Hospital standardised mortality ratio: A reliable indicator of quality of care?

BACKGROUND: This study investigates (1) whether the hospital standardised mortality ratio (HSMR) model underestimates or overestimates disease severity and (2) the completeness of the data collected by administrators to calculate HSMR in a cohort of deceased patients with the diagnosis of pneumonia. METHODS: In this retrospective cohort study Pneumonia Severity Index (PSI) and Abbreviated Mortality in Emergency Department Sepsis (abbMEDS) scores and associated mortality probabilities were obtained from 32 deceased pneumonia patients over the year 2014 in the VU University Medical Centre. These were compared with mortality probabilities of the Central Bureau for Statistics (CBS) calculated for every patient using the HSMR model. Clinical charts were examined to extract relevant comorbidities to determine the reliability of data sent to the national registration of hospital care. RESULTS: Risk categories determined by using the PSI and the abbMEDS were significantly higher compared with the risk categories according to HSMR (p = 0.001, respectively p = 0.000). The mean difference between the number of comorbidities in our registration and the coders' registration was 1.97 (p = 0.00). The mean difference was 0.97 (p = 0.000) for the number of comorbidities of influence on the Charlson Comorbidity Index (CCI) and 1.25 (p = 0.001) for the calculated CCI. CONCLUSION: The results of this study suggest that the mortality probabilities as calculated by the CBS are an underestimation of the risk of dying for each patient. Our study also showed that the registration of data sent to the CBS underestimated the actual comorbidities of the patient, and could possibly influence the HSMR.

Orphan drugs: expensive yet necessary.

Whether the prices of certain orphan treatments are justified is highly controversial. One argument is that such therapies should not be funded through the public purse or private health plans because a patient with a rare disease requires more than their 'fair share' of a limited health care budget. Orphan medications can also be denied because they fare poorly in the cost-effectiveness assessments of drugs. This paper takes the unusual line that life-saving treatments should be provided regardless of their cost. This contention is based on the Harvard philosopher John Rawls' theory of justice. We offer three rules to limit the use of cost-effectiveness approaches: efficiency assessments should not be deployed (i) when the choice is between an only treatment and no treatment, or to (ii) prioritise between different patients and patient groups. However a well considered cost efficiency calculation may have its place (iii) where a patient has a choice between two or more equally safe and effective treatments. We rebut potential objections to this analysis, and conclude that there has been a tendency to classify appeals for orphan treatments as a minority interest and in conflict with the aims of public health and society at large. Rawls' concept of societal justice shows that a distinction between the individual and society in this context is bogus. The funding of orphan therapies is as much a matter for public health as the funding of treatments for other conditions. Treatment must not be withheld on economic grounds.

Limits on use of health economic assessments for rare diseases.

Funding of expensive treatments for rare (orphan) diseases is contentious. These agents fare poorly on 'efficiency' or health economic measures, such as the quality-adjusted life years, because of high cost and frequently poor gains in quality of life and survival. We show that cost-effectiveness assessments are flawed, and have only a limited role to play in reimbursement decisions for orphan drugs and beyond.

[The formation of infliximab and anti-infliximab immune complexes as an explanation for non-responding to infliximab treatment of rheumatoid arthritis: observational study in 4 patients]. / Het ontstaan van immuuncomplexen van infliximab en anti-infliximab als een verklaring voor het falen van infliximabtherapie bij reumatoïde artritis: observationeel onderzoek bij 4 patiënten.

