Early Diagnosis and Treatment of COPD and Asthma - A Randomized, Controlled Trial.

BACKGROUND: Many persons with chronic obstructive pulmonary disease (COPD) or asthma have not received a diagnosis, so their respiratory symptoms remain largely untreated. METHODS: We used a case-finding method to identify adults in the community with respiratory symptoms without diagnosed lung disease. Participants who were found to have undiagnosed COPD or asthma on spirometry were enrolled in a multicenter, randomized, controlled trial to determine whether early diagnosis and treatment reduces health care utilization for respiratory illness and improves health outcomes. Participants were assigned to receive the intervention (evaluation by a pulmonologist and an asthma-COPD educator who were instructed to initiate guideline-based care) or usual care by their primary care practitioner. The primary outcome was the annualized rate of participant-initiated health care utilization for respiratory illness. Secondary outcomes included changes from baseline to 1 year in disease-specific quality of life, as assessed with the St. George Respiratory Questionnaire (SGRQ; scores range from 0 to 100, with lower scores indicating better health status); symptom burden, as assessed with the COPD Assessment Test (CAT; scores range from 0 to 40, with lower scores indicating better health status); and forced expiratory volume in 1 second (FEV1). RESULTS: Of 38,353 persons interviewed, 595 were found to have undiagnosed COPD or asthma and 508 underwent randomization: 253 were assigned to the intervention group and 255 to the usual-care group. The annualized rate of a primary-outcome event was lower in the intervention group than in the usual-care group (0.53 vs. 1.12 events per person-year; incidence rate ratio, 0.48; 95% confidence interval [CI], 0.36 to 0.63; P<0.001). At 12 months, the SGRQ score was lower than the baseline score by 10.2 points in the intervention group and by 6.8 points in the usual-care group (difference, -3.5 points; 95% CI, -6.0 to -0.9), and the CAT score was lower than the baseline score by 3.8 points and 2.6 points, respectively (difference, -1.3 points; 95% CI, -2.4 to -0.1). The FEV1 increased by 119 ml in the intervention group and by 22 ml in the usual-care group (difference, 94 ml; 95% CI, 50 to 138). The incidence of adverse events was similar in the trial groups. CONCLUSIONS: In this trial in which a strategy was used to identify adults in the community with undiagnosed asthma or COPD, those who received pulmonologist-directed treatment had less subsequent health care utilization for respiratory illness than those who received usual care. (Funded by Canadian Institutes of Health Research; UCAP ClinicalTrials.gov number, NCT03148210.).

Serum Prolactin Levels as a Novel, Practical Marker for Predicting Malignant Diseases of the Breast.

Background and objective Prolactin (PRL) has a high specificity toward breast cancer (BC), making it a valuable marker in both diagnosis and prognosis. In this study, we aimed to compare serum PRL levels between pre- and post-menopausal women with BC, as well as normal reference values. We also investigated the association of various risk factors with PRL levels in women with BC. Methods The study involved adult women diagnosed with BC based on clinical features and tissue histopathology receiving treatment at a tertiary care center in Pune, India. General and demographic information, anthropometric measurements (height, weight, and BMI), menstrual status (age at menarche and menopausal state), clinical presentation (signs and symptoms), duration of symptoms, and parity were recorded by using a pre-tested proforma based on hospital records or in-person interviews. Serum PRL was measured by the RIA method (sandwich assay). Results A total of 67 women (average age: 47.5 ± 11.8 years; 33 of them post-menopausal) with BC were included in the study. The participants had an average BMI of 24.9 ± 3.5 kg/m2, and 26 (39%) of them were overweight. The majority of women had BC stage IIA disease, involvement of the right side or upper outer quadrant, and had attained menarche after 14 years of age; 47 women had a BC duration of >3 months. Seven women were nulliparous, and the remaining had given birth to their first child before the age of 26 years. The average serum PRL level among the participants was 9.27 ± 7.62 ng/mL, with higher levels found in post-menopausal women compared to pre-menopausal women (11.08 vs. 7.51 ng/mL, respectively; p=0.08). Women with a higher stage and greater duration of disease had significantly higher serum PRL levels (p<0.001 for both). When compared with reference values, pre-menopausal women showed significantly lower (6.25 vs. 10.9, respectively; p=0.001) and post-menopausal women showed significantly higher (8.55 vs. 5.95; p=0.004) serum PRL levels. A positive correlation was found between serum PRL and age at the time of birth of the first child (p=0.068). Conclusions Based on our findings, PRL is an important hormone in the development of BC in women. Therapeutic modulation of PRL may be a realistic and novel approach to curing human BC, either administered alone or in combination with conventional treatments.

