Timeliness of care in patients with lung cancer: a systematic review.

BACKGROUND: Timeliness is an important dimension of health care quality. It is unclear whether timeliness improves clinical outcomes in patients with lung cancer. METHODS: This study systematically reviewed studies that described timeliness of care, examined associations between timeliness and clinical outcomes or tested an intervention to improve timeliness of care in patients with lung cancer. English language studies published between 1 January 1995 and 1 June 2007 were included. Two reviewers independently abstracted data on study methods, population, sample size, relevant time intervals and outcomes. RESULTS: 49 studies were identified that reported at least one time interval in lung cancer care, 18 studies that examined the association between timeliness and clinical outcomes and 8 studies that described interventions aimed at improving timeliness. Most studies were performed in European Union member countries, including 24 studies performed in Great Britain and Ireland. Median times to diagnosis (range 8-60 days) and times to treatment (range 30-84 days) often exceeded published recommendations. Three studies found that timely care was associated with better survival, eight found no association and four reported better survival in patients who received less timely care. Interventions that improved timeliness included nurse-led care coordination, multidisciplinary meetings via teleconference and a standardised expedited "two-stop" diagnostic process. CONCLUSIONS: Times to diagnosis and treatment of lung cancer are often longer than recommended. Factors associated with timeliness have been incompletely examined, and it remains unclear whether more timely care improves outcomes.

Validation of two models to estimate the probability of malignancy in patients with solitary pulmonary nodules.

BACKGROUND: Effective strategies for managing patients with solitary pulmonary nodules (SPN) depend critically on the pre-test probability of malignancy. OBJECTIVE: To validate two previously developed models that estimate the probability that an indeterminate SPN is malignant, based on clinical characteristics and radiographic findings. METHODS: Data on age, smoking and cancer history, nodule size, location and spiculation were collected retrospectively from the medical records of 151 veterans (145 men, 6 women; age range 39-87 years) with an SPN measuring 7-30 mm (inclusive) and a final diagnosis established by histopathology or 2-year follow-up. Each patient's final diagnosis was compared with the probability of malignancy predicted by two models: one developed by investigators at the Mayo Clinic and the other developed from patients enrolled in a VA Cooperative Study. The accuracy of each model was assessed by calculating areas under the receiver operating characteristic (ROC) curve and the models were calibrated by comparing predicted and observed rates of malignancy. RESULTS: The area under the ROC curve for the Mayo Clinic model (0.80; 95% CI 0.72 to 0.88) was higher than that of the VA model (0.73; 95% CI 0.64 to 0.82), but this difference was not statistically significant (Delta = 0.07; 95% CI -0.03 to 0.16). Calibration curves showed that the probability of malignancy was underestimated by the Mayo Clinic model and overestimated by the VA model. CONCLUSIONS: Two existing prediction models are sufficiently accurate to guide decisions about the selection and interpretation of subsequent diagnostic tests in patients with SPNs, although clinicians should also consider the prevalence of malignancy in their practice setting when choosing a model.

(Acylaryloxy)acetic acid diuretics. 1. (2-Alkyl- and 2,2-dialkyl-1-oxo-5-indanyloxy)acetic acids.

The discovery of the (acryloylaryloxy)acetic acids as a new class of potent diuretics prompted the investigation of related bicyclic compounds. Annelated analogues of the parent series, the (2-alkyl- and 2,2-dialkyl-1-oxo-5-indanyloxy)acetic acids, were the subjects of this study. Those compounds, unlike the monocyclic parent compound, lacked the double bond adjacent to the carbonyl group. More importantly, they possessed both saluretic and uricosuric properties. The optimal single 2-substituents for maximal saluretic and uricosuric activity were determined. In general, better activity was observed when a second 2-alkyl substituent (especially methyl) was present in the molecule. Replacement of the carboxy substituent by 5-tetrazolyl generally resulted in a reduction in activity.

