Systematic review: chronic obstructive pulmonary disease and work-related outcomes.

Background: Several studies have assessed the impact of chronic obstructive pulmonary disease (COPD) on work ability and work productivity; however, this relationship is poorly understood. Aims: To undertake a systematic review to assess the effects of COPD on employment, absenteeism and presenteeism. Methods: A comprehensive search using CINAHL, Embase, MEDLINE and the Cochrane Library was conducted to include epidemiological studies from 1937 to August 2017. One reviewer screened all citations. Shortlisted full-text articles were independently assessed by a second reviewer. Data were extracted by one reviewer with a random sample of papers (45%) checked by a second reviewer. Results: Forty-four studies were included; the majority of evidence was from cross-sectional studies, and some cohort studies. COPD patients had lower employment rates than those without COPD. Among those in work, most studies showed patients with COPD took more time off work than those without and reported poorer work performance (presenteeism), although evidence for this association was weaker. The influence of disease severity on these outcomes was unclear; however, it appeared that increasing severity of airflow obstruction was associated with reduced likelihood of being employed. A number of methodological limitations were found among the evidence, including the lack of adjustment for important confounders. Conclusions: Future studies are required which assess the impact of COPD on presenteeism using validated presenteeism instruments and consistent reporting methods. Robust studies are now needed to identify modifiable factors associated with these poorer working outcomes to inform future interventions aimed at improving work productivity among those with COPD.

Accuracy and economic evaluation of screening tests for undiagnosed COPD among hypertensive individuals in Brazil.

In Brazil, prevalence of diagnosed COPD among adults aged 40 years and over is 16% although over 70% of cases remain undiagnosed. Hypertension is common and well-recorded in primary care, and frequently co-exists with COPD because of common causes such as tobacco smoking, therefore we conducted a cross-sectional screening test accuracy study in nine Basic Health Units in Brazil, among hypertensive patients aged ≥40 years to identify the optimum screening test/combinations to detect undiagnosed COPD. We compared six index tests (four screening questionnaires, microspirometer and peak flow) against the reference test defined as those below the lower limit of normal (LLN-GLI) on quality diagnostic spirometry, with confirmed COPD at clinical review. Of 1162 participants, 6.8% (n = 79) had clinically confirmed COPD. Peak flow had a higher specificity but lower sensitivity than microspirometry (sensitivity 44.3% [95% CI 33.1, 55.9], specificity 95.5% [95% CI 94.1, 96.6]). SBQ performed well compared to the other questionnaires (sensitivity 75.9% [95% CI 65.0, 84.9], specificity 59.2% [95% CI 56.2, 62.1]). A strategy requiring both SBQ and peak flow to be positive yielded sensitivity of 39.2% (95% CI 28.4, 50.9) and specificity of 97.0% (95% CI 95.7, 97.9). The use of simple screening tests was feasible within the Brazilian primary care setting. The combination of SBQ and peak flow appeared most efficient, when considering performance of the test, cost and ease of use (costing £1690 (5554 R$) with 26.7 cases detected per 1,000 patients). However, the choice of screening tests depends on the clinical setting and availability of resources.ISRCTN registration number: 11377960.

Airflow obstruction and metabolic syndrome: the Guangzhou Biobank Cohort Study.

There is some evidence that chronic obstructive pulmonary disease (COPD) and metabolic syndrome may be related, perhaps through systemic inflammation, which is common to both. However, the association between the two conditions has not yet been clearly shown. The present study involved 7,358 adults aged > or =50 yrs from a population-based survey who underwent spirometry, a structured interview and measurement of fasting metabolic marker levels. Airflow obstruction (forced expiratory volume in 1 s/forced vital capacity ratio of less than the lower limit of normal) was present in 6.7%, and the International Diabetes Federation metabolic syndrome criteria were met by 20.0%. The risk of metabolic syndrome was higher in those with airflow obstruction than in those without (odds ratio (OR) 1.47; 95% confidence interval (CI) 1.12-1.92), after controlling for potential confounders. Of the five components of metabolic syndrome, only central obesity was significantly associated with airflow obstruction (OR 1.43; 95% CI 1.09-1.88) after adjusting for body mass index. A similar association was observed in both never and current smokers. In this Chinese sample, airflow obstruction was associated with metabolic syndrome, and, in particular, its central obesity component. This may help explain the increased risk of cardiovascular diseases in COPD, and so could guide future clinical practice.

