Understanding the role of community resilience in addressing the Ebola virus disease epidemic in Liberia: a qualitative study (community resilience in Liberia).

Background: There is an increasing recognition that community resilience plays a significant role in addressing health shocks like the Ebola virus disease (EVD) epidemic. However, the factors that constitute community resilience, and how these operate dynamically with other health system factors are less understood. Objective: This paper seeks to understand key factors that constitute community resilience and their role in responding to the EVD outbreak in Liberia. Methods: Key informant interviews were conducted between November 2017 and April 2018 with community representatives in Bomi, Margibi and Montserrado counties, and other national stakeholders involved in the EVD response in Liberia from 2014 to 2016. A national stakeholder meeting was conducted to verify and interpret information emerging from the interviews. Results: Factors that were critical for addressing the EVD epidemic in Liberia were identified as: strong leadership, tight bonds and sense of kinship at the community level; trusted communication channels; and trust among various health system stakeholders. These factors facilitated collective actions within communities and helped to direct response initiatives from other levels of the health system to the community. Foreign assistance was seen as crucial for recovery and revitalization of affected communities. However, such aid is often not targeted at addressing critical challenges in a sustainable way, especially when the assistance is highly restricted to specific activities, and those activities are determined without consultation with local actors and community groups. Conclusion: Efforts to systematically build responsible leadership and social capital at community level, including those that strengthen bonds in communities and trust across key actors in the health system, are needed to address health shocks like EVD outbreaks. Without building such capabilities in community resilience, it will be difficult to reap the expected gains from investments focusing on building physical capital and technical capabilities in health services and emergency preparedness.

Improving health systems performance in low- and middle-income countries: a system dynamics model of the pay-for-performance initiative in Afghanistan.

System dynamics methods were used to explore effective implementation pathways for improving health systems performance through pay-for-performance (P4P) schemes. A causal loop diagram was developed to delineate primary causal relationships for service delivery within primary health facilities. A quantitative stock-and-flow model was developed next. The stock-and-flow model was then used to simulate the impact of various P4P implementation scenarios on quality and volume of services. Data from the Afghanistan national facility survey in 2012 was used to calibrate the model. The models show that P4P bonuses could increase health workers' motivation leading to higher levels of quality and volume of services. Gaming could reduce or even reverse this desired effect, leading to levels of quality and volume of services that are below baseline levels. Implementation issues, such as delays in the disbursement of P4P bonuses and low levels of P4P bonuses, also reduce the desired effect of P4P on quality and volume, but they do not cause the outputs to fall below baseline levels. Optimal effect of P4P on quality and volume of services is obtained when P4P bonuses are distributed per the health workers' contributions to the services that triggered the payments. Other distribution algorithms such as equal allocation or allocations proportionate to salaries resulted in quality and volume levels that were substantially lower, sometimes below baseline. The system dynamics models served to inform, with quantitative results, the theory of change underlying P4P intervention. Specific implementation strategies, such as prompt disbursement of adequate levels of performance bonus distributed per health workers' contribution to service, increase the likelihood of P4P success. Poorly designed P4P schemes, such as those without an optimal algorithm for distributing performance bonuses and adequate safeguards for gaming, can have a negative overall impact on health service delivery systems.

Awareness of anti-malarial policy and malaria treatment practices of patent medicine vendors in three Nigerian states.

