Sufficiently important difference: expanding the framework of clinical significance.

BACKGROUND: It is generally agreed that randomized controlled trials should be powered to detect small but clinically significant treatment effects. Toward these ends, minimal important difference (MID) was proposed as a benchmark for designing trials and for interpreting health-related quality-of-life instrument scores. MID was defined in 1989 as "the smallest difference in score in the domain of interest which patients perceive as beneficial and which would mandate, in the absence of troubling side effects and excessive cost, a change in the patient's management." OBJECTIVE: 1) To expand the idea of minimal clinically important difference so as to take into account harms as well as benefits. 2) To propose concepts and methods with which to do so. SUMMARY: The authors define sufficiently important difference (SID) as the smallest amount of patient-valued benefit that an intervention would require to justify associated costs, risks, and other harms. As a means toward estimation of SID, the authors propose benefit-harm tradeoff methods, in which domains of benefit and harm are systematically traded off against each other and assessed in relation to the global decision of whether a treatment choice is worthwhile. Specific SID estimates can be used to power and interpret clinical trials or to inform health services research and/or public health policy. This article briefly describes the evolution of the important difference concept and outlines similarities and differences between MID and SID.     

The Cost-Utility of Sequential Adjuvant Trastuzumab in Women with Her2/Neu-Positive Breast Cancer: An Analysis Based On Updated Results from the HERA Trial

Background:  The efficacy of sequential adjuvant trastuzumab (aTZ) after chemotherapy in women with early-stage human epidermal growth factor-2 (HER2/neu)-positive breast cancer reported by the updated Herceptin Adjuvant (HERA) trial appears less favorable than originally reported. Based on these updated results, we estimated the cost-utility (CU) of sequential aTZ relative to chemotherapy alone in terms of incremental cost per quality-adjusted life-year (QALY) gained.
Methods:  A Markov model estimated incremental costs and outcomes of 12 months of aTZ after adjuvant chemotherapy in women with HER2/neu-positive breast cancer over a 25-year horizon. The model incorporated four broad health states (disease-free, local recurrence [LCR], distant recurrence [DCR], death), stratified with or without symptomatic cardiotoxicity. Baseline event rates and 3-year relative risk (RR = 0.75) were derived from the HERA trial. As the duration of the benefit remains uncertain, the analysis considered 5-year and 3-year duration of benefit in two scenarios. Costs and utility weights were from the literature. The analysis took a direct payer perspective, with costs reported in 2007 Canadian dollars. Costs and QALYs were discounted by 3% annually.
Results:  The mean CU of sequential aTZ at a 25-year horizon was $72,292 per QALY gained in the 5-year scenario and $127,862 per QALY gained in the 3-year scenario. Results were particularly sensitive to the magnitude and duration of carryover benefit.
Conclusions:  The CU of sequential aTZ is primarily dependent on the magnitude and duration of benefit. Further clinical research is required to establish the optimum sequence and duration of aTZ therapy and clarify the magnitude and duration of treatment benefit.     

A trial of ascorbic acid in the treatment of the common cold.

A randomised controlled trial was carried out to study the effect of 10 g of ascorbic acid taken during the first 2 1/2 days on the symptoms of the common cold. Altogether 1524 volunteers were recruited from a number of working groups in different parts of the country; 482 developed colds. There was no evidence that upper respiratory or general constitutional symptoms were alleviated by ascorbic acid. Among the men who had any colds at all, significantly fewer on active than on placebo treatment had two or more colds; however, this effect was not seen in women. Ascorbic acid is of no value in the treatment of the common cold; its preventive effect, if any, is not such as to justify advising its general use as a prophylactic measure.     

A trial of ascorbic acid in the treatment of the common cold.

A randomised controlled trial was carried out to study the effect of 10 g of ascorbic acid taken during the first 2 1/2 days on the symptoms of the common cold. Altogether 1524 volunteers were recruited from a number of working groups in different parts of the country; 482 developed colds. There was no evidence that upper respiratory or general constitutional symptoms were alleviated by ascorbic acid. Among the men who had any colds at all, significantly fewer on active than on placebo treatment had two or more colds; however, this effect was not seen in women. Ascorbic acid is of no value in the treatment of the common cold; its preventive effect, if any, is not such as to justify advising its general use as a prophylactic measure.     

