Associations of metabolic syndrome and diabetes mellitus with 16-year survival after CABG.

BACKGROUND: The associations of metabolic syndrome (MetS) or diabetes mellitus (DM) on long-term survival after coronary artery bypass grafting (CABG) have not been extensively evaluated. The aim of the present study was to assess the impact of MetS and DM on the 16-year survival after CABG. METHODS: Diabetic and metabolic status together with relevant cardiovascular data was established in 910 CABG patients operated in 1993-94. They were divided in three groups as follows: neither DM nor MetS (375 patients), MetS alone (279 patients) and DM with or without MetS (256 patients). The 16-year follow-up of patient survival was carried out using national health databases. The relative survival rates were analyzed using the Life Table method comparing the observed survival rates of three patient groups to the rates based on age-, sex- and time-specific life tables for the whole population in Finland. To study the independent significance of MetS and DM for clinical outcome, multivariate analysis was made using an optimizing stepwise procedure based on the Bayesian approach. RESULTS: Bayesian multivariate analysis revealed together six variables to predict clinical outcome (2 months to 16 years) in relation to the national background population, i.e. age, diabetes, left ventricular ejection fraction, BMI, perfusion time during the CABG and peripheral arterial disease. Our principal finding was that after postoperative period the 16-year prognosis of patients with neither DM nor MetS was better than that of the age-, sex-and time-matched background population (relative survival against background population 1.037, p < 0.0001). The overall survival of MetS patients resembled that of the matched background population (relative survival 0.998, NS). DM was associated with significantly increased mortality (relative survival 0.86, p < 0.0001). Additionally, mortality was even higher in patients receiving insulin treatment than in those without. Excess death rate of DM patients was predominantly caused by cardiovascular causes. CONCLUSION: In this long-term follow-up study patient groups without diabetes had at least equal 16 years' survival after CABG than their matched background populations. Survival of DM patients started to deteriorate already few years after the operation.

Development of renal cell carcinoma (RCC) diagnostics and impact on prognosis.

OBJECTIVE: To evaluate imaging methods and prognoses between small renal cell carcinomas (RCCs) and larger tumours according to the era of diagnostics. PATIENTS AND METHODS: In all, 784 consecutive patients diagnosed with RCC between 1964 and 1997 at the Pirkanmaa Hospital District in Finland were included. Patients were divided into two groups: tumours of ≤3.0 and >3.0 cm in diameter. Prognosis was analysed according to the era of diagnostics: (i) pre-computed tomography (CT) and pre-ultrasound (US), (ii) US era and (iii) CT era. RESULTS: Small tumours became more common: in the pre-CT and pre-US era, only 4.4% of tumours were small; however, in the CT era 16% were small tumours. More diagnostic methods were used in studying small tumours. CT proved to be the most reliable method, although it was actually better at diagnosing large tumours. Relapses occurred less frequently among patients with small tumours; more than half of the tumours that developed distant metastases (16.0%) already evinced them at the time of diagnosis. There were no relapses after 14 years of follow-up among small tumours, whereas large tumours relapsed within that time. RCC was the cause of death in 14.9% of patients with small tumours vs 50.7% with large tumours. The best prognosis was among patients with small tumours diagnosed with CT. CONCLUSION: Among patients with small tumours, prognosis has improved along with better diagnostics, although some showed relapse during a surveillance period of up to 14 years.

Prognostic accuracy of five simple scales in childhood bacterial meningitis.

BACKGROUND: In childhood acute bacterial meningitis, the level of consciousness, measured with the Glasgow coma scale (GCS) or the Blantyre coma scale (BCS), is the most important predictor of outcome. The Herson-Todd scale (HTS) was developed for Haemophilus influenzae meningitis. Our objective was to identify prognostic factors, to form a simple scale, and to compare the predictive accuracy of these scales. METHODS: Seven hundred and twenty-three children with bacterial meningitis in Luanda were scored by GCS, BCS, and HTS. The simple Luanda scale (SLS), based on our entire database, comprised domestic electricity, days of illness, convulsions, consciousness, and dyspnoea at presentation. The Bayesian Luanda scale (BLS) added blood glucose concentration. The accuracy of the 5 scales was determined for 491 children without an underlying condition, against the outcomes of death, severe neurological sequelae or death, or a poor outcome (severe neurological sequelae, death, or deafness), at hospital discharge. RESULTS: The highest accuracy was achieved with the BLS, whose area under the curve (AUC) for death was 0.83, for severe neurological sequelae or death was 0.84, and for poor outcome was 0.82. Overall, the AUCs for SLS were ≥0.79, for GCS were ≥0.76, for BCS were ≥0.74, and for HTS were ≥0.68. CONCLUSIONS: Adding laboratory parameters to a simple scoring system, such as the SLS, improves the prognostic accuracy only little in bacterial meningitis.

