Nakul Singh

Leveraging a critical care database: selective serotonin reuptake inhibitor use prior to ICU admission is associated with increased hospital mortality.

BACKGROUND Observational studies have found an increased risk of adverse effects such as hemorrhage, stroke, and increased mortality in patients taking selective serotonin reuptake inhibitors (SSRIs). The impact of prior use of these medications on outcomes in critically ill patients has not been previously examined. We performed a retrospective study to determine if preadmission use of SSRIs or serotonin norepinephrine reuptake inhibitors (SNRIs) is associated with mortality differences in patients admitted to the ICU. METHODS The retrospective study used a modifiable data mining technique applied to the publicly available Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) 2.6 database. A total of 14,709 patient records, consisting of 2,471 in the SSRI/SNRI group and 12,238 control subjects, were analyzed. The study outcome was in-hospital mortality. RESULTS After adjustment for age, Simplified Acute Physiology Score, vasopressor use, ventilator use, and combined Elixhauser score, SSRI/SNRI use was associated with significantly increased in-hospital mortality (OR, 1.19; 95% CI, 1.02-1.40; P=.026). Among patient subgroups, risk was highest in patients with acute coronary syndrome (OR, 1.95; 95% CI, 1.21-3.13; P=.006) and patients admitted to the cardiac surgery recovery unit (OR, 1.51; 95% CI, 1.11-2.04; P=.008). Mortality appeared to vary by specific SSRI, with higher mortalities associated with higher levels of serotonin inhibition. CONCLUSIONS We found significant increases in hospital stay mortality among those patients in the ICU taking SSRI/SNRIs prior to admission as compared with control subjects. Mortality was higher in patients receiving SSRI/SNRI agents that produce greater degrees of serotonin reuptake inhibition. The study serves to demonstrate the potential for the future application of advanced data examination techniques upon detailed (and growing) clinical databases being made available by the digitization of medicine.

Original Research: Critical CareLeveraging a Critical Care Database: Selective Serotonin Reuptake Inhibitor Use Prior to ICU Admission Is Associated With Increased Hospital Mortality

BACKGROUND Observational studies have found an increased risk of adverse effects such as hemorrhage, stroke, and increased mortality in patients taking selective serotonin reuptake inhibitors (SSRIs). The impact of prior use of these medications on outcomes in critically ill patients has not been previously examined. We performed a retrospective study to determine if preadmission use of SSRIs or serotonin norepinephrine reuptake inhibitors (SNRIs) is associated with mortality differences in patients admitted to the ICU. METHODS The retrospective study used a modifiable data mining technique applied to the publicly available Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) 2.6 database. A total of 14,709 patient records, consisting of 2,471 in the SSRI/SNRI group and 12,238 control subjects, were analyzed. The study outcome was in-hospital mortality. RESULTS After adjustment for age, Simplified Acute Physiology Score, vasopressor use, ventilator use, and combined Elixhauser score, SSRI/SNRI use was associated with significantly increased in-hospital mortality (OR, 1.19; 95% CI, 1.02-1.40; P=.026). Among patient subgroups, risk was highest in patients with acute coronary syndrome (OR, 1.95; 95% CI, 1.21-3.13; P=.006) and patients admitted to the cardiac surgery recovery unit (OR, 1.51; 95% CI, 1.11-2.04; P=.008). Mortality appeared to vary by specific SSRI, with higher mortalities associated with higher levels of serotonin inhibition. CONCLUSIONS We found significant increases in hospital stay mortality among those patients in the ICU taking SSRI/SNRIs prior to admission as compared with control subjects. Mortality was higher in patients receiving SSRI/SNRI agents that produce greater degrees of serotonin reuptake inhibition. The study serves to demonstrate the potential for the future application of advanced data examination techniques upon detailed (and growing) clinical databases being made available by the digitization of medicine.

Prevalence and Causes of Blindness and Visual Impairment and Their Associated Risk Factors, in Three Tribal Areas of Andhra Pradesh, India