A randomized controlled trial of vitamin C in the prevention and amelioration of the common cold.

A randomized controlled trial of the effect of 1 g ascorbic acid per day in the prevention of the common cold was conducted on 688 adult women. There is evidence of a small reduction by vitamin C in the mean number of chest colds, but no evidence of any effect on simple colds. The existence of a subgroup of vulnerable women in the community who benefit from vitamin C was considered but further examination of the data gives no support to this conclusion.     

Calling acute bronchitis a chest cold may improve patient satisfaction with appropriate antibiotic use

BACKGROUND: Overuse of antibiotics for acute respiratory infections is an important public health problem and occurs in part because of pressure on physicians by patients to prescribe them. We hypothesized that if acute respiratory infections are called "chest colds" or "viral infections" rather than "bronchitis," patients will be satisfied with the diagnosis and more satisfied with not receiving antibiotics. METHODS: Family medicine patients were presented with a written scenario describing a typical acute respiratory infection where they were given one of 3 different diagnostic labels: chest cold, viral upper respiratory infection, and bronchitis, followed by a treatment plan that excluded antibiotic treatment. Data was analyzed for satisfaction with the diagnosis and treatment plan based on the diagnostic label. A total of 459 questionnaires were collected. RESULTS: Satisfaction (70%, 63%, and 68%) and dissatisfaction (11% 13%, and 13%) with the diagnostic labels of cold, viral upper respiratory infection, and bronchitis, respectively, showed no difference (chi(2) = 0.368, P = .832). However, more patients were dissatisfied with not receiving an antibiotic when the diagnosis label was bronchitis. A total of 26% of those that were told they had bronchitis were dissatisfied with their treatment, compared with 13% and 17% for colds and viral illness, respectively, (chi(2) = 9.380, P = .009). Binary logistic regression showed no difference in satisfaction with diagnosis for educational attainment, age, and sex (odds ratio (OR) = 1.09, 1.00, 0.98, respectively), or for satisfaction with treatment (OR = 1.1, 1.02, 1.00, respectively). CONCLUSIONS: Provider use of benign-sounding labels such as chest cold when a patient presents for care for an acute respiratory infection may not affect patient satisfaction but may improve satisfaction with not being prescribed an antibiotic.     

Enhancing the comparability of costing methods: cross-country variability in the prices of non-traded inputs to health programmes

Background

Given the size of the HIV epidemic in South Africa and other developing countries, scaling up antiretroviral treatment (ART) represents one of the key public health challenges of the next decade. Appropriate priority setting and budgeting can be assisted by economic data on the costs and cost-effectiveness of ART. The objectives of this research were therefore to estimate HIV healthcare utilisation, the unit costs of HIV services and the cost per life year (LY) and quality adjusted life year (QALY) gained of HIV treatment interventions from a provider's perspective.

Methods

Data on service utilisation, outcomes and costs were collected in the Western Cape Province of South Africa. Utilisation of a full range of HIV healthcare services was estimated from 1,729 patients in the Khayelitsha cohort (1,146 No-ART patient-years, 2,229 ART patient-years) using a before and after study design. Full economic costs of HIV-related services were calculated and were complemented by appropriate secondary data. ART effects (deaths, therapy discontinuation and switching to second-line) were from the same 1,729 patients followed for a maximum of 4 years on ART. No-ART outcomes were estimated from a local natural history cohort. Health-related quality of life was assessed on a sub-sample of 95 patients. Markov modelling was used to calculate lifetime costs, LYs and QALYs and uncertainty was assessed through probabilistic sensitivity analysis on all utilisation and outcome variables. An alternative scenario was constructed to enhance generalizability.

