The impact of waiting time for orthopaedic consultation on pain levels in individuals with osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: Time spent waiting for access to orthopaedic specialist health services has been suggested to result in increased pain in individuals with osteoarthritis (OA). We assessed whether time spent on an orthopaedic waiting list resulted in a detrimental effect on pain levels in patients with knee or hip OA. METHODS: We searched Ovid MEDLINE, EMBASE and EBSCOhost databases from inception until September 2021. Eligible articles included individuals with OA on an orthopaedic waitlist and not receiving active treatment, and reported pain measures at two or more time points. Random-effects meta-analysis was used to estimate the pooled effect of waiting time on pain levels. Meta-regression was used to determine predictors of effect size. RESULTS: Thirty-three articles were included (n = 2,490 participants, 67 ± 3 years and 62% female). The range of waiting time was 2 weeks to 2 years (20.8 ± 18.8 weeks). There was no significant change in pain over time (effect size = 0.082, 95% CI = -0.009, 0.172), nor was the length of time associated with longitudinal changes in pain over time (ß = 0.004, 95% CI = -0.005, 0.012). Body mass index was a significant predictor of pain (ß = -0.043, 95% CI = -0.079, 0.006), whereas age and sex were not. CONCLUSIONS: Pain remained stable for up to 1 year in patients with OA on an orthopaedic waitlist. Future research is required to understand whether pain increases in patients waiting longer than 1 year.

Beneficial effects of metoprolol in heart failure associated with coronary artery disease: a randomized trial.

OBJECTIVES: This clinical trial was performed to determine the safety and clinical impact of titrated metoprolol therapy in patients with heart failure, documented coronary artery disease and a low ejection fraction. BACKGROUND: Despite known cardiodepressant effects, long-term use of beta-adrenergic antagonists appears to be beneficial in patients with idiopathic dilated cardiomyopathy. However, this therapy has not been critically evaluated in patients with heart failure and coronary artery disease. METHODS: In 50 patients with heart failure, known coronary artery disease and an ejection fraction < or = 0.40, we examined the impact of metoprolol therapy in a 6-month double-blind, placebo-controlled randomized trial, assessing the frequency of heart failure exacerbations and changes in symptoms (New York Heart Association functional class), ejection fraction and exercise duration. Placebo-treated patients who completed 6-month follow-up studies then underwent a trial with metoprolol therapy (crossover group). RESULTS: Metoprolol was titrated to a mean maximal dose of 87 mg/day (range 25 to 100) without serious adverse reactions. During double-blind therapy, use of a beta-blocker was associated with a significant reduction in the number of hospital admissions (4% vs. 32%, p < 0.05), overall improved functional class (p = 0.02), increased ejection fraction (4 +/- 7% [mean +/- SD] compared with 0 +/- 6%, p < 0.05) and a greater increase in exercise duration (193 +/- 276 vs. 38 +/- 213 s with placebo, p < 0.01). Crossover outcome paralleled the favorable impact seen during randomized metoprolol therapy. CONCLUSIONS: Cautious use of titrated metoprolol appears to be safe and beneficial when added to standard heart failure therapy in patients with dilated cardiomyopathy associated with coronary artery disease.

Metabolic advantages of spreading the nutrient load: effects of increased meal frequency in non-insulin-dependent diabetes.

The acute effect of increasing meal frequency as a model of slow absorption was studied for 1 d in 11 patients with non-insulin-dependent diabetes. On 1 d they took 13 snacks (the nibbling diet) and on another day the same diet was taken as three meals and one snack (the three-meal diet). The nibbling diet reduced mean blood glucose, serum insulin, and C peptide concentrations over the 9.5 h of observation and 24-h urinary C peptide output by 12.7 +/- 3.7% (mean +/- SE) (P = 0.0062), 20.1 +/- 5.8% (P = 0.0108), 9.2 +/- 2.6% (P = 0.0073), and 20.37 +/- 8.12% (P = 0.039), respectively, compared with the three-meal diet. Serum triglyceride concentrations were lower by 8.5 +/- 3.2% (P = 0.037). Despite lower insulin concentrations on the nibbling diet, the concentrations of free fatty acids, 3-hydroxybutyrate, and the insulin-sensitive branched-chain amino acids responded similarly on both treatments. Metabolic benefits seen with increased meal frequency may explain the success of similar agents that prolong absorption, including fiber and enzyme inhibitors.

Low-glycemic index diet in hyperlipidemia: use of traditional starchy foods.

