The Dutch multidisciplinary guideline osteoporosis and fracture prevention, taking a local guideline to the international arena.

BACKGROUND: In 2018, a grant was provided for an evidence-based guideline on osteoporosis and fracture prevention based on 10 clinically relevant questions. METHODS: A multidisciplinary working group was formed with delegates from Dutch scientific and professional societies, including representatives from the patient's organization and the Dutch Institute for Medical Knowledge. The purpose was to obtain a broad consensus among all participating societies to facilitate the implementation of the updated guideline. RESULTS: Novel recommendations in our guideline are as follows: - In patients with an indication for DXA of the lumbar spine and hips, there is also an indication for VFA. - Directly starting with anabolic drugs (teriparatide or romosozumab) in patients with a very high fracture risk; - Directly starting with zoledronic acid in patients 75 years and over with a hip fracture (independent of DXA); - Directly starting with parenteral drugs (denosumab, teriparatide, zoledronic acid) in glucocorticoid-induced osteoporosis with very high fracture risk; - A lifelong fracture risk management, including lifestyle, is indicated from the start of the first treatment. CONCLUSION: In our new multidisciplinary guideline osteoporosis and fracture prevention, we developed 5 "relatively new statements" that are all a crucial step forward in the optimization of diagnosis and treatment for fracture prevention. We also developed 5 flowcharts, and we suppose that this may be helpful for individual doctors and their patients in daily practice and may facilitate implementation.

Magnesium hydroxide versus macrogol/electrolytes in the prevention of opioid-induced constipation in incurable cancer patients: study protocol for an open-label, randomized controlled trial (the OMAMA study).

BACKGROUND: Opioid-induced constipation (OIC) is a common symptom in cancer patients treated with opioids with a prevalence of up to 59%. International guidelines recommend standard laxatives such as macrogol/electrolytes and magnesium hydroxide to prevent OIC, although evidence from randomized controlled trials is largely lacking. The aim of our study is to compare magnesium hydroxide with macrogol /electrolytes in the prevention of OIC in patients with incurable cancer and to compare side-effects, tolerability and cost-effectiveness. METHODS: Our study is an open-label, randomized, multicenter study to examine if magnesium hydroxide is non-inferior to macrogol/electrolytes in the prevention of OIC. In total, 330 patients with incurable cancer, starting with opioids for pain management, will be randomized to treatment with either macrogol/electrolytes or magnesium hydroxide. The primary outcome measure is the proportion of patients with a score of < 30 on the Bowel Function Index (BFI), measured on day 14. The Rome IV criteria for constipation, side effects of and satisfaction with laxatives, pain scores, quality of life (using the EQ-5D-5L), daily use of laxatives and escape medication, and cost-effectiveness will also be assessed. DISCUSSION: In this study we aim to examine if magnesium hydroxide is non-inferior to macrogol/electrolytes in the prevention of OIC. The outcome of our study will contribute to prevention of OIC and scientific evidence of guidelines on (opioid-induced) constipation. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov: NCT05216328 and in the Dutch trial register: NTR80508. EudraCT number 2022-000408-36.

Cancer survivors' needs during various treatment phases after multimodal treatment for colon cancer - is there a role for eHealth?

BACKGROUND: More colon cancer patients are expected to fully recover after treatment due to earlier detection of cancer and improvements in general health- and cancer care. The objective of this study was to gather participants' experiences with full recovery in the different treatment phases of multimodal treatment and to identify their needs during these phases. The second aim was to propose and evaluate possible solutions for unmet needs by the introduction of eHealth. METHODS: A qualitative study based on two focus group discussions with 22 participants was performed. The validated Supportive Care Needs Survey and the Cancer Treatment Survey were used to form the topic list. The verbatim transcripts were analyzed with Atlas.ti. 7th version comprising open, axial and selective coding. The guidelines of the consolidated criteria for reporting qualitative research (COREQ) were used. RESULTS: Experiences with the treatment for colon cancer were in general positive. Most important unmet needs were 'receiving information about the total duration of side effects', 'receiving information about the minimum amount of chemo needed to overall survival' and 'receiving a longer aftercare period (with additional attention for psychological guidance)'. More provision of information online, a chat function with the oncological nurse specialist via a website, and access to scientific articles regarding the optimal dose of chemotherapy were often mentioned as worthwhile additions to the current health care for colon cancer. CONCLUSIONS: Many of the unmet needs of colon cancer survivors occur during the adjuvant treatment phase and thereafter. To further optimize recovery and cancer care, it is necessary to have more focus on these unmet needs. More attention for identifying patients' problems and side-effects during chemotherapy; and identifying patients' supportive care needs after finishing chemotherapy are necessary. For some of these needs, eHealth in the form of blended care will be a possible solution.

