Estimating the Effect of Preventable Treatment Discontinuation on Health Outcomes.

BACKGROUND: There is increased interest in studying the effects of medication adherence on health outcomes. However, if patients appropriately stop treatment because of side effects and treatment failure, it is neither possible nor clinically meaningful to estimate the effect of full medication adherence. METHODS: We present an analysis designed to estimate the effect of nonmedical (preventable) discontinuation of cinacalcet, an oral medication approved to treat secondary hyperparathyroidism in patients with end-stage renal disease on dialysis on mortality and heart failure. The approach involves artificially censoring patients who discontinue treatment for a reason that does not appear to be related to an adverse effect of treatment. We address potential bias from informative censoring through inverse-probability of censoring weighted estimation. RESULTS: Although the analysis is subject to possible residual confounding by the healthy adherer effect and other limitations, we find that potentially preventable discontinuation associates with 2.9 excess deaths at 1 year per 100 patients treated (95% confidence interval, 2.4, 3.5), and 4.6 excess deaths at 2 years (95% confidence interval, 3.5, 5.5). The association between cinacalcet persistence and heart failure hospitalization risk was sensitive to the outcome definition. CONCLUSIONS: Inverse-probability of censoring weighted estimation can be used to estimate the effect of potentially preventable treatment discontinuation in populations where treatment can be stopped for both medical and nonmedical reasons. Estimates from such approaches may represent an upper bound of what would be achievable by an adherence improvement intervention.

Prospective study of sickle cell trait and venous thromboembolism incidence.

BACKGROUND: Sickle cell trait may increase risk of venous thromboembolism, but this is not fully established. OBJECTIVES: We sought to determine the association of sickle cell trait with deep vein thrombosis and pulmonary embolism. METHODS: Middle-aged African Americans participating in a prospective, population-based cohort investigation, the Atherosclerosis Risk in Communities Study, were followed from 1987 through 2011 for incident hospitalized pulmonary embolism (n = 111) or isolated deep vein thrombosis (n = 138), verified by physician review of medical records. Sickle cell trait (heterozygosity for hemoglobin S, n = 268) was compared with no sickle cell trait (n = 3748). RESULTS: Over a median of 22 years of follow-up, 249 participants had an incident venous thromboembolism. The hazard ratio of venous thromboembolism was 1.50 (95% confidence interval [CI] 0.96-2.36) for participants with vs. without sickle cell trait, after adjustment for age, sex, ancestry, hormone replacement therapy (women), body mass index, diabetes, and estimated glomerular filtration rate. This hazard ratio was 2.05 (95% CI 1.12-3.76) for pulmonary embolism and 1.15 (95% CI 0.58-2.27) for deep vein thrombosis without pulmonary embolism. CONCLUSIONS: Sickle cell trait in African Americans carries a 2-fold increased risk of pulmonary embolism but does not elevate deep vein thrombosis risk. Because neonatal screening for sickle hemoglobin is being conducted in the United States, consideration should be paid to the increased pulmonary embolism risk of individuals with sickle cell trait.

The association of retinopathy and low GFR in type 2 diabetes.

AIMS: We sought to determine characteristics which strengthen the association between markers of diabetic kidney disease and retinopathy. METHODS: Multivariate regression analyses of NHANES 2005-2008 assessed the association of retinopathy with renal insufficiency and albuminuria. Analyses were stratified to evaluate ethnicity/race, obesity, and use of renin-angiotensin-aldosterone system antagonists as effect modifiers of this relationship. RESULTS: Of 269 participants with renal insufficiency, 35% had no microalbuminuria and no retinopathy; 16.1% had retinopathy with no microalbuminuria; 27.1% had microalbuminuria and no retinopathy and 22% had both microalbuminuria and retinopathy. Stratified, multivariate logistic regression analyses demonstrated retinopathy to be significantly predictive of renal insufficiency only in nonHispanic Blacks (OR=2.7; 95% CI 1.2, 6.1), obesity (OR=2.6; 95% CI 1.3, 5.5) and in those participants not using renin-angiotensin-aldosterone blockers (OR=2.5; 95% CI 1.1, 5.7). Analyses showed an independent relationship between retinopathy and albuminuria only when albuminuria was modeled continuously. CONCLUSIONS: In older onset diabetes, the absence of albuminuria and retinopathy is common among individuals with renal insufficiency. The relationship between microvascular complications of the eye and kidney may vary according to ethnicity, obesity and use of renin-angiotensin-aldosterone antagonists. These findings need to be confirmed in other large, diverse cohorts.

