District-level epidemiology, hot spots and sociodemographic determinants of tobacco use in Indian men and women: analysis of national family health survey-4 (2015-16).

OBJECTIVES: To map district-level tobacco hot spots and understand the Sociodemographic Indices (SDI) influencing tobacco consumption in Indian men and women. STUDY DESIGN: Cross-sectional study. METHODS: Tobacco use data from 640 districts of India were extracted from National Family Health Survey-4, carried out from 2015 to 2016 with a sample size of 103,411 men and 699,686 women. Geographic Information System was used to map the tobacco prevalence, and hot spots were identified by spatial statistics (Getis-OrdGi∗). SDI were studied by bivariate analyses and binary logistic regression. RESULTS: India has two major tobacco hot spots; one comprising the districts of North-Eastern states, excluding Sikkim, and the second cluster is formed by the districts of Central-Eastern states. These hot spots coincide well with demographic determinants: North-East (adjusted odds ratio [aOR] men, 5.74; aOR women, 13.54) and Central India (aOR men, 4.5; aOR women, 3.5) have higher odds of Tobacco consumption. In men, respondents with no education (aOR 2.52; 95% confidence interval [CI]: 2.26-2.81) and Muslims (aOR 3.53; 95% CI: 2.93-4.26) have higher odds of tobacco consumption. The poorest (men aOR, 2.06; 95% CI: 1.87-2.27; women aOR, 3.36: 95% CI: 2.69-4.19) and ST women (aOR 1.89; 95% CI: 1.68-2.13) have higher odds of tobacco consumption. CONCLUSIONS: We have identified tobacco hot spots and detailed the SDI affecting tobacco use separately in men and women to guide public health policies for targeted intervention of tobacco consumption.

Blood flow surveillance of hemodialysis grafts and the dysfunction hypothesis.

It is widely recommended that hemodialysis graft surveillance programs should be implemented and that significant stenosis should be corrected when it is accompanied by graft dysfunction. The rationale for surveillance depends on the dysfunction hypothesis, which states that stenosis causes graft dysfunction [such as a decrease in graft blood flow (Qa)], and this dysfunction reliably precedes and accurately predicts thrombosis. The usefulness of Qa surveillance depends on accurate prediction of thrombosis so that stenosis can be corrected prior to thrombosis. An analysis of the dysfunction hypothesis indicates that some or all of its underlying assumptions are invalid. Most importantly, the presence of wide hemodynamic variation during Qa measurements makes Qa a relatively inaccurate predictor of thrombosis. A number of studies have evaluated the value of surveillance with intervention in reducing thrombosis rates and prolonging graft life. Review of these studies show that few have been prospective and randomized, and many have included historical control groups. It is debatable whether these studies have established that Qa surveillance with intervention should be applied to all grafts. Data from several studies suggest that severity of stenosis may be at least as accurate as Qa in predicting thrombosis. Consequently, inclusion of stenosis measurements (e.g., by duplex ultrasound) may improve the results of surveillance. These unresolved issues indicate it is premature to recommend routine Qa surveillance with intervention of all hemodialysis patients with grafts.

Hemodynamic reproducibility during blood flow measurements of hemodialysis synthetic grafts.

We have previously shown that graft blood flow (Qa) has a poor accuracy in predicting graft thrombosis. In this study, we determined whether hemodynamic variation helps explain this poor predictive accuracy. We also determined whether standardized timing of Qa measurements, which is widely recommended, will promote measurement reproducibility. We analyzed variations in mean arterial pressure (MAP) in seven consecutive dialysis sessions for 51 patients and determined the influence of MAP on Qa (by ultrasound dilution). We used a pooled coefficient of variation (CV) to summarize MAP variation within individual patients (computed as +/-2 CVs). MAPs from the seven sessions varied widely, and most variation was present with the first MAPs at the beginning of the sessions. These first MAPs varied by +/-23%, whereas variation for the entire session was +/-28%. The influence of MAP on Qa was determined by measuring the two together during consecutive thirds of a single session. The percentage of change in MAP (DeltaMAP) and Qa (DeltaQa) from the first to middle or last thirds of the session varied over wide ranges: -37% to 86% and -43% to 78%, respectively. The DeltaQa versus DeltaMAP correlation was relatively strong for changes between the first and middle thirds (r = 0.666) and first and last thirds (r = 0.646) of the session (both P: < 0.01). We conclude that MAP varies far more widely during dialysis than previously recognized. This variation is associated with large changes in Qa that may impair accuracy in predicting thrombosis. This wide MAP variation also indicates hemodynamic reproducibility is not feasible when measuring Qa. Thus, we do not recommend standardized timing of Qa measurements during dialysis. A practical method of addressing poor Qa reproducibility may be to take frequent measurements so that trends can be recognized before thrombosis occurs.

