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C Hendriksen

Publications and source records attributed to C Hendriksen.

At least 19 recordsLinked to original sources

Medication for older people--aspects of rational therapy from the general practitioner's point of view.

This paper discusses GP perspectives on the principles underlying rational pharmacotherapy for older people. The rising use of prescription medicine forces the GP to balance the benefit of evidence group-based appropriate drug use against the problems arising when medication is given to older people and to consider different approaches when evaluating evidence of risk and benefit for the individual. Old people are facing a considerable risk of adverse drug reactions and recent initiatives, including the Continuous Medical Educational Efforts Programme, address issues of inappropriate prescribing practices. The authors recommend and present tools enabling the GP to focus on 'the core prescribing situation'. The logistics to optimise medication including compliance, the use of modern IT and better collaboration and communication between primary and secondary care are discussed. The authors state that a number of pharmacological regimens for older people are outperformed by non-pharmacological treatment alternatives involving competent individualised counselling and public provision of easy (transportation) possibilities for joining centres offering staff and equipment for physical and social activity (including basal aids for hearing and sight).

Aged↗

Polypharmacy and older people--the GP perspective.

It is well known that problems with compliance rise exponentially when more that 4 drugs are prescribed. The rising use of prescription medicine forces the GP to balance the benefit of evidence group-based appropriate drug use against the problems arising when medication is given to older people and to consider different approaches when evaluating evidence of risk and benefit for the individual. Old people are facing a considerable risk of adverse drug reactions and recent initiatives, including the Continuous Medical Educational Efforts Programme, address issues of inappropriate prescribing practices. The authors recommend and present tools enabling the GP to focus on 'the core prescribing situation'. The logistics to optimise medication including compliance, the use of modern IT and better collaboration and communication between primary and secondary care are in focus. Since medication review is recommended at every encounter, and time consuming comprehensive follow-up will be demanded, 'polypharmacy consultations' surely will be built into GP contracts in the future. The authors state that a number of pharmacological regimens for older people are outperformed by non-pharmacological treatment alternatives involving competent individualised counselling and public provision of easy (transportation) possibilities for joining centres offering staff and equipment for physical and social activity (including basal aids for hearing and sight).

Aged↗

Preventive home visits to elderly people in Denmark.

During the last 20 years several randomised controlled trials have been published about preventive home visits to old people, but the benefit of the visits is still controversial and under debate. Based on a state law from the Ministry of Social Affairs in 1998, the municipalities in Denmark are obliged to offer home visits twice a year to all citizens 75 years and older. After six years with this law, there is still variation of how the law is managed and implemented. About 60% of the elderly people accept and receive the visits. Less than 50% of the municipalities have made specific guidelines and quality assurance indicators. More than the half have systematically used the visits to collect information of community needs and older people' wishes to be used for administrative and political purposes. In a prospective, controlled, feasibility study conducted over a 3-year period we found that a brief, manageable and ongoing educational intervention towards professionals working with preventive home visits is feasible and improves older people's functional mobility.

Aged↗

Toxicity and immunogenicity of pertussis whole cell vaccine in one animal model.

The required in vivo assays for the release of Whole Cell Pertussis Vaccine are the Mouse Weight Gain test (MWGT) for assessment of specific toxicity and the Mouse Protection test (MPT) to estimate the potency. Despite the fact that both assays are criticised for the use of large number of animals, poor precision or insensitivity, more precise alternatives--such as the Leukocytosis Promotion test (LP-test) and Pertussis Serological Potency Test (PSPT)--are still not fully accepted. During the optimisation of the production process, the need for more accurate parameters to determine toxicity and potency became essential. To reduce substantially the number of animals, we have combined the MWGT with the LP-test and PSPT in one model, named the Mouse Toxicity and Immunogenicity test (MTI-test). Animals are inoculated with half a human dose and are weighed individually pre-immunisation and 16 hours (parameter for endotoxin), three and seven days post immunisation. Additionally, the number of leukocytes (parameter for PT) is determined on day 7 and after 28 days the animals are bled individually for immunogenicity testing (parameter for potency). A lyophilised reference vaccine is included as a positive control to standardise the assay and to determine its reproducibility. The advantage of this modified procedure is that the data on toxicity and immunogenicity are obtained from the individual mouse, which enables statistical analysis to be made. The leucocytosis data can be used to check whether mice were vaccinated correctly, allowing for the elimination of incorrectly vaccinated mice from the assay. Furthermore, this assay can be used to determine the consistency of production, the influence of adjuvant on toxicity, as well as the composition and stability of vaccines.