Accuracy of Vitalograph lung monitor as a screening test for COPD in primary care.

Microspirometry may be useful as the second stage of a screening pathway among patients reporting respiratory symptoms. We assessed sensitivity and specificity of the Vitalograph® lung monitor compared with post-bronchodilator confirmatory spirometry (ndd Easy on-PC) among primary care chronic obstructive pulmonary disease (COPD) patients within the Birmingham COPD cohort. We report a case-control analysis within 71 general practices in the UK. Eligible patients were aged ≥40 years who were either on a clinical COPD register or reported chronic respiratory symptoms on a questionnaire. Participants performed pre- and post-bronchodilator microspirometry, prior to confirmatory spirometry. Out of the 544 participants, COPD was confirmed in 337 according to post-bronchodilator confirmatory spirometry. Pre-bronchodilator, using the LLN as a cut-point, the lung monitor had a sensitivity of 50.5% (95% CI 45.0%, 55.9%) and a specificity of 99.0% (95% CI 96.6%, 99.9%) in our sample. Using a fixed ratio of FEV1/FEV6 < 0.7 to define obstruction in the lung monitor, sensitivity increased (58.8%; 95% CI 53.0, 63.8) while specificity was virtually identical (98.6%; 95% CI 95.8, 99.7). Within our sample, the optimal cut-point for the lung monitor was FEV1/FEV6 < 0.78, with sensitivity of 82.8% (95% CI 78.3%, 86.7%) and specificity of 85.0% (95% CI 79.4%, 89.6%). Test performance of the lung monitor was unaffected by bronchodilation. The lung monitor could be used in primary care without a bronchodilator using a simple ratio of FEV1/FEV6 as part of a screening pathway for COPD among patients reporting respiratory symptoms.

Heparin promotes the inactivation of antithrombin by neutrophil elastase.

Heparin is an acceleratory cofactor for antithrombin, a circulating inhibitor of blood coagulation enzymes. The presence of heparin on blood vessel walls is believed to contribute to the nonthrombogenic properties of those surfaces. In apparent opposition to this function, heparin was found to greatly accelerate the in vitro inactivation of antithrombin by neutrophil elastase. Inactivation rates in solution were potentiated several hundredfold by specific heparin fractions with anticoagulant activity. Although the data suggest that a heparin-antithrombin complex is essential for the inactivation by elastase to occur, the enzyme itself interacts tightly with heparin. These results suggest a mechanism which, if operating in vivo, could lead to a localized neutralization of the anticoagulant function of heparin at the endothelial surface.

Systematic review of the effectiveness of community-based self-management interventions among primary care COPD patients.

COPD self-management reduces hospital admissions and improves health-related quality of life (HRQoL). However, whilst most patients are managed in primary care, the majority of self-management trials have recruited participants with more severe disease from secondary care. We report the findings of a systematic review of the effectiveness of community-based self-management interventions in primary care patients with COPD. We systematically searched eleven electronic databases and identified 12 eligible randomised controlled trials with seven included in meta-analyses for HRQoL, anxiety and depression. We report no difference in HRQoL at final follow-up (St George's Respiratory Questionnaire total score -0.29; 95%CI -2.09, 1.51; I2 0%), nor any difference in anxiety or depression. In conclusion, supported self-management interventions delivered in the community to patients from primary care do not appear to be effective. Further research is recommended to identify effective self-management interventions suitable for primary care populations, particularly those with milder disease.

Circulating immune complexes in cutaneous vasculitis. Detection with C1q and monoclonal rheumatoid factor.