OBJECTIVE: To investigate the in vivo mechanism of non-responding to infliximab treatment of patients with rheumatoid arthritis (RA) and the role of anti-infliximab antibodies by using radiolabeled infliximab. DESIGN: Descriptive and comparative study. METHOD: Two responding and two non-responding RA patients were infused with radiolabeled infliximab. Subsequently imaging investigations and serum analysis were performed at set times. RESULTS: The scintigrams showed that the labelled infliximab was mainly present in the blood until 24 h after infusion. There was a trend of faster blood clearance and higher liver and spleen uptake of 99mTc-infliximab in one non-responding patient. Labelled infliximab was taken up by inflamed joints. The anti-infliximab level was high (1008 and 1641 U/ml) in the non-responders and low or not detectable in the responders. Sucrose gradients of serum revealed antibody complexes in both non-responders. Various sizes of antibody complexes, including very large ones, were observed in one non-responder who developed a serious infusion reaction. CONCLUSION: Infliximab-anti-infliximab immune complexes were found to form in RA non-responders due to the presence of significant quantities of anti-infliximab. This finding may partly explain the failure of the infliximab treatment.

A single mechanism for the timing of spontaneous and evoked saccades.

The study of saccadic latency-the reaction time between presenting a visual stimulus and initiating an eye movement to look at it--has led to a better understanding of decision mechanisms in general, through the development of quantitative models such as LATER. But outside the laboratory, evoked saccades of this kind are rare. Most saccades are made spontaneously while viewing static scenes. Can their initiation be explained by the same decision mechanism? We suggest that in a series of spontaneous saccades, each can be considered to be evoked by the new retinal image generated by its predecessor, so that the intersaccadic interval (ISI) can be regarded as equivalent to latency. We measured ISIs in subjects spontaneously viewing static scenes, and found their distributions to be qualitatively similar to those of evoked saccades, differing quantitatively in just two respects: (1) the main part of the distribution is slower; and (2) there is an increased number of very early responses. By using novel saccadic tasks we show that (1) can be accounted for by lateral inhibition between multiple, suddenly presented image elements, and (2) by the fact that the stimulus is necessarily extremely predictable. Adding these two factors to an evoked saccadic task produced latency distributions indistinguishable from those of spontaneous ones. This suggests that the mechanisms generating evoked and spontaneous movements may be less functionally distinct than is commonly assumed. Both clinically and scientifically, a common, unified framework for explaining both spontaneous and evoked movements is an exciting prospect.

[Abdominal ultrasound: a task for the internist]. / Abdominale echografie: zaak van de internist.

For the internist, ultrasound echography is the ideal bedside imaging technique to increase his diagnostic capabilities. It is not harmful, easy to apply, and cheap. It obviates the need to send a patient to the radiologist, which saves time and thus shortens the course of the illness. Echography should be integrated into the training of internists.

Imaging and serum analysis of immune complex formation of radiolabelled infliximab and anti-infliximab in responders and non-responders to therapy for rheumatoid arthritis.

BACKGROUND: Many patients with rheumatoid arthritis are currently successfully treated with infliximab (anti-tumour necrosis factor); however, about 30% of the patients do not respond to infliximab. One of the postulated hypotheses of not responding is the fast clearance of infliximab due to the development of infliximab-anti-infliximab complexes. OBJECTIVE: To investigate the in vivo mechanism of not responding and the role of human anti-chimeric antibodies (HACAs) by using radiolabelled infliximab. METHODS: Two responding and two non-responding patients with rheumatoid arthritis, infused with radiolabelled infliximab, were investigated by both imaging and serum analysis. RESULTS: Images showed predominant presence of infliximab in blood up to 24 h, with a trend of faster blood clearance and of higher liver/spleen uptake in a non-responding patient. Clinically inflamed joints showed uptake of the drug. The HACA level in the non-responders was high (1641 and 1008 U/ml), but low or not detectable in responders. Sucrose gradients of serum showed antibody complexes in both non-responders. Various sizes of antibody complexes, including very large ones, were observed in a non-responder who developed a serious infusion reaction. CONCLUSION: Formation of infliximab-anti-infliximab complexes were found in non-responders due to the presence of large amounts of HACA. This finding, supported by both imaging and serum analysis data, may explain failure of infliximab treatment.

Additional weight bearing during exercise and estrogen in the rat: the effect on bone mass, turnover, and structure.