Results

Discounted lifetime costs for No-ART and ART were US$2,743 and US$9,435 over 2 and 8 QALYs respectively. The incremental cost-effectiveness ratio through the use of ART versus No-ART was US$1,102 (95% CI 1,043-1,210) per QALY and US$984 (95% CI 913-1,078) per life year gained. In an alternative scenario where adjustments were made across cost, outcome and utilisation parameters, costs and outcomes were lower, but the ICER was similar.

Conclusion

Decisions to scale-up ART across sub-Saharan Africa have been made in the absence of incremental lifetime cost and cost-effectiveness data which seriously limits attempts to secure funds at the global level for HIV treatment or to set priorities at the country level. This article presents baseline cost-effectiveness data from one of the longest running public healthcare antiretroviral treatment programmes in Africa that could assist in enhancing efficient resource allocation and equitable access to HIV treatment.     

Cost-Based Price Calculation of Mexiletine for Nondystrophic Myotonia

ObjectivesMexiletine is a long-known drug used for the treatment of arrhythmias and repurposed in the 1980s for patients with nondystrophic myotonia (NDM). Recently, the price of mexiletine in Europe increased significantly after registration as an orphan drug for NDM. This led to international discussions on affordability and willingness to reimburse mexiletine in the absence of background information that would justify such a price. Our objective was to calculate a cost-based price for mexiletine for adult patients with NDM based on detailed information on development costs.MethodsWe calculated a fair price based on a cost-based pricing model for commercial mexiletine to treat adults with NDM using a recent European drug-pricing model as a framework to include actual costs incurred. Three scenarios were applied: 1 with minimum estimated costs, 1 with maximum estimated costs, and 1 with costs as if mexiletine was innovative.ResultsThe calculated fair price of mexiletine per patient per year (PPPY) is €452 for the minimum scenario and €1996 for the maximum scenario. By using hypothetical R&D costs used for innovative drugs, the price would be €6685 PPPY. In Europe, the list price of mexiletine ranges from €30 707-60 730 PPPY, based on 600 mg daily.ConclusionsThe current list price for mexiletine in Europe is manifold higher than any scenario of the cost-based models. Accounting for the reduced costs for clinical development in a repurposing scenario, the cost-based pricing model provides a fair commercial price range, which can be used as benchmark for pricing negotiations and/or reimbursement decisions.     

Evaluation of an alpha agonist alone and in combination with a nonsteroidal antiinflammatory agent in the treatment of experimental rhinovirus colds.

The pathogenesis of symptoms of the common cold and their optimal treatment are incompletely understood. To evaluate the role of an oral alpha agonist alone and in combination with a nonsteroidal anti-inflammatory drug in the treatment of experimental rhinovirus colds, 58 subjects were randomized to receive pseudoephedrine 60 mg alone, pseudoephedrine 60 mg plus ibuprofen 200 mg, or placebo, four times daily for 4 1/2 days beginning 30 hours after intranasal rhinovirus inoculation under double-blind conditions. The frequencies of infection, colds occurrence, and viral shedding did not differ significantly between the groups. Total symptom scores were reduced by 59% by pseudoephedrine plus ibuprofen (p less than 0.05) and 48% by pseudoephedrine alone compared with placebo. Nasal symptom scores tended to be lower in recipients of pseudoephedrine plus ibuprofen compared with pseudoephedrine alone (p = 0.09), but other parameters showed no significant treatment differences between the groups. Rhinorrhea, as determined by nasal secretion weights, was significantly reduced in both treatment groups compared to placebo. Nasal patency measurements tended to show the greatest improvement in recipients of pseudoephedrine plus ibuprofen. Therapy was clinically well tolerated. The results suggest that an oral alpha agonist is effective in modifying certain manifestations of experimental rhinovirus infection and that the addition of a nonsteroidal anti-inflammatory drug may provide additional benefit in nasal symptoms and patency. Studies involving large numbers of patients with natural colds are needed to determine the clinical significance of these findings.     