INTRODUCTION: This paper assesses Patent Medicine Vendors' (PMVs) practices, awareness of new Nigerian Artemisinin Combination Therapy (ACT) policy, the anti-malarial drugs in stock and how the PMVs identify fake drugs. METHODOLOGY: PMVs and medicine shops were selected through a multi-stage random sampling process, beginning with the purposive selection of three states that reflect major geographic and ethnolinguistic areas of Nigeria: Oyo (Southwest-Yoruba), Kaduna (Northcentral-Hausa), and Enugu (Southeast-Igbo). Local Government Areas (LGAs) in selected states were stratified into urban and rural strata, with two LGAs randomly sampled from each stratum in each state, and one ward (urban LGAs) or community (rural LGAs) randomly sampled from a list in each LGA. A complete listing of PMVs and drug shops was constructed at each site, yielding 111 PMVs and 106 medicine shops. Out of this number, a total of 110 PMVs consented to be interviewed. RESULTS: Some PMVs (43.1%) were aware of the 2005 government policy that changed the recommended first-line treatment for malaria from chloroquine (CQ) to ACT, but significant differences were found between states (p < 0.001). PMV shops stocked many brands of anti-malarial drugs (average 5.5 brands), with ACTs stocked in only 8.5% of the stores at a mean price of N504 ($4) per treatment, compared to sulfadoxine-pyrimethamine (92% of shops, mean price of N90 ($0.7) and even monotherapy artesunates (32% of shops, mean price of N39 ($0.3). The PMVs identify a drug not bearing the National Agency for Food & Drug Administration and Control (NAFDAC) identification number as being fake or counterfeit. CONCLUSION: PMVs need to be a part of the strategy to change treatment to ACTs if there are to be meaningful changes in the anti-malarial drugs that Nigerians receive.

Comparative analysis of exit interviews and direct clinical observations in pediatric ambulatory care services in Afghanistan.

OBJECTIVE: To assess the receiver operating curves (ROCs) for counseling in the management of common childhood diseases comparing direct observations with exit interviews. DESIGN: Eight thousand six hundred and fifty-nine randomly selected new outpatient consultations of sick children under 5 years were assessed by observation using a standardized checklist and an exit interview with their parent/guardian, taken between 2005 and 2007 from 948 health facilities in Afghanistan. The observation checklist was used as a 'gold standard' for counseling provided. MAIN MEASURE: Sensitivity, specificity and ROCs were estimated for five counseling items, including explanations of: a working diagnosis; what to do at home; possible adverse reactions to medicine; signs that require a return to the health facility; and a time to return. RESULTS: The prevalence of counseling items was relatively low (ranging from 8 to 80%), but generally increasing each year. Exit interviews had relatively low levels of sensitivity for the counseling items, ranging from 33 to 88%, with higher levels of specificity (ranging from 63 to 91%), whereas the ROCs ranged from 61 to 77%. Although ROCs varied significantly from year to year (P < 0.002 for each item), there was little difference based on the sex or type of the health provider. CONCLUSIONS: Exit interviews did not provide reliable measurements of provider performance compared with direct observations. Observations identified low prevalence of counseling tasks though increasing over time. The differences between observation and exit interviews identified significant gaps in communication, suggesting that exit interviews are of low accuracy and should not be used alone.

Regular use of alcohol and tobacco in India and its association with age, gender, and poverty.

This study provides national estimates of regular tobacco and alcohol use in India and their associations with gender, age, and economic group obtained from a representative survey of 471,143 people over the age of 10 years in 1995-96, the National Sample Survey. The national prevalence of regular use of smoking tobacco is estimated to be 16.2%, chewing tobacco 14.0%, and alcohol 4.5%. Men were 25.5 times more likely than women to report regular smoking, 3.7 times more likely to regularly chew tobacco, and 9.7 times more likely to regularly use alcohol. Respondents belonging to scheduled castes and tribes (recognized disadvantaged groups) were significantly more likely to report regular use of alcohol as well as smoking and chewing tobacco. People from rural areas had higher rates compared to urban dwellers, as did those with no formal education. Individuals with incomes below the poverty line had higher relative odds of use of chewing tobacco and alcohol compared to those above the poverty line. The regular use of both tobacco and alcohol also increased significantly with each diminishing income quintile. Comparisons are made between these results and those found in the United States and elsewhere, highlighting the need to address control of these substances on the public health agenda.

Benchmarks for health expenditures, services and outcomes in Africa during the 1990s.

