Sex Differences in Outcome and Prescribing Practice in ST-elevation MI Patients with Multivessel Disease and Incomplete Revascularisation.

Objective: To investigate the extent to which multivessel disease, incomplete revascularisation and prescribing differences contribute to sex-based outcome disparities in patients with ST-elevation MI (STEMI) and establish whether differences in cardiac death and MI (CDMI) rates persist at long-term follow-up. Methods and results: This observational study evaluates sex-based outcome differences (median follow-up 3.6 years; IQR [2.4-5.4]) in a consecutive cohort of patients (n=2,083) presenting with STEMI undergoing percutaneous coronary intervention). Of the studied patients 20.3% (423/2,083) were women and 38.3% (810/2,083) had multivessel disease (MVD). Incomplete revascularisation was common. The median residual SYNTAX score (rSS) was 5.0 (IQR [0-9]) in women and 5.0 (IQR [1-11]) in men (p=0.369), and in patients with MVD it was 9 (IQR [6-17]) in women and 10 (IQR [6-15]) in men (p=0.838). The primary endpoint CDMI occurred in 20.3% of women (86/423) and in 13.2% of men (219/1,660) (p=0.028). Differences persisted following multivariable risk adjustment: female sex was independently associated with CDMI (aHR 1.33; IQR [1.02-1.74]). Women with MVD had CDMI more often than all other groups (p<0.001 for all). Significant sex-based prescribing differences were evident: women were less likely to receive guideline-recommended potent P2Y12 inhibitors than men (31% versus 43%; p=0.012), and differences were particularly evident in patients with MVD (25% in women versus 45% in men, p=0.011). Conclusion: Sex-based differences in STEMI patient outcome persist at long-term follow-up. Poor outcomes were disproportionately found in women with MVD and those with rSS>8. Observed differences in P2Y12 prescribing practices may contribute to poor outcomes for women with MVD and incomplete revascularisation.

Quantifying the role of airborne transmission in the spread of COVID-19.

There is an ongoing debate on the different transmission modes of SARS-CoV-2 and their relative contributions to the pandemic. In this paper, we employ a simple mathematical model, which incorporates both the human-to-human and environment-to-human transmission routes, to study the transmission dynamics of COVID-19. We focus our attention on the role of airborne transmission in the spread of the disease in a university campus setting. We conduct both mathematical analysis and numerical simulation, and incorporate published experimental data for the viral concentration in the air to fit model parameters. Meanwhile, we compare the outcome to that of the standard SIR model, utilizing a perturbation analysis in the presence of multiple time scales. Our data fitting and numerical simulation results show that the risk of airborne transmission for SARS-CoV-2 strongly depends on how long the virus can remain viable in the air. If the time for this viability is short, the airborne transmission route would be inconsequential in shaping the overall transmission risk and the total infection size. On the other hand, if the infectious virus can persist in aerosols beyond a few hours, then airborne transmission could play a much more significant role in the spread of COVID-19.

Late outcomes of ST-elevation myocardial infarction treated by pharmaco-invasive or primary percutaneous coronary intervention.

AIMS: Pharmaco-invasive percutaneous coronary intervention (PI-PCI) is recommended for patients with ST-elevation myocardial infarction (STEMI)who are unable to undergo timely primary PCI (pPCI). The present study examined late outcomes after PI-PCI (successful reperfusion followed by scheduled PCI or failed reperfusion and rescue PCI)compared with timely and late pPCI (>120 min from first medical contact). METHODS AND RESULTS: All patients with STEMI presenting within 12 h of symptom onset, who underwent PCI during their initial hospitalization at Liverpool Hospital (Sydney), from October 2003 to March 2014, were included. Amongst 2091 STEMI patients (80% male), 1077 (52%)underwent pPCI (68% timely, 32% late), and 1014 (48%)received PI-PCI (33% rescue, 67% scheduled). Mortality at 3 years was 11.1% after pPCI (6.7% timely, 20.2% late) and 6.2% after PI-PCI (9.4% rescue, 4.8% scheduled); P < 0.01. After propensity matching, the adjusted mortality hazard ratio (HR) for timely pPCI compared with scheduled PCI was 0.9 (95% CIs 0.4-2.0) and compared with rescue PCI was 0.5 (95% CIs 0.2-0.9). The adjusted mortality HR for late pPCI, compared with scheduled PCI was 2.2 (95% CIs 1.2-3.1)and compared with rescue PCI, it was 1.5 (95% CIs 0.7-2.0). CONCLUSION: Patients who underwent late pPCI had higher mortality rates than those undergoing a pharmaco-invasive strategy. Despite rescue PCI being required in a third of patients, a pharmaco-invasive approach should be considered when delays to PCI are anticipated, as it achieves better outcomes than late pPCI.

Patient-reported outcomes in a pilot clinical trial of twice-weekly hemodialysis start with adjuvant pharmacotherapy and transition to thrice-weekly hemodialysis vs conventional hemodialysis.

