Temporal trends in colorectal cancer mortality rates (1999-2022) in the United States.

Colorectal cancer (CRC) ranks as the third leading cause of cancer-related deaths in the United States (U.S.). Our study aims to analyze CRC mortality patterns in the U.S., focusing on gender and age groups from 1999 to 2022. We analyzed Age-Adjusted Mortality Rates (AAMRs) for CRC-related deaths using the CDC Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database and assessed differences between age and sex. CRC-related mortality decreased significantly from 1999 to 2011 (-2.81% APC) and from 2011 to 2020 (-1.95% APC) but a not significant uptrend from 2020 to 2022 (2% APC). Males experienced a more significant decrease. Among age groups, crude mortality decreased until 2020, except in age group 45-54, which showed an annual increase in mortality of 0.9% from 2004 to 2022. Furthermore, individuals aged 75-84 and 85+ saw a nonsignificant annual increase of 1.8% and 4.5% from 2020 to 2022, respectively. Our study highlights a significant decline in age and gender-specific CRC-related mortality from 1999 to 2020. However, the worrisome uptrend observed in the younger age group of 45-54 emphasizes the importance of implementing targeted public health measures and evidence-based interventions.

Clinical predictors of right ventricular dysfunction and association with adverse outcomes in peripartum cardiomyopathy.

AIMS: We sought to identify factors associated with right ventricular (RV) dysfunction and elevated pulmonary artery systolic pressure (PASP) and association with adverse outcomes in peripartum cardiomyopathy (PPCM). METHODS AND RESULTS: We conducted a multi-centre cohort study to identify subjects with PPCM with the following criteria: left ventricular ejection fraction (LVEF) < 40%, development of heart failure within the last month of pregnancy or 5 months of delivery, and no other identifiable cause of heart failure with reduced ejection fraction. Outcomes included a composite of (i) major adverse events (need for extracorporeal membrane oxygenation, ventricular assist device, orthotopic heart transplantation, or death) or (ii) recurrent heart failure hospitalization. RV function was obtained from echocardiogram reports. In total, 229 women (1993-2017) met criteria for PPCM. Mean age was 32.4 ± 6.8 years, 28% were of African descent, 50 (22%) had RV dysfunction, and 38 (17%) had PASP ≥ 30 mmHg. After a median follow-up of 3.4 years (interquartile range 1.0-8.8), 58 (25%) experienced the composite outcome of adverse events. African descent, family history of cardiomyopathy, LVEF, and PASP were significant predictors of RV dysfunction. Using Cox proportional hazards models, we found that women with RV dysfunction were three times more likely to experience the adverse composite outcome: hazard ratio 3.21 (95% confidence interval: 1.11-9.28), P = 0.03, in a multivariable model adjusting for age, race, body mass index, preeclampsia, hypertension, diabetes, kidney disease, and LVEF. Women with PASP ≥ 30 mmHg had a lower probability of survival free from adverse events (log-rank P = 0.04). CONCLUSIONS: African descent and family history of cardiomyopathy were significant predictors of RV dysfunction. RV dysfunction and elevated PASP were significantly associated with a composite of major adverse cardiac events. This at-risk group may prompt closer monitoring or early referral for advanced therapies.

The Reporting and Methodological Quality of Systematic Reviews Underpinning Clinical Practice Guidelines Focused on the Management of Cutaneous Melanoma: Cross-Sectional Analysis.

BACKGROUND: Clinical practice guidelines (CPGs) inform evidence-based decision-making in the clinical setting; however, systematic reviews (SRs) that inform these CPGs may vary in terms of reporting and methodological quality, which affects confidence in summary effect estimates. OBJECTIVE: Our objective was to appraise the methodological and reporting quality of the SRs used in CPGs for cutaneous melanoma and evaluate differences in these outcomes between Cochrane and non-Cochrane reviews. METHODS: We conducted a cross-sectional analysis by searching PubMed for cutaneous melanoma guidelines published between January 1, 2015, and May 21, 2021. Next, we extracted SRs composing these guidelines and appraised their reporting and methodological rigor using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklists. Lastly, we compared these outcomes between Cochrane and non-Cochrane SRs. All screening and data extraction occurred in a masked, duplicate fashion. RESULTS: Of the SRs appraised, the mean completion rate was 66.5% (SD 12.29%) for the PRISMA checklist and 44.5% (SD 21.05%) for AMSTAR. The majority of SRs (19/50, 53%) were of critically low methodological quality, with no SRs being appraised as high quality. There was a statistically significant association (P<.001) between AMSTAR and PRISMA checklists. Cochrane SRs had higher PRISMA mean completion rates and higher methodological quality than non-Cochrane SRs. CONCLUSIONS: SRs supporting CPGs focused on the management of cutaneous melanoma vary in reporting and methodological quality, with the majority of SRs being of low quality. Increasing adherence to PRISMA and AMSTAR checklists will likely increase the quality of SRs, thereby increasing the level of evidence supporting cutaneous melanoma CPGs.