Immunoglobulins for primary or secondary immunodeficiency or for immunomodulation in neurological autoimmune diseases: insights from the prospective SIGNS registry

Aim

Outside the context of clinical trials, there is a lack of data on the management and long-term outcomes of patients with primary or secondary antibody deficiency (PID and SID), or those with neurological autoimmune diseases (AID) treated with immunoglobulins (IG).

Methods

SIGNS is a large-scale prospective observational cohort study with up to 550 patients in currently 50 sites throughout Germany. It investigates treatment patterns, effectiveness, quality of life and long-term outcomes of IG administered for PID, SID or AID. The study identifier at ClinTrials.Gov is NCT01287689.

Results

Of 306 patients currently included (1 Nov 2011), 108 had PID (49 children), 147 SID and 51 neurological AIDs. First symptoms had occurred 7.9 (PID children), 10.4 (PID adults), 5.5 (SID) and 7.2?years (AID) before entry, and disease duration since diagnosis was 4.8 (PID children), 7.0 (PID adults), 5.3 (SID) and 5.9?years (AID). Newly initiated IG therapy was reported in 45% (PID), 54% (SID) and 56% (AID). 13 different IG preparations were utilized at inclusion. In PID, only 25.0% of children and 24.1% of adults had no infection in the past 12?months; while 3 serious bacterial infections (1 meningitis, 2 pneumonia) were reported in children, and 1 in adults. With respect to AID, 21 patients had chronic inflammatory demyelinating polyneuropathy (CIDP), 7 had multifocal motor neuropathy (MMN), 11 multiple sclerosis (MS), 6 myasthenia gravis, 2 myositis, 4 other (no cases of Guillain Barré Syndrome). Quality of life of patients in all groups was reduced as assessed by ED-5D and SF-36.

Conclusions

A broad spectrum of indications and IG preparations is documented in SIGNS. It is expected that the registry will contribute to optimization of therapy in this diverse patient population.     

Eliminating artificial trans fatty acids in Argentina: estimated effects on the burden of coronary heart disease and costs

Objective

To estimate the impact of Argentine policies to reduce trans fatty acids (TFA) on coronary heart disease (CHD), disability-adjusted life years (DALYs) and associated health-care costs.

Methods

We estimated the baseline intake of TFA before 2004 to be 1.5% of total energy intake. We built a policy model including baseline intake of TFA, the oils and fats used to replace artificial TFAs, the clinical effect of reducing artificial TFAs and the costs and DALYs saved due to averted CHD events. To calculate the percentage of reduction of CHD, we calculated CHD risks on a population-based sample before and after implementation. The effect of the policies was modelled in three ways, based on projected changes: (i) in plasma lipid profiles; (ii) in lipid and inflammatory biomarkers; and (iii) the results of prospective cohort studies. We also estimated the present economic value of DALYs and associated health-care costs of coronary heart disease averted.

Findings

We estimated that projected changes in lipid profile would avert 301 deaths, 1066 acute CHD events, 5237 DALYs and 17 million United States dollars (US$) in health-care costs annually. Based on the adverse effects of TFA intake reported in prospective cohort studies, 1517 deaths, 5373 acute CHD events, 26 394 DALYs and US$ 87 million would be averted annually.

Conclusion

Even under the most conservative scenario, reduction of TFA intake had a substantial effect on public health. These findings will help inform decision-makers in Argentina and other countries on the potential public health and economic impact of this policy.     

Rhinovirus infections in an isolated antarctic station. Transmission of the viruses and susceptibility of the population

It is commonly believed that living in polar isolation causes high susceptibility to respiratory illness. At McMurdo Station, a US research base in Antarctica, we tested this belief by comparing, over 36 days (August 31-October 5, 1976), the incidence and severity of respiratory illness in 64 men finishing six months isolation and in 136 men just arrived from the United States. The colds in the two intermingled populations were essentially equivalent. Forty-three per cent of the newcomers and 39% of the wintering group reported colds; symptoms and duration were nearly identical between the two populations. Movement of the colds was slow. The newcomers brought in 31 colds; subsequently, only 52 evenly spaced illnesses arose. Incidence of respiratory illness was twice higher in the smaller living units than in the spacious main dormitory. Two nontypable rhinoviruses, McMurdo 4 and McMurdo 88, were brought in by the new population and were the only viruses isolated. Only McMurdo 88 spread, although more than 65% of the men were antibody-free (less than 1:3) to either agent. McMurdo 88 caused an estimated 60% of antarctic-contracted colds. In brief, this isolated polar group was not especially susceptible to respiratory illness, and virus movement through the group was deliberate.     