BACKGROUND: Physical and emotional symptoms are prevalent in patients with kidney-dysfunction requiring dialysis (KDRD) and the rigors of thrice-weekly hemodialysis (HD) may contribute to deteriorated health-related quality of life. Less intensive HD schedules might be associated with lower symptom and/or emotional burden. METHODS: The TWOPLUS Pilot study was an individually-randomized trial conducted at 14 dialysis units, with the primary goal to assess feasibility and safety. Patients with incident KDRD and residual kidney function were assigned to incremental HD start (twice-weekly HD for 6 weeks followed by thrice-weekly HD) vs conventional HD (thrice-weekly HD). In exploratory analyses, we compared the two treatment groups with respect to three patient-reported outcomes measures. We analyzed the change from baseline in the score on Dialysis Symptom Index (DSI, range 0-150), Generalized Anxiety Disorder-7 (GAD-7, range 0-21), and Patient Health Questionnaire-9 (PHQ-9, range 0-27) at 6 (n = 20 in each treatment group) and 12 weeks (n = 21); with lower scores denoting lower symptom burden. Analyses were adjusted for age, race, gender, baseline urine volume, diabetes mellitus, and malignancy. Participants' views on the intervention were sought using a Patient Feedback Questionnaire (n = 14 in incremental and n = 15 in conventional group). RESULTS: The change from baseline to week 6 in estimated mean score (standard error; P value) in the incremental and conventional group was - 9.7 (4.8; P = 0.05) and - 13.8 (5.0; P = 0.009) for DSI; - 1.9 (1.0; P = 0.07) and - 1.5 (1.4; P = 0.31) for GAD-7; and - 2.5 (1.1; P = 0.03) and - 3.5 (1.5; P = 0.02) for PHQ-9, respectively. Corresponding changes from week 6 to week 12 were - 3.1 (3.2; P = 0.34) and - 2.4 (5.5; P = 0.67) in DSI score; 0.5 (0.6; P = 0.46) and 0.1 (0.6; P = 0.87) in GAD-7 score; and - 0.3 (0.6; P = 0.70) and - 0.5 (0.6; P = 0.47) in PHQ-9 score, respectively. Majority of respondents felt their healthcare was not jeopardized and expressed their motivation for study participation was to help advance the care of patients with KDRD. CONCLUSIONS: This study suggests a possible mitigating effect of twice-weekly HD start on symptoms of anxiety and depression at transition from pre-dialysis to KDRD. Larger clinical trials are required to rigorously test clinically-matched incrementally-prescribed HD across diverse organizations and patient populations. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study identifier NCT03740048, registration date 14/11/2018.

Twice-Weekly Hemodialysis With Adjuvant Pharmacotherapy and Transition to Thrice-Weekly Hemodialysis: A Pilot Study.

RATIONALE & OBJECTIVE: Thrice-weekly hemodialysis (HD) is the most common treatment modality for kidney failure in the United States. We conducted a pilot study to assess the feasibility and safety of incremental-start HD in patients beginning maintenance HD. STUDY DESIGN: Pilot study. SETTING & PARTICIPANTS: Adults with estimated glomerular filtration rate (eGFR) ≥5 mL/min/1.73 m2 and urine volume ≥500 mL/d beginning maintenance HD at 14 outpatient dialysis units. EXPOSURE: Randomized allocation (1:1 ratio) to twice-weekly HD and adjuvant pharmacologic therapy for 6 weeks followed by thrice-weekly HD (incremental HD group) or thrice-weekly HD (conventional HD group). OUTCOME: The primary outcome was feasibility. Secondary outcomes included changes in urine volume and solute clearance. RESULTS: Of 77 patients invited to participate, 51 consented to do so, representing 66% of eligible patients. We randomized 23 patients to the incremental HD group and 25 patients to the conventional HD group. Protocol-based loop diuretics, sodium bicarbonate, and patiromer were prescribed to 100%, 39%, and 17% of patients on twice-weekly HD, respectively. At a mean follow-up of 281.9 days, participant adherence was 96% to the HD schedule (22 of 23 and 24 of 25 in the incremental and conventional groups, respectively) and 100% in both groups to serial timed urine collection. The incidence rate ratio for all-cause hospitalization was 0.31 (95% CI, 0.08-1.17); and 7 deaths were recorded (1 in the incremental and 6 in the conventional group). At week 24, the incremental HD group had lower declines in urine volume (a difference of 51.0 [95% CI, -0.7 to 102.8] percentage points) and in the averaged urea and creatinine clearances (a difference of 57.9 [95% CI, -22.6 to 138.4] percentage points). LIMITATIONS: Small sample size, time-limited twice-weekly HD. CONCLUSIONS: It is feasible to enroll patients beginning maintenance HD into a randomized study of incremental-start HD with adjuvant pharmacotherapy who adhere to the study protocol during follow-up. Larger multicenter clinical trials are indicated to determine the efficacy and safety of incremental HD with longer twice-weekly HD periods. FUNDING: Funding was provided by Vifor Inc. TRIAL REGISTRATION: Registered at ClinicalTrials.gov, identifier NCT03740048.

Endogenous Candida endophthalmitis: Who is really at risk?