Mechanical loading and estrogen play important roles in bone homeostasis. The aim of this study was to evaluate the effects of mechanical loading on trabecular bone in the proximal femur of ovariectomized rats. We hypothesized that mechanical loading suppresses bone resorption and increases bone formation, which differs from the suppressive effects of estrogen on both resorption and formation. Furthermore, we expected to find changes in trabecular architecture elicited by the effects of mechanical loading and estrogen deficiency. Sixty female Wistar rats, 12 weeks old, were assigned to either the sedentary groups sham surgery (SED), ovariectomy (SED+OVX), and ovariectomy with estrogen replacement (SED+OVX+E2) or to the exercise groups EX, EX+OVX, EX+OVX+E2. Following ovariectomy, 5 microg 17beta-estradiol was given once weekly to the estrogen replacement groups. Exercise consisted of running with a backpack (load +/-20% of body weight) for 15 minutes/day, 5 days/week, for 19 weeks. Dual-energy X-ray absorptiometry (DXA) scans were performed before (T0), during (T6), and after (T19) the exercise period to obtain bone mineral content (BMC) and bone mineral density (BMD) data. After the exercise program, all rats were killed and right and left femora were dissected and prepared for micro-CT scanning and histomorphometric analysis of the proximal femoral metaphysis. After 19 weeks, increases in BMC (P = 0.010) and BMD (P = 0.031) were significant. At T19, mechanical loading had a significant effect on BMC (P = 0.025) and BMD (P = 0.010), and an interaction between mechanical loading and estrogen (P = 0.023) was observed. Bone volume and trabecular number decreased significantly after ovariectomy, while trabecular separation, mineralizing surface, bone formation rate, osteoclast surface, degree of anisotropy, and structure model index increased significantly after ovariectomy (P < 0.05). Trabecular bone turnover and structural parameters in the proximal femur were not affected by exercise. Estrogen deficiency resulted in a less dense and more oriented trabecular bone structure with increased marrow cavity and a decreased number of trabeculae. In conclusion, mechanical loading has beneficial effects on BMC and BMD of the ovariectomized rat. This indicates that the load in the backpack was high enough to elicit an osteogenic response sufficient to compensate for the ovariectomy-induced bone loss. The results confirm that estrogen suppresses both bone resorption and bone formation in the proximal metaphysis in the femoral head of our rat-with-backpack model. The effects of mechanical loading on the trabecular bone of the femoral head were not significant. This study suggests that the effect of mechanical loading in the rat-with-backpack model mainly occurs at cortical bone sites.

Reproducibility of bone mineral density measurement in daily practice.

BACKGROUND: Bone mineral density (BMD) measurements are frequently performed repeatedly for each patient. Subsequent BMD measurements allow reproducibility to be assessed. OBJECTIVE: To examine the reproducibility of BMD by dual energy x ray absorptiometry (DXA) and to investigate the practical value of different measures of reproducibility in a group of postmenopausal women. METHODS: Ninety five women, mean age 59.9 years, underwent two subsequent BMD measurements of spine and hip. Reproducibility was expressed as smallest detectable difference (SDD), coefficient of variation (CV), and intraclass correlation coefficient (ICC). Sources of variation were investigated by multilevel analysis. RESULTS: The median interval between measurements was 0 days (range 0-45). The mean difference (SD) between the measurements (g/cm(2)) was -0.001 (0.02) and -0.0004 (0.02) at L1-4 and the total hip, respectively. At L1-4 and the total hip, SDD (g/cm(2)) was +/-0.05 and +/-0.04 and CV (%) was 1.92 and 1.59, respectively. The ICC at spine and hip was 0.99. CONCLUSIONS: Reproducibility in the postmenopausal women studied was good. In a repeated DXA scan a BMD change exceeding 2 radical 2CV (%), the least significant change (LSC), or the SDD should be regarded as significant. Use of the SDD is preferable to use of the CV and LSC (%) because of its independence from BMD and its expression in absolute units. Expressed as SDD, a BMD change of at least +/-0.05 g/cm(2) at L1-4 and +/-0.04 g/cm(2) at the total hip should be considered significant.

