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The study examines the prevalence of depressive syndromes among unselected primary care attenders, as well as doctors' recognition and treatment rates, in order to examine patient and doctor-related factors associated with poor recognition. This nationwide study included a total of 20421 patients (aged 15-99 years) attending their primary care doctors (n = 633) on the study's target day in April 1999. Patients received a self-report questionnaire, including the Depression Screening Questionnaire (DSQ), to provide diagnoses of depressive disorders according to the criteria of DSM-IV and ICD-10. Doctors completed: (1) a pre-study questionnaire assessing data on doctors' psychosocial, professional and training background, as well as current practices in patients with depression and (2) an evaluation form for each patient seen to assess his diagnostic decision, clinical severity and treatment choices. Taking the DSQ as a yardstick, 4.2% of all primary care attenders fulfilled criteria for a major depressive episode according to DSM-IV; considerably higher rates of 11.3% were obtained using the ICD-10 criteria for mild depressive episodes. Rates of depression were higher in females, increased by age, and were also elevated in those retired, unemployed as well as non-working housemen/wives. Taking the doctors' decision of definite or probable depression, 75% of all DSM and 59% of all ICD-10 diagnoses were recognized by the treating physician. However, doctors also assigned diagnoses of definite depression in an additional 11.7% of patients not meeting either ICD-10 nor DSM-IV criteria. Among correctly identified depression cases doctors decided to prescribe drug treatments in 72.7% (DSM) and 60.8% (ICD). Some 16.2% of DSM and 10.1% of ICD-cases were referred to mental health specialists; non-drug interventions were prescribed for 19.8% (DSM) and 24.9% (ICD), respectively. Multiple logistic regression analyses revealed that recognition is associated with prior treatment episodes, increasing number of depression symptoms, patients higher age, practice experience of treating physician greater 5 years and psychomotor retardation. These findings confirm the high prevalence of depressive syndromes in primary care settings and underline the particular challenge posed by a high proportion of with near-threshold symptomology patients. Although recognition rates among more severe major depressive patients as well as treatments prescribed appear to be more favourable than in previous studies, the situation in less severe cases, and the high proportion of doctors' definite depression diagnoses in patients with depression symptoms that are clearly below even the subthreshold level, raises significant concerns.

Lignocaine is widely used as a local anaesthetic and antiarrhythmic drug. It is commonly administered to patients with acute myocardial infarction as prophylaxis for ventricular fibrillation, although its efficacy in preventing primary ventricular fibrillation is still debated. Toxicity, sometimes with serious clinical consequence, is not uncommom and is usually related to overdosage. Blood lignocaine concentrations correlate roughly with antiarrhythmic and toxic effects and might be useful as an end point for monitoring prophylactic therapy. Administration of lignocaine as a local anaesthetic may result in blood lignocaine concentration in the antiarrhythmic or even toxic ranges. Expected peak levels for various routes of local anaesthesia are tabulated so that 'safe' total doses can be calculated. Intramuscular injection of high doses results in sustained therapeutic levels but is often associated with early minor toxicity. Lignocaine is eliminated primarily by hepatic metabolism, which appears to be limited by liver perfusion. Active metabolites may contribute to therapeutic and/or toxic effects. Disease states such as cardiac failure or drugs that alter hepatic blood flow may significantly affect lignocaine clearance. Pharmacokinetic studies in man show wide variability in drug disposition between patients, even when cardiac and hepatic status is considered, making specific dosing recommendations a problem. With intravenous injection, multicompartment kinetics is observed, with an initial rapid decline phase and initial decline in antiarrhythmic activity due to redistribution. With constant infusion, steady state concentrations of lignocaine are seen after 3 to 4 hours in normal subjects and after 8 to 10 hours in patients with myocardial infarction without circulatory insufficiency. In patients with cardiac failure, blood lignocaine concentration may continue to rise for 24 to 48 hours. In the presence of cardiac failure, decreased volumes of distribution and clearance require reduction in loading and maintenance doses. Lignocaine clearance is reduced in patients with liver disease and appears to be a sensitive index of liver dysfunction. A dosing algorithm for treatment of patients with myocardial infarction is presented.