To investigate the pathogeneic significance of immune complexes in cutaneous vasculitis, 107 patients with various forms of cutaneous vasculitis, including 59 patients with necrotizing (leukocytoclastic) vasculitis (group 1), and 48 patients with lymphocytic vasculitis, or a predominately lymphocytic perivascular infiltrate (group 2), were studied. Immunoglobulins or complement components in cutaneous blood vessels were detected by direct immunofluorescence in high frequency in both groups (91 and 88%, respectively). Using two radioassays for circulating immune complexes, Clq or monoclonal rheumatoid factor (mRF) reactive material was detected in 68% of the patients with necrotizing vasculitis but only 44% of the patients in the lymphocytic-perivascular group. The mRF radioassay was elevated in 58% of the first group of patients and 41% of the patients in group 2, although Clq binding activity was increased in 54% of the patients with necrotizing vasculitis but only in 9% of the patients with a lymphocytic vasculitis or lymphocytic perivascular infiltrate. By using both sucrose density gradient ultracentrifugation and Sepharose 6B gel filtration, the Clq and mRF reactive material detected in some patients with necrotizing vasculitis eluted in high molecular weight fractions that were also anticomplementary. In one patient with necrotizing vasculitis and hepatitis B antigenemia, these heavy molecular weight Clq and mRF reactive fractions contained a two- to three-fold increase in hepatitis B surface antigen when compared with lighter molecular weight fractions. Heavy and light molecular weight mRF reactive material could be detected in selected patients in the lymphocytic-perivascular group as well as in the necrotizing vasculitis group. These studies suggest that cutaneous vasculitis, including acute necrotizing (leukocytoclastic) vasculitis and some forms of lymphocytic vasculitis, and perhaps some diseases characterized by a lymphocytic perivascular infiltrate, may represent cutaneous expressions of immune complex disease.

Abciximab readministration: results of the ReoPro Readministration Registry.

BACKGROUND: Platelet glycoprotein IIb/IIIa blockade with abciximab (ReoPro) improves the clinical outcomes of percutaneous coronary intervention. This registry was conducted to characterize the effects of repeated administration of abciximab during intervention. METHODS AND RESULTS: We recruited 500 consecutive patients at 22 centers in the United States who were receiving abciximab for at least a second time during percutaneous coronary intervention. Safety was measured as the incidence of hypersensitivity reactions, major bleeding, and thrombocytopenia. Efficacy was assessed as event-free clinical success. Human antichimeric antibody (HACA) responses were also characterized. There were no cases of hypersensitivity (95% upper confidence bound, 0.3%), major bleeding, or death. Clinical success was 94.4%. Thrombocytopenia occurred in 23 patients (4.6%; 95% CI, 2.8% to 6.4%), including 12 (2.4%; 95% CI, 1.1% to 3.7%) who developed profound thrombocytopenia (<20x10(9) cells/L). In 2 patients (0.4%), profound thrombocytopenia did not develop until after hospital discharge; in 4 (0.8%), profound thrombocytopenia recurred despite platelet transfusion. Before a first readministration, a positive HACA titer was present in 22 of 454 patients (4.8%); after a first readministration, an additional 82 of 432 (19.0%) became HACA-positive. HACA did not neutralize the in vitro inhibition of platelet aggregation by abciximab or correlate with clinical events. CONCLUSIONS: The results, including overall rates of thrombocytopenia, were consistent with randomized clinical trials of first abciximab treatment. However, there was a shift from mild to profound thrombocytopenia, and cases of delayed presentation and of recurrent thrombocytopenia were seen. These findings suggest that indications and guidelines for first-time use apply to retreatment, particularly the systematic monitoring for thrombocytopenia.

Physiological variant of antithrombin-III lacks carbohydrate sidechain at Asn 135.

Both normal antithrombin-III (AT-III alpha) and the high heparin affinity form (AT-III beta) were isolated from pooled human plasma. AT-III beta had a lower negative charge and lower molecular mass than AT-III alpha. Sialidase and endo-F digestion indicated that the inherent difference resided in the oligosaccharide component of the molecule. CNBr fragmentation showed there was an oligosaccharide sidechain missing between residues 104 and 251, subdigestion with trypsin indicated that Asn 135 was not glycosylated in AT-III beta. Chromatography of total tryptic digests on concanavalin A-Sepharose confirmed that the high heparin affinity form of antithrombin lacked an oligosaccharide moiety at Asn 135.

Antithrombin inactivation by neutrophil elastase requires heparin.