Patient-specific factors affecting survival following hip fractures-a 14-year follow-up study in Finland.

The mortality of elderly hip fracture patients is high. Eighty-five percent of all patients were followed until death. The three most protective factors for 1-year survival were ASA class; BMI; and age, and the four most protective factors for 14-year survival were age; BMI; ASA class; and subtrochanteric fracture type. OBJECTIVE: Hip fractures are associated with increased mortality. The purpose of this study was to evaluate the protective preoperative factors regarding the survival of short-term (1 year) and long-term (14 years) follow-up in a hip fracture cohort in Finland. METHODS: A total of 486 patients, operated on in 2005 and 2006, were retrospectively evaluated. Survival was analyzed using Bayesian multivariate analysis and relative survival with the life table method. All patients were followed for a minimum of 14 years. RESULTS: We analyzed 330 women and 156 men, whose mean ages were 82.4 and 72.0 years, respectively. The overall mortality rate was 7% at 1 month, 22% at 12 months, and 87% at 14 years. Protective factors against mortality at 1 year were ASA class (1-3), BMI ≥ 20 kg/m2, age < 85 years, alcohol involvement, Alzheimer's disease, no comorbidities, certain operative methods, and female sex. Factors promoting survival at 14 years were age < 75 years, BMI ≥ 20 kg/m2, ASA class (1-2), subtrochanteric fracture, certain operative methods, alcohol involvement, and no comorbidities. CONCLUSIONS: Protective factors for 1-year survival in order of importance were ASA class, BMI, and age, and, correspondingly, for 14-year survival, age, certain operative methods, BMI, and ASA class. The relative survival of hip fracture patients was lower than that of the general population.

Changes in symptoms of renal cell carcinoma over four decades.

OBJECTIVE: To determine whether there has been a change in typical symptoms of renal cell carcinoma (RCC), by evaluating the symptoms of patients diagnosed during four decades, as although the increasing incidence of a diagnosis of incidental RCC has been widely reported, the change in other symptoms has not. PATIENTS AND METHODS: The study included RCC cases diagnosed in the Pirkanmaa Hospital District between 1964 and 1997. The original medical records of 970 patients with 982 RCC tumours were analysed. Primary symptoms were recorded and changes were analysed in three groups, i.e. diagnoses made before 1980, in the 1980s and in the 1990s. Symptoms were also analysed according to stage, tumour class, gender and age. RESULTS: The incidence of haematuria (P < 0.01) and an increased erythrocyte sedimentation rate (P < 0.001) decreased, but there was no change in other symptoms. Incidental diagnoses increased from 12% to 19% (P < 0.01). Less chronic or systemic symptoms were noted more recently. Stage and tumour class were highly correlated with symptoms: systemic symptoms increased (24% in stage I to 72% in stage IV, a highly statistically significant increase) and asymptomatic tumours became rarer (27% in stage I to 8% in stage IV, again a highly significant increase) with increasing stage. Haematuria was more common in male patients, anaemia and flank pain in women. Elderly patients were more often asymptomatic than younger patients, with 70-79-year-olds being the least symptomatic. CONCLUSIONS: Incidental cases of RCC have recently become more common. Haematuria, hypersedimentation, chronic and systemic symptoms have decreased. Stage, tumour class, gender and age are correlated with symptoms.

Post-fracture prescribed calcium and vitamin D supplements alone or, in females, with concomitant anti-osteoporotic drugs is associated with lower mortality in elderly hip fracture patients: a prospective analysis.