Effect of vitamin C on common cold: randomized controlled trial

OBJECTIVE: To investigate the relationship between the common cold and vitamin C supplementation. DESIGN: A double-blind, 5-year randomized controlled trial. SETTING: A village in Akita prefecture, one of the regions in Japan with the highest mortality from gastric cancer. SUBJECTS: Participants in annual screening programs for circulatory diseases conducted under the National Health and Welfare Services Law for the Aged, and diagnosed as having atrophic gastritis. Of the 439 eligible subjects, 144 and 161 were assigned to receive 50 or 500 mg of vitamin C, respectively, after protocol amendment. During the supplementation phase, 61 dropped out, and 244 completed the trial. Intervention: Daily vitamin C supplementation of 50 mg (low-dose group) or 500 mg (high-dose group). RESULTS: Total number of common colds (per 1000 person-months) was 21.3 and 17.1 for the low- and high-dose groups, respectively. After adjustment for several factors, the relative risks (95% confidence interval (CI)) of suffering from a common cold three or more times during the survey period was 0.34 (0.12-0.97) for the high-dose group. No apparent reduction was seen for the severity and duration of the common cold. CONCLUSION: A randomized, controlled 5-year trial suggests that vitamin C supplementation significantly reduces the frequency of the common cold but had no apparent effect on the duration or severity of the common cold. However, considering several limitations due to protocol amendment, the findings should be interpreted with caution.     

Parental preferences for rotavirus vaccination in young children: A discrete choice experiment

Objective

This study aimed to identify characteristics that affect parental decisions about rotavirus vaccination, to determine the relative importance of those characteristics and subsequently to estimate vaccination coverage for different implementation strategies.

Methods

A Discrete choice experiment (DCE) questionnaire was sent to the parents of 1250 newborns aged 6 weeks (response rate 37.3%). Mixed-logit models were used to estimate the relative importance of the five included rotavirus vaccine and implementation characteristics; vaccine effectiveness, frequency of severe side effects, protection duration, the healthcare facility that administrates vaccination and out-of-pocket costs. Based on the utility functions of the mixed-logit model, the potential vaccination coverage was estimated for different vaccine scenarios and implementation strategies.

Results

All characteristics, except for healthcare facility that administrates vaccination, influenced parental willingness to vaccinate their newborn against rotavirus. Parents were willing to trade 20.2 percentage points vaccine effectiveness for the lowest frequency of severe side effects (i.e., 1 in 1,000,000) or 20.8 percentage points for a higher protection duration. Potential vaccination coverage ranged between 22.7 and 86.2%, depending on vaccine scenario (i.e., vaccine effectiveness and protection duration) and implementation strategy (i.e., out-of-pocket costs and healthcare facility that administrates vaccination).

Conclusions

When deciding about vaccination against rotavirus, parents are mostly driven by the out-of-pocket costs, vaccine effectiveness, protection duration, and frequency of severe side effects. The highest vaccination coverage is expected for a vaccine with high effectiveness and protection duration that is implemented within the current National Immunization Program context. Implementation of the same rotavirus vaccine in the free market will result in lowest coverage.     

Assessing the Cost Utility of Response-Guided Therapy in Patients with Chronic Hepatitis C Genotype 1 in the UK Using the MONARCH Model

Background

European guidelines advocate the measurement of on-treatment hepatitis C virus (HCV) RNA in order to determine optimal therapy duration (response-guided therapy [RGT]) in patients with rapid virological response (RVR) or delayed virological response (DVR). Treatment response is highly dependent upon the extent of liver fibrosis yet there is little evidence quantifying the cost effectiveness of RGT particularly conditional upon fibrosis stage.