Animals↗

Serological methods for potency testing of tetanus toxoid vaccines for human use.

A collaborative study has been performed to validate two in vitro serological assays, ELISA and ToBI test, as alternatives to the direct challenge procedure for potency testing of tetanus toxoid vaccines for human use (Ph.Eur. monograph Tetanus vaccine (adsorbed) (0452)). In six laboratories, guinea-pigs were immunised with tetanus toxoid vaccines from different manufacturers representing various types of combined products, including one product of borderline quality. Blood samples were taken two to four days before challenge. Parameters that were analysed included: (i) correlation of vaccine potencies obtained by direct challenge test and by serological assays, (ii) prediction of survival based on antibody concentrations, and (iii) correlation of antibody concentrations obtained in ELISA, ToBI test and in vivo Toxin Neutralisation test. In addition, ELISA and ToBI test repeatability and reproducibility were further studied by titration of a total of 28 serum samples in 23 laboratories. This paper provides background information, gives an outline of the experimental design and discusses the study results. It is concluded that ELISA and ToBI test are valid alternatives to the challenge procedure. Implementation of the serological assays as alternatives to the challenge procedure for batch release of tetanus vaccines for human use will result in a marked refinement as well as a substantial reduction of numbers of laboratory animals.

Animals↗

The Pertussis Serological Potency Test. Collaborative study to evaluatereplacement of the Mouse Protection Test.

The Pertussis Serological Potency Test (PSPT)--based on in vitro assessment of the humoral immune response against Bordetella pertussis--was developed as an alternative for the Mouse Protection Test (MPT). A small-scale collaborative study was carried out in five laboratories to evaluate the relevance and reliability of the PSPT. The study has been divided into three separate phases, each with its own objective. A pilot-phase study of the antibody detection assay, the 18323-whole cell ELISA (WCE), was included for training purposes. Significant differences in absorbance and antibody concentrations between the laboratories were found. In the Phase I study, the intra-assay, inter-assay and inter-laboratory precisions of the 18323-WCE were assessed. Although a precision of less than 20% was not always established and significant differences in antibody concentrations were found at random throughout the Phase I study, the ranking of the antibody concentrations corresponded well between the laboratories and should warrant a reliable potency estimation of whole cell vaccines (WCV's) in the PSPT. Phase II was a comparative study of the PSPT and the MPT to evaluate the implementation of the PSPT, to demonstrate correlation and to compare the reproducibility and reliability of both tests. The mean antibody concentrations per vaccine dose in the PSPT and the survival of mice in the MPT differed significantly within and between the laboratories. Nevertheless, the potencies of the vaccines under test estimated in both test models did not differ significantly (P>0.05). The PSPT and MPT correlated well in chi2-test of homogeneity within and between the laboratories. The potencies were similar (overall ratio=0.877), but the PSPT is more reproducible and reduces the chance of re-testing due to the smaller 95% confidence intervals. We have demonstrated that the PSPT is a valid model to estimate the potencies of pertussis WCV's from different manufacturers. Moreover, the 18323-WCE is easy to carry out and the intra-assay precision and antibody ranking warrants a reliable potency testing of pertussis WCV's in the PSPT.

Animal Testing Alternatives↗

Serological assays as alternatives to the Ph Eur challenge test for batch release of tetanus vaccines for human use.