There is limited information on national health expenditures, services, and outcomes in African countries during the 1990s. We intend to make statistical information available for national level comparisons. National level data were collected from numerous international databases, and supplemented by national household surveys and World Bank expenditure reviews. The results were tabulated and analysed in an exploratory fashion to provide benchmarks for groupings of African countries and individual country comparison. There is wide variation in scale and outcome of health care spending between African countries, with poorer countries tending to do worse than wealthier ones. From 1990-96, the median annual per capita government expenditure on health was nearly US$ 6, but averaged US$ 3 in the lowest-income countries, compared to US$ 72 in middle-income countries. Similar trends were found for health services and outcomes. Results from individual countries (particularly Ethiopia, Ghana, Côte d'Ivoire and Gabon) are used to indicate how the data can be used to identify areas of improvement in health system performance. Serious gaps in data, particularly concerning private sector delivery and financing, health service utilization, equity and efficiency measures, hinder more effective health management. Nonetheless, the data are useful for providing benchmarks for performance and for crudely identifying problem areas in health systems for individual countries.

Fludarabine. An update of its pharmacology and use in the treatment of haematological malignancies.

Fludarabine is an antineoplastic agent which has been studied in patients with a variety of lymphoproliferative malignancies. Clinical evidence from comparative studies in chronic lymphocytic leukaemia (CLL) suggests that fludarabine is at least as effective as CAP (cyclophosphamide, doxorubicin and prednisone) or CHOP (cyclophosphamide, vincristine, doxorubicin and prednisone) in previously treated or chemotherapy-naive patients and significantly more effective than chlorambucil in terms of response rate and duration and survival in chemotherapy-naive patients. Promising results have also been reported with fludarabine-based combination therapy in the treatment of patients with CLL. In addition, sequential therapy with fludarabine and cytarabine has demonstrated good efficacy in the treatment of acute leukaemias, as has fludarabine monotherapy and combination therapy in low grade non-Hodgkin's lymphoma. A favourable cytoreductive response has been reported in patients with lymphoplasmacytoid lymphoma and in a smaller number of patients with cutaneous T cell lymphomas, CLL of T cell origin or prolymphocytic leukaemia. Recent data also support the use of fludarabine, either as a component of a nonmyeloablative conditioning regimen or in the attainment of minimal residual disease, in patients undergoing peripheral blood stem cell or bone marrow transplantation. The tolerability profile of fludarabine is similar to that of CAP, with the most common adverse events being granulocytopenia, thrombocytopenia, anaemia and infection. Alopecia and nausea/vomiting appear to be less frequent with fludarabine therapy than with CAP although the development of immune cytopenias is more frequent with fludarabine. Severe neurotoxicity has been reported with fludarabine but this is mostly confined to the use of high doses. Clinical experience therefore indicates that fludarabine is an effective and generally well-tolerated antineoplastic agent for the second-line treatment of advanced CLL. Recent data from comparative studies also support the earlier use of fludarabine in the treatment of chemotherapy-naive patients with CLL. Furthermore, results of available studies are increasingly highlighting an important future role for fludarabine in the treatment of acute leukaemias and low grade NHL and possibly other lymphoproliferative disorders, particularly when used as a component of combination chemotherapy.

Zalcitabine. An update of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in the management of HIV infection.