Case Report of Rare Solitary Fibrous Tumour of Nape of Neck with Review of Literature.

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor with an indolent course but variable metastatic potential. Less than 50 cases of neck SFTs have been documented since 1991. We present a case report of rare presentations of SFT of nape of neck typifying the hypercellular variant of SFT (hemangiopericytoma) with challenges in treatment. Patient underwent excision and was subjected to adjuvant radiation. We concluded that SFT though a rare diagnosis should be considered while dealing with soft tissue tumors and multi-disciplinary pre-operative planning is must to avoid complications and recurrence. Surgical excision remains treatment of choice, but long follow-up is must.

Voice Restoration after Traumatic Subglottic Tracheal Stenosis.

Tracheal stenosis post intubation is one of the most common complication for which resection and anastomosis is done. Here we present a 21 year male patient who was intubated post organophosphorous poisoning. Diagnosed with tracheal stenosis post intubation and managed with tracheal resection and anastomosis with uneventful recovery. Post intubation tracheal stenosis is one of the serious complications and requires a multidisciplinary team and high volume centre for adequate management. Considering the fact that this case report has tracheal stenosis of grade IV type with resected length of tracheal cartilage of more than 3 cm and trachea- tracheal anastomosis makes this a rare case report.

Abnormal Colorectal Cancer Test Follow-Up: A Quality Improvement Initiative at a Federally Qualified Health Center.

INTRODUCTION/OBJECTIVES: Colonoscopy completion rates after an abnormal fecal immunochemical test (FIT) are suboptimal, resulting in missed opportunities for early detection and prevention of colorectal cancer. Patient navigation and structured follow-up may improve colonoscopy completion, but implementation of these strategies is not widespread. METHODS: We conducted a quality improvement study using a Plan-Do-Study-Act (PDSA) Model to increase colonoscopy completion after abnormal FIT in a large federally qualified health center serving a diverse and low-income population. Intervention components included patient navigation, and a checklist to promote completion of key steps required for abnormal FIT follow-up. Primary outcome was proportion of patients achieving colonoscopy completion within 6 months of abnormal FIT, assessed at baseline for 156 patients pre-intervention, and compared to 208 patients during the intervention period from April 2017 to December 2019. Drop offs at each step in the follow-up process were assessed. RESULTS: Colonoscopy completion improved from 21% among 156 patients with abnormal FIT pre-intervention, to 38% among 208 patients with abnormal FIT during the intervention (P < .001; absolute increase: 17%, 95% CI: 6.9%-25.2%). Among the 130 non-completers during the intervention period, lack of completion was attributable to absence of colonoscopy referral for 7.7%; inability to schedule a pre-colonoscopy specialist visit for 71.5%; failure to complete a pre-colonoscopy visit for 2.3%; the absence of colonoscopy scheduling for 9.2%; failure to show for a scheduled colonoscopy for 9.2%. CONCLUSIONS: Patient navigation and structured follow-up appear to improve colonoscopy completion after abnormal FIT. Additional strategies are needed to achieve optimal rates of completion.

A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening.

BACKGROUND: Colorectal cancer is the third most diagnosed cancer in adults in the United States. Early detection could prevent more than 90% of colorectal cancer-related deaths, yet more than one third of the screening-eligible population is not up to date with screening despite multiple available tests. A blood-based test has the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer-related mortality. METHODS: We assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions. RESULTS: The clinical validation cohort included 10,258 persons, 7861 of whom met eligibility criteria and were evaluable. A total of 83.1% of the participants with colorectal cancer detected by colonoscopy had a positive cfDNA test and 16.9% had a negative test, which indicates a sensitivity of the cfDNA test for detection of colorectal cancer of 83.1% (95% confidence interval [CI], 72.2 to 90.3). Sensitivity for stage I, II, or III colorectal cancer was 87.5% (95% CI, 75.3 to 94.1), and sensitivity for advanced precancerous lesions was 13.2% (95% CI, 11.3 to 15.3). A total of 89.6% of the participants without any advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions) identified on colonoscopy had a negative cfDNA blood-based test, whereas 10.4% had a positive cfDNA blood-based test, which indicates a specificity for any advanced neoplasia of 89.6% (95% CI, 88.8 to 90.3). Specificity for negative colonoscopy (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0 to 90.7). CONCLUSIONS: In an average-risk screening population, this cfDNA blood-based test had 83% sensitivity for colorectal cancer, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions. (Funded by Guardant Health; ECLIPSE ClinicalTrials.gov number, NCT04136002.).

