agent chemotherapy rather than combination chemotherapy, although combination regimens may be offered for highly symptomatic or life-threatening disease. Patients with HR-positive MBC with disease progression on an endocrine agent may be offered treatment with either endocrine therapy with or without targeted therapy or single-agent chemotherapy. Patients with HR-positive MBC with germline BRCA mutations no longer benefiting from endocrine therapy may be offered a poly (ADP-ribose) polymerase inhibitor rather than chemotherapy. No recommendation regarding when a patient's care should be transitioned to hospice or best supportive care alone is possible. Additional information is available at www.asco.org/breast-cancer-guidelines .

With the incidence of breast cancer steadily rising, it is important to explore novel technologies that can allow for earlier detection of disease as well more a personalized and effective treatment approach. The concept of “liquid biopsies” and the data they provide have been increasingly studied in the recent decades. More specifically, circulating tumor DNA (ctDNA) has emerged as a potential biomarker for various cancers, including breast cancer. While methods such as mammography and tissue biopsies are the current standards for the detection and surveillance of breast cancer, ctDNA analysis has shown some promise. This review discusses the versatility of ctDNA by exploring its multiple emerging uses for the management of breast cancer. Its efficacy is also compared to current biomarkers and technologies.

Purpose : There is an unknown percentage of transgender and gender non-confirming individuals who undergo gender affirmation surgeries (GAS) that experiences regret. Regret could lead to physical and mental morbidity, also questioning the appropriateness of these procedures in selected patients. The aim of this study is to evaluate the prevalence of regret in transgender individuals who underwent GAS and evaluate associated factors. Methods : A systematic review was conducted following the PRISMA guidelines. A comprehensive research strategy was performed including the following databases: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. Random-effects meta-analysis of proportions, subgroup analysis, meta-regression, publication bias, and sensitivity analyses were performed. Results: A total of 27 studies, pooling 7,928 transgender patients that underwent any type of GAS were included in this review. The pooled prevalence of regret after GAS was 1% (95% Confidence interval [CI] <1-2%). Overall, 33% underwent transmasculine surgical procedures and 67% transfeminine procedures. The prevalence of regrets among patients undergoing transmasculine and transfeminine surgeries was <1% (IC<1-<1%) and 1% (CI<1-2%), respectively. A total of 77 patients regretted having had GAS. Of them, 28 had minor and 34 had major regrets based on Pfäfflin’s regret classification. The majority of these had “clear regret” based on Kuiper and Cohen Kettenis’ classification. Conclusion: Based on this review, there is an extremely low prevalence of regret in transgender patients after GAS. We believe this study corroborates the improvements made in regard to selection criteria for GAS. However, there is high subjectivity in the assessment of regret and lack of standardized questionnaires, which highlight the importance of developing validated questionnaires in this population.

Objectives The objective of this study was to estimate the amount of oxycodone tablets required for pain control in the 2-week postoperative period after laparoscopic hysterectomy (LH) and vaginal hysterectomy (VH) for benign disease. Methods We conducted a prospective cohort study of English-speaking women 18 years or older undergoing hysterectomy for benign indications. Participants completed a pain survey at baseline and daily for 2 weeks postoperatively. In addition, they recorded the number of oxycodone tablets and other pain medications taken daily for 2 weeks. The primary outcome was the median number of oxycodone tablets (5 mg) consumed after LH or VH during 2 weeks postoperative. Results Eighty-one women underwent VH and 82 underwent LH. Women who underwent VH were older (mean ± SD, 64.2 ± 10.3 years vs 47.5 ± 7.7 years), more parous (2 [interquartile range (IQR), 2–3] vs 2 [IQR, 1–2]), and less likely to be sexually active (51.9% vs 79.3%, P < 0.02). Women in the VH group also had significantly lower baseline pain levels (0 [IQR, 0–1] vs 1 [IQR, 0–4], P < 0.001). All VH participants had surgery for prolapse, whereas only 12.2% in the LH group had surgery for this indication ( P < 0.001). Most in the LH group had surgery for fibroids (61%) or abnormal uterine bleeding (15.9%). Women in the VH group consumed significantly less oxycodone tablets postoperatively (median, 4.5 [IQR, 1–9] vs 7 [IQR, 2–18]; P = 0.047) and took oxycodone for less days after discharge (median, 1 [IQR, 0–3] vs 3 [IQR, 1–6]; P < 0.001). Conclusions Women consume less oxycodone after minimally invasive hysterectomy than previously thought. Those who undergo VH may consume less oxycodone than those who undergo LH.