To define those patients most likely to benefit from the hypolipidemic effect of low-glycemic-index (GI) traditional starchy foods, 30 hyperlipidemic patients were studied for 3 mo. During the middle month, low-GI foods were substituted for those with a higher GI with minimal change in dietary macronutrient and fiber content. Only in the group (24 patients) with raised triglyceride levels (types IIb, III, and IV) were significant lipid reductions seen: total cholesterol 8.8 +/- 1.5% (p less than 0.001), LDL cholesterol 9.1 +/- 2.4% (p less than 0.001), and serum triglyceride 19.3 +/- 3.2% (p less than 0.001) with no change in HDL cholesterol. The percentage reduction in serum triglyceride related to the initial triglyceride levels (r = 0.56, p less than 0.01). The small weight loss (0.4 kg) on the low-GI diet did not relate to the lipid changes. Low-GI diets may be of use in the management of lipid abnormalities associated with hypertriglyceridemia.

Leguminous seeds in the dietary management of hyperlipidemia.

Seven male hyperlipidemic patients substituted approximately 140g dried beans daily for other sources of starch in their diet over a 4-month period. After this, mean fasting serum triglyceride levels were reduced by 25 +/- 5% (p less than 0.01) while total serum cholesterol levels were 7 +/- 2% (p less than 0.5) lower than the values measured during the previous five clinic attendances (12 +/- 2.5 months). However, low- and high-density lipoprotein cholesterol levels remained unaltered. While taking beans a nonsignificant fall (0.7 kg) was seen in body weight. Nevertheless no change was seen in macronutrient intake determined by 1-wk diet histories recorded both before and four times during the study, although cholesterol intake decreased by 80 mg (p less than 0.02). Reintroduction of dried leguminous seeds into a Western diet may be a useful adjunct to the management of hyperlipidemia.

Method of administration influences the serum cholesterol-lowering effect of psyllium.

To determine whether psyllium must be mixed with food to lower serum cholesterol, 18 modestly hypercholesterolemic subjects were studied for three 2-wk periods, in random order, separated by a 2-wk return to a National Cholesterol Education Program Step 2 diet. Compared with values for subjects consuming control wheat-bran cereal (63 g/d), after 2 wk of 54 g psyllium-enriched cereal/d containing 7.3 g psyllium, serum total, LDL, and HDL cholesterol, respectively, were reduced by 8% (6.15 +/- 0.15 vs 6.71 +/- 0.19 mmol/L, P < 0.01), 11% (4.24 +/- 0.15 vs 4.78 +/- 0.19 mmol/L, P < 0.02), and 7% (0.99 +/- 0.05 vs 1.07 +/- 0.05 mmol/L, P < 0.01). When 7.6 g of the same type of psyllium as in the test cereal was taken between meals, serum total (6.50 +/- 0.19 mmol/L), LDL (4.50 +/- 0.21 mmol/L), and HDL (1.06 +/- 0.06 mmol/L) cholesterol were no different from control values, and total cholesterol was greater than after psyllium cereal (P < 0.05). We conclude that psyllium must be mixed with foods to have the maximum effect on serum cholesterol.

Low glycemic index carbohydrate foods in the management of hyperlipidemia.

Reduction in the mean glycemic index (GI) of diets of 12 hyperlipidemic patients from 82 +/- 1 to 69 +/- 2 units (p less than 0.001) for a 1 mo period resulted in a significant reduction in total and LDL serum cholesterol and serum triglyceride by comparison with the mean lipid values for the preceding and following control months. The change in GI of the diet was achieved largely through manipulation of the cereal products and was not related to large differences in the amount of dietary fiber. In addition, apart from a small mean increase in unsaturated fat and calorie intake during the control periods, no difference was seen between the proportion of macronutrients on either treatment as determined by 1 wk diet histories recorded on alternate weeks throughout the 3 mo study. Selection of low glycemic index foods may therefore be a useful adjunct to the management of hyperlipidemia.

Low-glycemic-index starchy foods in the diabetic diet.

Eight patients with noninsulin-dependent diabetes underwent two 2-wk study periods in random order during which they were provided with carbohydrate foods with either a high or low glycemic index (GI). Over both high-GI and low-GI periods there were significant reductions in body weight, serum fructosamine, and cholesterol. Reductions in fasting blood glucose, HbA1c, and urinary c-peptide-to-creatinine ratio were significant only over the low-GI period despite a smaller mean weight loss. Reductions in triglyceride were significant only over the high-GI diet. Inclusion of low-GI foods into diets of patients with diabetes may be an additional measure that favorably influences carbohydrate metabolism without increasing insulin demand.

Effect of psyllium in hypercholesterolemia at two monounsaturated fatty acid intakes.