Objective To assess the prevalence of blindness and visual impairment (VI), their associated causes and underlying risk factors in three tribal areas of Andhra Pradesh, India and compare this data in conjunction with data from other countries with low and middle income settings. Methods Using a validated Rapid Assessment of Avoidable Blindness methodology, a two stage sampling survey was performed in these areas involving probability proportionate to size sampling and compact segment sampling methods. Blindness, VI and severe visual impairment (SVI) were defined as per the WHO guidelines and Indian definitions. Results Based on a prior enumeration, 7281 (97.1%) subjects were enrolled (mean age  = 61.0+/−7.9 years). Based on the presenting visual acuity (PVA), the prevalences of VI, SVI and blindness were 16.9% (95% CI: 15.7–18.1), 2.9% (95% CI: 2.5–3.4), and 2.3% (95% CI: 1.9–2.7), respectively. When based on the Pinhole corrected visual acuity (PCVA), the prevalences were lower in VI (6.2%, 95% CI: 5.4–6.9), SVI (1.5%, 95% CI: 1.2–1.9) and blindness (2.1%, 95% CI: 1.7–2.5). Refractive error was the major cause of VI (71.4%), whereas, cataract was the major cause of SVI and blindness (70.3%). Based on the PVA, the odds ratio (OR) of blindness increased in the age groups of 60–69 years (OR = 3.8, 95% CI: 2.8, 5.1), 70–79 years (OR = 10.6, 95% CI: 7.2, 15.5) and 80 years and above (OR = 30.7, 95% CI: 19.2, 49). The ORs were relatively higher in females (OR = 1.3, 95% CI: 1.0, 1.6) and illiterate subjects (OR = 4.3, 95% CI: 2.2, 8.5), but lower in those wearing glasses (OR = 0.2, 95% CI: 0.1, 0.4). Conclusions This is perhaps the first study to assess the prevalence of blindness and VI in these tribal regions and the majority of the causes of blindness and SVI were avoidable (88.5%). These findings may be useful for planning eye care services in these underserved regions.

Uveal Melanoma Regression after Brachytherapy: Relationship with Chromosome 3 Monosomy Status

Aim: The objective was to evaluate the relationship between the regression rate of ciliary body melanoma and choroidal melanoma after brachytherapy and chromosome 3 monosomy status. Methods: We conducted a prospective and consecutive case series of patients who underwent biopsy and brachytherapy for ciliary/choroidal melanoma. Tumor biopsy performed at the time of radiation plaque placement was analyzed with fluorescence in situ hybridization to determine the percentage of tumor cells with chromosome 3 monosomy. The regression rate was calculated as the percent change in tumor height at months 3, 6, and 12. The relationship between regression rate and tumor location, initial tumor height, and chromosome 3 monosomy (percentage) was assessed by univariate linear regression (R version 3.1.0). Results: Of the 75 patients included in the study, 8 had ciliary body melanoma, and 67 were choroidal melanomas. The mean tumor height at the time of diagnosis was 5.2 mm (range: 1.90-13.00). The percentage composition of chromosome 3 monosomy ranged from 0-20% (n = 35) to 81-100% (n = 40). The regression of tumor height at months 3, 6, and 12 did not statistically correlate with tumor location (ciliary or choroidal), initial tumor height, or chromosome 3 monosomy (percentage). Conclusion: The regression rate of choroidal melanoma following brachytherapy did not correlate with chromosome 3 monosomy status.

Extranodal Marginal Zone Lymphoma of Ocular Adnexa: Outcomes following Radiation Therapy

Aim: The aim of this study was to report outcomes following radiation therapy in patients with biopsy-proven extranodal marginal zone lymphoma of the ocular adnexa and uvea. Methods: Records from a single institution were retrospectively reviewed from January 1997 to December 2015. The mean follow-up duration was 38 months (range 0-194). Radiation therapy was administered to 77 eyes (60 patients); 57 of the 77 eyes (74%) were treated with radiation only (range 20-36 Gy, median 15 fractions). Radiation cataract, radiation retinopathy, and optic neuropathy assessments were performed on all eyes treated with radiation. Results: 100% of the 47 patients treated with radiation therapy only had local control with an average dose of 26.5 Gy (median 25.2 [range 20-36] Gy; 150-200 cGy per fraction). Four patients lost 2 lines or more of vision after radiation. The most common complication of radiation therapy was cataract formation/progression in 19 eyes (25%). Radiation retinopathy was observed only in 1 patient (1%). Conclusion: Our results confirm that radiation therapy (median 25 Gy) for extranodal marginal zone lymphoma of the ocular adnexa is associated with high local control and low risk of visually significant complications.