Unexpected diagnosis of visceral leishmaniasis in a patient presenting with an infected ICD lead.

Visceral leishmaniasis (VL) is a rare disease in Western countries. Infection with Leishmania parasites usually remains asymptomatic, but may cause significant disease in children and immunocompromised adults in endemic areas. Here, we report a case of sporadic VL caused by Leishmania infantum in an immunocompetent patient who had visited Southern France one year ago and presented with implantable cardioverter defibrillator (ICD) lead infection.

The (a)-Symptomatic Vertebral Fracture: A Frequently Discovered Entity With Clinical Relevance in Fracture Patients Screened on Osteoporosis.

OBJECTIVE: Description of the prevalence of vertebral fractures in a fracture and osteoporosis outpatient clinic (FO-Clinic) and evaluation of the value of spinal radiographs by screening on osteoporosis. DESIGN: Retrospective data collection, description, and analysis. METHODS: All patients admitted to the FO-Clinic during the period of December 2005 until October 2006 were enrolled in this study. At the FO-Clinic spinal radiographs were obtained and bone mineral density (BMD) was measured by Dual energy X-ray-Absorptiometry (DXA). RESULTS: During the study period, a total of 176 patients were screened at our FO-Clinic. In 41.5% of these patients, a vertebral fracture was diagnosed. There appeared to be an indication for anti-osteoporotic medication in 95 of the 176 patients. Of these 95 patients, 77% could be identified by spinal radiographs. Moreover, only 36% of all patients with a vertebral fracture did suffer from osteoporosis. CONCLUSION: The prevalence of vertebral fractures in patients screened at an FO-Clinic is high and spinal radiographs can identify up to 77% of patients in which anti-osteoporotic medication should be considered. However, fracture risk is not only dependent on bone quality but also on bone density. Therefore, the preferred method of screening on osteoporosis is DXA with vertebral fracture assessment and, if necessary, spinal radiographs. If DXA is not available, spinal radiographs might be used as a first step in osteoporosis screening.

An illustrated case of doxorubicin-induced radiation recall dermatitis and a review of the literature.

Radiation recall dermatitis (RRD) is a rare cutaneous reaction occurring within a previously irradiated field, precipitated by certain drugs. A case of RRD most likely induced by doxorubicin is presented and illustrated together with a review of the literature.

Rabies in South Africa between 1993 and 2005--what has been achieved?

Epidemiological analyses in time and space were carried out on all animal rabies cases reported in South Africa for the period 1993-2005. Validation of state veterinary records was done by comparing these with data from the 2 diagnostic laboratories mandated to test for animal rabies. A discrepancy between state veterinary records and laboratory results was found and is discussed. The total number of positive rabies cases reported to veterinary services between 1993 and 2005 was 4767. During this period the proportion of domestic animal rabies had increased to 79% (19% more than for the period 1980-1994), with 59% of the total cases being domestic dogs. Of the domestic animal cases 74 % were canine and only 21% were bovine; when compared to the data from 1985-1994 there was an increase of 6% of rabies in canine and a 3% decrease in bovine cases. A disturbing trend is the increase in the incidence of rabies over the last 16 years in provinces neighbouring KwaZulu-Natal province, where rabies used to be concentrated, and in Limpopo province.

Building capacity for improved veterinary epidemiosurveillance in southern Africa.