We performed two studies to determine whether the lipid-lowering effect of viscous soluble fiber was modified by monounsaturated fatty acid (MUFA). First, psyllium (1.4 g/MJ) was compared with wheat bran (control) in 1-mo metabolic diets by using a randomized crossover design (n = 32 hyperlipidemic subjects). The background diet contained approximately 6% of energy as MUFA (20% of total fat). The second study (n = 27 hyperlipidemic subjects) was similar to the first but the background diet contained approximately 12% MUFA (29% of total fat) because of the addition of canola oil. At both fat intakes, psyllium resulted in significant reductions in total, low-density-lipoprotein (LDL), and high-density-lipoprotein (HDL) cholesterol compared with the wheat bran control. For the psyllium diet at 6% compared with 12% MUFA, the decreases in LDL cholesterol were 12.3 +/- 1.5% (P < 0.001) and 15.3 +/- 2.4% (P < 0.001), respectively. With the higher-MUFA diet triacylglycerol fell significantly over the control phase (16.6 +/- 5.5%, P = 0.006) and the ratio of LDL to HDL cholesterol fell significantly over the psyllium phase (7.3 +/- 2.8%, P = 0.015). Psyllium and MUFA intakes were negatively related to the percentage change in the ratio of LDL to HDL cholesterol (r = -0.34, P = 0.019 and r = -0.44, P = 0.002, respectively). Chenodeoxycholate synthesis rate increased (30 +/- 13%, P = 0.038) with the psyllium diet in the 12 subjects in whom this was assessed. We conclude that psyllium lowered LDL- and HDL-cholesterol concentrations similarly at both MUFA intakes. However, there may be some advantage in combining soluble fiber and MUFA to reduce the ratio of LDL to HDL cholesterol.

Limb-body wall complex: II. Limb and spine defects.

Limb defects from 25 fetuses with limb-body wall (LBW) complex were evaluated to determine the mechanism of limb damage. The limb defects could be divided into 3 pathogenetic groups: (1) secondary to disruption of embryonic vessels and surrounding tissue (84%), (2) secondary to amniotic bands or adhesions (16%), and (3) deformation versus hemorrhage (44% with club feet), with some fetuses having more than one pathogenetic mechanism causing limb defects. The hypothesis that the majority of limb defects resulted from disruption of embryonic vessels was supported by the following findings: 96% of the LBW complex fetuses had limb defects; the lower limbs were at greater risk of damage than the upper limbs (28% rt arm, 52% lt arm, 60% rt leg, 72% lt leg); there was a distal to proximal progression of limb damage in 92% of the fetuses; statistical analysis of comparing the location of the most severe limb defect and the body wall defect did not find concordance between the side (p = 1.0) and the region (p = 0.18) of the body wall defect; and limb defects found in the human specimens were similar to those produced in experimental animals following disruption of embryonic vessels at a corresponding gestation. In the specimens with amniotic band related limb defects (16%), the most likely pathogenesis is mechanical rupture through the amnion in the presence of a persistent extraembryonic coelom or from adhesion of the amnion to necrotic embryonic tissue after the initial disruptive event. Club feet were present in 44% and may be due either to disruption of embryonic vessels or to deformation. Further studies are needed to resolve this question.

Diagnostic performance of magnetic resonance imaging for the diagnosis of rotator cuff tears using supplemental images in the oblique sagittal plane.

RATIONALE AND OBJECTIVES: The authors evaluated the diagnostic utility of supplemental imaging in the oblique sagittal (OS) plane for the magnetic resonance imaging (MRI) diagnosis of rotator cuff tears. METHODS: Two radiologists with varying levels of MRI experience blindly reviewed shoulder MR examinations of 50 patients for rotator cuff tears. Shoulder examinations were interpreted twice, initially using only double-echo spin-echo images obtained in the oblique coronal (OC) plane and later using double-echo spin-echo images obtained in the both the OC and OS planes. Tears were characterized according to size, location, and extent, and levels of diagnostic confidence were evaluated. RESULTS: Sensitivity and specificity of MR for the diagnosis of rotator cuff tear was 85% and 80%, respectively, with the OC series increasing to 95% and 93%, respectively with OCOS scans. However, these increases were not statistically significant. Receiver operating characteristic (ROC) curves suggest a trend toward increased diagnostic confidence when supplemental OS scans are available, especially for the less experienced reader. Characterization of rotator cuff tears was not improved with additional OS images. CONCLUSIONS: Supplemental OS scans did not demonstrate a definite improvement in diagnostic accuracy for rotator cuff tears compared to OC scans alone. Estimations based on sample size calculations indicate that a much larger population of patients would be needed to show a statistically significant difference.

Pathogenesis of acidosis in hereditary fructose intolerance.