Impact of Helicobacter pylori Infection and Treatment on Colorectal Cancer in a Large, Nationwide Cohort.

PURPOSE: Helicobacter pylori is the most common cause of infection-associated cancer worldwide. We aimed to evaluate the impact of H. pylori infection and treatment on colorectal cancer (CRC) incidence and mortality. PATIENTS: US Veterans who completed H. pylori testing between 1999 and 2018. METHODS: We conducted a retrospective cohort analysis among adults within the Veterans Health Administration who completed testing for H. pylori. The primary exposures were (1) H. pylori test result (positive/negative) and (2) H. pylori treatment (untreated/treated) among H. pylori-positive individuals. The primary outcomes were CRC incidence and mortality. Follow-up started at the first H. pylori testing and continued until the earliest of incident or fatal CRC, non-CRC death, or December 31, 2019. RESULTS: Among 812,736 individuals tested for H. pylori, 205,178 (25.2%) tested positive. Being H. pylori-positive versus H. pylori-negative was associated with higher CRC incidence and mortality. H. pylori treatment versus no treatment was associated with lower CRC incidence and mortality (absolute risk reduction 0.23%-0.35%) through 15-year follow-up. Being H. pylori-positive versus H. pylori-negative was associated with an 18% (adjusted hazard ratio [adjusted HR], 1.18 [95% CI, 1.12 to 1.24]) and 12% (adjusted HR, 1.12 [95% CI, 1.03 to 1.21]) higher incident and fatal CRC risk, respectively. Individuals with untreated versus treated H. pylori infection had 23% (adjusted HR, 1.23 [95% CI, 1.13 to 1.34]) and 40% (adjusted HR, 1.40 [95% CI, 1.24 to 1.58]) higher incident and fatal CRC risk, respectively. The results were more pronounced in the analysis restricted to individuals with nonserologic testing. CONCLUSION: H. pylori positivity may be associated with small but statistically significant higher CRC incidence and mortality; untreated individuals, especially those with confirmed active infection, appear to be most at risk.

Screening for Colorectal Cancer: The Role of Clinical Laboratories.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer incidence and mortality. Screening can result in reductions in incidence and mortality, but there are many challenges to uptake and follow-up. CONTENT: Here, we will review the changing epidemiology of CRC, including increasing trends for early and later onset CRC; evidence to support current and emerging screening strategies, including noninvasive stool and blood-based tests; key challenges to ensuring uptake and high-quality screening; and the critical role that clinical laboratories can have in supporting health system and public health efforts to reduce the burden of CRC on the population. SUMMARY: Clinical laboratories have the opportunity to play a seminal role in optimizing early detection and prevention of CRC.

Trial of Selective Early Treatment of Patent Ductus Arteriosus with Ibuprofen.

BACKGROUND: The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus (PDA) in preterm infants. Whether selective early treatment of large PDAs with ibuprofen would improve short-term outcomes is not known. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial evaluating early treatment (≤72 hours after birth) with ibuprofen for a large PDA (diameter of ≥1.5 mm with pulsatile flow) in extremely preterm infants (born between 23 weeks 0 days' and 28 weeks 6 days' gestation). The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia evaluated at 36 weeks of postmenstrual age. RESULTS: A total of 326 infants were assigned to receive ibuprofen and 327 to receive placebo; 324 and 322, respectively, had data available for outcome analyses. A primary-outcome event occurred in 220 of 318 infants (69.2%) in the ibuprofen group and 202 of 318 infants (63.5%) in the placebo group (adjusted risk ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). A total of 44 of 323 infants (13.6%) in the ibuprofen group and 33 of 321 infants (10.3%) in the placebo group died (adjusted risk ratio, 1.32; 95% CI, 0.92 to 1.90). Among the infants who survived to 36 weeks of postmenstrual age, moderate or severe bronchopulmonary dysplasia occurred in 176 of 274 (64.2%) in the ibuprofen group and 169 of 285 (59.3%) in the placebo group (adjusted risk ratio, 1.09; 95% CI, 0.96 to 1.23). Two unforeseeable serious adverse events occurred that were possibly related to ibuprofen. CONCLUSIONS: The risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age was not significantly lower among infants who received early treatment with ibuprofen than among those who received placebo. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Baby-OSCAR ISRCTN Registry number, ISRCTN84264977.).

Colorectal Neoplasia in Asian Americans Undergoing First Time Asymptomatic Average-risk Screening Colonoscopies.