BACKGROUND: Several studies have shown excess mortality among hip fracture patients compared with the normal population of the same age. Finnish guidelines for medical treatment of hip fracture patients recommend anti-osteoporosis medication and the daily concomitant use of prescribed calcium and vitamin D supplements. However, whether post-fracture use of calcium and vitamin D supplements is associated with survival in such patients has not been evaluated. OBJECTIVE: To study the association between survival in hip fracture patients and patients' sex and age, pre-fracture vitamin D status, American Society of Anesthesiologists - Physical Status (ASA-PS) class, type of fracture and post-fracture use of prescribed calcium plus vitamin D and anti-osteoporotic medication. METHODS: The study population was 221 hip fracture patients primarily treated in acute care for a new hip fracture in 2003-4 in two Finnish hospitals. After a median of 27.5 months from the fracture, a questionnaire was sent to all patients who were still alive at the time (n = 137). The patients were queried about their use of prescribed calcium plus vitamin D supplementation and of anti-osteoporotic drugs. The follow-up time for use of anti-osteoporotic medication and prescribed calcium and vitamin D was 19.5-36 months (median 27.5 months). Data on the use of prescribed calcium plus vitamin D supplementation and anti-osteoporotic drugs were checked against information on reimbursement of drug prescriptions held by the Finnish Social Insurance Institution. A total of 4 years' (48 months') survival data for all patients in the study population was also obtained, with the dates of patient deaths being checked against Official National and Regional population statistics. Patient survival was analysed using both the Bayesian multivariate analysis and the life table method. RESULTS: In the multivariate analysis, the combination of variables that best explained post-fracture survival was as follows: age <80 years; ASA-PS class 1-2 (ASA-PS class 1 and 2 data were combined in calculations); post-fracture use of prescribed calcium plus vitamin D supplements concomitantly with anti-osteoporotic drugs; post-fracture use of prescribed calcium plus vitamin D supplements; post-fracture use of anti-osteoporotic drugs only; and type of fracture (femoral neck or subtrochanteric). This model correctly predicted 74% of cases. At 36 months, we observed a 36% reduction in deaths in females who used prescribed calcium plus vitamin D supplementation and a corresponding 43% reduction in males. Survival of females who used anti-osteoporotic drugs concomitantly was even greater (43% reduction in deaths) over the entire follow-up period. Excess mortality was highest in females and males who used neither anti-osteoporotic drugs nor prescribed calcium and vitamin D. CONCLUSION: Our results indicate a potential relationship between reduced mortality and post-fracture use of prescribed calcium plus vitamin D supplementation and, in females, concomitant use of anti-osteoporotic drugs. However, further investigations are needed to understand the reason for the reduction in the risk of death. Population-based, randomized, placebo-controlled trials with total mortality as the main endpoint should be conducted to verify our results.

Return to work after coronary artery bypass surgery. A 10-year follow-up study.

OBJECTIVES: To establish which factors influence patients' return to work and how well they remain at work after coronary artery bypass grafting (CABG). DESIGN: Five hundred and sixty nine consecutive CABG patients aged less than 65 years were followed for 10 years. Data were collected from patient records and by questionnaires supplemented with information from Finnish national archives. RESULTS: Multivariate analysis showed the best predictors for return to work to be younger age, preoperative working, as well as absence of diabetes or perioperative cardiac damage. Almost half of the patients aged less than 60 and preoperatively not retired were working one year after CABG. Five years postoperatively, 85% of patients younger than 60 years and once returned to work were still working. Correspondingly, of subjects remaining under 60 years during a 10-year follow-up, 75% continued working. CONCLUSIONS: Younger age and preoperative employment were the most important predictors of successful return to work. Once returned after CABG, patients' staying at work was comparable with that in the general population.

Prognostic factors and long-term survival in renal cell cancer patients.

OBJECTIVE: The long-term survival of renal cell cancer (RCC) patients is not reported in the recent literature. This study evaluated the significance of known clinical prognostic factors and long-term survival in a large centrally treated Finnish RCC population. MATERIAL AND METHODS: In 948 patients diagnosed between 1964 and 1997 the relative overall survival (OS) was calculated up to 25 years by Bayesian analysis and the life-table method. The effect of gender, age, cancer stage, TNM (tumour, node, metastasis) class, Fuhrman's grade, symptoms and year of diagnosis was studied. RESULTS: Women and patients aged 40-49 years had better survival. Stage, TNM class and grade proved relevant for prognosis. The relative 5-year overall survival was 88%, 63%, 65% and 15% in stages I-IV, respectively. Asymptomatic patients had better survival, their median survival being 8.1 years as against 9.1 years in patients with local symptoms and only 1.7 years in patients with systemic symptoms. The year of diagnosis was not significant in prognosis. CONCLUSIONS: The most important explanatory factors were stage, age and clinical presentation of the tumour. RCC patients showed diminishing overall survival in the follow-up, with no plateau; almost 57% of patients developed local recurrence or distant metastases even after a very long disease-free interval.