An 18-yr-old man with a classical history of hereditary fructose intolerance (HFI) developed typical biochemical changes following an oral fructose load: fructosemia, hypoglycemia, hypophosphatemia, hyperuricemia, and metabolic acidosis. Hypokalemia (3.1 meq/liter) was also noted. Three aspects of this case expand the published literature on this syndrome: (1) Metabolic acidosis was found to be due to both lactic acidosis and proximal renal tubular acidosis (RTA). We could quantitate the relative contribution of each, and found that urinary bicarbonate loss due to proximal RTA accounted for less than 10% of the fall in serum bicarbonate. The major cause of the metabolic acidosis was lactic acidosis. (2) Hypokalemia was found to be due to movement of potassium out of the extracellular space rather than to urinary loss. Potassium may have entered cells with phosphate or may have been sequestered in the gastrointestinal tract. (3) The coexistence of proximal RTA and acidemia made it possible to study the effect of acidemia on the urine-blood partial pressure of carbon dioxide (PCO2) gradient in alkaline urine (U-B PCO2). The U-B PCO2 measured during acidemia was much higher at the same urine bicarbonate concentration than in normal controls during alkalemia, providing evidence in humans that acidemia stimulates distal nephron hydrogen-ion secretion.

Effect of a diet high in vegetables, fruit, and nuts on serum lipids.

We assessed the effect of a diet high in leafy and green vegetables, fruit, and nuts on serum lipid risk factors for cardiovascular disease. Ten healthy volunteers (seven men and three women aged 33 +/- 4 years [mean +/- SEM]; body mass index, 23 +/- 1 kg/m2) consumed their habitual diet (control diet, 29% +/- 2% fat calories) and a diet consisting largely of leafy and other low-calorie vegetables, fruit, and nuts (vegetable diet, 25% +/- 3% fat calories) for two 2-week periods in a randomized crossover design. After 2 weeks on the vegetable diet, lipid risk factors for cardiovascular disease were significantly reduced by comparison with the control diet (low-density lipoprotein [LDL] cholesterol, 33% +/- 4%, P < .001; ratio of total to high-density lipoprotein [HDL] cholesterol, 21% +/- 4%, P < .001; apolipoprotein [apo] B:A-I, 23% +/- 2%, P < .001; and lipoprotein (a) [Lp(a)], 24% +/- 9%, P = .031). The reduction in apo B was related to increased intakes of soluble fiber (r = .84, P = .003) and vegetable protein (r = -.65, P = .041). On the vegetable compared with the control diet, the reduction in total serum cholesterol was 34% to 49% greater than would be predicted by differences in dietary fat and cholesterol. A diet consisting largely of low-calorie vegetables and fruit and nuts markedly reduced lipid risk factors for cardiovascular disease. Several aspects of such diets, which may have been consumed early in human evolution, have implications for cardiovascular disease prevention.

Aflatoxins and disease.

These days it is widely believed by experts that most cancers are caused by environment factors. The epidemiology of most of these suspected factors is still equivocal. One such factor which has been widely studied is aflatoxin, a chemical produced by the fungus Aspergillus flavus. Because of the widespread distribution of this agent, its known toxicity, and its frequent ingestion by humans, aflatoxin may well be a significant cause of cancer worldwide. This paper attempts to summarize some of the historical and epidemiological evidence regarding aflatoxins and disease.

The fetal genitourinary tract.

Early recognition of fetal urinary tract anomalies may dramatically influence obstetric or neonatal management. Major fetal urinary abnormalities, including renal agenesis, obstructive lesions, and cystic disease, may be clinically silent but readily identified by sonography. Careful evaluation of the fetal genitourinary tract should therefore be an important component of the routine screening obstetric sonogram. Appreciation of normal sonographic appearances of the fetal genitourinary tract may facilitate early recognition of the abnormal fetus. Accurate prenatal sonographic characterization of a renal abnormality and evaluation of renal function are essential for fetal prognosis and management.

Cranial irradiation of young rats impairs later learning and growth.

Young rats (26 days) were exposed to ionizing radiation of the head of 0, 1200, 2400, or 3000 rads total in 200 rads/day doses. The subsequent growth of irradiated rats was permanently impaired: such impairment was positively related to amount of irradiation. Beginning in adolescence, rats were trained on a horizontal/vertical visual discrimination in a runway task, and although all four groups mastered the discrimination, they differed in their patterns of acquisition. These results indicate long term effects are associated with a cranial irradiation regimen similar to that given to children suffering acute lymphocytic leukemia (ALL).

Psyllium reduces blood lipids in men and women with hyperlipidemia.