A workshop to produce recommendations on training requirements for improved epidemiosurveillance of livestock diseases in southern Africa was organised at the Department of Veterinary Tropical Diseases in the Veterinary Faculty of the University of Pretoria. It was attended by 23 persons representing 10 different southern African countries. The majority of the participants were actively involved in veterinary epidemiosurveillance and many of them were members of the SADC Epidemiology and Informatics Subcommittee. Discussions focused on (i) epidemiosurveillance networks and their 2 main components, i.e. (ii) diagnosis and (iii) information flow. The debates were guided by 3 questions; (i) what are the requirements for an effective network, (ii) what cannot be achieved with existing capacity and (iii) how can the current capacity be improved. Workshop participants developed lists of realistic capacity building needs, which were divided into structural needs and training requirements. Structural needs mainly concerned communication means and quality assurance. With regard to training, the need for appropriate continuing education of all actors at the various disease management levels (non-professional, para-professional, professional) was expressed. Special emphasis was put on capacity building at the lowest level, i.e. the livestock owner and the para-professionals at the community level. At the international level, it was felt that special emphasis should be put on building capacity to improve the understanding of international agreements on trade in animals and animal products and to improve the capacity of negotiating such agreements.

[Cystic adventitial degeneration of the popliteal artery; an unexpected cause of intermittent claudication]. / Cysteuze adventitiadegeneratie van de A. poplitea; een onverwachte oorzaak van claudicatio intermittens.

Three men, aged 48, 44 and 51 years, were referred to the vascular surgery outpatient clinic because of acute intermittent claudication in one leg. The first patient had no medical history and no vascular risk factors, the second patient was receiving drug treatment for hypercholesterolaemia and diabetes mellitus and the third patient smoked. After additional radiological diagnostics, cystic adventitial degeneration of the popliteal artery was diagnosed in all patients. All 3 patients were operated. Only circumferential resection of the cystic adventitia and the outer layer of the media, so-called exarteriectomy, was performed in the second patient. The other 2 patients underwent resection of the affected popliteal artery followed by an autologous vein graft. The post-operative course was uncomplicated. The diagnosis of cystic adventitial degeneration was confirmed histopathologically. Cystic adventitial degeneration is localised only in the popliteal artery in 85-90% of cases. It is probably caused by incorporation of mesenchymal cells in the wall of the popliteal artery during embryogenesis. The disease is often progressive and, if left untreated, may lead to critical ischaemia due to arterial occlusion. Surgical intervention is therefore necessary, with exarteriectomy as the preferred technique, especially because the patients are often young.

When ideal and real culture clash--trust, infidelity and condom use.

With high rates of HIV transmission in South Africa, the correct and consistent use of condoms has become critically important. The findings reported in this article form part of a larger study that investigated the vulnerability of women to HIV infection. This article concentrates on one dimension of the study: how a clash between real and ideal culture negatively impacts upon condom use. This study, conducted in Bloemfontein, revealed that an ideal culture of trust, resulted in non condom use. On the other hand, this study also revealed that despite the emphasis on an ideal culture of trust, a real culture of infidelity exists. This places individuals at risk of contracting HIV, as condom use is guided by ideal rather than real culture.

Phase I and pharmacological study of daily oral administration of perifosine (D-21266) in patients with advanced solid tumours.

Alkylphosphocholines are a novel class of antitumour agents structurally related to ether lipids that interact with the cell membrane and influence intracellular growth signal transduction pathways. We performed a phase I trial with an analogue of miltefosine, perifosine (D-21266), which was expected to induce less gastrointestinal toxicity. Objectives of the trial were: to determine the maximum-tolerated dose (MTD) for daily administration, to identify the dose-limiting toxicity (DLT) of this schedule, to assess drug accumulation and to determine the relevant pharmacokinetic parameters. 22 patients with advanced solid tumours were treated at doses ranging from 50 to 350 mg/day for 3 weeks, followed by 1 week of rest. Toxicity consisted mainly of gastrointestinal side-effects: nausea was reported by 11 patients (52%, 10 patients Common Toxicity Criteria (CTC) grades 1-2 and 1 patient CTC grade 3), vomiting by 8 (38%, all CTC grades 1-2), and diarrhoea by 9 (43%, 8 patients CTC grades 1-2 and 1 patient CTC grade 3). The severity of these side effects appeared to increase with increasing doses. Another common side-effect was fatigue, occurring in 9 patients (43%). No haematology toxicity was observed. Dose-limiting toxicity (DLT) was not reached, but gastrointestinal complaints led to an early treatment discontinuation in an increasing number of patients at the higher dose levels. Therefore, MTD was established at 200 mg/day. The pharmacokinetic studies suggested dose proportionality.