According to the European Pharmacopoeia (Ph Eur) monograph on Tetanus Vaccine (adsorbed) (1997: 0452), assessment of potency is based on a challenge test in guinea pigs or mice. The end-point is taken as paralysis or death. The test requires a large number of animals and causes severe distress. The aim of the present study was to refine the test, and reduce the number of animals needed, for batch release purposes. Serological assays having the potential of being internationally accepted, have been compared with Ph Eur assays. The study included five tetanus vaccines of various combinations and produced by different manufacturers. The results indicated an excellent correlation between enzyme-linked immunosorbent assay (ELISA) and the challenge test (about 93% predictive value), as well as between the toxin binding inhibition (ToBI) test and the challenge test (about 95% predictive value) and between ELISA and the ToBI test (r = 0.92). Antitoxin concentrations determined by ELISA and ToBI were generally in the same range. An overall good correlation was also seen for serum pools of the guinea pigs injected with equal vaccine doses, between toxin neutralisation test in mice (TNT) and ELISA (r = 0.93) as well as between TNT and ToBI (r = 0.97). The ultimate goal of this project was to determine whether serological assays can be used for testing combined vaccines, particularly for tetanus and diphtheria components, using sera from the same animals.

Animal Testing Alternatives↗

A clinical trial of combination of artesunate and mefloquine in the treatment of acute uncomplicated falciparum malaria: a short and practical regimen.

The difficulties in treating drug-resistant falciparum malaria in Thailand are compounded by the necessity of giving antimalarials over long periods of time. The resultant fall in patient compliance not only lowers cure rates but also predisposes to the further spread of drug-resistance. Sequential treatment with artesunate given over 5 days followed by mefloquine produced 100% cure rates in previous study, but might not be a suitable regimen for field treatment. We conducted a clinical trial of a combination of artesunate and mefloquine given twice daily for 2 days in 150 patients with acute uncomplicated falciparum malaria. The dose of artesunate (200 mg) and mefloquine (312.5 mg) were given simultaneously in a separate package. All patients were admitted to a hospital in Bangkok for 28 days to exclude re-infection and monitor the possible adverse effects. One hundred and thirty patients completed the study with 28 days follow up. Twenty patients (13%) left the hospital prior to completion of follow-up for reasons unrelated to their treatment. Cure rate was 97% (126/130). There were no RII or RIII failures and all four patients with treatment failures were of the RI type. The mean parasite clearance time and fever clearance time were 46.4 and 42.5 hours, respectively. All patients were tolerated the combination drugs well and there were no serious toxic adverse reactions. The results indicate that combination of artesunate and mefloquine given twice daily for 2 days is effective and well tolerated in patients with acute, uncomplicated falciparum malaria and suitable as an alternative treatment for multidrug resistant falciparum malaria.

Adolescent↗

[Early geriatric intervention. Consequences of reduced length of stay in a geriatric department].

The aim of the study was to evaluate if an experienced reduction in length of stay in a geriatric department had negative influence on rehabilitation in terms of more readmissions, nursing home replacements or deaths in the first six months after discharge from the geriatric department. In a retrospective study all inpatients discharged from geriatric department RL, Kommunehospitalet, in the first six months of 1990 and 1992 respectively were evaluated. The main contributor to reduction in hospital length of stay was found to be an earlier geriatric intervention combined with shorter waiting time for transfer to the geriatric department. In the study populations we found no significant difference in the number and time of readmissions, the number of nursing home replacements or deaths in the first six months after discharge. Short length of stay is not in itself an aim of a geriatric department. We conclude that geriatric assessment should take place as soon as possible after admission to hospital and acute/subacute admission to the geriatric department is to be intensified.

Aged↗

Validation of the toxin-binding inhibition (ToBI) test for the estimation of the potency of the tetanus toxoïd component in vaccines.

A validation study has been performed to determine the suitability of the toxin binding inhibition (ToBI) test for the serological estimation of the potency of the tetanus toxoïd component in vaccines. 37 Murine serum pools over a wide range of antibody levels were titrated in both toxin neutralization (TN) and ToBI test. A good correlation was found between both assays. Sixteen DPT-polio, twelve DT-polio and seven T vaccines were tested in the mouse lethal challenge test and the in vitro serological test, using the ToBI test for determining vaccine-induced tetanus antibodies. For all three types of vaccine a statistically valid correlation between both assays was found. However, for two batches of DPT-polio vaccine an "overestimation" of the tetanus potency was observed in the serological assay compared to the challenge assay. This phenomenon could not be explained by the difference in immunization period nor by misinterpretation of the ToBI test of DPT-polio-induced antibodies. In the LPF test high LPF activity was observed for the deviating DPT-polio vaccines. Therefore, the effect of pertussis toxin (PT) on the potency of the tetanus component in the serological assay was examined. The addition of 2 micrograms of PT to a "normal" DPT-polio vaccine resulted in a nearly twofold increase of the tetanus potency. It was concluded that pertussis toxin has a vaccine dose-dependent adjuvant effect on the potency of tetanus toxoïd resulting in high potency values when determined by ToBI procedure. It is unclear how these findings should be interpreted with respect to the behaviour of such vaccines in man.