Zalcitabine is a dideoxynucleoside antiretroviral agent that is phosphorylated to the active metabolite 2',3'-dideoxycytidine 5'-triphosphate (ddCTP) within both uninfected and HIV-infected cells. At therapeutic concentrations, ddCTP inhibits HIV replication by inhibiting the enzyme reverse transcriptase and terminating elongation of the proviral DNA chain. The results of 3 large pivotal trials comparing zidovudine monotherapy with combination therapy have now clearly established that zalcitabine plus zidovudine combination with an improvement in viral load and CD4+ cell count compared with zidovudine monotherapy. More recently, clinical end-point and surrogate marker data have established the efficacy of zalcitabine in combination with the protease inhibitor saquinavir in zidovudine-experienced patients. Other studies have demonstrated the utility of zalcitabine in combination with ritonavir and the nucleoside analogue lamivudine. Importantly, early use of zalcitabine in the treatment sequence does not appear to limit the therapeutic efficacy of subsequent therapy with other nucleoside analogues such as lamivudine. Peripheral neuropathy is the most frequent dose-limiting adverse effect associated with zalcitabine therapy and is generally reversible on discontinuation of treatment. Stomatitis and mouth ulcers may occur frequently with zalcitabine therapy but tend to resolve with continuing treatment. Haematological toxicity, which is a common adverse effect associated with zidovudine, is reported infrequently with zalcitabine. Overall, combination therapy with zalcitabine plus zidovudine or saquinavir has been shown to have a tolerability profile comparable to that of either agent alone, although treatment with zidovudine plus zalcitabine was associated with a significant increase in the incidence of haematological toxicity compared with zidovudine monotherapy in one study. Therefore, current data suggest that zalcitabine is a useful antiretroviral agent for inclusion as a component of initial double combination therapy with zidovudine or as part of triple combination therapy including zidovudine plus a protease inhibitor in the management of patients with HIV infection.

Metformin. A review of its pharmacological properties and therapeutic use in non-insulin-dependent diabetes mellitus.

The biguanide metformin (dimethylbiguanide) is an oral antihyperglycaemic agent used in the management of non-insulin-dependent diabetes mellitus (NIDDM). It reduces blood glucose levels, predominantly by improving hepatic and peripheral tissue sensitivity to insulin without affecting the secretion of this hormone. Metformin also appears to have potentially beneficial effects on serum lipid levels and fibrinolytic activity, although the long term clinical implications of these effects are unclear. Metformin possesses similar antihyperglycaemic efficacy to sulphonylureas in obese and nonobese patients with NIDDM. Additionally, interim data from the large multicentre United Kingdom Prospective Diabetes Study (UKPDS) indicated similar antihyperglycaemic efficacy for metformin and insulin in newly diagnosed patients with NIDDM. Unlike the sulphonylureas and insulin, however, metformin treatment is not associated with increased bodyweight. Addition of metformin to existing antidiabetic therapy confers enhanced antihyperglycaemic efficacy. This may be of particular use in improving glycaemic control in patients with NIDDM not adequately controlled with sulphonylurea monotherapy, and may serve to reduce or eliminate the need for daily insulin injections in patients with NIDDM who require this therapy. The acute, reversible gastrointestinal adverse effects seen with metformin may be minimised by administration with or after food, and by using lower dosages, increased slowly where necessary. Lactic acidosis due to metformin is rare, and the risk of this complication may be minimised by observance of prescribing precautions and contraindications intended to avoid accumulation of the drug or lactate in the body. Unlike the sulphonylureas, metformin does not cause hypoglycaemia. Thus, metformin is an effective antihyperglycaemic agent which appears to improve aberrant plasma lipid and fibrinolytic profiles associated with NIDDM. Possible long term clinical benefits of this drug with regard to cardiovascular mortality and morbidity are not yet established but are being assessed in a major ongoing study. Since metformin does not promote weight gain or hypoglycaemia it should be considered first-line pharmacotherapy in obese patients with NIDDM inadequately controlled by nonpharmacological measures. Metformin appears similarly effective for the pharmacological management of NIDDM in nonobese patients.

Fleroxacin. A review of its pharmacology and therapeutic efficacy in various infections.