Proprotein convertase subtilisn/kexin type 9 inhibitors and small interfering RNA therapy for cardiovascular risk reduction: A systematic review and meta-analysis.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein cholesterol (LDL-c) in the arterial system. Thus, lipid lowering therapy is essential for both primary and secondary prevention. Proprotein convertase subtilisn/kexin type 9 (PCSK9) inhibitors (Evolocumab, Alirocumab) and small interfering RNA (siRNA) therapy (Inclisiran) have been demonstrated to lower LDL-c and ASCVD events in conjunction with maximally tolerated statin therapy. However, the degree of LDL-c reduction and the impact on reducing major adverse cardiac events, including their impact on mortality, remains unclear. OBJECTIVE: The purpose of this study is to examine the effects of PCSK9 inhibitors and small interfering RNA (siRNA) therapy on LDL-c reduction and major adverse cardiac events (MACE) and mortality by conducting a meta-analysis of randomized controlled trials. METHODS: Using Pubmed, Embase, Cochrane Library and clinicaltrials.gov until April 2023, we extracted randomized controlled trials (RCTs) of PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) for lipid lowering and risk of MACE. Using random-effects models, we pooled the relative risks and 95% CIs and weighted least-squares mean difference in LDL-c levels. We estimated odds ratios with 95% CIs among MACE subtypes and all-cause mortality. Fixed-effect model was used, and heterogeneity was assessed using the I2 statistic. RESULTS: In all, 54 studies with 87,669 participants (142,262 person-years) met criteria for inclusion. LDL-c percent change was reported in 47 studies (n = 62,634) evaluating two PCSK9 inhibitors and siRNA therapy. Of those, 21 studies (n = 41,361) included treatment with Evolocumab (140mg), 22 (n = 11,751) included Alirocumab (75mg), and 4 studies (n = 9,522) included Inclisiran (284mg and 300mg). Compared with placebo, after a median of 24 weeks (IQR 12-52), Evolocumab reduced LDL-c by -61.09% (95% CI: -64.81, -57.38, p<0.01) and Alirocumab reduced LDL-c by -46.35% (95% CI: -51.75, -41.13, p<0.01). Inclisiran 284mg reduced LDL-c by -54.83% (95% CI: -59.04, -50.62, p = 0.05) and Inclisiran 300mg reduced LDL-c by -43.11% (95% CI: -52.42, -33.80, p = 0.01). After a median of 8 months (IQR 6-15), Evolocumab reduced the risk of myocardial infarction (MI), OR 0.72 (95% CI: 0.64, 0.81, p<0.01), coronary revascularization, 0.77 (95% CI: 0.70, 0.84, p<0.01), stroke, 0.79 (95% CI: 0.66, 0.94, p = 0.01) and overall MACE 0.85 (95% CI: 0.80, 0.89, p<0.01). Alirocumab reduced MI, 0.57 (0.38, 0.86, p = 0.01), cardiovascular mortality 0.35 (95% CI: 0.16, 0.77, p = 0.01), all-cause mortality 0.60 (95% CI: 0.43, 0.84, p<0.01), and overall MACE 0.35 (0.16, 0.77, p = 0.01). CONCLUSION: PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) significantly reduced LDL-c by >40% in high-risk individuals. Additionally, both Alirocumab and Evolocumab reduced the risk of MACE, and Alirocumab reduced cardiovascular and all-cause mortality.

Beyond the norm: A rare case of cardiac and extracardiac metastatic urothelial carcinoma.