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Cardiac failure is often associated with disturbances in cardiac output, autonomic nervous system activity, central and systemic venous pressures, and sodium and water metabolism. These disturbances influence the extent and pattern of tissue perfusion, may lead to tissue hypoxia and visceral congestion, and may alter gastrointestinal motility. By these mechanisms, cardiac failure potentially affects absorption and disposition characteristics of drugs, which may necessitate adjustment in dosage regimen for optimum therapy. Lignocaine is the drug which has been studied most extensively in cardiac failure. Volumes of distribution and clearance are decreased. As a drug whose metabolism is largely limited by liver blood flow, decreased blood flow to the liver accounts for some of the change in clearance, but impaired hepatic metabolism appears also to play a role in some patients. Accumulation of active metabolites of lignocaine and procainamide in patients with cardiac failure can influence therapeutic and toxic effects. Theophylline metabolism, which is largely independent of blood flow, appears to be reduced significantly in patients with severe cardiac failure and necessitates reduction of dosage. In the presence of severe cardiac failure, digoxin clearance may be less than anticipated on the basis of estimates of renal function. Quinidine plasma levels may be higher after single doses due to reduced volume of distribution. Quinidine metabolites are believed not to be pharmacologically active but may create confusion with nonspecific assays. Specific assays are recommended in cardiac failure, especially complicated by renal insufficiency. Data are lacking relating pharmacokinetic alterations to haemodynamic measurements in patients with cardiac failure. Whereas the direction of change in pharmacokinetic parameters may be predicted, variability in the magnitude of change is so great that determination of drug concentration in blood remains as essential adjunct to therapy.

To clarify the controversy regarding the benefits of long-term oral digoxin in the treatment of heart failure, we evaluated hemodynamics at rest and during exercise in nine patients in sinus rhythm with symptomatic heart failure. Patients were studied during long-term digoxin therapy, after withdrawal of the drug, and six hours after readministration. Upon withdrawal of digoxin, pulmonary capillary-wedge pressure increased from 21 +/- 8 to 29 +/- 10 mm Hg, and cardiac index decreased from 2.4 +/- 0.7 to 2.1 +/- 0.6 liters per minute per square meter of body-surface area, suggesting a deterioration in left ventricular function. In addition, heart rate tended to increase and stroke-work index, stroke-volume index, and radioangiographic ejection fraction decreased. Acute readministration restored the hemodynamic values to those observed during long-term digoxin therapy. The improvement in hemodynamics during long-term digoxin administration was also observed during exercise. This improvement demonstrated the value of long-term oral digoxin therapy in congestive heart failure.

In view of the fact that controlled prospective studies on the benefits of dose escalation of the selective serotonin re-uptake inhibitor (SSRI) paroxetine are lacking, we conducted a double-blind, randomized, parallel-group multicentre study designed to compare the possible benefits of dose escalation of paroxetine and maprotiline in patients suffering from major or minor depression according to modified Research Diagnostic Criteria (RDC) with inadequate treatment response. The study sample consisted of 544 out-patients with different degrees of severity of depression. Patients received either 20 mg paroxetine (n = 271) or 100 mg maprotiline (n = 273) for the first 3 weeks in a double-blind manner. Response after 3 weeks was defined using explicit operationalized criteria. Patients with inadequate treatment response (paroxetine group, n = 86; maprotiline group, n = 88) were again randomized to either continuation of the previous dosage (paroxetine, n = 36; maprotiline, n = 48) or increased doses, i.e. 40 mg paroxetine (n = 50) or 150 mg maprotiline (n = 40), respectively. Intention-to-treat and completer analyses were performed. Defining response as a reduction in Hamilton Depression Rating Scale (17-item version) (HAMD-17) score of at least 50% from baseline, no significant benefits of dose escalation were found for either paroxetine or maprotiline. Stratification according to baseline severity of depression also revealed no significant benefits of dose escalation. After dose escalation, new adverse events that had not been present during treatment with lower doses rarely occurred. Our results support the view that a dose of 20 mg paroxetine is optimal for the acute treatment of depression in the majority of patients.

This survey summarises the observations of physicians who prospectively recorded clinically relevant data on their patients with an episode of herpes zoster. These included demography of patients, signs and symptoms during the prodromal phase, relevant history, description of disease at the first visit, therapeutic measures and description of disease, and occurrence of postherpetic neuralgia (pain 4–5 weeks after crusting) at the second visit. A total of 2,063 patients were reported to the data management centre. The age distribution resembles that reported in the literature including the notable increase in zoster frequency with advancing age. Almost 20% of the patients, however, were 30 years old or less, and this contrasts markedly with the published literature. Age modifies the frequency of the dermatome afflicited: more cranial and less thoracic manifestations were observed with increasing age. Almost all patients reported symptoms which may be attributed to a prodromal phase, especially pain in the affected dermatome (82%). The incidence of postherpetic neuralgia was 28%. A complicated disease course such as visceral, ocular, or otological involvement, or progression to additional dermatomes was seen in almost 10% of the patients.