Duodenal stenosis in a child.

We present a case of incomplete duodenal obstruction having a delayed presentation, making diagnosis and early intervention more challenging. Failure of recanalization of the duodenal lumen during the eighth to tenth week of gestation, results in duodenal atresia. Incomplete recanalization can lead to duodenal stenosis or the presence of a duodenal web. In the absence of other serious anomalies or prematurity, the overall survival for duodenal stenosis or atresia is nearly 100%.

Invasive Papillary Breast Carcinoma.

We present the case of a 55-year-old postmenopausal female who presented with complaints of a gradually increasing painless subareolar mass in the left breast of 4 months' duration. Left-sided modified radical mastectomy was performed and the specimen was histopathologically diagnosed as invasive papillary carcinoma. Immunohistochemistry confirmed this diagnosis. All 8 excised axillary lymph nodes were negative for malignant cells. Postoperative chemotherapy was given and for the past 6 months, the patient has maintained a regular follow-up on an outpatient basis. She does not have any evidence of either local or distant recurrence of tumour metastases.

Hygrophila spinosa: A comprehensive review.

Hygrophila spinosa T Ander, belonging to the family Acanthaceae, is a promising medicinal plant with great economic potential. The medicinal value of H. spinosa has been appreciated in the ancient medical literature. The plant contains terpenoids, alkaloids, flavonoids, and is traditionally known as an aphrodisiac, renal tonic, and for its health-promoting properties. The plant is cultivated throughout India. However, systematic information on the different aspects of this species is not available. In this review, an attempt has been made to present this information.

Metaplastic carcinoma with predominant chondrosarcoma of the right breast.

A 45-year-old female presented with complaint of a lump in the right breast for the last 6 months. Excisional biopsy had been performed outside our institution, which was suggestive of a pure mammary chondrosarcoma. Modified radical mastectomy of the right breast was performed and histopathology was suggestive of a pure mammary chondrosarcoma of the right breast. One axillary lymph node was positive for metastasis, the rest of the lymph nodes were free of metastasis. Immunohistochemistry was suggestive of a metaplastic carcinoma with a predominant chondrosarcoma in the right breast. Postoperative radiotherapy was given to the patient with a further plan of chemotherapy.

Microalbuminuria, peripheral artery disease, and cognitive function.

Kidney disease may be linked to a decline in cognitive activity. We examined the association of microalbuminuria and cognitive function in a general population of older adults in the United States drawn from the National Health and Nutrition Examination Survey of 1999-2002. Cognitive function was measured by digit symbol substitution in 2,386 participants 60 years of age and older of whom 448 had microalbuminuria. Covariates included age, gender, race/ethnicity, education, smoking, diabetes, and hypertension. Among participants with peripheral artery disease, those with microalbuminuria had a significantly lower cognitive function score compared to those with a normal albumin-to-creatinine ratio. The association between microalbuminuria and cognitive function was weak in those without peripheral artery disease. But in those with peripheral artery disease, the odds of microalbuminuria associated with cognitive function in the lowest and middle tertiles was 6.5 and 3.5, respectively.

Phosphodiesterase 11: a brief review of structure, expression and function.

Phosphodiesterase 11 (PDE11) is the latest isoform of the phosphodiesterase family to be identified. Interest in PDE11 has increased recently because tadalafil, an oral phosphodiesterase 5 inhibitor, cross reacts with PDE11. The function of PDE11 remains largely unknown, but growing evidence points to a possible role in male reproduction. The published literature on PDE11 structure, function and expression is reviewed.