2-(Aminomethyl)phenols, a new class of saluretic agents. 5. Fused-ring analogues.

A number of bicyclic ring-fused analogues of 2-(aminomethyl)phenol were synthesized and tested orally in rats and intravenously in dogs for saluretic and diuretic effects. Of the 15 alicylic, aromatic, and heterocyclic ring-fused compounds tested, only 2-(aminomethyl)-4-chloro-1-naphthalenol hydrochloride (2) and 7-(aminomethyl)-6-hydroxy-5,8-dimethyl-1,2,3,4-tetrahydronaphthalene hydrochloride (6) displayed a high order of activity.

2-(Aminomethyl)phenols, a new class of saluretic agents. 6. Effects of N,O-spiroannulation and subsequent quaternization.

The synthesis of a number of 3,4-dihydrospiro-2H-1,3-benzoxazines and their corresponding benzoxazinium salts are reported. The saluretic effects displayed by these N,O-spiroannulated 2-(aminomethyl)phenols appear to be, in part, inversely related to their respective in vivo rates of hydrolysis. Good antihypertensive effects are found only in spirobenzoxazinium 22. Thus, a combination of spiroannulation and quaternization on 2 to produce 22 leads to a loss of saluretic effects with maintenance of antihypertensive effects and, thereby, serves to separate these pharmacological properties.

(Vinylaryloxy)acetic acids. A new class of diuretic agents. 3. ((2-Nitro-1-alkenyl)aryloxy)acetic acids.

A series of [(2-nitro-1-alkenyl)aryloxy]acetic acids was synthesized and tested in dogs for saluretic and diuretic activity. A number of these compounds exhibit a high order of activity on iv or po administration; representative of these is (E)-[2,3-dichloro-4-(2-nitropropenyl)phenoxy]acetic acid (5). The most highly active compounds are qualitatively similar in action to [2,3-dichloro-4-(2-methylenebutyryl)phenoxylacetic acid (ethacrynic acid) in causing a prompt increase in the excretion of water and of sodium and chloride ions in approximately equimolar amounts but are three to five times as potent. Potassium ion excretion is increased but less markedly than sodium excretion.

2-(Aminomethyl)phenols, a new class of saluretic agents. 4. Effects of oxygen and/or nitrogen substitution.

A series of oxygen and/or nitrogen substituted 2-(aminomethyl)phenols was synthesized and tested orally in rats for saluretic and diuretic effects. Intravenous dog data are included as supplementary material to demonstrate diuretic responses, or lack thereof, in a second species. In general, substitution on nitrogen with groups other than lower alkyl or substitution on nitrogen and/or oxygen with groups resistant to hydrolysis substantially diminished or ablated saluretic effects.

2-(Aminomethyl)phenols, a new class of saluretic agents. 3. Effects of functional group reorientation and modification.

A series of modified 2-(aminomethyl)phenols was synthesized and tested orally in rats for saluretic and diuretic effects. Intravenous dog data are included as supplementary material to show that the diuretic responses, or lack thereof, may be obtained in a second species. Reorientation of the 2-(aminomethyl) group either meta or para to the hydroxyl substituent resulted in loss of diuretic effects. Similarly, replacement of either the phenolic hydroxyl or the aminomethyl group with other functional moieties substantially diminished saluretic effects.

2-(Aminomethyl)phenols, a new class of saluretic agents. 1. Effects of nuclear substitution.

A series of 2-(aminomethyl)phenols was synthesized and tested in rats and dogs for saluretic and diuretic activity. A number of these compounds exhibit a high order of activity on iv or po administration. The most active compounds belong to a subseries of 4-alkyl-6-halo derivatives of which 2, 2-(aminomethyl)-4-(1,1-dimethylethyl)-6-iodophenol, is the most active. Compound 2 also possesses significant antihypertensive activity, an adjunctive pharmacological parameter which distinguishes 2 from the other compounds prepared in this series. In addition, 2 displays both topical saluretic and antiinflammatory activities.