Radioimmunodiagnosis of lymph node metastases in head and neck cancer.

INTRODUCTION: Reliable staging of the neck remains a diagnostic challenge in head and neck squamous cell carcinoma (HNSCC) patients. Monoclonal antibodies (MAbs) directed against tumour-associated antigens can be used for selective tumour targeting. When labelled with a gamma-emitting radionuclide like 99mTechnetium, such MAbs can be used for tumour detection by radioimmunoscintigraphy (RIS). OBJECTIVE: The aim of this study was to assess the potential of RIS for the detection of lymph node metastases in HNSCC patients. PATIENTS AND METHODS: In 49 patients with HNSCC, who were scheduled to undergo surgery including neck dissection, RIS using 99mTc-labelled squamous cell specific MAb E48 or U36 administered intravenously was compared with clinical palpation, computed tomography (CT), magnetic resonance imaging (MRI) and histopathological outcome. RESULTS: RIS detected lymph node metastases in 35 of 51 positive sides (sensitivity 69%). Interpretation of RIS was correct in 47 of 65 sides (accuracy 72%). Accuracy of palpation, CT and MRI were comparable. Immunohistochemical staining of lymph node metastases missed by RIS showed that the injected MAb had targeted these small tumour deposits but these were not visualized. CONCLUSIONS: RIS at its current stage of development is not superior to CT or MRI for the detection of lymph node metastases. As small tumour deposits were probably not visualized because of the limited sensitivity and/or spatial resolution of the gamma camera, positron emission tomography (PET) using MAbs labelled with positron emitters may improve the detection. As MAb-PET studies in an animal model showed promising results we will soon start a clinical MAb-PET study.

[Iodine prophylaxis to prevent radiation damage following nuclear disasters]. / Jodiumprofylaxe bij nucleaire rampen ter voorkoming van stralingsschade.

After the Twin Tower attack on 11 September 2001, much attention is being given to possible terrorist attacks on nuclear targets. However, most of this interest is in countries outside of the Netherlands. Iodine is a simple and effective means of preventing part of the radiation damage following a nuclear disaster. Non-radioactive (stable) iodine plays an important part in blocking the absorption of radioactive iodine by the thyroid gland, if it is administered as soon as possible after the nuclear accident has occurred. Prophylaxis with 100 mg non-radioactive iodide has a minimal toxic effect. Effective iodine prophylaxis is dependent on the government ensuring a well-regulated distribution. The government and hospitals should have thorough protocols that staff are sufficiently familiar with.

Alendronate in the prevention of bone loss after a fracture of the lower leg.

Fracture of a leg and the consequent absence from weight-bearing lead to local bone loss. A 1-year, single-center, prospective, randomized, double-blind study was conducted, to determine whether bone loss would occur in the proximal femur and the calcaneus after a fracture of the lower leg and whether this loss could be prevented by the antiresorptive drug bisphosphonate alendronate. Twenty-three men and 18 women with a recent unstable fracture of the lower leg were randomized to receive either 10 mg of alendronate daily or placebo. Bone mineral density (BMD) of both hips and the lumbar spine was measured at baseline and 6 weeks and 3, 6, and 12 months after start of the treatment. Quantitative ultrasound (QUS) measurements of the calcaneus were performed at baseline on the noninjured side and at 6 weeks and 3, 6, and 12 months after start of treatment on both sides. After 1 year, in the placebo group, there was a significant decrease from baseline in BMD of the hip on the side of the fracture. In the alendronate group, there was no significant change from baseline. The differences in BMD between the two treatment groups on the side of the fracture were significant in all sites of the hip: 4.4% (p = 0.016) in the trochanter, 4.6% (p = 0.016) in the femoral neck, and 3.9% (p = 0.009) in the total hip. In the hip on the contralateral side, there were no significant changes from baseline in either treatment group and there was no difference between the two treatment groups. BMD in the lumbar spine increased in the alendronate group, and after 1 year there was a significant difference between the active treatment and placebo group of 3.4% (p = 0.04). One year after fracture, ultrasound parameters of the calcaneus in the placebo group were significantly lower on the fractured side compared with the contralateral side (p < 0.01). In the alendronate group, no significant difference between the two sides was observed. In conclusion, BMD of the proximal femur was still decreased 1 year after a fracture of the lower leg. Alendronate prevented this bone loss.