The fluoroquinolone antibacterial agent fleroxacin has a broad spectrum of in vitro activity which encompasses most Gram-negative species (particularly Enterobacteriaceae) and a number of Gram-positive organisms, including methicillin-sensitive staphylococci. It is available as oral and intravenous formulations. In clinical trials, fleroxacin has been evaluated in the treatment of uncomplicated urinary tract infections (single or multiple once-daily oral doses of 200 or 400mg), gonorrhoea and chancroid (single oral doses of 200 or 400mg), complicated urinary tract, nonpneumococcal lower respiratory tract and skin and soft tissue infections and typhoid fever (multiple once-daily oral or intravenous regimens, usually 400 mg/day), bacterial enteritis, and traveller's diarrhoea (single or multiple once-daily oral doses of 400mg). Bacteriological cure rates were generally around 90% or higher in complicated and uncomplicated urinary tract infections, uncomplicated gonorrhoea (approximately 100%), pyelonephritis, bacterial enteritis and typhoid fever, and exceeded 80% in lower respiratory tract, and skin and soft tissue infections and chancroid. These cure rates were similar to, or better than, those achieved with standard comparator antibacterial agents such as penicillins, cephalosporins, cotrimoxazole, or other quinolones. Fleroxacin 400mg once daily also achieved bacteriological cure in approximately 80% of patients with bone and joint infections in preliminary studies. In Japanese studies using a lower dosage of 200 or 300 mg/day, fleroxacin was reported to be bacteriologically effective in a range of infections, including urinary tract and upper and lower respiratory tract infections. Fleroxacin has a relatively long elimination half-life, which allows once-daily administration, and it appears to have less propensity for interactions with other medications in comparison to many other fluoroquinolones. Its tolerability profile is typical of this class of compound, with adverse events mostly relating to the gastrointestinal tract, CNS, and skin and appendages (including phototoxicity). Recent pooled tolerability data from worldwide clinical trials indicate that adverse events are reported by approximately 27% of patients receiving 200 mg/day orally or 400 mg/day orally or intravenously, and 17% of those receiving a single oral dose of 400mg. These exceed incidences reported for established fluoroquinolones, possibly indicating recent trends towards increased rates of reported adverse effects with these agents. However, in direct comparative studies with twice-daily fluoroquinolones, fleroxacin 400mg once daily produced a similar incidence of adverse effects to ofloxacin 800 mg/day and a slightly higher incidence than ciprofloxacin 1000 mg/day, while fleroxacin 200mg once daily produced a similar incidence to norfloxacin 800 mg/day.(ABSTRACT TRUNCATED AT 400 WORDS)

Salmeterol. An appraisal of its quality-of-life benefits and potential pharmacoeconomic positioning in asthma.

Salmeterol is a selective beta 2-receptor agonist with a long duration of action that permits twice daily administration. It is effective in the prophylaxis of asthma symptoms, including nocturnal and exercise-induced asthma, and it has shown clinical benefits in both adults and children. Because of its slow onset of action, salmeterol is not intended for relief of acute symptoms. The addition of salmeterol 50 micrograms twice daily to existing asthma therapy has a positive effect on patient quality of life in the short term (up to 3 months), as assessed by the Living With Asthma Questionnaire and Asthma Quality of Life Questionnaire. This improvement in well-being appears to be greater than that associated with salbutamol (albuterol). Furthermore, in patients with asthma symptoms despite inhaled corticosteroid therapy, a reduced dose of corticosteroid plus salmeterol produced a greater improvement in quality of life as assessed by a daily symptom diary (but not by the Living With Asthma Questionnaire), and was more clinically effective than a higher dose of corticosteroid alone. Evaluation of the effects of salmeterol on quality of life compared with other standard therapies, and extension of these results into the long term are required to consolidate these conclusions. Salmeterol 50 micrograms twice daily was associated with an estimated incremental cost of 736 pounds per symptom-free patient in the final week of 7.5 months' therapy, 648 pounds per patient with improved morning (am) peak expiratory flow rate (PEFR) and 1013 pounds per patient with improved evening (pm) PEFR compared with salbutamol (400 micrograms twice daily) in a cost-effectiveness analysis. However, these results should be tested by sensitivity analyses and compared with the incremental costs of other asthma interventions more applicable to recommended clinical practice. The cost effectiveness of salmeterol relative to other asthma therapies, and the effect of salmeterol on patient quality of life in the long term require further investigation. However, when added to existing asthma therapy, salmeterol improves patient quality of life in the short term (up to 3 months). It may also have some beneficial effects on patient well-being when used to provide a steroid-sparing effect.