Obesity paradox disappears in coronary artery bypass graft patients during 20-year follow-up.

AIMS: Although obesity is a risk factor for coronary heart disease (CHD), it might be associated with a favourable prognosis in patients with CHD. The aim of the study was to evaluate this so called 'obesity paradox' during a follow-up period of 20 years in patients who had undergone coronary artery bypass grafting (CABG). METHODS AND RESULTS: The study population consisted of 922 CHD patients who had undergone CABG between 1993 and 1994. Pre and perioperative data was collected from patient records and supplemented with patient questionnaires, telephone contacts and data from national archives. The 10-year postoperative prognosis of normal-weight patients (body mass index (BMI) 18.5-24.9 kg/m2) was inferior to that of overweight (BMI 25.0-29.9 kg/m2) and obese patients (BMI⩾30.0 kg/m2) and to the background population. Beyond 10 years the prognosis of obese patients deteriorated when compared with the overweight group. At the end of the 20-year follow-up, survival of the normal weight group was 0.68 (95% confidence interval (CI), 0.49-0.87; p<0.001), the overweight group 0.82 (95% CI, 0.71-0.92; p<0.001), and the obese group 0.67 (95% CI, 0.49-0.85; p<0.001), when compared with their background populations (=1.00). Obese patients developed diabetes more frequently and died more frequently of cardiovascular disease than patients in the two other study groups during the second postoperative decade ( p<0.01). CONCLUSION: During long-term follow-up the obesity paradox seems to disappear due to progression of cardiometabolic disease in patients who have undergone CABG.

Use of benzodiazepines and benzodiazepine-related drugs among 223 patients with an acute hip fracture in Finland: Comparison of benzodiazepine findings in medical records and laboratory assays.

BACKGROUND AND OBJECTIVE: CNS drugs are a risk factor for falls and fractures among older people. Our aim was to describe the use of benzodiazepines and benzodiazepine-related drugs among patients admitted to two Finnish hospitals as a result of an acute hip fracture, and to analyse the concordance of benzodiazepine findings from different data sources. PATIENTS AND METHODS: We studied the use of benzodiazepines and benzodiazepine-related drugs by (i) asking the patient or his/her relatives about his/her use of hypnotics; (ii) checking the patient's medical records; and (iii) analysing for the presence of benzodiazepines in serum and urine. Blood and urine samples were taken at admission. Detection of benzodiazepines in serum and urine was achieved by the fluorescence polarisation method. Concordance in benzodiazepine findings between medical records and laboratory results was estimated by calculating the degree of agreement (kappa) and described graphically using a Venn diagram. RESULTS: A total of 223 patients were enrolled in the study. Of these, 71% were women. The mean age of women was 80.5 years (SD: 10) and of men, 73 years (SD: 12) [p < 0.0001]. Thirty percent of the patients reported that they used hypnotics. Benzodiazepine in serum or urine was detected in 83 (37%) patients. Over half of the patients coming from residential homes (53%) and institutions (54%) were benzodiazepine-positive. For home dwellers the proportion of patients that were benzodiazepine-positive was 29%. In 48% (40/83) of the benzodiazepine-positive patients, the type of benzodiazepine could not be identified because of a lack of drug records regarding benzodiazepines. A total of 113 (51%) patients used benzodiazepines or benzodiazepine-related drugs when both laboratory results and medical drug records were taken into account. Thirty-nine percent of these patients were home dwellers, 69% came from residential care and 76% from institutional care. The concordance between medical records and laboratory results expressed as overlap area was 32% in men and 59% in women, 38% in community-dwelling patients, 63% in residential home patients, and 68% in patients from institutions. CONCLUSION: Half of patients with an acute hip fracture used benzodiazepines or benzodiazepine-related drugs. The highest prevalences were found in institutional and residential care where it should be well known that the use of CNS drugs increases the risk of hip fracture. Concordance of benzodiazepine findings was moderate in all patients and poorest among men. Concordance was poorer among home dwellers than among those living in residential homes and institutions. Analysing benzodiazepine in serum seems to be the most reliable method for ascertaining benzodiazepine exposure. This laboratory test could be performed routinely when the elderly patient is admitted to hospital because of a fall or, at least, in case of hip fracture. Then, if needed, the patient should be informed about the risks of benzodiazepine use, and further falls and fractures could be prevented.