Body composition in infants with chronic lung disease after treatment with dexamethasone.

UNLABELLED: The aim of this study was to study the effect of chronic lung disease (CLD) and dexamethasone treatment on body composition in preterm infants (birthweight < 1500 g). In addition, anthropometric measurement of body composition were compared with dual-energy X-ray absorptiometry (DXA). Fourteen preterm infants with CLD and a comparison group of 18 preterm infants were studied until 3 mo corrected age. CLD infants received approximately 20 kcal kg-1 per day extra nutritional intake during dexamethasone treatment until term. At term no differences were found between CLD and no CLD infants for percentage bone mass (1.4 +/- 0.2 vs 1.4 +/- 0.1%), fat mass (18.7 +/- 4.5 vs 17.4 +/- 3.5%), lean body mass (79.9 +/- 4.6 vs 81.2 +/- 3.5%) or bone mineral density (0.15 +/- 0.02 vs 0.15 +/- 0.01%). At 3 mo corrected age both groups were also similar for bone mass (1.6 +/- 0.1 vs 1.6 +/- 0.2%), fat mass (22.6 +/- 5.5 vs 24.5 +/- 5.7%), lean body mass (75.8 +/- 5.7 vs 74.0 +/- 5.8%) and bone mineral density (0.20 +/- 0.02 vs 0.20 +/- 0.01%). All anthropometric measurements showed a high correlation with body composition. However, calculated fat mass was 56.7 +/- 8.8% lower than fat mass measured with DXA. CONCLUSION: Body composition at term and 3 mo corrected age in preterm infants treated with dexamethasone for CLD, who received extra caloric intake until term, did not differ from that in preterm infants without CLD.

[Comparable case finding percentages of osteoporosis despite diverging reasons for ordering bone densitometry by general practitioners and specialists]. / Uiteenlopende redenen voor het aanvragen van een botdichtheidsmeting in de praktijk van huisartsen en specialisten, maar vergelijkbare opsporingspercentages van osteoporose.

OBJECTIVE: To assess the use of bone densitometry in practice. DESIGN: Retrospective. METHOD: General practitioners who had ordered bone densitometry for their patients were asked to fill in a questionnaire on the reasons for the request and the subsequent treatment they prescribed. For a similar number of patients from the outpatient clinics of general internal medicine and endocrinology, the medical records were examined to obtain the same information. RESULTS: In 9 months, general practitioners requested 150 bone density measurements; for 117 of these the data were complete. In one year, 150 measurements were requested by the outpatient clinics. Marked differences in the reasons for the request were seen in loss of body height, back pain and requests from the patient (indications for general practitioners) and in osteoporotic fractures and the use of corticosteroids (indications for specialists). The average result of the measurements, however, was the same, with mean T-scores in the lumbar spine of -2.26 and -2.19, respectively and case-finding percentages of osteoporosis of 21% on the basis of the lumbar spine and 40% on the basis of the spine or hip. Bone densitometry carried out after an osteoporotic fracture was associated with the lowest mean bone mineral density, followed by measurement on the basis of abnormal X-rays. Bone densitometry at the patient's request was associated with the highest bone density. The percentage of patients found to have osteoporosis turned out to be dependent on the site of measurement, the used reference ranges, and the method of reporting, especially for patients older than 70 years. When the bone density corresponded to a diagnosis of osteoporosis, nearly all patients were treated, mainly with a bisphosphonate. Treatment was also frequently started when the bone density was reduced, i.e. in case of osteopenia. Some patients with normal bone density were treated as well. The reason for such treatment was not always clear. CONCLUSION: General practitioners and specialists used different risk factors in deciding whether bone densitometry was indicated. However, the two groups used this diagnostic tool with equal efficiency, since both the percentages of osteoporosis detected and the average bone densities were the same.