Phase I clinical and pharmacologic study of chronic oral administration of the farnesyl protein transferase inhibitor R115777 in advanced cancer.

PURPOSE: To determine the maximum-tolerated dose, toxicities, and pharmacokinetics of R115777, a farnesyl transferase inhibitor, when administered continuously via the oral route. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with R115777 using an interpatient dose escalation scheme starting at 50 mg bid. Pharmacokinetics were assessed on days 1, 28, and 56. RESULTS: Twenty-eight patients were entered onto the study and the median duration of treatment was 55 days. The dose-limiting toxicities were myelosuppression and neurotoxicity. At a dose of 400 mg bid, grade 4 leukocytopenia and neutropenia were seen in two of four patients. Neurotoxicity grade 3 developed in one of five patients at 500 mg bid and in one of 13 at 300 mg bid after 8 weeks of treatment. Common nonhematologic toxicities were nausea, vomiting, and fatigue. The recommended dose for phase II/III testing in this scheme is 300 mg bid. The pharmacokinetic studies indicated dose proportionality. Little accumulation occurred and steady-state levels were reached within 2 to 3 days. Analyses of historic tumor material showed that five of 15 of patients had a K-ras mutation in codon 12. Three patients with pancreatic, colon, and cervix carcinomas had stable disease and one patient with a colon carcinoma had a minor response accompanied by a more than 50% decrease in carcinoembryonic antigen tumor marker. A fifth patient, with platinum-refractory non-small-cell lung cancer, showed a partial response that lasted for 5 months. CONCLUSION: Continuous dosing of R115777 is feasible with an acceptable toxicity profile at a dose of 300 mg bid.

Evaluation of the bioequivalence of tablets and capsules containing the novel anticancer agent R115777 (Zarnestra) in patients with advanced solid tumors.

R115777 (Zamestra) is a novel anticancer agent, currently undergoing phase III clinical testing. An open, cross-over trial was performed in 24 patients with solid tumors to compare the bioavailability of a new tablet formulation with the standard capsule formulation. Both dosage forms were administered once daily in doses of 300 or 400 mg. Patients received R115777 as a capsule on day I and as a tablet on day 2, or vice versa. Blood samples were drawn up to 24 hours after drug intake and R115777 levels were measured using a validated high performance liquid chromatography (HPLC) method. The following pharmacokinetic parameters were determined and compared for the two formulations: time to maximal plasma concentration (Tmax), half-life (t 1/2), maximal plasma concentration (Cmax) and area under the curve at twenty-four hours (AUC24h). For the latter two parameters, 90% classical confidence intervals of the ratio tablet/capsule were calculated after a log-transformation, using an Analysis of Variance (ANOVA). For t 1/2 and Tmax, no statistically significant differences were found between tablet and capsule. The point estimates of the ratio's of the log-normalized Cmax and AUC24h were 0.94 and 0.92, respectively, and the 90% confidence intervals were 0.81-1.09 and 0.83-1.03, which is within the critical range for bioequivalence of 0.80-1.25. In conclusion, the established pharmacokinetic parameters demonstrate that the capsule and tablet formulations of R115777 are interchangeable.

[Diagnostic image (86). A man with thirst and diplopia]. / Diagnose in beeld (86). Een man met dorst en dubbelzien. Multipel myeloom met N.-abducensparese links.