Positive Effects of a Sufficient Pre-fracture Serum Vitamin D Level on the Long-Term Survival of Hip Fracture Patients in Finland: A Minimum 11-Year Follow-Up.

BACKGROUND: Several studies have shown that the mortality of elderly hip fracture patients is higher than that in the general population, and is higher in male than in female hip fracture patients. OBJECTIVE: The objective of this study was to investigate factors affecting overall mortality at a minimum of 11 years following a new hip fracture. METHODS: The sex, age, pre-fracture serum 25-hydroxyvitamin D level, American Society of Anesthesiologists physical status classification (ASA class), 1- to 12-month mortality, and 2- to 11-year mortality of hip fracture patients were collected. The use of anti-osteoporotic medication and prescribed calcium and vitamin D supplements during the first 3 post-operative years were checked. The survival of the patients was analyzed using both the Bayesian multivariate analysis and the life table method. RESULTS: The mean age of females at the time of the index hip fracture was 80.5 years and of males was 73 years. The protective factors were age <80 years; ASA class 1-2; serum 25-hydroxyvitamin level ≥ 50 nmol/L; post-fracture use of calcium and vitamin D supplementation; post-fracture concomitant use of calcium and vitamin D supplementation and anti-osteoporotic drugs; and male sex. The excess mortality was higher among women than men. Survival was highest among patients with a vitamin D level of ≥ 50 nmol/L. Post-fracture concomitant use of calcium and vitamin D and anti-osteoporotic drugs was positively associated with survival. CONCLUSION: Our results indicate a positive relationship between a sufficient pre-fracture vitamin D serum concentration (≥ 50 nmol/L) and survival, and a potential relationship between reduced mortality and the concomitant post-fracture use of prescribed calcium plus vitamin D supplementation and anti-osteoporotic medication.

Performance of three preoperative risk indices; CABDEAL, EuroSCORE and Cleveland models in a prospective coronary bypass database.

OBJECTIVES: The aim of the present study was to evaluate the performance of three different preoperative risk models in the prediction of postoperative morbidity and mortality in coronary artery bypass (CAB) surgery. METHODS: Data on 1132 consecutive CAB patients were prospectively collected, including preoperative risk factors and postoperative morbidity and in-hospital mortality. The preoperative risk models CABDEAL, EuroSCORE and Cleveland model were used to predict morbidity and mortality. A C statistic (receiver operating characteristic (ROC) curve) was used to test the discrimination of these models. RESULTS: The area under the ROC curve for morbidity was 0.772 for the CABDEAL, 0.694 for the EuroSCORE and 0.686 for the Cleveland model. Major morbidity due to postoperative complications occurred in 268 patients (23.6%). The mortality rate was 3.4% (n=38 patients). The ROC curve areas for prediction of mortality were 0.711 for the CABDEAL, 0.826 for the EuroSCORE and 0.858 for the Cleveland model. CONCLUSIONS: The CABDEAL model was initially developed for the prediction of major morbidity. Thus, it is not surprising that this model evinced the highest predictive value for increased morbidity in this database. Both the Cleveland and the EuroSCORE models were better predictive of mortality. These results have implications for the selection of risk indices for different purposes. The simple additive CABDEAL model can be used as a hand-held model for preoperative estimation of patients' risk of postoperative morbidity, while the EuroSCORE and Cleveland models are to be preferred for the prediction of mortality in a large patient sample.

Dental maturity curves in Finnish children: Demirjian's method revisited and polynomial functions for age estimation.

Dental maturity was studied from 2213 dental panoramic radiographs of healthy ethnic Finns from southern Finland, aged between 2 and 19 years. The aim was to provide new Finnish maturity tables and curves and to compare the efficiency of Demirjian's method when differently weighted scores and polynomial regressions are used. The inter-ethnic variations lead us to calculate specific Finnish weighted scores. Demirjian's method gives maturity score as a function of age and seems better adapted for clinicians because, in their case, the maturity score is unknown. Polynomial functions give age as a function of maturity score and are statically adapted for age estimation studies. Finnish dental maturity tables and development curves are given for Demirjian's method and for polynomial functions. Sexual dimorphism is established for the same weighted score for girls and boys, and girls present a greater maturity than boys for all of age groups. Polynomial functions are highly reliable (0.19% of misclassifies) and the percentile method, using Finnish weighted scores, is very accurate (+/- 1.95 years on average, between 2 and 18 years of age). This suggests that polynomial functions are most useful in forensic sciences, while Demirjian's method is most useful for dental health clinicians.