Accuracy of decrease in blood flow in predicting hemodialysis graft thrombosis.

We recently showed that a single low graft blood-flow measurement (Qa) does not accurately predict graft thrombosis. In this study, we prospectively determined whether percentage of decrease in Qa (DeltaQa) or adjustment of Qa for mean arterial pressure (Qa/MAP; Delta(Qa/MAP)) provides greater predictive accuracy than a single Qa. We monitored 83 grafts from 80 patients for thrombosis over periods up to 12 months. Qa (by ultrasound dilution) and MAP were measured monthly during the study. Receiver operating characteristic curves were used to determine whether Qa, DeltaQa, Qa/MAP, or Delta(Qa/MAP) provided the combination of high sensitivity (>80%) and low false-positive rate (FPR; <20%) needed for clinical use. This level of predictive accuracy requires an area under the curve (AUC) of approximately 0.90. We analyzed the four predictors by a number of criteria and found that all AUCs were less than 0.90 and adjustment for MAP reduced the AUC. In predicting thrombosis within 1 month, for example, AUCs for Qa and net DeltaQa (over 3 months) were 0.84 and 0.82, respectively, whereas AUCs for Qa/MAP and net Delta(Qa/MAP) were 0.78 and 0.75, respectively. At a sensitivity of 80%, FPRs for all predictors were at least 30%. Thus, a high sensitivity always required a high FPR. These results show that DeltaQa and adjustment for MAP are not more accurate than a single low Qa in predicting thrombosis. None of these predictors provide enough predictive accuracy to be the sole criterion for clinical decision making. A successful monitoring and intervention program will likely require the inclusion of other predictors that, together with Qa, may provide the needed accuracy.

Does blood flow accurately predict thrombosis or failure of hemodialysis synthetic grafts? A meta-analysis.

A number of studies have reported that a single low blood flow (Qa) measurement in synthetic hemodialysis grafts predicts thrombosis or failure. In a meta-analysis of these studies, we computed receiver operating characteristic (ROC) curves that evaluated the predictive accuracy of a Qa measurement. The ROC curves plotted sensitivity versus false-positive rate for predicting thrombosis or failure at different Qa thresholds. A perfect predictor has an area under the curve (AUC) of 1.0, whereas a predictor with no discriminative ability has an AUC of 0.5. We identified studies through a literature search and included our own unpublished data. A random-effects model was used to combine the ROC curves from different studies. Of 19 identified studies, 12 were suitable for computing binormal ROC curves (6 predicted thrombosis; 6 predicted failure). The studies measured Qa and then observed outcome during periods of 1.5 to more than 6 months. The combined AUCs from these studies indicate Qa was a relatively poor predictor, with 0.70 +/- 0. 04 (range, 0.61 to 0.84) for thrombosis and 0.76 +/- 0.07 (range, 0. 62 to 0.90) for failure. The wide range of AUCs also shows there was much heterogeneity between studies. We conclude that a single Qa measurement does not appear to have enough accuracy to be a clinically useful predictor of graft thrombosis or failure. Serial Qa measurements and identification of factors that caused heterogeneity between studies may be needed to achieve sufficient accuracy.

Wide variation in serum anion gap measurements by chemistry analyzers.