In certain thrombotic states, large declines in the levels of functional circulating antithrombin occur, which may reflect the highly active nature of the endothelial surface in suppressing excessive amounts of activated coagulation enzymes. Alternatively, we have recently observed an unexpected and paradoxical in vitro functioning of heparin that could result in the inactivation of antithrombin in pathologic conditions. Specifically, antithrombin was rendered nonfunctional as an inhibitor of clotting enzymes as a result of a limited, heparin-dependent cleavage by neutrophil elastase. This inactivation occurred only in the presence of the active anticoagulant heparin fraction, which suggested that the heparin-antithrombin complex was the substrate for elastase attack. Interestingly, neutrophil elastase was found to bind tightly to heparin and heparin-like materials. Neutrophil elastase has been previously linked to nonspecific proteinolysis occurring in inflammatory thrombotic reactions. This affinity of both antithrombin and elastase for heparin suggests a novel mechanism of potential specificity. An important component of this hypothesis is the localization of the elastase/antithrombin reaction away from the high circulating levels of elastase inhibitors. The proposed inactivation of antithrombin on the vascular surface would likely occur only in pathologic states associated with neutrophil sequestration and activation. Nevertheless, this mechanism could lead to a localized reversal of the nonthrombogenic nature of the endothelium and potentially lead to significant reductions of functional antithrombin in certain disease states.

Effect of Ca2+ chelation on the platelet inhibitory ability of the GPIIb/IIIa antagonists abciximab, eptifibatide and tirofiban.

OBJECTIVE: Enhanced GPIIb/IIIa binding and inhibition of platelet aggregation of eptifibatide by the reduction of ionized plasma calcium concentrations have been reported. The present study compared the importance of Ca2+ chelation on the in vitro platelet inhibitory profiles of the GPIIb/IIIa antagonists abciximab, eptifibatide and tirofiban. METHODS AND RESULTS: Turbidimetric platelet aggregation dose response curves of the various GPIIb/IIIa antagonists were performed using platelet rich plasma (PRP) anticoagulated with either trisodium citrate, or the non-chelating anticoagulant, PPACK. The concentrations of antagonist that resulted in 50% inhibition of TRAP-induced (10 microM) platelet aggregation (IC50) were measured in the presence of either citrate or PPACK. In addition, the influence of Ca2+ chelation on the binding properties (relative affinity, on- and off-rates) of abciximab for the GPIIb/IIIa receptor on platelets was measured. For all three agonists, the IC50 concentrations were lower for platelets treated with citrate than PPACK, but the degree of difference varied among the agents. The mean TRAP IC50 values for citrate and PPACK were 88.2 +/- 12.2 nM and 126.1 +/- 28.4 nM for abciximab (1.4 fold enhancement; p = 0.0007), 75.9 +/- 13.3 nM and 142.6 +/- 32.6 nM for tirofiban (1.9-fold enhancement; p = 0.001), and 260.2 +/- 62.5 nM and 810.3 +/- 182.5 nM for eptifibatide (3.1-fold enhancement; p = 0.001). A similar shift in effective inhibitor concentrations for abciximab was observed with ADP (10 microM). The relative affinities (EC50), on- and off-rates of abciximab for the platelet GPIIb/IIIa receptor in the presence of trisodium citrate and PPACK were equivalent. CONCLUSIONS: These data confirm previous observations that Ca2+ chelation afforded by citrate decreases the effective inhibitor concentrations of GPIIb/IIIa antagonists, as assessed by turbidimetric platelet aggregation. However, the extent of decrease was less for abciximab and tirofiban, compared to eptifibatide.

7E3 F(ab')2, an effective antagonist of rat alphaIIbbeta3 and alphavbeta3, blocks in vivo thrombus formation and in vitro angiogenesis.

Abciximab (c7E3 Fab, ReoPro) blocks GPIIb/IIIa and alphavbeta3 and inhibits thrombotic and proliferative events only in humans and non-human primates. The bivalent F(ab')2 fragment is an effective anti-thrombotic agent in canine models. In the present study, 7E3 F(ab')2 was also found to bind to rat GPIIb/IIIa (KD = 27 +/- 4 microg/mL) and alphavbeta3 (KD = 9 +/- 8 microg/mL), to block in vitro rat platelet aggregation (IC50 = 16 +/- 6 microg/mL), and to inhibit alphavbeta3-mediated microvessel sprout formation in a rat aortic ring assay. Following administration of 7E3 F(ab')2 (4 mg/kg) to rats, platelet aggregation was completely blocked for up to 6 h and thrombus formation in response to a rat abdominal aorta double crush injury was prevented. Effective chronic dosing was achieved with 6 mg/kg daily I.P. injections. In vitro mixing experiments indicated that 7E3 F(ab')2 redistributed to unlabeled platelets in 2 h. Ex vivo, 7E3 F(ab')2 was detected on platelets for up to 4 days after a single 4-mg/kg injection. These data suggest that 7E3 F(ab')2 may be a useful agent to study the effects of GPIIb/IIIa and alphavbeta3 blockade in rat models of thrombosis and vascular disease.