Ceftazidime. An update of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy.

Ceftazidime is a third generation cephalosporin antibacterial agent which, since its introduction in the early 1980s, has retained a broad spectrum of in vitro antimicrobial activity and clinical utility in serious infections. However, increasing resistance to ceftazidime and other third generation cephalosporins, particularly among Enterobacteriaceae, due to the emergence of plasmid-mediated extended spectrum beta-lactamases and the class I chromosomally mediated beta-lactamases, is of concern. There is now a wealth of information on the pharmacokinetics of the drug. enabling ceftazidime to be used predictably, and with a low potential for adverse effects, in a diversity of patient populations. Overall, ceftazidime remains an effective agent for the treatment of serious infection, particularly those due to major nosocomial pathogens, and respiratory infections in patients with cystic fibrosis. Ceftazidime-containing regimens also remain an important option for the empirical therapy of febrile episodes in neutropenic patients. The tolerability profile of ceftazidime makes the drug a useful option in seriously ill patients who are at risk of developing adverse events with other antibacterial agents. Although patterns of bacterial resistance have changed in the ensuing years since its introduction, judicious use of this important agent will help maintain its present clinical utility.

Enoxaparin. A reappraisal of its pharmacology and clinical applications in the prevention and treatment of thromboembolic disease.

Enoxaparin (enoxaparin sodium) is a low molecular weight derivative of unfractionated heparin which has been evaluated for the treatment and prevention of thromboembolic disease. Since a previous review in Drugs, well controlled clinical trials have confirmed the effectiveness of enoxaparin as prophylaxis in patients with a high risk for deep venous thrombosis (DVT), i.e. those undergoing hip or knee replacement surgery. Enoxaparin 30mg twice daily, initiated postoperatively, offers an overall balance of prophylactic efficacy and haemorrhagic tolerability which is superior to that of unfractionated heparin. In comparative clinical trials, this dosage demonstrated either improved efficacy and a similar haemorrhagic profile, or a similar degree of efficacy with a lower rate of haemorrhagic events, compared with unfractionated heparin 5000IU 3 times daily. Limited data indicate that an enoxaparin regimen of 40mg once daily, starting preoperatively, is more effective than unfractionated heparin in patients undergoing hip replacement and has a comparable haemorrhagic profile. In patients with a moderate risk for DVT, enoxaparin is similar to unfractionated heparin in both efficacy and haemorrhagic profile, while preliminary investigations have demonstrated the utility of enoxaparin in the prevention of DVT in elderly, nonsurgical patients. Enoxaparin may also be useful for the treatment of existing DVT and as an anticoagulant in haemodialysis. Thus, enoxaparin is an effective form of prophylaxis for thromboembolic disease in moderate to high risk surgical situations. Recent evidence for improved efficacy, together with a similar incidence of haemorrhagic complications in most situations, may lead to enoxaparin being preferred to unfractionated heparin for the routine prevention of DVT after high risk surgery. Although detailed comparisons with other low molecular weight heparins and antithrombotic agents are required before its relative clinical utility can be fully assessed, enoxaparin is likely to play a significant role in the prophylaxis of thromboembolic disorders.

Ramipril. An updated review of its therapeutic use in essential hypertension and heart failure.