Predicting hypogonadism in men based upon age, presence of erectile dysfunction, and depression.

Hypogonadism, a disorder associated with aging, can cause significant morbidity. As clinical manifestations of hypogonadism can be subtle, the challenge and the burden of diagnosis remain the responsibility of the clinician. Four different analytic methods were used to predict hypogonadism in men based upon age, the presence of erectile dysfunction (ED) and depression. 218 men were classified by age, serum testosterone level, the presence of ED and depression. Depression was determined by the Center for Epidemiologic Studies Depression Scale (CES-D). ED was assessed by the Sexual Health Inventory for Men (SHIM). Hypogonadism was defined as a serum testosterone level <300 ng/dl. An artificial neural network (ANN) was programmed and trained to predict hypogonadism based upon age, SHIM, and CES-D scores. Subject data was randomly partitioned into a training set of 148 (67.9%) and a test set of 70 (32.1%). The ANN processed the test set only after the training was complete. The discrete predicted binary output was set to (0) if testosterone level was <300 ng/dl or (1) if >300 ng/dl. The data was also analyzed by standard logistic regression (LR), linear and quadratic discriminant function analysis (LDFA and QDFA, respectively). Reverse regression (RR) analysis evaluated the statistical significance of each risk factor. The ANN can accurately predict hypogonadism in men based upon age, the presence of ED, and depression (receiver-operating characteristic=0.725). A four hidden node network was found to have the highest accuracy. RR revealed the depression index score to be most significant variable (P=0.0019), followed by SHIM score (P=0.00602), and then by age (P=0.015). Hypogonadism can be predicated by an ANN using the input factors of age, ED, and depression. This model can help clinicians assess the need for endocrinologic evaluation in men.

Pseudomyxoma peritonei presenting as sub-acute large bowel obstruction.

A case of pseudomyxoma peritonei, a rare mucin-secreting tumour in the peritoneum, in a 30-year-old male and presenting as sub-acute large bowel obstruction, is reported here with review of the literature.

Primary adenocarcinoma of the vermiform appendix: a case report.

Primary adenocarcinoma of the appendix is rare, and since Berger first recognised the neoplasm in 1882, fewer than 250 cases have been recorded. Adenocarcinoma of the appendix is never suspected pre-operatively, being usually first discovered by histological examination. Ileocaecal resection during the first operation and right hemicolectomy for a carcinoma diagnosed after appendicectomy remain the main stay of treatment.

Sensitivity and specificity of rapid HIV testing of pregnant women in India.

OBJECTIVE: Efforts to prevent HIV transmission from mother to infants in settings like India may benefit from the availability of reliable methods for rapid and simple HIV screening. Data from India on the reliability of rapid HIV test kits are limited and there are no data on the use of rapid HIV tests for screening of pregnant women. METHODS: Pregnant women attending an antenatal clinic and delivery room in Pune agreed to participate in an evaluation of five rapid HIV tests, including (a) a saliva brush test (Oraquick HIV-1/2, Orasure Technologies Inc.), (b) a rapid plasma test (Oraquick HIV-1/2) and (c) three rapid finger prick tests (Oraquick HIV-1/2; HIV-1/2 Determine, Abbott; NEVA HIV-1/2 Cadila). Results of the rapid tests were compared with three commercial plasma enzyme immunoassay (EIA) tests (Innotest HIV AB EIA, Lab systems/ELISCAN HIV AB EIA, UBI HIV Ab EIA). RESULTS: Between September 2000 and October 1, 2001, 1258 pregnant women were screened for HIV using these rapid tests. Forty-four (3.49%) of the specimens were HIV-antibody-positive by at least two plasma EIA tests. All of the rapid HIV tests demonstrated excellent specificity (96-100%). The sensitivity of the rapid tests ranged from 75-94%. The combined sensitivity and specificity of a two-step algorithm for rapid HIV testing was excellent for a number of combinations of the five rapid finger stick tests. CONCLUSION: In this relatively low HIV prevalence population of pregnant women in India, the sensitivity of the rapid HIV tests varied, when compared to a dual EIA algorithm. In general, the specificity of all the rapid tests was excellent, with very few false positive HIV tests. Based upon these data, two different rapid HIV tests for screening pregnant women in India would be highly sensitive, with excellent specificity to reliably prevent inappropriate use of antiretroviral therapy for prevention of vertical HIV transmission.