Spirometry values in adults in northern Finland.

OBJECTIVES: If reference values do not accurately reflect the distribution of lung function in the population, the interpretation of spirometry results may be incorrect. Differences in lung function exist between populations, which supports the use of local reference values. In Finland, the national reference values for spirometry are currently in use. The aim of this study was to assess the correlation between measured spirometric values from healthy adults and the reference values used in Finland. METHODS: In the present population-based study, spirometry results were assessed in healthy adults aged 21 to 70 years in northern Finland. After exclusions for any chronic pulmonary disease or symptom, 206 men and 215 women remained in the group. We calculated regression equations for spirometric reference values in adults and compared these with European recommendations, and with the reference values currently used in Finland. RESULTS: These comparisons revealed large differences. The linear models do not take into account the physiological changes in both young and old adults and, thus, the reference values calculated according to the European recommendations differed from the real measured results at both ends of the 20- to 70-year age scale. Moreover, values from the logarithmic Finnish reference equations also diverged from our measurements; the differences were largest in subjects younger than 30, and in elderly men. CONCLUSION: Differences between populations and reference equations make international comparisons difficult, and divergence between reference values and real results may lead to incorrect clinical interpretation.

Factors affecting time to death from start of treatment among children succumbing to bacterial meningitis.

BACKGROUND: Many risks of death in childhood bacterial meningitis are well-identified, but factors influencing survival time have received less attention. Better understanding of this issue could help explain why adjuvant medications have performed unevenly in different trials. METHODS: In a post hoc analysis of prospectively collected data from a large bacterial meningitis treatment trial in Luanda, Angola, we compared time to death after initiation of antimicrobial treatment among 206 children with etiology and other patient characteristics. The risks of dying very quickly (0-4 hours), quickly (4-8 hours) or after longer periods were analyzed by logistic regression. RESULTS: Median time to death was 18.5 hours, half the time in Streptococcus pneumoniae (11.8 hours) compared with Haemophilus influenzae (26.8 hours) meningitis. Of all deaths caused by pneumococcal or H.influenzae meningitis, 42% versus 16%, respectively, occurred within the first 8 hours. In addition, patients who succumbed within 8 hours, unlike those dying later, had a short disease history, shock, hypoglycemia and poor cerebrospinal fluid white cell response. CONCLUSIONS: Time to death in Angola is so short that hardly anything, except perhaps modern intensive care, is likely to improve outcome in a patient with meningitis, especially the pneumococcal disease.

Fluctuation in hearing thresholds during recovery from childhood bacterial meningitis.

BACKGROUND: Hearing loss from childhood bacterial meningitis is believed to develop early and have little tendency for recovery. We performed serial hearing evaluations in a large number of children with bacterial meningitis in Luanda, Angola to clarify if, and how often, the result changed. METHODS: Children with confirmed bacterial meningitis and hearing evaluations on admission, day 7 of treatment and the follow-up visit formed the study group. Hearing was tested by auditory brainstem response audiometry using stimuli of 40 dB, 60 dB and 80 dB. Threshold changes are described between the composite levels of 40/60 dB and 80/>80 dB. RESULTS: In all, 235 ears were tested. While the ≤ 60 dB and ≥ 80 dB levels were maintained through all 3 examinations in 54% and 5% of ears, respectively, changes occurred in 41%. Deterioration from the ≤ 60 dB level to ≥ 80 dB was found in 10% of the ears transiently and in 7% permanently. Improvement from the ≥ 80 dB level to ≤ 60 dB occurred in 22% of the ears. Half of the ears with ≥ 80 dB impairment at the follow-up visit arrived with this finding; the others lost hearing later. Maintaining the ≤ 60 dB level throughout was associated with milder disease (P = 0.003), fewer convulsions (P < 0.0001) and older age (P = 0.009). CONCLUSIONS: Almost half of the ears showed threshold changes after admission during recovery from bacterial meningitis, most frequently improvement of initially severely impaired hearing, but some normal ears or with moderate impairment became severely impaired.

Managing post-thoracotomy pain: Epidural or systemic analgesia and extended care - A randomized study with an "as usual" control group.