GOALS: We identified the prevalence and subtype of colorectal neoplasia removed during index screening colonoscopies in a large Asian American population. BACKGROUND: Asian Americans are the fastest growing demographic group in the United States yet there is a paucity of data on the characteristics of colorectal neoplasia found in this cohort. STUDY: Cross-sectional study of 2208 index colonoscopies performed on average-risk Asian and White patients at a large, tertiary academic center. Patients were identified via diagnostic or procedure codes between 2015 and 2020, with retrospective classification of polyp histopathology. Univariate and multivariate analysis were performed to identify risk factors associated with colorectal neoplasia. RESULTS: A total of 2208 patients were identified, of which 1085 were Asian. When adjusted for age and sex, Asians were as likely as Whites to have any type of colorectal neoplasia [44.2% vs. 43.5%, odds ratio (OR)=0.93, (CI: 0.78-1.11)]. On multivariate analysis, Asians were less likely to have sessile serrated polyps (5.5% vs. 9.9%, OR=0.53, 95% CI: 0.38-0.73) and more likely to have tubular adenomas in the left colon (22.6% vs. 18.0%, OR=1.33, 95% CI: 1.08-1.64) compared with Whites. CONCLUSIONS: Quality measures, such as sessile serrated polyp detection rates, may need to take into account demographic factors such as race. The prevalence of colorectal neoplasia among Asian Americans is substantial and warrants efforts to promote optimal uptake of colorectal cancer screening tests.

Birth Cohort Colorectal Cancer (CRC): Implications for Research and Practice.

Colorectal cancer (CRC) epidemiology is changing due to a birth cohort effect, first recognized by increasing incidence of early onset CRC (EOCRC, age <50 years). In this paper, we define "birth cohort CRC" as the observed phenomenon, among individuals born 1960 and later, of increasing CRC risk across successive birth cohorts, rising EOCRC incidence, increasing incidence among individuals aged 50 to 54 years, and flattening of prior decreasing incidence among individuals aged 55 to 74 years. We demonstrate birth cohort CRC is associated with unique features, including increasing rectal cancer (greater than colon) and distant (greater than local) stage CRC diagnosis, and increasing EOCRC across all racial/ethnic groups. We review potential risk factors, etiologies, and mechanisms for birth cohort CRC, using EOCRC as a starting point and describing importance of viewing these through the lens of birth cohort. We also outline implications of birth cohort CRC for epidemiologic and translational research, as well as current clinical practice. We postulate that recognition of birth cohort CRC as an entity-including and extending beyond rising EOCRC-can advance understanding of risk factors, etiologies, and mechanisms, and address the public health consequences of changing CRC epidemiology.

Risk of Esophageal Cancer in Achalasia: A Matched Cohort Study Using the Nationwide Veterans Affairs Achalasia Cohort.

INTRODUCTION: Achalasia is a postulated risk factor of esophageal cancer (EC); however, EC-associated risk in achalasia is understudied. We aimed to evaluate EC risk among individuals within the nationwide Veterans Affairs Achalasia Cohort. METHODS: We conducted a matched cohort study among US veterans aged 18 years or older from 1999 to 2019. Individuals with achalasia were age matched and sex matched 1:4 to individuals without achalasia. Follow-up continued from study entry until diagnosis with incident/fatal EC (primary outcome), death from non-EC-related causes, or end of the study follow-up (December 31, 2019). Association between achalasia and EC risk was examined using Cox regression models. RESULTS: We included 9,315 individuals in the analytic cohort (median age 55 years; 92% male): 1,863 with achalasia matched to 7,452 without achalasia. During a median 5.5 years of follow-up, 17 EC occurred (3 esophageal adenocarcinoma, 12 squamous cell carcinoma, and 2 unknown type) among individuals with achalasia, compared with 15 EC (11 esophageal adenocarcinoma, 1 squamous cell carcinoma, and 3 unknown type) among those without achalasia. EC incidence for those with achalasia was 1.4 per 1,000 person-years, and the median time from achalasia diagnosis to EC development was 3.0 years (Q1-Q3: 1.3-9.1). Individuals with achalasia had higher cumulative EC incidence at 5, 10, and 15 years of follow-up compared with individuals without achalasia, and EC risk was 5-fold higher (hazard ratio 4.6, 95% confidence interval: 2.3-9.2). DISCUSSION: Based on substantial EC risk, individuals with achalasia may benefit from a high index of suspicion and endoscopic surveillance for EC.

Helicobacter pylori Burden in the United States According to Individual Demographics and Geography: A Nationwide Analysis of the Veterans Healthcare System.