Ramipril is a second generation angiotensin converting enzyme (ACE) inhibitor. Like enalapril, it is a prodrug and is hydrolysed in vivo to release the active metabolite, ramiprilat, which has a long elimination half-life, permitting once-daily administration. The antihypertensive efficacy of ramipril has been confirmed in large-scale noncomparative studies conducted in general practice as well as in more rigorously controlled clinical trials. In the former, approximately 85% of patients with mild to moderate essential hypertension have responded successfully to treatment with ramipril 2.5 or 5 mg/day, while comparative trials indicate that the antihypertensive efficacy of the drug is equivalent to that of other established ACE inhibitors and the beta-adrenoceptor antagonist atenolol. As expected, the response rate to ramipril monotherapy is lower in patients with severe hypertension (around 40%), although the blood pressure lowering effect can be enhanced with the addition of a diuretic such as hydrochlorothiazide or piretanide. The antihypertensive efficacy of ramipril is maintained in patients with diabetes mellitus and preliminary data indicate that the drug has the beneficial effect of decreasing urinary albumin excretion in diabetic patients with nephropathy. Ramipril is superior to atenolol in causing regression of left ventricular hypertrophy, although the clinical significance of this effect per se remains to be established. The large-scale Acute Infarction Ramipril Efficacy (AIRE) study demonstrated that ramipril 5 or 10 mg/day significantly decreased the risk of all-cause mortality by 27% in patients with clinical evidence of heart failure after acute myocardial infarction, even if transient. The beneficial effect of ramipril was apparent by 30 days of treatment and appeared to be greatest in patients with more severe ventricular damage after infarction. Ramipril is well tolerated in general practice, with 5% or fewer patients discontinuing therapy because of drug intolerance. The data available suggest that ramipril shares a similar tolerability profile to that of other established ACE inhibitors. Thus, clinical data confirm ramipril as a useful alternative ACE inhibitor for the treatment of patients with mild to moderate hypertension, and indicate a beneficial effect of the drug in patients with clinical evidence of heart failure after acute myocardial infarction. It is also reasonable to assume that ramipril will be of value in the treatment of patients with more established heart failure or asymptomatic left ventricular dysfunction.

Dirithromycin. A review of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy.

Dirithromycin is a new macrolide with a spectrum and degree of in vitro antimicrobial activity similar to that of erythromycin. Compared with erythromycin, dirithromycin has a long elimination half-life enabling once-daily administration, and it also achieves a greater cellular:extracellular concentration ratio and higher concentration in some tissues. Multicentre double-blind clinical trials have shown dirithromycin to be similar in efficacy to erythromycin in the treatment of uncomplicated bacterial infections of the respiratory tract and of skin and soft tissues. Since dirithromycin is at least as well tolerated as erythromycin, with its convenient administration schedule and pharmacokinetic profile it is a useful alternative to erythromycin in the treatment of appropriate community-acquired infections. Definition of the place of dirithromycin relative to that of the other newer macrolides awaits the results of further suitably designed therapeutic trials.

Loratadine. A reappraisal of its pharmacological properties and therapeutic use in allergic disorders.

Loratadine is a long-acting antihistamine agent, exhibiting partial selectivity for peripheral histamine H1-receptors. To date, loratadine has been evaluated in allergic rhinitis, urticaria and, to a limited extent, in asthma. In several large controlled comparative clinical studies, loratadine was superior to placebo, faster acting than astemizole and as effective as azatadine, cetirizine, chlorpheniramine (chlorphenamine), clemastine, hydroxyzine, mequitazine and terfenadine in patients with allergic rhinitis and chronic urticaria. The clinical effectiveness of loratadine in asthma is at present unclear. Loratadine is well tolerated. At dosages of 10 mg daily, commonly reported adverse events were somnolence, fatigue and headache. Sedation occurred less frequently with loratadine than with azatadine, cetirizine, chlorpheniramine, clemastine and mequitazine. Serious ventricular arrhythmias, as reported with some other second generation histamine H1-receptor antagonists, have not been observed with loratadine to date. Thus, loratadine, with its attributes of once daily administration, fast onset of action and essentially nonsedating properties, would appear to be an appropriate first-line agent for the treatment of allergic rhinitis or urticaria.

Metoprolol: a pharmacoeconomic and quality-of-life evaluation of its use in hypertension, post-myocardial infarction and dilated cardiomyopathy.