Objective

This study describes an economic model designed to assess the costs and benefits of RGT compared with standard duration of therapy (SDT) in hepatitis C virus genotype 1 patients.

Methods

A Markov cohort simulation model with lifetime perspective was developed to undertake a cost utility analysis of RGT in the UK. Patients entered the model at Metavir disease stages F0–F4, and progressed through these stages via age and duration of HCV infection-dependent transition probabilities. Treated patients were partitioned according to virological response and shortened or extended duration of therapy was applied following European guidelines.

Results

For all patients, SDT and RGT was associated with an increase of 2.14 and 2.20 QALYs and £2,374 and £2,270 costs, respectively, compared with no treatment. Overall, RGT was a dominant scenario being associated with a lower risk of complications, increased QALYs (0.08) and cost saving (£101). RGT across fibrosis stages was either highly cost effective or dominant; in all cases RGT was associated with an increase in QALYs, driven by a reduction in complications in DVR subjects and reduced exposure to treatment disutility in RVR subjects; costs were lower in F1 and F2 fibrosis stages. At a willingness-to-pay threshold of £20,000 per QALY, overall RGT across fibrosis stages F2–F4 were associated with the highest probability of being cost effective. At this threshold, the probability of reduced/extended therapy in RVR/DVR patients being cost effective is 0.35 and 0.88, respectively.

Conclusions

This analysis suggests that the treatment of HCV genotype 1 patients in fibrosis stage F2 has the greatest potential for maximizing health benefit and cost saving within an RGT protocol. Predicting those patients most likely to respond to treatments is important from both a clinical and cost perspective and the tailoring of treatment duration with the current standard of care is likely to remain a priority for payers with budgetary constraints.     

Mother's willingness to pay for her own and her child's health: a contingent valuation study in Taiwan

We use the contingent valuation (CV) method to estimate mothers' willingness to pay (WTP) to protect themselves and their children from suffering a minor illness-a cold-in Taiwan. WTP is specified as a hedonic function of the duration and severity of the cold (measured alternatively by symptoms experienced and the Quality of Well-Being (QWB) index) and of respondents' socioeconomic characteristics. The average mother is willing to pay more to protect her child than herself from suffering a cold. Median WTP to avoid the average mother's and child's colds are US$37 and US$57, respectively. Adjusting for the greater duration and severity of the average mother's cold suggests that WTP to prevent comparable illnesses is approximately twice as large for the child as for the mother. We also find that mother's WTP is about 20% greater to prevent a son's than a daughter's illness.     

Oral cancer treatment costs in Greece and the effect of advanced disease

Background

The main purpose of the study was to quantify the direct costs of oral cancer treatment to the healthcare system of Greece. Another aim was to identify factors that affect costs and potential cost reduction items. More specifically, we examined the relationship between stage of disease, modality of treatment and total direct costs.

Methods

The medical records and clinic files of the Oral and Maxillofacial Clinic of the Athens General Hospital "Genimatas" were abstracted to investigate clinical treatment characteristics, including length of hospitalization, modes of treatment, stage of disease etc. Records of 95 patients with oral squamous cell carcinoma (OSSC), with at least six months of follow-up, were examined. The clinical data was then used to calculate actual direct costs, based on 2001 market values.

Results

The mean total direct costs for OSSC treatment estimated at euro 8,450 or approximately US$ 7,450. Costs depended on the stage of the disease, with significant increases in stages III and IV, as compared with stages I and II (p < 0.05). Multi-modality treatment applied mainly to patients in stages III and IV was the factor that affected the cost. Disease stage was also associated with the total duration of hospitalization (p < 0.05).

Conclusions

The clinical management of advanced oral cancer is strongly associated with higher costs. Although the ideal would be to prevent cancer, the combination of high-risk screening, early diagnosis and early treatment seems the most efficient way to reduce costs, and most importantly, prolong life.     