Retrospective classification of prostate-specific antigen tests: differentiating screening from diagnostic clinical encounters.

To assess the validity of retrospective medical chart review as a method of classifying prostate-specific antigen (PSA) tests as screening or diagnostic services, we reviewed PSA tests ordered at a university hospital (n = 95). PSA tests were reviewed by four raters: medicine resident (RES), oncologist (ONC), urologist (UR), medicine attending (GM)-and the physician who ordered the PSA test (ATTEND) using predefined standardized criteria. Agreement rates by individual rater and ATTEND were 0.79 (GM), 0.80 (ONC), 0.74 (UR), 0.83 (RES), for a composite percent agreement of 0.79. ATTEND incorrectly classified seven tests; exclusion of these tests raised agreement rates to 0.86 (GM), 0.86 (ONC), 0.80 (UR), 0.90 (RES), for a group composite percent agreement of 0.86. Of note, two raters had higher agreement rates when evaluating screening PSA tests than when evaluating diagnostic PSA tests. Standardized criteria applied to medical charts provide a valid method of retrospectively classifying PSA tests.

Effect of ACE inhibitors in diabetic and nondiabetic chronic renal disease: a systematic overview of randomized placebo-controlled trials.

Clinical trials have shown the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in delaying the progression of diabetic renal disease. There is less evidence from primary clinical trials of nondiabetic renal disease. We performed an updated meta-analysis to determine the efficacy of ACE inhibitors in slowing the progression of renal disease over a broad range of functional renal impairment. We included published and unpublished randomized, placebo-controlled, parallel trials with at least 1 year of follow-up available from January 1970 to June 1999. In nine trials of subjects with diabetic nephropathy and microalbuminuria, the relative risk for developing macroalbuminuria was 0.35 (95% confidence interval [CI], 0.24 to 0.53) for individuals treated with an ACE inhibitor compared with placebo. In seven trials of subjects with overt proteinuria and renal insufficiency from a variety of causes (30% diabetes, 70% nondiabetes), the relative risk for doubling of serum creatinine concentration or developing end-stage renal disease was 0.60 (95% CI, 0.49 to 0.73) for individuals treated with an ACE inhibitor compared with placebo. Treatment of individuals with chronic renal insufficiency with ACE inhibitors delays the progression of disease compared with placebo across a spectrum of disease causes and renal dysfunction.

Measurement of localized cartilage volume and thickness of human knee joints by computer analysis of three-dimensional magnetic resonance images.

RATIONALE AND OBJECTIVES: This work demonstrates a new method for computerized measurement of the dimensions (thickness and volume) of articular cartilage for any specified region of the human knee joint. Three-dimensional magnetic resonance (MR) images optimized for cartilage contrast have been analyzed using computerized edge-detection techniques, and the reproducibility of articular cartilage thickness and volume measurements is assessed. METHODS: A fat-suppressed, three-dimensional SPoiled GRass MR sequence (45/7.5/30 degrees) with total scan time of approximately 12 minutes was used to acquire volume images of human knee joints at spatial resolution of 0.6 x 1.2 x 1.2 mm. Measurements were made using six repeated scans for three healthy volunteers over a period of 2 months. The subsequent semi-automated image processing to establish total cartilage volume and cartilage thickness maps for the femur required approximately 60 minutes of operator time. RESULTS: The mean coefficient of variation for total cartilage volume for the six repeated scans for the three volunteers was 3.8%, and the average coefficient of variation for the user-selected cartilage plugs was 2.0%. The cartilage thickness maps from the repeated scans of the same knee were similar. CONCLUSIONS: Standard resolution MR images with fat-suppressed contrast lead to an objective and reproducible measurement of spatial dimensions of articular cartilage when analyzed semi-automatically using computerized edge-detection methods.