Metoprolol is a beta 1-selective adrenoceptor antagonist that is widely used in several indications. A recent investigation has also highlighted a potential role for metoprolol in selected patients with idiopathic dilated cardiomyopathy. Pharmacoeconomic and quality-of-life data for metoprolol are limited to the areas of hypertension, post-myocardial infarction and idiopathic dilated cardiomyopathy. In these settings, metoprolol has shown beneficial effects on morbidity and mortality, or closely-related end-points. Controlled release formulations offer the potential to maximise the confirmed antihypertensive benefits of metoprolol by maintaining clinically effective plasma drug concentrations within a narrow range over a 24-hour interval between doses. Recent data support the use of controlled release metoprolol at the low dose of 50 mg/day. Metoprolol is at least as effective as many other antihypertensive drugs, although compared with thiazide diuretics at relatively high doses in the MAPHY (Metoprolol Atherosclerosis Prevention in Hypertensives) trial, metoprolol was associated with a more favourable effect on mortality. Pharmacoeconomic analysis, also based on the MAPHY trial, indicates that metoprolol is more cost effective than high dose thiazide diuretics in middle-aged men with mild to moderate hypertension. However, the advantage for beta-blockade in this trial is not supported by results of other studies, and the applicability of these data to current medical practice using lower thiazide doses is therefore questionable. Quality of life in patients with mild to moderate hypertension did not deteriorate in most investigations with metoprolol. Furthermore, quality of life was similar for controlled release metoprolol and atenolol. With conventional/matrix-based sustained release metoprolol, quality of life was less satisfactory than with lisinopril but was only marginally different from that with diltiazem (at lower than usual therapeutic doses). Nevertheless, these newer agents have no proven beneficial effect on mortality, and further studies are also warranted with controlled release metoprolol 50 mg/day. When administered post-myocardial infarction, conventional metoprolol was associated with significant improvements in quality of life and was cost saving over a 3-year period. Significant improvements in quality of life were also evident for metoprolol-treated patients with idiopathic dilated cardiomyopathy. In summary, available data support the continued extensive usage of metoprolol as treatment for hypertension and as therapy post-myocardial infarction. Pharmacoeconomic data supporting an advantage for metoprolol over high dose thiazides in hypertension needs further assessment in settings reflecting usual general practice approaches to managing patients with hypertension, while differences in quality of life between metoprolol and other antihypertensive agents appear to be marginal.(ABSTRACT TRUNCATED AT 400 WORDS)

Tiapride. A review of its pharmacology and therapeutic potential in the management of alcohol dependence syndrome.

Tiapride, an atypical neuroleptic agent, is a selective dopamine D2-receptor antagonist with little propensity for causing catalepsy and sedation. It shows preferential activity at receptors previously sensitised to dopamine and those located extrastriatally. Tiapride demonstrates antidyskinetic activity reflecting antidopaminergic actions, and also anxiolytic activity mediated by mechanisms that are poorly understood. Unlike the benzodiazepines, tiapride does not affect vigilance and has a low potential for interaction with alcohol (ethanol), and possibly for abuse. Tiapride facilitates management of alcohol withdrawal, but its use in patients at risk of severe reactions in acute withdrawal should be accompanied by adjunct therapy for hallucinosis and seizures. Since it may prove difficult to identify such patients and there is also a small risk of neuroleptic malignant syndrome (particularly with parenteral administration), the usefulness of tiapride in this setting is likely to be limited. Nevertheless, relative freedom from the complications associated with benzodiazepine therapy suggest a possible role for the drug in the treatment of individuals suitable for alcohol detoxification as outpatients. Preliminary clinical studies in alcoholic patients following detoxification have shown that tiapride ameliorates psychological distress, improves abstinence, and reduces drinking behaviour, and in the short term facilitates reintegration within society. These benefits were associated with reduced consumption of health care resources. However, the potential risk of tardive dyskinesia at the dosage employed (300 mg/day) requires evaluation and necessitates medical supervision. Thus, with its lack of adverse effects on vigilance and low propensity for interaction with alcohol and possibly for abuse, tiapride will probably find particular use in the management of alcoholic patients suitable for detoxification in an outpatient setting; and, if initial findings are confirmed in large well-designed trials, in the short term (< or = 6 months) therapy of reformed alcoholic patients under medical supervision.