Activation of the cloned human NK3 receptor in Chinese Hamster Ovary cells characterized by the cellular acidification response using the Cytosensor microphysiometer.

1. The aim of the present study was to validate the Cytosensor microphysiometer, a novel system that measures the extracellular acidification rate as a reliable index of the integrated functional response to receptor activation, as a method for studying NK3 receptor pharmacology, and then to use this system to assess the functional activity of novel compounds at this receptor. 2. The selective NK3 agonist senktide caused reproducible, concentration-related increases in acidification ratein CHO-NK3 cells, with a pEC50 value of 8.72+/-0.11 (n=15). [Beta-Ala8]NKA(4-10), the selective NK2 agonist, elicited a much weaker response (pEC50=6.68+/-0.08, n=4), while the NK1-selective agonist substance P methylester only caused a very weak response at concentrations > or =3 microM (n=2). The rank order of potency for the endogenous tachykinins NKB>NKA>substance P (n=3) confirmed the response was mediated by the NK3 receptor. Moreover, the actual potencies obtained were consistent with affinities measured in radioligand binding studies. 3. The novel compounds PD156319-121 (0.3-1 microM), PD161182 (10-300 nM), PD168001 (10-100 nM) and PD168073 (10-100 nM) all acted as surmountable antagonists of the senktide-induced acidification response, with pA2 values of 7.49, 8.67, 9.17 and 9.25 respectively (n=3-5). In comparison the known NK3 antagonist SR142801 (10-100 nM) had a pA2 value of 8.83 (n=8) for the interaction with senktide. Again, these values are consistent with the radioligand binding data. 4. Amiloride (1 mM) inhibited the senktide-induced acidification response by 68.3+/-3.3 (n=4), indicating that the Na+/H+ antiporter plays an important role in this response, and this is consistent with the importance of this antiporter in other acidification responses. 5. Inhibition of protein kinase C with staurosporine (0.1 microM), or depletion of the intracellular Ca2+ stores with thapsigargin (1 microM), both resulted in a reduction in the maximum response to senktide (63.3+/-1.7 and 68.9+/-3.2% respectively, n=3-5), and co-application of these inhibitors abolished the response (n=3). This strongly suggested that the NK3 receptor was coupling via phospholipase C (PLC), as would be expected, although this could not be confirmed by the use of the putative PLC/PLA2 inhibitor U73122. 6. In conclusion, we have demonstrated the utility of the Cytosensor in the characterization of functional responses to agonists, and assessment of the affinities of antagonists in CHO cells expressing the human NK3, and have shown that our series of novel compounds are non-peptide NK3 antagonists of high affinity, as exemplified by PD168073.

Livedo vasculitis (the vasculitis of atrophie blanche). Immunohistopathologic study.

Hyalinizing segmental vasculitis or livedo vasculitis (atrophie blanche) is a clinical entity with a distinctive immunohistopathologic morphology that can be distinguished from other forms of cutaneous vasculitis by histologic and direct immunofluorescent studies. Our studies showed that immunoglobulins and complement components (C-1g, C-3, and properdin) were localized in diseased vessel walls, suggesting an immune pathogenesis.

Differential effects of c7E3 Fab on thrombus formation and rt-PA-Mediated thrombolysis under flow conditions.