The traditional anion gap [AG = Na-Cl-(total CO2)] mean value of 12 mEq/L was established during the 1970s with analyzer methods that are no longer used widely. No studies have systematically compared mean AG values from analyzers in current use. We used data from healthy subjects obtained from 27 clinical laboratories, 5 manufacturers, and 8 publications to compute mean AG values from 1970s analyzers and 8 current analyzers. We also compared mean AG values by evaluating Na, Cl, and total CO2 data from the College of American Pathologists Chemistry Surveys (1990-1996). Data from healthy subjects showed that overall mean AG values of the 9 analyzers ranged from 5.9 to 12.4 mEq/L. The pooled (i.e., average) AG SD was 2.3 mEq/L. We then used the data of the Surveys and the mean value from 1 analyzer to compute predicted mean values for the other 7 current analyzers. Almost all mean AG values predicted from the Surveys agreed (within 1.5 mEq/L) with mean values from healthy subjects. These results show that mean values of analyzers vary widely, indicating that analytic bias strongly influences the AG. The results should be a useful guide for the AG measurements that can be expected from different analyzers.

Accuracy of Doppler ultrasound in diagnosing anatomic stenosis of hemodialysis arteriovenous access as compared with fistulography.

A variety of techniques (physical examination, venous pump pressure, percent urea recirculation, Crit Line, Transonic Flow, and others) are helpful in detecting vascular access dysfunction with subsequent referral to fistulography for confirmation of stenosis and possible angioplasty. Although these techniques are adequate, it is not uncommon that the results in some patients may be borderline or equivocal. In these cases, Doppler ultrasound may play a role to confirm the presence or absence of significant stenosis before subjecting the patient to the more expensive and invasive fistulography. For Doppler ultrasound to play such a role, it must have a high degree of accuracy in diagnosing anatomic stenosis. In previous studies, percent stenosis by Doppler ultrasound as compared with percent stenosis by fistulography was examined only when stenosis was suspected, therefore not allowing the determination of Doppler ultrasound specificity in diagnosing negative stenosis when fistulography was negative. In this study, we evaluated 38 hemodialysis patients with Doppler ultrasound followed by fistulography, without regard to suspicion of stenosis (to access both the sensitivity and specificity of Doppler ultrasound). Nineteen patients (50%) had significant stenosis by fistulography (> or =50% narrowing). The same 19 patients had significant stenosis by Doppler ultrasound (significant stenosis at > or =40% with high-velocity flow turbulence or > or =50% without turbulent flow), whereas the remaining patients had no significant stenosis. In addition, the percent stenosis by Doppler ultrasound had a linear relationship to the percent stenosis by fistulography. In conclusion, Doppler ultrasound closely correlates to fistulography in diagnosing anatomic stenosis. In patients in whom other techniques for diagnosing access stenosis show borderline results, Doppler ultrasound may play an adjuvant role to confirm the presence or absence of significant stenosis.

Accuracy and reproducibility of urea recirculation in detecting haemodialysis access stenosis.

BACKGROUND: There is wide disagreement among studies that have evaluated the accuracy of urea recirculation (UR) in detecting vascular access stenosis. The 3-site method (UR3) has been discredited and replaced by the 2-site method (UR2), but few studies have evaluated UR2. METHODS: We compared the accuracies of UR2 and UR3 in detecting stenosis in 59 haemodialysis patients during a 12-month period. All patients were studied without regard to clinical suspicion of stenosis. Stenosis (> or = 50% luminal narrowing) was diagnosed by duplex ultrasound and confirmed by angiography. The reproducibility of UR2 was determined by computing its total standard deviation (SDTOT) from measurements during three dialysis sessions over a 15-day period. RESULTS: Stenosis was found in 32% of 124 access studies (mean luminal narrowing = 58%, range = 50%-83%). The mean UR values of stenotic accesses were only slightly higher than non-stenotic accesses for both UR2 (5.6% vs 2.9%, P < 0.01) and UR3 (13.1% vs 11.2%, P = 0.22). An increase in blood pump speed from 300 to 425 ml/min did not improve detection of stenosis by UR2. There were no UR thresholds that could adequately separate the presence of stenosis from its absence. The SDTOT of UR2 was 3.8%, indicating that a patient's UR2 measurement may vary over a range of 16% (+/- 2SDTOT = +/- 8%). CONCLUSION: Stenosis of the haemodialysis access does not predictably cause recirculation, and the reproducibility of the UR2 measurement is poor.