To see if a modest amount of soluble fiber reduced blood lipids in subjects with hyperlipidemia who were on a low-fat diet, 42 subjects (21 men, 21 women) consuming an American Heart Association step 2 diet took two servings of breakfast cereal daily for two 2-week periods in a randomized crossover trial. There were two types of test cereals, each providing 6.7 g psyllium fiber daily, and two types of wheat bran control cereals, matched for available carbohydrate and total fiber. Half the subjects tested each type of cereal, and the results were pooled because the psyllium cereals had similar effects on serum cholesterol levels. Comparing values at the end of 2 weeks, psyllium reduced serum total (6.33 +/- 0.12 mmol/L versus 6.76 +/- 0.12 mmol/L, p < 0.001), low-density lipoprotein (LDL; 4.36 +/- 0.11 mmol/L versus 4.73 +/- 0.12 mmol/L, p < 0.001) and high-density lipoprotein cholesterol levels (HDL; 1.10 +/- 0.05 mmol/L versus 1.14 +/- 0.05 mmol/L, p < 0.05) and the LDL/HDL cholesterol ratio (4.27 +/- 0.20 versus 4.48 +/- 0.22, p < 0.02) with no effect on triglycerides. There was no significant interaction between the effects of treatment and sex for any of the blood lipid variables. Women tended to have greater decreases in total, LDL, and HDL cholesterol levels than men, but the percent decrease in LDL/HDL ratio on psyllium was similar in men, 4.9%, and women, 4.7%. It is concluded that 6.7 g of psyllium fiber daily, with a low-fat diet, reduces serum cholesterol levels in both men and women with hyperlipidemia.

Results of a province-wide quality assurance program assessing the accuracy of cholesterol, triglycerides, and high-density lipoprotein cholesterol measurements and calculated low-density lipoprotein cholesterol in Ontario, using fresh human serum.

To evaluate laboratory performance, eight to 13 samples of fresh human serum from volunteers were sent to 250 laboratories in the Canadian province of Ontario licensed to perform lipid analysis. Fresh human specimens were used because of potential matrix effects with processed materials. We show that on all survey samples, 71% (range, 63% to 82%) of participating laboratories are within +/- 5% of the target cholesterol value and that 93% are within +/- 10%. The goal of the National Cholesterol Education Program for 1992 is total error of no more than +/- 9% for 95% of results. The unblanked triglycerides results show that on all samples 40% (14% to 59%) of participants are within +/- 5% and 68% (range, 31% to 86%) are within +/- 10% of the target value. For triglycerides results from 0.9 to 2.0 mmol/L, 80% or more are within +/- 0.2 mmol/L. Between 2.0 and 3.0 mmol/L, 90% are within +/- 0.3 mmol/L of the target values. For high-density lipoprotein cholesterol, for all samples 35% (range, 24% to 50%) of laboratories are within +/- 5% and 68% (range, 55% to 88%) are within +/- 10%. A range of 80% to 95% of participants are within +/- 0.2 mmol/L of the target values. For calculated low-density lipoprotein cholesterol, 51% and 62% of the laboratories surveyed are within +/- 5%, with 83% and 89% within +/- 10% of the target values. We conclude that the laboratory measurement of lipids is approaching the degree of accuracy and precision required for clinical purposes, and that the use of fresh human serum samples is a viable approach to their proficiency testing.

Isolated rupture of the cisterna chyli after blunt trauma.

An 8-year-old boy was evaluated for blunt abdominal trauma after a motor vehicle crash. In the course of his workup, a computed tomography (CT) scan of the abdomen was suspicious for a duodenal injury. At surgery, the duodenum was found to be normal; however, a rupture of the cisterna chyli was identified. This injury was repaired, and the boy made an uneventful recovery. This report is one of few in the literature describing isolated injury to the cisterna chyli after blunt abdominal trauma.

Twin growth problems: causes and sonographic analysis.

Understanding the significant increased risks associated with twin pregnancies requires knowledge of the embryogenesis of twins and the unique placental characteristics seen only in twin gestations. Dizygotic "fraternal" twins, 70% of all twins, are at relatively low risk when compared with monozygotic twins, largely due to abnormalities seen in association with monochorionic placentation. The sonographic determination of chorionicity and amnionicity allows better estimation of pregnancy risk--up to 50% mortality in monochorionic-monoamniotic twins. Careful evaluation of intrauterine twin growth assists in the early identification of fetal abnormalities because normal twin growth should parallel that of singleton pregnancies until late in the third trimester. A number of the unique complications affecting growth in twin pregnancies are discussed, including twin transfusion syndrome, the "stuck twin" phenomenon, twin embolization syndrome, and development of acardiac twins.