Although the Fab fragment of the mouse-human chimeric anti-alphaIIbbeta3 (GP IIb/IIIa) monoclonal antibody (MoAb) c7E3 facilitates recombinant tissue-type plasminogen activator (rt-PA)-mediated thrombolysis, it is not clear whether this is due to inhibition of new clot formation and/or a direct effect on the lysis rate. We employed an in vitro flow (re)circulation model to investigate how c7E3 Fab affected (a) platelet adhesion to clotted fibrin substrates under laminar flow at wall shear rates of 100 or 500 s(-1) and (b) rt-PA-induced lysis of preformed mural platelet-fibrin substrates at 500 s(-1). c7E3 Fab dose-dependently (0.5-5 microg/ml) inhibited platelet adhesion from flowing whole blood onto fibrin substrates ( approximately 14 microm thick) at each wall shear rate. When at 5 min after the onset of flow, c7E3 Fab (0.1-10 microg/ml) and rt-PA (1 microg/ml) were coinjected in flowing blood, it was found that modest fibrinolysis caused major platelet release from fibrin substrates and there was no difference in the lysis rate in the presence of rt-PA + c7E3 Fab compared to rt-PA alone. Platelet pretreatment with c7E3 Fab (10 microg/ml) had no effect on the lysis rate of thin ( approximately 40 microm), and slightly delayed the lysis rate of thick (< 250 microm), platelet-fibrin substrates containing evenly dispersed platelets (10(9)/ml). When the platelets within thick platelet-fibrin substrates were organized in platelet-rich regions ("residual thrombi"), these substrates followed a nonuniform lysis pattern, where fibrin between the thrombi lysed first and the residual thrombi lysed at a slower rate. Platelet pretreatment with c7E3 Fab (10 microg/ml) abolished the formation of the lytic-resistant residual thrombi and the associated platelet-protected fibrin zones. Hence, treatment with c7E3 Fab has no direct effect on the rate of rt-PA-mediated lysis, but is expected to block platelet-fibrin interactions that lead to clot retraction, thus maintaining a fibrin architecture that is more susceptible to lysis.

Laser resurfacing for facial acne scars.

BACKGROUND: Most people have acne at some stage during their life, with about one per cent being left with permanent acne scars. Recent laser techniques are thought to be more effective than chemical peels and dermabrasion. OBJECTIVES: To assess the effects of laser resurfacing for treating facial acne scars. SEARCH STRATEGY: We searched MEDLINE (1966 to April 1999), EMBASE (1980 to April 1999), Science Citation Index (1981 to April 1999), the Cochrane Controlled Trials Register (April 1999), DARE (April 1999), INAHTA (April 1999), NHS HTA Internet site (April 1999). Dermatological Surgery (1995 to March 1999) and the British Journal of Dermatology (1995 to September 1999) were handsearched. We searched the reference lists of relevant articles and contacted experts and commercial laser manufacturers. SELECTION CRITERIA: Randomised controlled trials which compare different laser resurfacing techniques for treating patients with facial acne scars, or compare laser resurfacing with other resurfacing techniques or no treatment. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected studies, assessed the quality of studies and extracted data. MAIN RESULTS: No randomised controlled trials where laser treatment was compared to either placebo or a different type of laser were found. Most of the 27 studies uncovered were poor quality case series with small numbers of acne-scarred patients. REVIEWER'S CONCLUSIONS: The lack of good quality evidence does not enable any conclusions to be drawn about the effectiveness of lasers for treating atrophic or ice-pick acne scars. Well designed randomised controlled comparisons of carbon dioxide versus Erbium:YAG laser are urgently needed.

Studies on lysyl oxidase of bovine ligamentum nuchae and bovine aorta.

Lysyl oxidase had been purified to near homogeneity from bovine aorta and bovine ligamentum nuchae employing a modification of methods described by Harris et al., and Stassen and his colleagues. The aortic enzyme gives rise to at least three peaks and the ligament enzyme resolves into at least four peaks upon chromatography on DEAE cellulose. The molecular weight of each peak of both enzymes is approximately 30,000 daltons in sodium dodecyl sulfate. The aortic enzyme aggregates to species with molecular weights varying from approximately 60,000 to 1,000,000 daltons upon dialysis out of urea into phosphate-buffered saline. Temperature studies reveal that lysyl oxidase is stable to temperatures as high as 80 degrees C, although the assay optimum is 52 degrees C. Studies in progress suggest the temperature dependency of assay may reflect conformational changes in the elastin substrate.

Posterior composite restorations. Where and how they work best.

Despite its increased use, composite resin is still technique-sensitive. The authors offer correct placement steps and indicate where these restorations will do well.

Glass ionomer-composite sandwich technique.

Glass ionomer cement characteristics of biological acceptability, fluoride release, dentin bondability, and marginal integrity are excellent; at the same time, they have always been regarded as secondary choices for anterior and posterior restorations. Slow set, brittleness, poor finishability, lack of translucency, and the technique-sensitive nature of the glass ionomers hardly compare with the composite resins which are easier to handle, polishable, and esthetically acceptable. The combined ionomer-composite restoration provides a reliable chemical bond to dentin, micromechanical bonding of the composite to ionomer surface, and an acceptable esthetic result.