Intestinal lipid absorption in the nephrotic rat.

There is limited data on intestinal lipid absorption in the nephrotic syndrome. This study investigated whether the efficiency of intestinal lipid absorption is altered in nephrotic lymph-fistula rats. The nephrotic syndrome was induced in nine Sprague-Dawley rats by an i.v. injection of puromycin aminonucleoside in saline; seven control rats received saline only. At 10 to 14 days after injection, the main intestinal lymph duct was cannulated for collection of lymph. The duodenum was also cannulated and a fasting saline-glucose solution was infused overnight at 3 mL/h. The next day, the infusate was changed to a lipid emulsion that contained (14C) cholesterol and (3H)triglyceride (triolein) that was infused at 3 mL/h for 8 h. During the last hour of fasting and during the lipid infusion, lymph flow in the Nephrotic group averaged 0.6 mL/h higher than the Control group (P = 0.02). No significant differences were found between the two groups in recovery of infused radioactive cholesterol (P = 0.37) or triglyceride (P = 0.38) from the gastrointestinal lumen, small intestinal mucosa, or lymph. Lymphatic output of chemically measured cholesterol was also similar (P = 0.96). These results suggest that mucosal uptake and lymphatic output of cholesterol and triglyceride are not altered in the nephrotic syndrome.

Anion gap in turpentine-induced pleural effusions. Correlation with pH and protein level.

Since the pleural fluid proteins and lactate are unmeasured anions, the pleural fluid anion gap (Na+K-Cl-total CO2) should vary with the protein level and should be high in acidic effusions (which have high lactate levels). The anion gap is also convenient and inexpensive to measure, and less subject to artifact than the pH measurement. To test the hypothesis that the anion gap correlates with the pH, protein level, and other traditional pleural fluid measurements, we used a well-described model of turpentine-induced effusions in nine New Zealand white rabbits. Nonacidic exudative effusions were induced by an intrapleural injection of turpentine; acidic exudative effusions were induced by a second injection. Pleural fluid and blood were obtained just before (0 h) and 9, 24, 48, and 72 h after the second injection. We found the anion gap correlated with pH, the glucose, protein, and lactate dehydrogenase levels, pleural-fluid/plasma protein and lactate dehydrogenase ratios, and WBC count (all p < 0.001). The pH and protein ratio together accounted for 95% of all anion gap variation within individual subjects. We also found the influence of the PCO2 level on pH was not significant after taking into account the influence of the anion gap. These results suggest the anion gap may be useful in the clinical evaluation of pleural effusions and could potentially replace the pH measurement.

Effect of acute pH change on serum anion gap.

The serum anion gap is decreased in hyperchloremic (HCl) acidosis and increased in diuretic-induced alkalosis. These anion gap changes have been largely attributed to titration-induced variations in the net negative charge of the serum proteins, which are the predominant non-HCO3 buffers of serum. It has recently been shown, however, that albumin has all of the net protein charge, and titration-induced changes in charge are smaller than have been widely believed. Because the non-HCO3 buffers are also titrated in acute hypocapnia and hypercapnia, these disorders were induced in 16 anesthetized dogs for 10 min in order to assess the effect of acute changes in pH on the anion gap. Although the mean arterial pH varied from 7.04 to 7.65, the calculated mean albumin charge only varied from 6.8 to 9.0 mEq/L. When the anion gap was computed with HCO3 (AGHCO3 = Na + K - Cl - HCO3), the change in AGHCO3 per 0.1 change in pH (delta AGHCO3/ delta pH) was only 0.15 mEq/L per 0.1 pH. When the anion gap was computed with total CO2 content (AGTCO2 = Na + K - Cl - TCO2), delta AGTCO2/delta pH was larger (0.51 mEq/L per 0.1 pH) because of the effect of variable PCO2 levels on TCO2. In a review of 22 previous studies in humans and dogs, similar estimates of delta AG/delta pH were obtained (after adjusting for the lower albumin level in dogs). These results show that simple titration processes that occur within 10 min of a change in pH cause minimal changes in the anion gap. Titration of the known non-HCO3 buffers of serum does not explain the much larger anion gap changes of HCl acidosis and diuretic alkalosis.