Background and aims Thoracotomies can cause severe pain, which persists in 21-67% of patients. We investigated whether NSAID + intravenous patient-controlled analgesia (IV-PCA) with morphine is an efficacious alternative to thoracic epidural analgesia (TEA). We also wanted to find out whether an extended controlled pain management protocol within a clinical study can decrease the incidence of persistent post-thoracotomy pain. Methods Thirty thoracotomy patients were randomized into 3 intervention groups with 10 patients in each. G1: preoperative diclofenac 75mg orally+150 mg/24h IV for 44h, then PO; G2: valdecoxib 40mg orally+parecoxib 80mg/24h IV for 44h, then PO. IV-PCA morphine was available in groups 1 and 2 during pleural drainage, and an intercostal nerve block at the end of surgery was performed; G3: parac-etamol+patient controlled epidural analgesia (PCEA) with a background infusion of bupivacaine with fentanyl. After PCA/PCEA oxycodone PO was provided when needed. These patients were contacted one week, 3 and 6 months after discharge. Patients (N = 111) not involved in the study were treated according to hospital practice and served as a control group. The control patients' data from the perioperative period were extracted, and a prospective follow-up questionnaire at 6 months after surgery similar to the intervention group was mailed. Results The intended sample size was not reached in the intervention group because of the global withdrawal of valdecoxib, and the study was terminated prematurely. At 6 months 3% of the intervention patients and 24%ofthe control patients reported persistent pain (p<0.01). Diclofenac and valdecoxib provided similar analgesia, and in the combined NSAID group (diclofenac+valdecoxib) movement-related pain was milder in the PCEA group compared with the NSAID group. The duration of pain after coughing was shorter in the PCEA group compared with the NSAID+IV-PCA group. The only patient with persistent painat6 months postoperatively had a considerably longer duration ofpain after coughing than the other Study patients. The patients with mechanical hyperalgesia had more pain on movement. Conclusions Both PCEA and NSAID+IV-PCA morphine provided sufficient analgesia with little persistent pain compared with the incidence of persistent pain in the control group. High quality acute pain management and follow-up continuing after discharge could be more important than the analgesic method per se in preventing persistent post-thoracotomy pain. In the acute phase the measurement of pain when coughing and the duration of pain after coughing could be easy measures to recognize patients having a higher risk for persistent post-thoracotomy pain. Implications To prevent persistent post-thoracotomy pain, the extended protocol for high quality pain management in hospital covering also the sub-acute phase at home, is important. This study also provides some evidence that safe and effective alternatives to thoracic epidural analgesia do exist. The idea to include the standard "as usual" care patients as a control group and to compare them with the intervention patients provides valuable information of the added value of being a study patient, and deserves further consideration in future studies.

Predictive value of cerebrospinal fluid matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 concentrations in childhood bacterial meningitis.

BACKGROUND: Increased concentrations of matrix metalloproteinases (MMP) in cerebrospinal fluid are part of the host response in bacterial meningitis (BM). We investigated whether the concentrations of MMP-9 and the tissue inhibitor of metalloproteinase (TIMP)-1 predict the outcome in childhood BM. METHODS: Cerebrospinal fluid MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were quantified by an enzyme-linked immunosorbent assay from 264 and 335 patients, respectively; 43 children without BM served as controls. The results were compared with previously known independent predictors of death and sequelae. RESULTS: Higher MMP-9 and TIMP-1 values distinguished the controls from the BM patients (P < 0.0001). A MMP-9 concentration >940 ng/mL proved an independent predictor of death [adjusted odds ratio: 4.03; 95% confidence interval (CI): 2.09-7.77; P < 0.0001]. If the patient additionally presented with a Glasgow Coma Score below 9, the odds increased to 13.21 (95% CI: 5.44-32.08; P < 0.0001). TIMP-1 levels correlated with the severity of sequelae (ρ: 0.30; P < 0.0001), but not with death. Its concentration above 390 ng/mL increased the likelihood of sequelae 3.43-fold (95% CI: 1·73-6·79; P = 0.0004), and up to 31.18-fold (95% CI: 4.05-239.8; P = 0.0009) if the patient also presented a Glasgow Coma Score < 12. CONCLUSIONS: Elevated cerebrospinal fluid MMP-9 and TIMP-1 values predict 2 important outcomes in childhood BM. Combined with a clinical evaluation, quantification of these indices augments the chances to identify the patients in greatest need of better treatment modalities.