Animal Testing Alternatives↗

Pertussis serological potency test as an alternatively to the intracerebral mouse protection test.

The current potency test for pertussis vaccines, the intracerebral protection test (MPT), is still the only mandatory laboratory model available. This test, however, is a valid, but inhumane and imprecise test and therefore a good candidate for replacement. Recently we have developed the Pertussis Serological Potency Test (PSPT) as an alternative for the MPT. The PSPT is based on in vitro assessment of the humoral immune response against the whole range of surface -antigens of B. pertussis in mice after immunisation with Whole Cell Vaccine (WCV). We have demonstrated a relationship between the mean pertussis antibody concentration at the day of challenge and the proportion of surviving mice at each vaccine dose in the MPT (R = 0.91). The PSPT is a model in which mice (20-24 g) are immunised i.p. with graded doses of vaccine and bled after four weeks. Sera are titrated in a whole cell ELISA and potency based on the vaccine dose-dependent antibody response is estimated by means of a parallel line analysis. In an in-house validation study 13 WCVs were tested in the PSPT and MPT. Homogeneity of both tests was proven by means of the chi-square test; potencies were significantly similar (p = 0.95). Compared to the MPT, the PSPT is more reproducible as is indicated by its smaller 95% confidence intervals. Moreover, by using the PSPT the animal distress can be reduced to an acceptable level and the PSPT also results in a reduction of more than 25% in use of mice. Additional experiments showed that estimation of WCV-potency in the PSPT based on specific antibody responses against protective antigens (PT, FHA, 69- and 92-kDa OMPS) was not possible or did not correlate with protection in MPT. Sera obtained from the PSPT showed a correlation between pertussis antibody levels and complement-mediated killing by pertussis antibodies in in vitro assays. In conclusion, the PSPT is a promising substitute for the MPT though further validation and additional studies on functional validity should finally warrant replacement of the MPT by this serological model.

Animal Testing Alternatives↗

Development of pertussis serological potency test. Serological assessment of antibody response induced by whole cell vaccine as an alternative to mouse protection in an intracerebral challenge model.

The current potency test for pertussis vaccines, the mouse protection test (MPT), has many disadvantages. However, no alternative is yet available. The purpose of this study is to develop a serological alternative for the MPT based on in vitro assessment of the humoral immune response against pertussis in mice. After immunization with pertussis whole cell vaccine, the MPT shows a normal primary and secondary antibody response. Moreover, the i.c. challenge has a distinct booster effect on the pertussis IgG response. The relationship between the concentration of IgG antibodies against the surface-antigens of pertussis bacteria and the survival of mice after the i.c. challenge was demonstrated in a modified MPT (R = 0.91). To this end a protecting antibody level of > or = 45 EU/ml was selected as a level at which concentration most of the mice survived. Survival of mice in the MPT could be predicted, based on the antibody concentration at the day of challenge. Potencies estimated with the predicted and actual survival corresponded well (P = 0.990). This confirmed the essential role of vaccine induced pertussis antibodies in the protection against a lethal i.c. challenge and offered a possibility to develop a pertussis potency test based on serology. We developed a model in which mice (20-24 g) are immunized (i.p.) with graded doses of vaccine and bled after four weeks. Sera are titrated in Bordetella pertussis whole cell ELISA and potency based on vaccine dose dependent antibody response is estimated by means of a parallel line analysis. The potency of vaccines tested in the Pertussis Serological Potency Test (PSPT) and MPT are significantly similar, a P-value of 0.92 was found by means of the chi 2 test. Compared to the MPT, the PSPT is more reproducible as is indicated by its smaller 95% confidence intervals. Moreover, by using the PSPT the animal distress can be reduced to an acceptable level and the PSPT also results in a reduction of more than 25% in use of mice.

Animals↗