Cost Effectiveness of Paliperidone Palmitate for the Treatment of Schizophrenia in Germany

Background

Treatment with antipsychotic medication is an important element of relapse prevention in the management of schizophrenia, and can reduce inpatient stays. Recently, the long-acting atypical antipsychotic paliperidone long-acting injectable (PLAI), a once-monthly LAI antipsychotic, was approved for treatment of schizophrenia in Germany.

Objective

To estimate, based on a previously published model, the cost effectiveness of PLAI compared with other common antipsychotic treatment strategies in patients diagnosed with schizophrenia in Germany.

Methods

A Markov decision analytic model was adapted to the German healthcare system. The model considers the cost effectiveness for PLAI as a maintenance treatment for patients with schizophrenia from the payer perspective. The patients transition between eight health states on a monthly basis over a 5-year time horizon. As therapeutic strategies, PLAI, quetiapine, risperidone long-acting injections (RLAI), oral olanzapine, oral risperidone, zuclopenthixol decanoate, olanzapine long-acting injections (OLAI), oral typical and oral atypical were compared. Probability of relapse, level of adherence, side effects and treatment discontinuation were derived from the Swedish original model. Input factors regarding resource use and costs were estimated and adjusted for the German healthcare system. A probabilistic sensitivity analyses (PSA) using cost-effectiveness scatter plots was performed to visualize the robustness of the results.

Results

In base-case scenario, PLAI is superior to RLAI in gained quality-adjusted life-years (QALYs) and avoided relapses. Relative to all other treatment strategies, PLAI is more effective with regard to gained QALYs and avoided relapses but results in higher treatment costs over a 5-year horizon in base-case scenario. The results were tested in PSA. If a cost-effectiveness threshold of €30,000 is assumed, for example, PLAI can be considered to be cost effective compared with RLAI in about 92.5 % of cases regarding gained QALYs, and in 78.6 % of cases regarding avoided relapse. Compared with OLAI, in about 94.4 % of cases regarding gained QALYs and in 99.9 % of cases regarding avoided relapse, cost effectiveness can be considered. Comparing PLAI and zuclopenthixol decanoate, cost effectiveness can be assumed in about 90.4 % of cases regarding gained QALYs, and in all cases regarding avoided relapse.

Conclusions

PLAI dominates RLAI and compared with the other treatment strategies PLAI has shown to be more effective but results in higher costs in base-case scenario.     

The common cold in patients with a history of recurrent sinusitis: increased symptoms and radiologic sinusitislike findings

BACKGROUND: We evaluated whether the symptoms and signs and radiologic findings during a common cold are similar in patients who have and have not suffered from recurrent sinusitis. METHODS: We recruited 2 series of volunteer cases from February 1, 1996, to December 31, 1996. Twenty-three adults who claimed to have suffered from recurrent sinusitis and 25 who had never had sinusitis were examined during the period of a self-diagnosed cold of 48 to 96 hours' duration and again after 21 days. Symptom scores were recorded, nasoendoscopy and computed tomography scans were performed, and viral and bacterial specimens were taken. RESULTS: The patients with a history of sinusitis had significantly higher symptom scores than the control patients (P=.04) and had radiologic sinusitislike changes more often (65% [15] vs 36% [9]; difference 29% [95% confidence interval, 2%-56%]; P=.04). The viral etiology of the common cold (verified in 67% of the episodes) was similar in both groups. Pathogenic bacteria were isolated from the middle meatus in 24% (6) of the control patients and only 9% (2) of the sinusitis-prone patients (P=.15). On the basis of the symptomatology, radiologic findings, and bacterial cultures only 2 patients in the sinusitis-prone group should have been treated with antimicrobials. CONCLUSIONS: Some patients are susceptible to both sinusitislike symptoms and radiologic findings during viral common colds. This may cause them to consult their physicians earlier and more often during viral colds, which may result in unnecessary antibiotic treatments. Nasopharyngeal bacteriological cultures may prove to be useful in ruling out bacterial sinusitis.