Why History Matters for Quantitative Target Setting: Long-Term Trends in Socioeconomic and Racial/Ethnic Inequities in US Infant Death Rates (1960-2010)

Policy-oriented population health targets, such as the Millennium Development Goals and national targets to address health inequities, are typically based on trends of a decade or less. To test whether expanded timeframes might be more apt, we analyzed 50-year trends in US infant death rates (1960–2010) jointly by income and race/ethnicity. The largest annual per cent changes in the infant death rate (between −4 and −10 per cent), for all racial/ethnic groups, in the lowest income quintile occurred between the mid-1960s and early 1980s, and in the second lowest income quintile between the mid-1960s and 1973. Since the 1990s, these numbers have hovered, in all groups, between −1 and −3 per cent. Hence, to look back only 15 years (in 2014, to 1999) would ignore gains achieved prior to the onset of neoliberal policies after 1980. Target setting should be informed by a deeper and longer-term appraisal of what is possible to achieve.

Reproductive Justice and the Pace of Change: Socioeconomic Trends in US Infant Death Rates by Legal Status of Abortion, 1960–1980

US infant death rates for 1960 to 1980 declined most quickly in (1) 1970 to 1973 in states that legalized abortion in 1970, especially for infants in the lowest 3 income quintiles (annual percentage change = -11.6; 95% confidence interval = -18.7, -3.8), and (2) the mid-to-late 1960s, also in low-income quintiles, for both Black and White infants, albeit unrelated to abortion laws. These results imply that research is warranted on whether currently rising restrictions on abortions may be affecting infant mortality.

Iodine-125 Brachytherapy for Uveal Melanoma: A Systematic Review of Radiation Dose

Aim: To investigate whether lower radiation doses may yield similar outcome measures to those from the COMS trial. Methods: A literature review of English language articles was performed using the PubMed database of the U.S. National Library of Medicine and the Cochrane Central Register of Controlled Trials using the following keywords: uveal melanoma, choroidal melanoma, primary uveal malignant melanoma, iodine-125 brachytherapy, local recurrence, local treatment failure, and local tumor control. The relationships between study local recurrence rate and median dosage were tested by linear regression, with each study weighted by the number of patients included. Results: Fifteen retrospective and prospective studies were selected for systematic review (2,662 patients). Ranges of reported mean or median radiation dose to tumor apex were 62.5-104.0 Gy. Local recurrence rates ranged from 0 to 24%. A 1.0-Gy increase in the average study dose was associated with a 0.14% decrease in local recurrence rate, which was not statistically significant (p value 0.336). Conclusion: The gold standard empirically derived 85.0-Gy radiation dose for the treatment of uveal melanoma could be tested in a randomized study.

Reproductive justice & preventable deaths: State funding, family planning, abortion, and infant mortality, US 1980–2010

Introduction Little current research examines associations between infant mortality and US states’ funding for family planning services and for abortion, despite growing efforts to restrict reproductive rights and services and documented associations between unintended pregnancy and infant mortality. Material and methods We obtained publicly available data on state-only public funding for family planning and abortion services (years available: 1980, 1987, 1994, 2001, 2006, and 2010) and corresponding annual data on US county infant death rates. We modeled the funding as both fraction of state expenditures and per capita spending (per woman, age 15–44). State-level covariates comprised: Title X and Medicaid per capita funding, fertility rate, and percent of counties with no abortion services; county-level covariates were: median family income, and percent: black infants, adults without a high school education, urban, and female labor force participation. We used Possion log-linear models for: (1) repeat cross-sectional analyses, with random state and county effects; and (2) panel analysis, with fixed state effects. Results Four findings were robust to analytic approach. First, since 2000, the rate ratio for infant death comparing states in the top funding quartile vs. no funding for abortion services ranged (in models including all covariates) between 0.94 and 0.98 (95% confidence intervals excluding 1, except for the 2001 cross-sectional analysis, whose upper bound equaled 1), yielding an average 15% reduction in risk (range: 8–22%). Second, a similar risk reduction for state per capita funding for family planning services occurred in 1994. Third, the excess risk associated with lower county income increased over time, and fourth, remained persistently high for counties with a high percent of black infants. Conclusions Insofar as reducing infant mortality is a government priority, our data underscore the need, despite heightened contention, for adequate public funding for abortion services and for redressing health inequities.

Ophthalmic oncology: how to search, appraise, and report evidence.

Because of their rareness, many conditions encountered in the field of ophthalmic oncology have not been studied with statistical rigor. As a result, many clinical decisions relating to care of these patients rely on expert opinion or clinical experience, often without evidence that supports one particular option over another. The incorporation of appropriate evidence into these decisions will surely lead to better outcomes for patients. This process of incorporating the best evidence into clinical practice is called evidence-based medicine (EBM), and the following chapter provides an introductory overview of the subject, as well as a guide to additional resources.