A 71-year-old man was thirsty, had bone pains and a double vision. Multiple myeloma with hypercalcemia was diagnosed. One tumour in the clivus turned out to be compressing the left N. abducens.

Ras biochemistry and farnesyl transferase inhibitors: a literature survey.

Over the last decades, knowledge on the genetic defects involved in tumor formation and growth has increased rapidly. This has launched the development of novel anticancer agents, interfering with the proteins encoded by the identified mutated genes. One gene of particular interest is ras, which is found mutated at high frequency in a number of malignancies. The Ras protein is involved in signal transduction: it passes on stimuli from extracellular factors to the cell nucleus, thereby changing the expression of a number of growth regulating genes. Mutated Ras proteins remain longer in their active form than normal Ras proteins, resulting in an overstimulation of the proliferative pathway. In order to function, Ras proteins must undergo a series of post-translational modifications, the most important of which is farnesylation. Inhibition of Ras can be accomplished through inhibition of farnesyl transferase, the enzyme responsible for this modification. With this aim, a number of agents, designated farnesyl transferase inhibitors (FTIs), have been developed that possess antineoplastic activity. Several of them have recently entered clinical trials. Even though clinical testing is still at an early stage, antitumor activity has been observed. At the same time, knowledge on the biochemical mechanisms through which these drugs exert their activity is expanding. Apart from Ras, they also target other cellular proteins that require farnesylation to become activated, e.g. RhoB. Inhibition of the farnesylation of RhoB results in growth blockade of the exposed tumor cells as well as an increase in the rate of apoptosis. In conclusion, FTIs present a promising class of anticancer agents, acting through biochemical modulation of the tumor cells.

A randomised, multicentre study of ceftriaxone versus standard therapy in the treatment of lower respiratory tract infections.

In this study the efficacy and cost-effectiveness of i.v. ceftriaxone 1 g once daily (CTX) was compared with standard i.v. antibiotic treatment (STD) for lower respiratory tract infections (LRTI). STD was given according to the guidelines of the American Thoracic Society and consisted of either cefuroxime 1500 mg three times daily (q8h), amoxicillin/clavulanic acid 1200 mg q8h or ceftriaxone 2 g once daily; each with or without a macrolide. After a minimum of 5 days i.v. therapy, patients could be switched to oral therapy. One hundred patients were enrolled in the study; 52 patients received CTX and 48 STD. Groups were comparable with respect to demographic and baseline characteristics. Seventy patients had a confirmed diagnosis of pneumonia. Twenty-nine patients had a severe type I exacerbation of chronic bronchitis. In one patient the diagnosis of LRTI could not be confirmed. In approximately 50% of the patients a microbiological diagnosis could be made. The most important isolated pathogens from sputum and blood were (positive blood cultures in brackets): Streptococcus pneumoniae 14 (9) and Haemophilus influenzae 16. Mean duration of i.v. therapy was 7.4 days in both groups. Average duration of hospitalisation was 15.0 days for CTX patients and 15.9 days for STD patients. Overall cure and improvement rate at the end of treatment was 47 (90%) for patients receiving ceftriaxone 1 g compared to 37 (77%) for patients receiving standard therapy. Pathogens were eradicated or presumed to be eradicated in 84% of the CTX patients and in 76% of the STD patients. Mean total costs per treatment were lower for CTX than for STD treatment: NLG 169 versus 458. These results show, that i.v. ceftriaxone 1 g once daily is as effective as standard therapy in the treatment of LRTI and that its use reduces treatment costs, in view of the multiple daily dosing regimens of most standard therapies.

Accessibility of professional health care (PRHC) in greater Bloemfontein.

The health of citizens is usually a priority in any society. In order to prevent/cure disease, people make use of various forms of care, ranging from lay care to professional health care (PRHC). Professional health care, however, is not equally accessible to all members of a society. This article attempts to indicate how factors such as costs, distance, consultation hours, attitude of medical personnel can result in PRHC being less accessible for some members and totally inaccessible for other members of a society. It is imperative that health care planners should once again review this issue in order to ensure that all South Africans are able to exercise their basic right to health care.