Bone metabolism markers and bone mass in healthy pubertal boys and girls.

OBJECTIVE: During puberty, bone growth and mineralization as well as bone turnover increase dramatically. The relation between height velocity and bone turnover is already known, but there are few studies in which both bone metabolism markers and bone mass throughout puberty have been measured. DESIGN: Semi-longitudinal study. In 155 healthy boys (12.0 +/- 1.5 years; range 8.8-15.7 years) and 151 healthy girls (11.2 +/- 1.6 years; range 8.2-14.0 years) markers of bone formation and bone resorption were measured as well as sex steroids, IGF-1 and IGF-BP3, together with bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine, femur and total body during puberty. All bone measurements were repeated after 1 year. RESULTS: BMC and BMD increased throughout puberty in both sexes. Bone turnover markers increased significantly until maximum values were reached at stage G4 in boys and stage B3 in girls. Height velocity (HV) had a similar changing pattern. Sex steroids and IGF-1 increased and reached adult values at pubertal stage 4. The correlations between bone metabolism markers and BMC were highly significant in boys, while correlations between bone metabolism markers and the increase in BMC over 1 year were significant in both sexes, as was observed for the correlations with HV. CONCLUSIONS: Our data suggest that bone metabolism markers are good predictors of bone mass in boys and of bone mass increase in both sexes. In early puberty, sex steroids stimulate the pubertal growth spurt in conjunction with GH and IGF-1. The fast increase in height gives rise to an increase in bone turnover and bone mineral apposition. It is known that at the end of puberty high levels of oestradiol inhibit chondrocyte proliferation. This leads to a decline in height velocity and bone turnover. Bone mass still increases under the influence of sex steroids and IGF-1. The data in our study confirm previous reports that markers of bone turnover relate positively to height velocity.

Effect of 1 year of discontinuation of raloxifene or estrogen therapy on bone mineral density after 5 years of treatment in healthy postmenopausal women.

The beneficial effects of hormone replacement therapy (HRT), selective estrogen receptor modulators (SERMs), or bisphosphonates in the prevention and treatment of osteoporosis in postmenopausal women have been well established. However, little is known about the effects of discontinuation of treatment on bone mineral density. We investigated the effect of 1 year of discontinuation of the SERM raloxifene (Ral; 60 mg and 150 mg), conjugated equine estrogen (CEE; 0.625 mg), and placebo after 5 years of treatment in a double-blind, randomized study. Thirty-eight of 59 healthy and hysterectomized postmenopausal women (mean age 55 years) completed the treatment and 1 year follow-up period. Lumbar spine and femoral neck bone mineral density (BMD) were performed with dual-energy X-ray absorptiometry, before, during, and at the end of treatment, as well as after 1 year of discontinuation of therapy. One year of discontinuation significantly reduced the mean lumbar spine BMD in the raloxifene- and estrogen-treated women (p < 0.05), whereas mean femoral neck BMD was reduced significantly only in women treated with 60 mg Ral (p < 0.05). The mean percentage change (+/-SD) in lumbar spine BMD was: CEE, -6.2% (+/-3.7%); Ral 60 mg, -2.4% (+/-2.4%); Ral 150 mg, -2.6% (+/-3.1%); and placebo, -1.6% (+/-4.3%). Our results show that 5 years of treatment with either Ral or CEE did not protect against bone loss after 1 year of withdrawal of therapy, and that the rate of bone loss was not significantly different from that of placebo-treated women.