Diagnosis of mixed acid-base disorders in diabetic ketoacidosis.

In diabetic ketoacidosis, a mixed acid-base disorder is suggested when the anion gap increase (delta AG) does not equal the bicarbonate decrease (delta HCO3), or when the delta AG/delta HCO3 ratio does not equal 1.0. It is widely assumed that delta AG/delta HCO3 is significantly different from 1.0 when it is less than 0.8 or greater than 1.2. The validity of these ratio limits were examined by analyzing a normal control group of 68 subjects and 27 diabetic ketoacidosis admissions that had no evidence of mixed disorders. In the 27 ketoacidosis admissions, regression analysis showed that delta AG was predicted to equal delta HCO3, as expected in pure anion gap acidosis: delta AG = 1.0 delta HCO3 (r = 0.744, p < 0.001). It was found that delta AG is significantly different from delta HCO3 when they differ by more than 8 mEq/L, and equivalently, delta AG/delta HCO3 is significantly different from 1.0 when it is less than (1.0 - 8/delta HCO3) or greater than (1.0 + 8/delta HCO3). These criteria from regression analysis suggested that 4% of the 27 pure anion gap acidoses, and 3% of the control group, had mixed disorders. In contrast, the ratio limits of 0.8 and 1.2 suggested 56% of the pure anion gap acidoses, and 94% of the control group, had mixed disorders. It was concluded that mixed disorders are overdiagnosed by the ratio limits of 0.8 and 1.2. Mixed disorders are more accurately detected by noting whether delta AG and delta HCO3 differ by more than 8 mEq/L.

Routine serologic tests in the differential diagnosis of the adult nephrotic syndrome.

From 1980 to 1985, we performed biopsies on 87 adults with nephrotic syndrome (NS). The patients were tested for whether serologic studies obtained routinely at biopsy added to clinical diagnostic accuracy. Using history, physical examination, complete blood cell count (CBC), chemistry panel, urinalysis, and urine creatinine and protein, four nephrologists each predicted whether the patient had primary NS (PNS) or secondary NS (SNS), and the most likely histopathologic entity. Six months later, each nephrologist used this information, with results of tests of sera for fluorescent antinuclear antibody (FANA), rheumatoid factor (RF), complement components, hepatitis B surface antigen (HBsAg), venereal disease research laboratory serology (VDRI), cryoglobulins and protein electrophoresis (SPEP), with an erythrocyte sedimentation rate (ESR) and protein electrophoresis of the urine (UPEP), to make identical predictions. Histopathology was established by renal biopsy. We analyzed the concordance between nephrologists' choices and biopsy results both before and after serologic tests were available with a kappa statistic. Preserology concordance was moderate (kappa = 0.52), and identical to postserology concordance (kappa = 0.51) for both PNS versus SNS and actual histopathology. Serologies were rarely abnormal without clinical suspicion. These results suggest routine serologic testing does not improve diagnostic accuracy in adult NS.

Hyponatremia in the very young chronic peritoneal dialysis patient.

Two anuric infants had recurrent hyponatremia during chronic peritoneal dialysis (PD). This occurred because at normal serum sodium concentrations ([Na]), Na losses from ultrafiltration (UF) were greater than the Na ingested from infant formula. Hyponatremia was corrected with increased oral Na intake or with increased dialysis solution [Na]. Anuric infants undergoing PD have hyponatremia because of their high UF requirements/body weight and the low Na content of proprietary infant formulas.