BACKGROUND & AIMS: There are no contemporary large-scale studies evaluating the burden of Helicobacter pylori in the United States according to detailed demographics. The primary objective was to evaluate H pylori positivity in a large national healthcare system according to individual demographics and geography. METHODS: We conducted a nationwide retrospective analysis of adults in the Veterans Health Administration who completed H pylori testing between 1999 and 2018. The primary outcome was H pylori positivity overall, as well as according to zip code-level geography, race, ethnicity, age, sex, and time period. RESULTS: Among 913,328 individuals (mean, 58.1 years; 90.2% male) included between 1999 and 2018, H pylori was diagnosed in 25.8%. Positivity was highest in non-Hispanic black (median, 40.2%; 95% confidence interval [CI], 40.0%-40.5%) and Hispanic (36.7%; 95% CI, 36.4%-37.1%) individuals and lowest in non-Hispanic white individuals (20.1%; 95% CI, 20.0%-20.2%). Although H pylori positivity declined in all racial and ethnic groups over the timeframe, the disproportionate burden of H pylori in non-Hispanic black and Hispanic compared with non-Hispanic white individuals persisted. Approximately 4.7% of the variation in H pylori positivity was explained by demographics, with race and ethnicity accounting for the vast majority. CONCLUSIONS: The burden of H pylori is substantial in the United States among veterans. These data should (1) motivate research aimed at better understanding why marked demographic differences in H pylori burden persist so that mitigating interventions may be implemented and (2) guide resource allocation to optimize H pylori testing and eradication in high-risk groups.

Physiologic changes in the hepatopulmonary syndrome before and after liver transplant: A longitudinal and predictor analysis.

BACKGROUND AND AIMS: Hepatopulmonary syndrome (HPS) is a common complication of liver disease defined by abnormal oxygenation and intrapulmonary vascular dilatation, treated with liver transplantation. Little is known about changes in HPS physiological parameters over time. We sought to describe baseline clinical and physiological characteristics in HPS and their relationships, temporal changes in physiological parameters before and after transplant, and predictors of changes in oxygenation. APPROACH AND RESULTS: This was a retrospective cohort study in the Canadian HPS Program (n = 132). Rates of change after diagnosis were: -3.7 (-6.4, -0.96) mm Hg/year for partial pressure of arterial oxygen (PaO 2 ); -26 (-96, 44) m/year for 6-minute walk distance, and 3.3% (-6.6, -0.011) predicted/year for diffusion capacity. Noninvasive shunt of ≥ 20% predicted a slower PaO 2 decline by 0.88 (0.36, 1.4) mm Hg/month. We identified 2 PaO 2 deterioration classes-"very severe disease, slow decliners" (PaO 2 45.0 mm Hg; -1.0 mm Hg/year); and "moderate disease, steady decliners" (PaO 2 65.5 mm Hg; -2.5 mm Hg/year). PaO 2 increased by 6.5 (5.3, 7.7) mm Hg/month in the first year after transplant. The median time to normalization was 149 (116, 184) days. Posttransplant improvement in PaO 2 was 2.5 (0.1, 4.9) mm Hg/month faster for every 10 mm Hg greater pretransplant orthodeoxia. CONCLUSIONS: We present a large and long longitudinal data analysis in HPS. In addition to rates of physiological decline and improvement before and after liver transplantation, we present novel predictors of PaO 2 decline and improvement rates. Our findings enhance our understanding of the natural history of HPS and provide pathophysiologic clues. Importantly, they may assist providers in prognostication and prioritization before and after transplant.

Pancreatic cyst features predict future development of pancreatic cancer: results of a nested case-control study.

BACKGROUND AND AIMS: Risk factors for pancreatic cancer among patients with pancreatic cysts are incompletely characterized. The primary aim of this study was to evaluate risk factors for development of pancreatic cancer among patients with pancreatic cysts. METHODS: We conducted a retrospective case-control study of U.S. veterans with a suspected diagnosis of branch-duct intraductal papillary mucinous neoplasm from 1999 to 2013. RESULTS: Age (hazard ratio [HR], 1.03 per year; 95% confidence interval [CI], 1.00-1.06), larger cyst size at cyst diagnosis (HR, 1.03 per mm; 95% CI, 1.01-1.04), cyst growth rate (HR, 1.22 per mm/y; 95% CI, 1.14-1.31), and pancreatic duct dilation (5-9.9 mm: HR, 3.78; 95% CI, 1.90-7.51; ≥10 mm: HR, 13.57; 95% CI, 5.49-33.53) were found to be significant predictors for pancreatic cancer on multivariable analysis. CONCLUSIONS: Age, cyst size, cyst growth rate, and high-risk or worrisome features were associated with a higher risk of developing pancreatic cancer. Applying current and developing novel strategies is required to optimize early detection of pancreatic cancer after cyst diagnosis.