Screening echocardiography aids in identifying cardiac emboli causes and asymptomatic cardiac metastases in high-grade neoplasms. Conversely, cardiac MRI provides advanced tissue characterization and broader extracardiac assessment.

Lithium-Induced Bradycardia and Cardiomyopathy in a Patient With Bipolar Disorder and Paranoid Schizophrenia.

Lithium is primarily known to cause neurological and gastrointestinal side effects, however, cardiac effects have been rarely reported. We present a unique case of lithium cardiotoxicity causing bradyarrhythmia and cardiomyopathy. A 68-year-old man with a history of paranoid schizophrenia and bipolar disorder presented with altered mental status. On examination, the patient was lethargic, afebrile, with dry oral mucosa, and a regular pulse of 42 bpm. Labs revealed acute kidney injury and elevated lithium levels. Electrocardiogram (ECG) revealed a junctional escape rhythm with a right bundle morphology. Lithium toxicity was strongly suspected in the setting of raised serum lithium levels, decreased oral intake and acute kidney injury. The patient was found to have lithium-induced junctional bradycardia. Transvenous pacing was not indicated as the patient responded to fluids and atropine and had no severe hemodynamic compromise. As his serum lithium levels decreased, the bradycardia gradually improved. His echocardiogram revealed moderate left ventricular systolic dysfunction. Workup of cardiomyopathies was negative: no obstructive coronary artery disease; viral panel, and autoimmune markers were unremarkable. Thus, his cardiomyopathy was attributed to lithium toxicity. Lithium cardiotoxicity may manifest as arrhythmias and/or cardiomyopathy. Clinicians should have a high index of suspicion for lithium cardiotoxicity due to the narrow therapeutic range of lithium.

A Rare Case of Chronic Liver Disease in a Patient Who Previously Presented With Hepatitis E.

Hepatitis E virus (HEV) is among the most common causes of acute viral hepatitis. It typically causes acute infection, but some cases of chronic infection have also been recorded. These cases were particularly seen in developed countries, in patients who were immunocompromised, organ transplant recipients, or those with underlying hematological malignancy. However, we encountered a case of hepatitis E presenting as a chronic liver disease in an immunocompetent patient from a developing country. Therefore, more underlying risk factors need to be studied, which may lead to such a rare presentation of hepatitis E.

Incomplete reporting of patient-reported outcomes in multiple sclerosis: A meta-epidemiological study of randomized controlled trials.

BACKGROUND: Multiple Sclerosis significantly affects quality of life, which is often measured by patient-reported outcomes. The incorporation of patient-reported outcomes within clinical trials supplements the efficacy of outcomes in order to provide a patient's perspective for clinicians. Our objective was to evaluate current literature for completeness of reporting of PROs in randomized controlled trials (RCTs) for the management of MS. METHODS: We used MEDLINE, Embase, and Cochrane Central Register of Controlled Trials to search for RCT publications investigating the management of MS. After duplicate screening via Rayyan, RCTs fitting our inclusion criteria were abstracted employing the Consolidated Standards of Reporting Trials - Patient-Reported Outcome (CONSORT-PRO) adaptation and the Cochrane Collaboration Risk of Bias (RoB) 2.0 tool. Mean percent completion of an adaptation of CONSORT-PRO was calculated to address completeness of reporting. In addition, bivariate regression models were used to evaluate relationships between trial characteristics and completeness of reporting. RESULTS: Our search returned 3,966 results and 92 RCTs were included for data abstraction and analysis. We found an overall completion of 48.68% (SD=19.03). Sixty-five (of 92; 70.65%) of the RCTs were evaluated as having 'high' RoB. There were significant associations between completeness of reporting and the following: mention of CONSORT within published RCTs (t=2.55, p=.013), length of PRO follow-up (t=2.9, p=.005; t=2.14, p=.035), and sample size (t=3.12, p=.002). No other significant associations were found. CONCLUSION: Our study found incomplete adherence to the CONSORT-PRO adaptation among RCTs pertaining to MS. Of the most underreported items, the failure to report a hypothesis and define an approach to missing data threaten the validity of the evidence acquired from RCTs. Furthermore, PROs provide an opportunity to supplement trial outcomes with the patient's perspective. Thus, trialists of future RCTs may improve PRO reporting with increased adherence to the CONSORT-PRO adaptation.