OBJECTIVES: The Infectious Disease Society of America recommends that all patients with candidemia undergo a dilated retinal exam to exclude endogenous Candida endophthalmitis. Our objective was to determine if there are significant risk factors in candidemic patients for developing endogenous Candida endophthalmitis METHODS: We conducted a retrospective study of all candidemic patients at three academic medical centers between 2012 and 2017. We extracted risk factors for Candida endophthalmitis based on prior literature and compared them between patients with and without endophthalmitis. We then built a multivariate logistic regression model to assess which ones were significant. RESULTS: We found 771 patients with candidemia. 120 (15.6%) of these patients were diagnosed with Candida endophthalmitis. In our logistic regression analysis, central venous catheter presence (OR 8.35), intravenous drug use (OR 4.76), immunosuppression (OR 2.40), total parenteral nutrition recipient (OR 2.28), race (OR 1.65), age (OR 1.02), and gender (OR 0.57) were risk factors for developing Candida endophthalmitis. Additionally, Candida albicans was more likely to result in Candida endophthalmitis (OR 1.86). CONCLUSIONS: This cohort represents the largest study of risk factors for candidemic patients who developed endogenous Candida endophthalmitis. Based on our findings, clinicians should develop targeted and cost-effective strategies for endophthalmitis screening.

Cardiac mortality, diabetes mellitus, and multivessel disease in ST elevation myocardial infarction.

BACKGROUND: In patients with diabetes mellitus presenting with ST elevation myocardial infarction (STEMI) the degree to which cardiac death rates may be attributed to an increased burden of coronary artery disease is not clear. METHODS: This prospective observational study examines rates of cardiac death between those with and without diabetes at long term follow up, stratified by presence of multivessel disease (MVD), in consecutive STEMI patients from 5 Australian hospitals. RESULTS: Amongst 2083 patients, 393 patients had diabetes (18.8%), and 810 (38.8%) had MVD. Patients with diabetes were more likely to have MVD 48.6% (191/393) than patients without diabetes 36.6% (619/1690; p < .001). At final follow up (median 3.6 years [IQR 2.4-5.4]) cardiac death occurred in 37/393 diabetic patients and 92/1690 nondiabetic patients (adjusted HR1.67, 95% CI 1.10-2.52). In those with MVD cardiac death occurred in 27/191 diabetic patients, and 54/619 non-diabetic patients (adjusted HR 1.94; 95% CI 1.17-3.23). In single vessel disease (SVD) cardiac death occurred in 10/202 diabetic patients, and 38/1071 non-diabetic patients (adjusted HR 1.37; 95% CI 0.65-2.89). Both diabetes and MVD were independently associated with cardiac death. CONCLUSIONS: STEMI patients with diabetes are more likely to have MVD, with an absolute difference in MVD rates of 12%, and higher rates of cardiac death. Randomized trials studying these high risk patients are needed to reduce cardiac mortality in patients with diabetes, MVD and STEMI.

Tendon Transfers to Restore Ankle Dorsiflexion After Anterior Compartment Myonecrosis: A Case Report.

CASE: A 47-year-old Caucasian woman spontaneously developed an isolated anterior compartment pressure of >100 mm Hg in the left leg. Despite fasciotomies, the musculature was nonviable and required debridement. Following Achilles tendon lengthening, a posterior tibial tendon (PTT) to anterior tibial tendon (ATT) transfer was supplemented with a flexor digitorum longus tendon transfer to the remaining PTT in order to prevent a flatfoot deformity while restoring active dorsiflexion. CONCLUSION: Preservation of the tendinous portion of the ATT during debridement allowed for transfer of the PTT to the ATT using a modified Pulvertaft transfer. This technique allowed early ambulation and restoration of active dorsiflexion, obviating the ongoing use of an ankle-foot orthosis.

T-Type Ca2+ Channel Inhibition Sensitizes Ovarian Cancer to Carboplatin.

Ovarian cancer is the deadliest gynecologic cancer, due in large part to the diagnosis of advanced stage disease, the development of platinum resistance, and inadequate treatment alternatives. Recent studies by our group and others have shown that T-type calcium (Ca(2+)) channels play a reinforcing role in cancer cell proliferation, cell-cycle progression, and apoptosis evasion. Therefore, we investigated whether T-type Ca(2+) channels affect ovarian tumor growth and response to platinum agents. Inhibition of T-type Ca(2+) channels with mibefradil or by silencing expression resulted in growth suppression in ovarian cancer cells with a simultaneous increase in apoptosis, which was accompanied by decreased expression of the antiapoptotic gene survivin (BIRC5). Analysis of intracellular signaling revealed mibefradil reduced AKT phosphorylation, increased the levels and nuclear retention of FOXO transcription factors that repress BIRC5 expression, and decreased the expression of FOXM1, which promotes BIRC5 expression. Combining carboplatin with mibefradil synergistically increased apoptosis in vitro. Importantly, mibefradil rendered platinum-resistant ovarian tumors sensitive to carboplatin in a mouse model of peritoneal metastasis. Together, the data provide rationale for future use of T-type channel antagonists together with platinum agents for the treatment of ovarian cancer.